BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatm...BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatment options,and associated risk factors among LT recipients with CRKP is now lacking.AIM To assess the incidence,resistance,therapy,and risk factors of CRKP infections post-LT,and to evaluate the impact of them on prognosis.METHODS A retrospective study was conducted,including 430 consecutive patients who underwent LT between January 2015 and June 2023.This study aimed to investigate the risk factors for CRKP infections and their influence on outcomes using logistic regression analysis.RESULTS Among the 430 patients who underwent LT,20(4.7%)experienced at least one documented CRKP infection within 3 months post-transplantation.The median time from LT to the onset of CRKP infections was 6.5 days.The lungs and bloodstream were the most common sites of CRKP infections.CRKP isolates were relatively susceptible to ceftazidime/avibactam(93.7%),polymyxin B(90.6%),and tigecycline(75.0%)treatment.However,all isolates were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin treatment.Recipients with CRKP infections had a mortality rate of 35%,the rate was 12.5%for those receiving ceftazidime/avibactam therapy.Multivariate analysis identified female sex[odds ratio(OR)=3.306;95%confidence interval(CI):1.239-8.822;P=0.017],intraoperative bleeding≥3000 mL(OR=3.269;95%CI:1.018-10.490;P=0.047),alanine aminotransferase on day 1 post-LT≥1500 U/L(OR=4.370;95%CI:1.686-11.326;P=0.002),and post-LT mechanical ventilation(OR=2.772;95%CI:1.077-7.135;P=0.035)as significant variables associated with CRKP.CRKP infections were related to an intensive care unit length(ICU)of stay≥7 days and 6-month all-cause mortality post-LT.CONCLUSION CRKP infections were frequent complications following LT,with poor associated outcomes.Risk factors for post-LT CRKP infections included female sex,significant intraoperative bleeding,elevated alanine aminotransferase levels,and the need for mechanical ventilation.CRKP infections negatively impacted survival and led to prolonged ICU stays.展开更多
Multidrug-resistant(MDR)gram-negative bacteria(GNB)are responsible for high mortality and morbidity in health care settings world-wide.They have been declared as priority pathogens by the WHO for their continuously es...Multidrug-resistant(MDR)gram-negative bacteria(GNB)are responsible for high mortality and morbidity in health care settings world-wide.They have been declared as priority pathogens by the WHO for their continuously escalating antimicrobial resistance.Neverthe-less,data associated with MDR GNB in health care–associated infections are insufficient.Surgical site infections(SSIs)are among the most commonly occurring health care–associated infections.Such infections are particularly common when bacteria from a patient’s normal microflora are transferred to the surgical sites during surgical procedures.SSIs affect approximately 0.5%–3%of patients under-going surgery,resulting in prolonged hospital stays compared with patients without SSIs.SSIs result in severe problems and lead to a heavy economic burden.Most SSIs can be avoided if suitable preventive measures are employed.Novel findings support the dedicated usage of oral preoperative surgical antimicrobial prophylaxis for specific surgeries based on sites/organs.Immediate interventions are sought to control the transmission of MDR GNB typically found in hospital settings.The present narrative review aims to describe MDR GNB in SSIs in different sites.Antimicrobial resistance epidemiology and preventive measures for SSIs are also discussed.Differ-ent intrinsic and extrinsic factors and control measures are elaborated for curbing SSIs.展开更多
Objective:This study investigated the clinical efficacy of bedaquilinecontaining regimens in the treatment of drug-resistant pulmonary tuberculosis and the diagnostic value of computed tomography(CT).Methods:We retros...Objective:This study investigated the clinical efficacy of bedaquilinecontaining regimens in the treatment of drug-resistant pulmonary tuberculosis and the diagnostic value of computed tomography(CT).Methods:We retrospectively analyzed the clinical diagnosis,treatment,and CT imaging data of patients with drug-resistant pulmonary tuberculosis treated in Wenzhou Central Hospital from 1 January to 31 December 2022.According to whether the treatment regimen contained bedaquiline,the patients were divided into an observation group(bedaquiline tablets t background regimen)and a control group(background regimen).The clinical efficacy and pulmonary CT changes before and after treatment were analyzed in both groups.Results:After 24 weeks of treatment,there was no statistically significant difference in the white blood cell count or concentrations of hemoglobin,alanine aminotransferase,serum albumin,or creatinine between the two groups(t=0.71,0.93,0.05,0.18,and 0.08,respectively;p>0.05).After 4,8,and 12 weeks of treatment,there was no statistically significant difference in the sputum culture-negative conversion rate between the two groups(χ^(2)=2.67,0.48,and 1.82,respectively;p>0.05).At 24 weeks of treatment,the sputum culture-negative conversion rate in the observation group reached 100%,which was significantly higher than that in the control group(χ^(2)=3.97,p<0.05).The effective absorption rates on chest imaging in the two groups of patients at 12 weeks were 83.33% and 57.89%,respectively.At 24 weeks of treatment,the effective absorption rates were 88.00% and 65.85% in the two groups,with a statistically significant difference(χ^(2)=3.98;p<0.05).There were significant differences in cavity absorption at 24 weeks(χ^(2)=4.33,p<0.05)and 48 weeks after treatment(χ^(2)=10.63,p<0.05).Conclusion:The addition of bedaquiline to the background regimen improved the sputum culture-negative conversion rate and chest imaging effective rate.Patients achieved good results at the end of the 24-week treatment period.展开更多
BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects ove...BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to eradication.It has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in vitro.METHODS In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients.In vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,respectively.The most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation.This assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation.Crystalline violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains.The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction.Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups.RESULTS HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the strain.QHD had strong bacteriostatic and bactericidal effects on HP,with MICs of 32-64 mg/mL.QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains,disrupt the biofilm structure,lower the accumulation of(p)ppGpp,decrease the expression of biofilm-related genes including LuxS,Spot,glup(HP1174),NapA,and CagE,and reduce the expression of efflux pump-related genes such as HP0605,HP0971,HP1327,and HP1489.Based on metabolomic analysis,QHD induced oxidative stress in HP,enhanced metabolism,and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate(AMP),thereby affecting HP growth,metabolism,and protein synthesis.CONCLUSION QHD exerts bacteriostatic and bactericidal effects on HP,and reduces HP drug resistance by inhibiting HP biofilm formation,destroying its biofilm structure,inhibiting the expression of biofilm-related genes and efflux pump-related genes,enhancing HP metabolism,and activating AMP in HP.展开更多
Drug resistance poses an escalating global challenge in the battle against infections.The effectiveness of conventional antibiotics and other anti-infective drugs is waning as microbes develop heightened resistance to...Drug resistance poses an escalating global challenge in the battle against infections.The effectiveness of conventional antibiotics and other anti-infective drugs is waning as microbes develop heightened resistance to existing treatments.Antimicrobial resistance poses a formidable challenge to global health and development,ranking among the top 10 public health threats to humanity as declared by the World Health Organization.Projections indicate that if left unaddressed,antimicrobial resistance could inflict an annual economic burden on the global GDP ranging from$1trillion to$3.4 trillion by 2030.Consequently,the management of common infections becomes increasingly arduous,while the likelihood of disease transmission,severe illness,and mortality escalates.展开更多
