BACKGROUND： L-3-n-butylphthalide （L-NBP） can inhibit phosphorylation of tau protein and reduce the neurotoxicity of beta-amyloid peptide 1-42 （Aβ1-42）. OBJECTIVE： To observe the neuroprotective effects of L-NBP...BACKGROUND： L-3-n-butylphthalide （L-NBP） can inhibit phosphorylation of tau protein and reduce the neurotoxicity of beta-amyloid peptide 1-42 （Aβ1-42）. OBJECTIVE： To observe the neuroprotective effects of L-NBP on caspase-3 and nuclear factor kappa-B （NF- K B） expression in a rat model of Alzheimer＇s disease. DESIGN, TIME AND SETTING： A cell experiment was performed at the Central Laboratory of Provincial Hospital affiliated to Shandong University between January 2008 and August 2008. MATERIALS： L-NBP （purity 〉 98%） was provided by Shijiazhuang Pharma Group NBP Pharmaceutical Company Limited. Aβ1-42, 3-[4,5-dimethylthiazolo-2]-2,5 iphenyltetrazolium bromide （MTT）, and rabbit anti-Caspase-3 polyclonal antibody were provided by Cell Signaling, USA; goat anti-choactase and rabbit anti-NF- kB antibodies were provided by Santa Cruz, USA. METHODS： Primary cultures were generated from rat basal forebrain and hippocampal neurons at 17 or 19 days of gestation. The cells were assigned into five groups： the control group, the Aβ1-42 group （2 μmol/L）, the Aβ1-42 ＋ 0.1 μmol/L L-NBP group, the Aβ1-42 ＋ 1 μ mol/L L-NBP group, and the Aβ1-42 ＋ 10μmol/L L-NBP group. The neurons were treated with Aβ1-42 （2 μmol/L） alone or in combination with L-NBP （0.1, 1, 10 μmol/L） for 48 hours. Cells in the control group were incubated in PBS. MAIN OUTCOME MEASURES： Morphologic changes were evaluated using inverted microscopy, viability using the M-I-I- method, and the changes in caspase-3 and NF- k B expression using Western blot. RESULTS： Induction with Aβ1-42 for 48 hours caused cell death and soma atrophy, and increased caspase-3 and NF- K B expression （P 〈 0.05）. L-NBP blocked these changes in cell morphology, decreased caspase-3 and NF- k B expression （P 〈 0.05）, and improved cell viability, especially at the high dose （P 〈 0.05）. CONCLUSION： AI3^-42 is toxic to basal forebrain and hippocampal primary neurons; L-NBP protects against this toxicity and inhibits the induction of caspase-3 and NF- K B expression.展开更多
The purpose of this study was to extract phyco-biliproteins (PBP) from Porphyra yezoensis using an optimized procedure and further establish a large scale process for protein production. According to our previous expe...The purpose of this study was to extract phyco-biliproteins (PBP) from Porphyra yezoensis using an optimized procedure and further establish a large scale process for protein production. According to our previous experiences on the extraction of PBP, salting out methods, e.g. ammonium sulfate precipitation, worked more efficiently than isoelectric precipitation, differential centrifugation or ultrafiltration. Thus, we chose ammonium sulfate to coprecipitate PBP in crude solution. After four times of precipitation followed by one time of high speed centrifugation, the maximum purity of crude phycoerythrin and phycocyanin reached 1.94 (A565/A280) and 0.85 (A615/A280), with a yield of 0.50% and 0.37%, respectively. A total of 0.94 mg phycoerythrin and 0.54 mg phycocyanin with purity of more than 3.2 were obtained from 1 g dried P. yezoensis after additional chromatography. We further scaled up the frozen dried P. yezoensis from 20 g to 400 g, with 1295 mg phycoerythrin and 593 mg phycocyanin obtained.展开更多
Receptor-like cytoplasmic kinases(RLCKs),which belong to a large subgroup of receptor-like kinases in plants,play crucial roles in plant development and immunity.However,their functions and regulatory mechanisms in pl...Receptor-like cytoplasmic kinases(RLCKs),which belong to a large subgroup of receptor-like kinases in plants,play crucial roles in plant development and immunity.However,their functions and regulatory mechanisms in plants remain unclear.Here,we report functional characterization of OsRLCK118 from the OsRLCK34 subgroup in rice(Oryza sativa L.).Expression of OsRLCK118 could be induced by infections with Xanthomonas oryzae pv.oryzae(Xoo)strains PXO68 and PXO99.Silencing of OsRLCK118 altered plant height,flag-leaf angle and second-topleaf angle.Silencing of OsRLCK118 also resulted in increasing susceptibility to Xoo and Magnaporthe oryzae(M.oryzae)in rice plants.OsRLCK118 knock-out plants were more sensitive to bacterial blight whereas OsRLCK118 overexpressor plants exhibited increased disease resistance.Expression levels of pathogenesis-related genes of OsPAL1,OsNH1,OsICS1,OsPR1a,OsPR5 and OsPR10 were reduced in the rlck118 mutant compared to wild-type rice(Dongjin)and knock-out of OsRLCK118 compromised the production of reactive oxygen species.These results suggest that OsRLCK118 may modulate basal resistance to Xoo and M.oryzae,possibly through regulation of ROS burst and hormone mediated defense signaling pathway.展开更多