Objectives:Non-small cell lung cancer(NSCLC)represents a formidable malignancy characterized by its marked metastatic potential and intrinsic resistance to therapeutic interventions.The identification of potential bio...Objectives:Non-small cell lung cancer(NSCLC)represents a formidable malignancy characterized by its marked metastatic potential and intrinsic resistance to therapeutic interventions.The identification of potential biomarkers delineating the progression and metastatic cascade of NSCLC assumes paramount importance in fostering advancements toward enhanced patient outcomes and prognostic stratification.Methods:The expression level of the actin-related protein 2/3 complex;subunit 1A(ARPC1A)in NSCLC was evaluated using The Cancer Genome Atlas(TCGA)and Gene Expression Profiling Interactive Analysis(GEPIA)databases;along with the LinkedOmics database for co-expression genes.Further verification of ARPC1A expression in normal lung cells and NSCLC cells;as well as in normal tissues and lung cancer tissues;was performed using quantitative real-time reverse transcription PCR(RTqPCR)and Western blotting.The function of ARPC1A was explored through Gene Set Enrichment Analysis(GSEA)and immune infiltration analysis;followed by functional experiments for validation.Results:ARPC1A is upregulated in NSCLC and is associated with unfavorable clinical prognoses.Additionally,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis highlights a potential link between the ARPC1A gene and the cell cycle and p53 signaling pathways.ARPC1A also promotes cell proliferation and resistance to chemotherapeutic drugs,thereby enhancing the oncogenic potential of NSCLC.Relevant cell-based experiments confirm that targeted inhibition of ARPC1A effectively suppresses cellular migratory and invasive capabilities.The immune infiltration analysis showed a close association between ARPC1A expression and various immune components,suggesting ARPC1A may interact with the tumor microenvironment.Mechanistically,ARPC1A promotes cell migration by stimulating the epithelialto-mesenchymal transition(EMT).Conclusion:The study results revealed the potential of ARPC1A as a valuable prognostic biomarker for NSCLC.Additionally,the associated mechanisms provide insights that may pave the way for therapeutic interventions for NSCLC patients.展开更多
Despite ongoing advancements in cancer treatment,the emergence of primary and acquired resistance poses a significant challenge for both traditional chemotherapy and immune checkpoint blockade therapies.The demand for...Despite ongoing advancements in cancer treatment,the emergence of primary and acquired resistance poses a significant challenge for both traditional chemotherapy and immune checkpoint blockade therapies.The demand for targeted therapeutics for multidrug-resistant cancer is more important than ever.Peptides,as emerging alternatives to current anticancer drugs,offer exquisite versatility in facilitating the design of novel oncology drugs,with the core superiorities of good biocompatibility and a low tendency to induce drug resistance.This review comprehensively introduces the pharmacological mechanisms of peptide-based drugs and strategies for overcoming multidrug resistance(MDR)in cancers,including inducing cell membrane lysis,targeting organelles,activating anticancer immune responses,enhancing drug uptake,targeting ATP-binding cassette(ABC)transporters,and targeting B-cell lymphoma-2(BCL-2)family proteins.Additionally,the current clinical applications of representative peptides in combating MDR cancers and their potential directions for medicinal chemistry research have been thoroughly discussed.This review offers essential insights into the novel treatment approaches for MDR cancers and highlights the trends and perspectives in this field.展开更多
Antibody-drug conjugates(ADCs)are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker.Currently,15 ADCs have been clinically approved worldwide.More than 100 clinical...Antibody-drug conjugates(ADCs)are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker.Currently,15 ADCs have been clinically approved worldwide.More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs.ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development.It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells,thereby producing promising antitumor efficacy and favorable adverse effect profiles.However,emergence of drug resistance has severely hindered the clinical efficacy of ADCs.In this review,we introduce the structure and mechanism of ADCs,describe the development of ADCs,summarized the latest research about the mechanisms of ADC resistance,discussed the strategies to overcome ADCs resistance,and predicted biomarkers for treatment response to ADC,aiming to contribute to the development of ADCs in the future.展开更多
c-Kit (CD117) is a type IIIa receptor tyrosine kinase (RTK) that plays a key role in regulating the normal physiological processes of cells. In addition, the activation of c-Kit activates the tyrosine kinase signal tr...c-Kit (CD117) is a type IIIa receptor tyrosine kinase (RTK) that plays a key role in regulating the normal physiological processes of cells. In addition, the activation of c-Kit activates the tyrosine kinase signal transduction pathway, which is closely related to the occurrence and development of gynecological tumors, especially ovarian cancer. This article reviews the mechanisms of platinum resistance in ovarian cancer and the research progress of c-Kit in ovarian cancer.展开更多
Recent studies have shown a noticeable increase in global Helicobacter pylori(H.pylori)resistance,with clarithromycin resistance surpassing 15%in various areas.However,inadequate epidemiological monitoring,especially ...Recent studies have shown a noticeable increase in global Helicobacter pylori(H.pylori)resistance,with clarithromycin resistance surpassing 15%in various areas.However,inadequate epidemiological monitoring,especially in developing countries,and the absence of uniform testing methods lead to discrepancies between regions and a possible underestimation of resistance levels.The complexity of treating H.pylori is driven by its highly dynamic genome,which is prone to frequent mutations contributing to phenotypical resistance.The usual course of action in empirical treatment involves using a combination of various drugs simultaneously,leading to significant resistance selection pressure and potential side effects.The emergence of H.pylori strains resistant to multiple drugs is closely tied to failures in first-line treatment,highlighting the need to prevent further resistance by using optimal initial empirical therapy or regimens guided by antibiotic susceptibility testing,requiring a collection of mixed samples and multiple isolates for accurate assessment.The emergence of new treatments like potassium-competitive acid blockers offers a hopeful approach to decrease antimicrobial usage while still ensuring effectiveness in comparison to traditional therapies with proton pump inhibitors.Additionally,the use of probiotics is under investigation to identify specific strains and formulations that may mitigate therapy-associated adverse effects.展开更多
Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of pu...Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of published data on the indirect costs incurred by patients with drug-resistant tuberculosis in Mozambique. Objective: To assess the indirect costs, income reduction, and work productivity incurred by patients undergoing diagnosis and treatment for Drug-Resistant Tuberculosis (DRTB) in Mozambique during their TB treatment. Methods: As part of a comprehensive mixed-methods study conducted from January 2021 to April 2023, this research utilized a descriptive cross-sectional approach, incorporating both quantitative and qualitative methods. The primary goal was to evaluate the costs incurred by the national health system due to drug-resistant TB. Additionally, to explore the indirect costs experienced by patients and their families during treatment, semi-structured interviews were conducted with 27 individuals who had been undergoing treatment for over six months. Results: All survey participants unanimously reported a significant decline in labour productivity, with 70.3% experiencing a reduction in their monthly income. Before falling ill, the majority of respondents (33.3%) earned up to $76.92 monthly, representing the minimum earnings range, while 29.2% had a monthly income above $230.77, the maximum earnings range. Among those who experienced income loss, the majority (22.2%) reported a decrease of up to $76.92 per month, and 18.5% cited a loss exceeding $230.77 per month. Notably, patients with Drug-Resistant Tuberculosis (DRTB) have not incurred the direct costs of the disease, as these are covered by the government. Conclusion: The financial burden of treating Drug-Resistant Tuberculosis (DRTB), along with the income reduction it causes, is substantial. Implementing a patient-centred, multidisciplinary, and multisector approach, coupled with strong psychosocial support, can significantly reduce the catastrophic costs DRTB patients incur.展开更多
With the continuous advancement of communication and unmanned aerial vehicle(UAV)technologies,the collaborative operations of diverse platforms,including UAVs and ground vehicles,have been significantly promoted.Howev...With the continuous advancement of communication and unmanned aerial vehicle(UAV)technologies,the collaborative operations of diverse platforms,including UAVs and ground vehicles,have been significantly promoted.However,battlefield uncertainties,such as equipment failures and enemy attacks,can impact these collaborative operations'stability and communication efficiency.To this end,we design a highly destruction-resistant air-ground cooperative resilient networking platform that aims to enhance the robustness of network communications by integrating ground vehicle information for UAV network deployment.It then incorporates the concept of virtual guiding force,enabling the UAV swarm to adaptively configure its network layout based on ground vehicle information,thereby improving network destruction resistance.Simulation results demonstrate that the UAV swarm involved in the proposed platform exhibits balanced flight energy consumption and excellent performance in network destruction resistance.展开更多
Transparent materials utilized as underwater optical windows are highly vulnerable to various forms of pollution or abrasion due to their intrinsic hydrophilic properties.This susceptibility is particularly pronounced...Transparent materials utilized as underwater optical windows are highly vulnerable to various forms of pollution or abrasion due to their intrinsic hydrophilic properties.This susceptibility is particularly pronounced in underwater environments where pollutants can impede the operation of these optical devices,significantly degrading or even compromising their optical properties.The glass catfish,known for its remarkable transparency in water,maintains surface cleanliness and clarity despite exposure to contaminants,impurities abrasion,and hydraulic pressure.Inspired by the glass catfish’s natural attributes,this study introduces a new solution named subaquatic abrasion-resistant and anti-fouling window(SAAW).Utilizing femtosecond laser ablation and electrodeposition,the SAAW is engineered by embedding fine metal bone structures into a transparent substrate and anti-fouling sliding layer,akin to the sturdy bones among catfish’s body.This approach significantly bolsters the window’s abrasion resistance and anti-fouling performance while maintaining high light transmittance.The sliding layer on the SAAW’s surface remarkably reduces the friction of various liquids,which is the reason that SAAW owns the great anti-fouling property.The SAAW demonstrates outstanding optical clarity even after enduring hundreds of sandpaper abrasions,attributing to the fine metal bone structures bearing all external forces and protecting the sliding layer of SAAW.Furthermore,it exhibits exceptional resistance to biological adhesion and underwater pressure.In a green algae environment,the window remains clean with minimal change in transmittance over one month.Moreover,it retains its wettability and anti-fouling properties when subjected to a depth of 30 m of underwater pressure for 30 d.Hence,the SAAW prepared by femtosecond laser ablation and electrodeposition presents a promising strategy for developing stable optical windows in liquid environments.展开更多
Layered double hydroxides(LDHs)as coatings attract much attention in corrosion and protection of light metals due to their interesting properties such as in-situ synthesis,unique layer-stacking structure,tunable compo...Layered double hydroxides(LDHs)as coatings attract much attention in corrosion and protection of light metals due to their interesting properties such as in-situ synthesis,unique layer-stacking structure,tunable composition,and good biocompatibility as well.Currently,single LDH coating faces challenges such as time-consumed synthesis,thin coating thickness and inadequate density.This paper provides a systematic review of the cutting-edge advancements in modulation of composition,synthesis and applications of LDHs on Mg and Al alloys in corrosion protection and biomedicalfields.The focus is concentrated on the intercalation of corrosion inhibitors into LDH coatings.Particularly the anti-corrosion mechanisms of both inorganic anions(nitrate,vanadate,and molybdate)and organic anion intercalation(carboxylic acid anions and hydroxyquinolines)were discussed within the context of corrosion inhibitor intercalation LDH.The modification of LDHs is introduced with low surface energy substances such as silanes and fatty acids.The formation mechanism of LDHfilms and the active anti-corrosion mechanisms were proposed.A comparison of LDH coatings between Mg alloy and Al alloy was carried out from different perspectives,and further researches on LDH corrosion protection were prospected.展开更多
Background:Pudilan Xiaoyan Oral Liquid(PDL)is a Chinese patent medicine with notable pharmacological properties,including anti-inflammatory and antibacterial effects.Drug-resistant Pseudomonas aeruginosa infection is ...Background:Pudilan Xiaoyan Oral Liquid(PDL)is a Chinese patent medicine with notable pharmacological properties,including anti-inflammatory and antibacterial effects.Drug-resistant Pseudomonas aeruginosa infection is a common and refractory bacterial infection in clinical practice.Due to its high drug resistance,it brings great challenges to treatment.This study aimed to assess the therapeutic efficacy of PDL in a murine model of pneumonia induced by drug-resistant Pseudomonas aeruginosa.Methods:Three different doses of PDL(11 mL/kg/d,5.5 mL/kg/d,2.75 mL/kg/d)were used to observe lung tissue pathology and inflammatory cytokine levels in pneumonia mouse models induced by multidrug-resistant Pseudomonas aeruginosa(MDR-PA).Additionally,the protective efficacy of PDL against mortality in infected mice was evaluated using a death model caused by MDR-PA.Finally sub-MIC concentration of levofloxacin was used to induce drug-resistant mice pneumonia model to evaluate the role of PDL in reversing drug resistance.Experimental data are expressed as mean±standard deviation.Statistical significance was determined by one-way analysis of variance followed by Tukey’s multiple-comparisons test.Results:Treatment effect of PDL on MDR-PA pneumonia:the medium and small doses of PDL can significantly reduce the lung index of multi-drug resistant bacteria infected pneumonia model mice(P<0.05),the lung index inhibition rates for these groups were 55.09%and 58.43%,and improve the degree of lung tissue lesions of mice;The expression of serum cytokines keratinocyte chemoattractant,tumor necrosis factor-αand monocyte chemoattractant protein-1 could be decreased in the three dosage groups of PDL(P<0.01).PDL treatment not only lowered the mortality but also extended the survival duration in mice infected with MDR-PA.It was found after sub-MIC concentration of levofloxacin induced resistance of Pseudomonas aeruginosa to pneumonia in mice.Compared with the model group,the lung index of mice in high and medium PDL doses was significantly reduced(P<0.05),with inhibition rates of 32.16%and 37.73%,respectively.Conclusion:PDL demonstrates protective effects against MDR-PA infection pneumonia,notably decreasing serum inflammatory factor levels.It shows promise in mitigating antibiotic resistance and offers potential for treating pneumonia resulting from Pseudomonas aeruginosa resistance.展开更多
Electronic auctions(e-auctions)remove the physical limitations of traditional auctions and bring this mechanism to the general public.However,most e-auction schemes involve a trusted auctioneer,which is not always cre...Electronic auctions(e-auctions)remove the physical limitations of traditional auctions and bring this mechanism to the general public.However,most e-auction schemes involve a trusted auctioneer,which is not always credible in practice.Some studies have applied cryptography tools to solve this problem by distributing trust,but they ignore the existence of collusion.In this paper,a blockchain-based Privacy-Preserving and Collusion-Resistant scheme(PPCR)for double auctions is proposed by employing both cryptography and blockchain technology,which is the first decentralized and collusion-resistant double auction scheme that guarantees bidder anonymity and bid privacy.A two-server-based auction framework is designed to support off-chain allocation with privacy preservation and on-chain dispute resolution for collusion resistance.A Dispute Resolution agreement(DR)is provided to the auctioneer to prove that they have conducted the auction correctly and the result is fair and correct.In addition,a Concise Dispute Resolution protocol(CDR)is designed to handle situations where the number of accused winners is small,significantly reducing the computation cost of dispute resolution.Extensive experimental results confirm that PPCR can indeed achieve efficient collusion resistance and verifiability of auction results with low on-chain and off-chain computational overhead.展开更多
BACKGROUND The prevalence of multidrug-resistant(MDR)bacteria has increased globally,with extensive drug-resistant(XDR)bacteria posing a threat to patients.CASE SUMMARY This case report describes a young man admitted ...BACKGROUND The prevalence of multidrug-resistant(MDR)bacteria has increased globally,with extensive drug-resistant(XDR)bacteria posing a threat to patients.CASE SUMMARY This case report describes a young man admitted for suspected tropical fever infections who experienced rapid deterioration in health.Despite negative results for tropical fever infections,he had neutrophilic leucocytosis,acute kidney injury,and chest imaging findings suggestive of bilateral consolidations.On day two,he was diagnosed with infective endocarditis with possible rheumatic heart disease and MDR methicillin-resistant Staphylococcus aureus bacteraemia,and communityacquired pneumonia.Despite treatment with broad-spectrum antibiotics,he did not respond and succumbed to death on day five.CONCLUSION This case highlights that clinicians/public should be aware of MDR communityacquired pneumonia,bacteraemia,and endocarditis which ultimately culminate in high rates of morbidity and mortality.Early identification of pathogenic strain and prompt antibiotic treatment are a mainstay for the management and prevention of early fatalities.Simultaneously,route cause analysis of communityacquired MDR/XDR pathogens is a global need.展开更多
Despite well-known limitations,mice remain useful as model animals to study tuberculosis(TB)pathogenesis,the basic immune response,the extent of lung pathology as well as efficacy of new drugs against Mycobacterium tu...Despite well-known limitations,mice remain useful as model animals to study tuberculosis(TB)pathogenesis,the basic immune response,the extent of lung pathology as well as efficacy of new drugs against Mycobacterium tuberculosis[1,2].There are four routes of tuberculosis infection in mice:aerosol generation and exposition,intravenous injection,intranasal administration,and subcutaneous administration[3].展开更多
Indonesia is one of the countries with the highest burden of tuberculosis and drug-resistant tuberculosis(DR-TB)across the world.Based on data from the World Health Organization(WHO)Global TB Report 2023,it is estimat...Indonesia is one of the countries with the highest burden of tuberculosis and drug-resistant tuberculosis(DR-TB)across the world.Based on data from the World Health Organization(WHO)Global TB Report 2023,it is estimated that there are 10000 cases of DR-TB in Indonesia.Bedaquiline,a novel antitubercular drug,has been implemented to treat DR-TB globally.It was administered either a shorter(9 months)or individualized treatment regimen(18 months).However,long treatment duration with various adverse events affects patient compliance.Therefore,a short treatment with less medication is urgently required.In 2022,the WHO announced an alternative regimen-bedaquiline,pretomanid,linezolid,and moxifloxacin(BPaLM)to treat DR-TB patients for six months without resistance to fluoroquinolones[1].This recommendation is based on previous clinical trials of TB,Zenix TB,and TB-PRACTECAL.The introduction of BPaL and BPaLM provided a bright future for treating DR-TB patients.展开更多
BACKGROUND A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs,resulting in heightened mortality rates,psychosocial challenges,and a diminished quality of life...BACKGROUND A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs,resulting in heightened mortality rates,psychosocial challenges,and a diminished quality of life.Genetic factors,particularly within the SCN1A gene,and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases.In this extended study,we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response.AIM To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response.METHODS The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases.We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique.The diagnostic performance of interleukin(IL)-1β,IL-6,and high mobility group box 1(HMGB1)protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis.RESULTS AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy.Serum biomarkers IL-6,IL1βand HMGB1 demonstrated diagnostic potential,with cutoff values of 4.63 pg/mL,59.52 pg/mL and 7.99 ng/mL,respectively,offering valuable tools for epilepsy management.Moreover,specific genotypes(AA and AT)were found to be linked to the elevated levels of IL-1βand IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy.CONCLUSION SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk.These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.展开更多
文摘BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatment options,and associated risk factors among LT recipients with CRKP is now lacking.AIM To assess the incidence,resistance,therapy,and risk factors of CRKP infections post-LT,and to evaluate the impact of them on prognosis.METHODS A retrospective study was conducted,including 430 consecutive patients who underwent LT between January 2015 and June 2023.This study aimed to investigate the risk factors for CRKP infections and their influence on outcomes using logistic regression analysis.RESULTS Among the 430 patients who underwent LT,20(4.7%)experienced at least one documented CRKP infection within 3 months post-transplantation.The median time from LT to the onset of CRKP infections was 6.5 days.The lungs and bloodstream were the most common sites of CRKP infections.CRKP isolates were relatively susceptible to ceftazidime/avibactam(93.7%),polymyxin B(90.6%),and tigecycline(75.0%)treatment.However,all isolates were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin treatment.Recipients with CRKP infections had a mortality rate of 35%,the rate was 12.5%for those receiving ceftazidime/avibactam therapy.Multivariate analysis identified female sex[odds ratio(OR)=3.306;95%confidence interval(CI):1.239-8.822;P=0.017],intraoperative bleeding≥3000 mL(OR=3.269;95%CI:1.018-10.490;P=0.047),alanine aminotransferase on day 1 post-LT≥1500 U/L(OR=4.370;95%CI:1.686-11.326;P=0.002),and post-LT mechanical ventilation(OR=2.772;95%CI:1.077-7.135;P=0.035)as significant variables associated with CRKP.CRKP infections were related to an intensive care unit length(ICU)of stay≥7 days and 6-month all-cause mortality post-LT.CONCLUSION CRKP infections were frequent complications following LT,with poor associated outcomes.Risk factors for post-LT CRKP infections included female sex,significant intraoperative bleeding,elevated alanine aminotransferase levels,and the need for mechanical ventilation.CRKP infections negatively impacted survival and led to prolonged ICU stays.
文摘Multidrug-resistant(MDR)gram-negative bacteria(GNB)are responsible for high mortality and morbidity in health care settings world-wide.They have been declared as priority pathogens by the WHO for their continuously escalating antimicrobial resistance.Neverthe-less,data associated with MDR GNB in health care–associated infections are insufficient.Surgical site infections(SSIs)are among the most commonly occurring health care–associated infections.Such infections are particularly common when bacteria from a patient’s normal microflora are transferred to the surgical sites during surgical procedures.SSIs affect approximately 0.5%–3%of patients under-going surgery,resulting in prolonged hospital stays compared with patients without SSIs.SSIs result in severe problems and lead to a heavy economic burden.Most SSIs can be avoided if suitable preventive measures are employed.Novel findings support the dedicated usage of oral preoperative surgical antimicrobial prophylaxis for specific surgeries based on sites/organs.Immediate interventions are sought to control the transmission of MDR GNB typically found in hospital settings.The present narrative review aims to describe MDR GNB in SSIs in different sites.Antimicrobial resistance epidemiology and preventive measures for SSIs are also discussed.Differ-ent intrinsic and extrinsic factors and control measures are elaborated for curbing SSIs.
基金2021 Science and Technology Bureau Project of Wenzhou City,Zhejiang Province,Grant/Award Numbers:Y20211047,Y20210844。
文摘Objective:This study investigated the clinical efficacy of bedaquilinecontaining regimens in the treatment of drug-resistant pulmonary tuberculosis and the diagnostic value of computed tomography(CT).Methods:We retrospectively analyzed the clinical diagnosis,treatment,and CT imaging data of patients with drug-resistant pulmonary tuberculosis treated in Wenzhou Central Hospital from 1 January to 31 December 2022.According to whether the treatment regimen contained bedaquiline,the patients were divided into an observation group(bedaquiline tablets t background regimen)and a control group(background regimen).The clinical efficacy and pulmonary CT changes before and after treatment were analyzed in both groups.Results:After 24 weeks of treatment,there was no statistically significant difference in the white blood cell count or concentrations of hemoglobin,alanine aminotransferase,serum albumin,or creatinine between the two groups(t=0.71,0.93,0.05,0.18,and 0.08,respectively;p>0.05).After 4,8,and 12 weeks of treatment,there was no statistically significant difference in the sputum culture-negative conversion rate between the two groups(χ^(2)=2.67,0.48,and 1.82,respectively;p>0.05).At 24 weeks of treatment,the sputum culture-negative conversion rate in the observation group reached 100%,which was significantly higher than that in the control group(χ^(2)=3.97,p<0.05).The effective absorption rates on chest imaging in the two groups of patients at 12 weeks were 83.33% and 57.89%,respectively.At 24 weeks of treatment,the effective absorption rates were 88.00% and 65.85% in the two groups,with a statistically significant difference(χ^(2)=3.98;p<0.05).There were significant differences in cavity absorption at 24 weeks(χ^(2)=4.33,p<0.05)and 48 weeks after treatment(χ^(2)=10.63,p<0.05).Conclusion:The addition of bedaquiline to the background regimen improved the sputum culture-negative conversion rate and chest imaging effective rate.Patients achieved good results at the end of the 24-week treatment period.
基金Supported by the National Natural Science Foundation of China,No.81973615 and No.82304930Natural Science Foundation of Beijing,No.7332323Capital’s Funds for Health Improvement and Research,No.CF2022-2-40711.
文摘BACKGROUND Helicobacter pylori(HP),the most common pathogenic microorganism in stomach,can induce inflammatory reactions in the gastric mucosa,causing chronic gastritis and even gastric cancer.HP infection affects over 4.4 billion people globally,with a worldwide infection rate of up to 50%.The multidrug resistance of HP poses a serious challenge to eradication.It has been monstrated that compared to bismuth quadruple therapy,Qingre Huashi decoction(QHD)combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions;in addition,QHD directly inhibit and kill HP in vitro.METHODS In this study,12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients.In vitro,the minimum inhibitory concentration(MIC)values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining,respectively.The most robust biofilm-forming strain of HP was selected,and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation.This assessment was performed using agar dilution,E-test,killing dynamics,and transmission electron microscopy(TEM).The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation.Crystalline violet method,scanning electron microscopy,laser confocal scanning microscopy,and(p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains.The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction.Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups.RESULTS HP could form biofilms of different degrees in vitro,and the intensity of formation was associated with the drug resistance of the strain.QHD had strong bacteriostatic and bactericidal effects on HP,with MICs of 32-64 mg/mL.QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains,disrupt the biofilm structure,lower the accumulation of(p)ppGpp,decrease the expression of biofilm-related genes including LuxS,Spot,glup(HP1174),NapA,and CagE,and reduce the expression of efflux pump-related genes such as HP0605,HP0971,HP1327,and HP1489.Based on metabolomic analysis,QHD induced oxidative stress in HP,enhanced metabolism,and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate(AMP),thereby affecting HP growth,metabolism,and protein synthesis.CONCLUSION QHD exerts bacteriostatic and bactericidal effects on HP,and reduces HP drug resistance by inhibiting HP biofilm formation,destroying its biofilm structure,inhibiting the expression of biofilm-related genes and efflux pump-related genes,enhancing HP metabolism,and activating AMP in HP.
文摘Drug resistance poses an escalating global challenge in the battle against infections.The effectiveness of conventional antibiotics and other anti-infective drugs is waning as microbes develop heightened resistance to existing treatments.Antimicrobial resistance poses a formidable challenge to global health and development,ranking among the top 10 public health threats to humanity as declared by the World Health Organization.Projections indicate that if left unaddressed,antimicrobial resistance could inflict an annual economic burden on the global GDP ranging from$1trillion to$3.4 trillion by 2030.Consequently,the management of common infections becomes increasingly arduous,while the likelihood of disease transmission,severe illness,and mortality escalates.
基金supported by the Natural Science Foundation of Anhui Province(ML 2308085MC80)the Anhui Medical University Research and Innovation Talent Team(KZ).
文摘Objectives:Non-small cell lung cancer(NSCLC)represents a formidable malignancy characterized by its marked metastatic potential and intrinsic resistance to therapeutic interventions.The identification of potential biomarkers delineating the progression and metastatic cascade of NSCLC assumes paramount importance in fostering advancements toward enhanced patient outcomes and prognostic stratification.Methods:The expression level of the actin-related protein 2/3 complex;subunit 1A(ARPC1A)in NSCLC was evaluated using The Cancer Genome Atlas(TCGA)and Gene Expression Profiling Interactive Analysis(GEPIA)databases;along with the LinkedOmics database for co-expression genes.Further verification of ARPC1A expression in normal lung cells and NSCLC cells;as well as in normal tissues and lung cancer tissues;was performed using quantitative real-time reverse transcription PCR(RTqPCR)and Western blotting.The function of ARPC1A was explored through Gene Set Enrichment Analysis(GSEA)and immune infiltration analysis;followed by functional experiments for validation.Results:ARPC1A is upregulated in NSCLC and is associated with unfavorable clinical prognoses.Additionally,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis highlights a potential link between the ARPC1A gene and the cell cycle and p53 signaling pathways.ARPC1A also promotes cell proliferation and resistance to chemotherapeutic drugs,thereby enhancing the oncogenic potential of NSCLC.Relevant cell-based experiments confirm that targeted inhibition of ARPC1A effectively suppresses cellular migratory and invasive capabilities.The immune infiltration analysis showed a close association between ARPC1A expression and various immune components,suggesting ARPC1A may interact with the tumor microenvironment.Mechanistically,ARPC1A promotes cell migration by stimulating the epithelialto-mesenchymal transition(EMT).Conclusion:The study results revealed the potential of ARPC1A as a valuable prognostic biomarker for NSCLC.Additionally,the associated mechanisms provide insights that may pave the way for therapeutic interventions for NSCLC patients.
基金supported by the Science and Technology Innovation Program of Hunan Province(No.2022RC1168)National Natural Science Foundation of China(Nos.82322073,82173846,82304533)+12 种基金CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2023-I2M-3-009)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)China Postdoctoral Science Foundation(No.2021M702215)Oriental Scholars of Shanghai Universities(No.TP2022081)Jiangxi Province Thousand Talents Program(No.jxsq2023102168)Young Talent Lifting Project of China Association of Chinese Medicine(No.CACM-(2021-QNRC2-A08))Shanghai Rising-Star Program(No.22QA1409100)Shanghai Sailing Program(No.22YF1445000)2021 Shanghai Science and Technology Innovation Action Plan(No.21S11902800)Three-year Action Plan for Shanghai TCM Development and Inheritance Program(Nos.ZY(2021-2023)-0208,ZY(2021-2023)-0401)High level Key Discipline of National Administration of Traditional Chinese Medicine(No.71)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202004)Innovation team of high-level local universities in Shanghai:Strategic Innovation Team of TCM Chemical Biology。
文摘Despite ongoing advancements in cancer treatment,the emergence of primary and acquired resistance poses a significant challenge for both traditional chemotherapy and immune checkpoint blockade therapies.The demand for targeted therapeutics for multidrug-resistant cancer is more important than ever.Peptides,as emerging alternatives to current anticancer drugs,offer exquisite versatility in facilitating the design of novel oncology drugs,with the core superiorities of good biocompatibility and a low tendency to induce drug resistance.This review comprehensively introduces the pharmacological mechanisms of peptide-based drugs and strategies for overcoming multidrug resistance(MDR)in cancers,including inducing cell membrane lysis,targeting organelles,activating anticancer immune responses,enhancing drug uptake,targeting ATP-binding cassette(ABC)transporters,and targeting B-cell lymphoma-2(BCL-2)family proteins.Additionally,the current clinical applications of representative peptides in combating MDR cancers and their potential directions for medicinal chemistry research have been thoroughly discussed.This review offers essential insights into the novel treatment approaches for MDR cancers and highlights the trends and perspectives in this field.
基金supported by the National Natural Science Foundation of China(Nos.U21A20421 and 82073882)the Key Project of Science Technology Program of Guangzhou(No.2023B03J0029)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2023B1515130009)Key-Area Research and Development Program of Guangdong Province(2023B1111020005).
文摘Antibody-drug conjugates(ADCs)are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker.Currently,15 ADCs have been clinically approved worldwide.More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs.ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development.It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells,thereby producing promising antitumor efficacy and favorable adverse effect profiles.However,emergence of drug resistance has severely hindered the clinical efficacy of ADCs.In this review,we introduce the structure and mechanism of ADCs,describe the development of ADCs,summarized the latest research about the mechanisms of ADC resistance,discussed the strategies to overcome ADCs resistance,and predicted biomarkers for treatment response to ADC,aiming to contribute to the development of ADCs in the future.
文摘c-Kit (CD117) is a type IIIa receptor tyrosine kinase (RTK) that plays a key role in regulating the normal physiological processes of cells. In addition, the activation of c-Kit activates the tyrosine kinase signal transduction pathway, which is closely related to the occurrence and development of gynecological tumors, especially ovarian cancer. This article reviews the mechanisms of platinum resistance in ovarian cancer and the research progress of c-Kit in ovarian cancer.
基金Supported by the Industrial Technological Initiation Scholarship of National Council for Scientific and Technological Development,CNPq,Brazil,No.0932204294929829 and No.7414780530977345the Scientific Initiation Scholarship Programme(PIBIC)of National Council for Scientific and Technological Development,CNPq,Brazil,No.5763023359532159,No.6472982965854452,and No.7340128440641417+2 种基金the Scientific Initiation Scholarship Programme(PIBIC)of Bahia State Research Support Foundation,FAPESB,Brazil,No.19.573.301.5418the PERMANECER Programme of Pro-Rectory of Student Assistance at Federal University of Bahia,No.R8EZ-4V4W-6LQX-5LC8the CNPq Research Productivity Fellow,No.4357511882624145.
文摘Recent studies have shown a noticeable increase in global Helicobacter pylori(H.pylori)resistance,with clarithromycin resistance surpassing 15%in various areas.However,inadequate epidemiological monitoring,especially in developing countries,and the absence of uniform testing methods lead to discrepancies between regions and a possible underestimation of resistance levels.The complexity of treating H.pylori is driven by its highly dynamic genome,which is prone to frequent mutations contributing to phenotypical resistance.The usual course of action in empirical treatment involves using a combination of various drugs simultaneously,leading to significant resistance selection pressure and potential side effects.The emergence of H.pylori strains resistant to multiple drugs is closely tied to failures in first-line treatment,highlighting the need to prevent further resistance by using optimal initial empirical therapy or regimens guided by antibiotic susceptibility testing,requiring a collection of mixed samples and multiple isolates for accurate assessment.The emergence of new treatments like potassium-competitive acid blockers offers a hopeful approach to decrease antimicrobial usage while still ensuring effectiveness in comparison to traditional therapies with proton pump inhibitors.Additionally,the use of probiotics is under investigation to identify specific strains and formulations that may mitigate therapy-associated adverse effects.
文摘Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of published data on the indirect costs incurred by patients with drug-resistant tuberculosis in Mozambique. Objective: To assess the indirect costs, income reduction, and work productivity incurred by patients undergoing diagnosis and treatment for Drug-Resistant Tuberculosis (DRTB) in Mozambique during their TB treatment. Methods: As part of a comprehensive mixed-methods study conducted from January 2021 to April 2023, this research utilized a descriptive cross-sectional approach, incorporating both quantitative and qualitative methods. The primary goal was to evaluate the costs incurred by the national health system due to drug-resistant TB. Additionally, to explore the indirect costs experienced by patients and their families during treatment, semi-structured interviews were conducted with 27 individuals who had been undergoing treatment for over six months. Results: All survey participants unanimously reported a significant decline in labour productivity, with 70.3% experiencing a reduction in their monthly income. Before falling ill, the majority of respondents (33.3%) earned up to $76.92 monthly, representing the minimum earnings range, while 29.2% had a monthly income above $230.77, the maximum earnings range. Among those who experienced income loss, the majority (22.2%) reported a decrease of up to $76.92 per month, and 18.5% cited a loss exceeding $230.77 per month. Notably, patients with Drug-Resistant Tuberculosis (DRTB) have not incurred the direct costs of the disease, as these are covered by the government. Conclusion: The financial burden of treating Drug-Resistant Tuberculosis (DRTB), along with the income reduction it causes, is substantial. Implementing a patient-centred, multidisciplinary, and multisector approach, coupled with strong psychosocial support, can significantly reduce the catastrophic costs DRTB patients incur.
基金supported by the Researchers Supporting Project of King Saud University,Riyadh,Saudi Arabia,under Project RSPD2025R681。
文摘With the continuous advancement of communication and unmanned aerial vehicle(UAV)technologies,the collaborative operations of diverse platforms,including UAVs and ground vehicles,have been significantly promoted.However,battlefield uncertainties,such as equipment failures and enemy attacks,can impact these collaborative operations'stability and communication efficiency.To this end,we design a highly destruction-resistant air-ground cooperative resilient networking platform that aims to enhance the robustness of network communications by integrating ground vehicle information for UAV network deployment.It then incorporates the concept of virtual guiding force,enabling the UAV swarm to adaptively configure its network layout based on ground vehicle information,thereby improving network destruction resistance.Simulation results demonstrate that the UAV swarm involved in the proposed platform exhibits balanced flight energy consumption and excellent performance in network destruction resistance.
基金supported by the National Science Foundation of China under Grant Nos(Nos.12127806,62175195)the International Joint Research Laboratory for Micro/Nano Manufacturing and Measurement Technologies。
文摘Transparent materials utilized as underwater optical windows are highly vulnerable to various forms of pollution or abrasion due to their intrinsic hydrophilic properties.This susceptibility is particularly pronounced in underwater environments where pollutants can impede the operation of these optical devices,significantly degrading or even compromising their optical properties.The glass catfish,known for its remarkable transparency in water,maintains surface cleanliness and clarity despite exposure to contaminants,impurities abrasion,and hydraulic pressure.Inspired by the glass catfish’s natural attributes,this study introduces a new solution named subaquatic abrasion-resistant and anti-fouling window(SAAW).Utilizing femtosecond laser ablation and electrodeposition,the SAAW is engineered by embedding fine metal bone structures into a transparent substrate and anti-fouling sliding layer,akin to the sturdy bones among catfish’s body.This approach significantly bolsters the window’s abrasion resistance and anti-fouling performance while maintaining high light transmittance.The sliding layer on the SAAW’s surface remarkably reduces the friction of various liquids,which is the reason that SAAW owns the great anti-fouling property.The SAAW demonstrates outstanding optical clarity even after enduring hundreds of sandpaper abrasions,attributing to the fine metal bone structures bearing all external forces and protecting the sliding layer of SAAW.Furthermore,it exhibits exceptional resistance to biological adhesion and underwater pressure.In a green algae environment,the window remains clean with minimal change in transmittance over one month.Moreover,it retains its wettability and anti-fouling properties when subjected to a depth of 30 m of underwater pressure for 30 d.Hence,the SAAW prepared by femtosecond laser ablation and electrodeposition presents a promising strategy for developing stable optical windows in liquid environments.
基金supported by the National Natural Science Foundation of China(Grant Nos.52471080 and 52071191).
文摘Layered double hydroxides(LDHs)as coatings attract much attention in corrosion and protection of light metals due to their interesting properties such as in-situ synthesis,unique layer-stacking structure,tunable composition,and good biocompatibility as well.Currently,single LDH coating faces challenges such as time-consumed synthesis,thin coating thickness and inadequate density.This paper provides a systematic review of the cutting-edge advancements in modulation of composition,synthesis and applications of LDHs on Mg and Al alloys in corrosion protection and biomedicalfields.The focus is concentrated on the intercalation of corrosion inhibitors into LDH coatings.Particularly the anti-corrosion mechanisms of both inorganic anions(nitrate,vanadate,and molybdate)and organic anion intercalation(carboxylic acid anions and hydroxyquinolines)were discussed within the context of corrosion inhibitor intercalation LDH.The modification of LDHs is introduced with low surface energy substances such as silanes and fatty acids.The formation mechanism of LDHfilms and the active anti-corrosion mechanisms were proposed.A comparison of LDH coatings between Mg alloy and Al alloy was carried out from different perspectives,and further researches on LDH corrosion protection were prospected.
基金supported by Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2021B015)the Fundamental Research Funds for the Central Public Welfare Research Institutes(JJPY2022017).
文摘Background:Pudilan Xiaoyan Oral Liquid(PDL)is a Chinese patent medicine with notable pharmacological properties,including anti-inflammatory and antibacterial effects.Drug-resistant Pseudomonas aeruginosa infection is a common and refractory bacterial infection in clinical practice.Due to its high drug resistance,it brings great challenges to treatment.This study aimed to assess the therapeutic efficacy of PDL in a murine model of pneumonia induced by drug-resistant Pseudomonas aeruginosa.Methods:Three different doses of PDL(11 mL/kg/d,5.5 mL/kg/d,2.75 mL/kg/d)were used to observe lung tissue pathology and inflammatory cytokine levels in pneumonia mouse models induced by multidrug-resistant Pseudomonas aeruginosa(MDR-PA).Additionally,the protective efficacy of PDL against mortality in infected mice was evaluated using a death model caused by MDR-PA.Finally sub-MIC concentration of levofloxacin was used to induce drug-resistant mice pneumonia model to evaluate the role of PDL in reversing drug resistance.Experimental data are expressed as mean±standard deviation.Statistical significance was determined by one-way analysis of variance followed by Tukey’s multiple-comparisons test.Results:Treatment effect of PDL on MDR-PA pneumonia:the medium and small doses of PDL can significantly reduce the lung index of multi-drug resistant bacteria infected pneumonia model mice(P<0.05),the lung index inhibition rates for these groups were 55.09%and 58.43%,and improve the degree of lung tissue lesions of mice;The expression of serum cytokines keratinocyte chemoattractant,tumor necrosis factor-αand monocyte chemoattractant protein-1 could be decreased in the three dosage groups of PDL(P<0.01).PDL treatment not only lowered the mortality but also extended the survival duration in mice infected with MDR-PA.It was found after sub-MIC concentration of levofloxacin induced resistance of Pseudomonas aeruginosa to pneumonia in mice.Compared with the model group,the lung index of mice in high and medium PDL doses was significantly reduced(P<0.05),with inhibition rates of 32.16%and 37.73%,respectively.Conclusion:PDL demonstrates protective effects against MDR-PA infection pneumonia,notably decreasing serum inflammatory factor levels.It shows promise in mitigating antibiotic resistance and offers potential for treating pneumonia resulting from Pseudomonas aeruginosa resistance.
基金supported by the National Key R&D Program of China (No.2020YFB1005500)the Leading-edge Technology Program of Jiangsu Natural Science Foundation (No.BK20202001)+1 种基金the Fundamental Research Funds for the Central Universities (No.XJSJ23040)the Postdoctoral Science Foundation of Jiangsu Province (No.2021K596C)。
文摘Electronic auctions(e-auctions)remove the physical limitations of traditional auctions and bring this mechanism to the general public.However,most e-auction schemes involve a trusted auctioneer,which is not always credible in practice.Some studies have applied cryptography tools to solve this problem by distributing trust,but they ignore the existence of collusion.In this paper,a blockchain-based Privacy-Preserving and Collusion-Resistant scheme(PPCR)for double auctions is proposed by employing both cryptography and blockchain technology,which is the first decentralized and collusion-resistant double auction scheme that guarantees bidder anonymity and bid privacy.A two-server-based auction framework is designed to support off-chain allocation with privacy preservation and on-chain dispute resolution for collusion resistance.A Dispute Resolution agreement(DR)is provided to the auctioneer to prove that they have conducted the auction correctly and the result is fair and correct.In addition,a Concise Dispute Resolution protocol(CDR)is designed to handle situations where the number of accused winners is small,significantly reducing the computation cost of dispute resolution.Extensive experimental results confirm that PPCR can indeed achieve efficient collusion resistance and verifiability of auction results with low on-chain and off-chain computational overhead.
文摘BACKGROUND The prevalence of multidrug-resistant(MDR)bacteria has increased globally,with extensive drug-resistant(XDR)bacteria posing a threat to patients.CASE SUMMARY This case report describes a young man admitted for suspected tropical fever infections who experienced rapid deterioration in health.Despite negative results for tropical fever infections,he had neutrophilic leucocytosis,acute kidney injury,and chest imaging findings suggestive of bilateral consolidations.On day two,he was diagnosed with infective endocarditis with possible rheumatic heart disease and MDR methicillin-resistant Staphylococcus aureus bacteraemia,and communityacquired pneumonia.Despite treatment with broad-spectrum antibiotics,he did not respond and succumbed to death on day five.CONCLUSION This case highlights that clinicians/public should be aware of MDR communityacquired pneumonia,bacteraemia,and endocarditis which ultimately culminate in high rates of morbidity and mortality.Early identification of pathogenic strain and prompt antibiotic treatment are a mainstay for the management and prevention of early fatalities.Simultaneously,route cause analysis of communityacquired MDR/XDR pathogens is a global need.
文摘Despite well-known limitations,mice remain useful as model animals to study tuberculosis(TB)pathogenesis,the basic immune response,the extent of lung pathology as well as efficacy of new drugs against Mycobacterium tuberculosis[1,2].There are four routes of tuberculosis infection in mice:aerosol generation and exposition,intravenous injection,intranasal administration,and subcutaneous administration[3].
文摘Indonesia is one of the countries with the highest burden of tuberculosis and drug-resistant tuberculosis(DR-TB)across the world.Based on data from the World Health Organization(WHO)Global TB Report 2023,it is estimated that there are 10000 cases of DR-TB in Indonesia.Bedaquiline,a novel antitubercular drug,has been implemented to treat DR-TB globally.It was administered either a shorter(9 months)or individualized treatment regimen(18 months).However,long treatment duration with various adverse events affects patient compliance.Therefore,a short treatment with less medication is urgently required.In 2022,the WHO announced an alternative regimen-bedaquiline,pretomanid,linezolid,and moxifloxacin(BPaLM)to treat DR-TB patients for six months without resistance to fluoroquinolones[1].This recommendation is based on previous clinical trials of TB,Zenix TB,and TB-PRACTECAL.The introduction of BPaL and BPaLM provided a bright future for treating DR-TB patients.
文摘BACKGROUND A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs,resulting in heightened mortality rates,psychosocial challenges,and a diminished quality of life.Genetic factors,particularly within the SCN1A gene,and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases.In this extended study,we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response.AIM To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response.METHODS The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases.We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique.The diagnostic performance of interleukin(IL)-1β,IL-6,and high mobility group box 1(HMGB1)protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis.RESULTS AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy.Serum biomarkers IL-6,IL1βand HMGB1 demonstrated diagnostic potential,with cutoff values of 4.63 pg/mL,59.52 pg/mL and 7.99 ng/mL,respectively,offering valuable tools for epilepsy management.Moreover,specific genotypes(AA and AT)were found to be linked to the elevated levels of IL-1βand IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy.CONCLUSION SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk.These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.