Lead sulfide quantum dots(PbS QDs) hold unique characteristics, including bandgap tunability, solutionprocessability etc., which make them highly applicable in tandem solar cells(TSCs). In all QD TSCs, its efficiency ...Lead sulfide quantum dots(PbS QDs) hold unique characteristics, including bandgap tunability, solutionprocessability etc., which make them highly applicable in tandem solar cells(TSCs). In all QD TSCs, its efficiency lags much behind to their single junction counterparts due to the deficient interconnection layer(ICL) and defective subcells. To improve TSCs performance, we developed three kinds of ICL structures based on 1.34 and 0.96 e V PbS QDs subcells. The control, 1,2-ethanedithiol capped PbS QDs(PbS-EDT)/Au/tin dioxide(SnO_(2))/zinc oxide(Zn O), utilized SnO_(2) layer to obtain high surface compactness.However, its energy level mismatch causes incomplete recombination. Bypassing it, the second ICL(PbS-EDT/Au/Zn O) removed SnO_(2) and boosted the power conversion efficiency(PCE) from 5.75% to 8.69%. In the third ICL(PbS-EDT/poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine](PTAA)/Au/Zn O), a thin layer of PTAA can effectively fill fissures on the surface of PbS-EDT and also protect the front cells from solvent penetration. This TSC obtained a PCE of 9.49% with an open circuit voltage of 0.91 V, a short circuit current density of 15.47 m A/cm~2, and a fill factor of 67.7%. To the best of our knowledge, this was the highest PCE achieved by all PbS QD TSCs reported to date. These TSCs maintained stable performance for a long working time under ambient conditions.展开更多
NR2B subunits are involved in regulating aging, in particular, age-related learning and memory deficits. We examined 19-month-old NR2B transgenic mice and their littermate controls. First, we detected expression of th...NR2B subunits are involved in regulating aging, in particular, age-related learning and memory deficits. We examined 19-month-old NR2B transgenic mice and their littermate controls. First, we detected expression of the NR2B subunit gene, Grin2b, in the neocortex of transgenic mice using real-time PCR. Next, we used microarrays to examine differences in neocortical gene expression. Pathway and signal-net analyses identified multiple pathways altered in the transgenic mice, in-cluding the P53, Jak-STAT, Wnt, and Notch pathways, as well as regulation of the actin cytoskeleton and neuroactive ligand-receptor interactions. Further signal-net analysis highlighted the P53 and insulin-like growth factor pathways as key regulatory pathways. Our results provide new insight into understanding the molecular mechanisms of NR2B regulated age-related memory storage, normal organismal aging and age-related disease.展开更多
Objective: Optical Nerve Atrophy is one of the most common causes of blindness worldwide. The condition is linked to several pathologies, which contribute to the damage of the optic nerve. The presence of a tumor on t...Objective: Optical Nerve Atrophy is one of the most common causes of blindness worldwide. The condition is linked to several pathologies, which contribute to the damage of the optic nerve. The presence of a tumor on the optic nerve, improper formation of the optic nerve, glaucoma, hereditary and central nervous system diseases, and anterior ischemic optic neuropathy promote deterioration of the optic nerve. The purpose of this review is to examine the efficacy of acupuncture therapy for ONA. Method: Clinical trials (case control-trials), and randomized control trials (RCTs) were assessed to observe the efficacy of acupuncture as well as the safety of acupuncture, needling manipulation, and acupoints selection. The data collected in this research include scientific research papers from China National Knowledge Infrastructure (CNKI), PUBMED library, National Library of Medicine (NLM), EMBASE, Cochrane Library, Chinese Biomedical Literature Database, and other literature library date present. Ophthalmoscope, OCT, pupils test, ocular alignment, nystagmus, and visual acuity check were the diagnostic tools used for ONA in the included study. ONA treatment has been a challenge to ophthalmologists over the past decades. At present, western approaches have no fixed treatment mechanism for the condition. Early diagnosis, the use of magnifying lenses, and reduction of increased fluid around the spinal cord and brain are the multiple disciplinary approaches used in western medicine for ONA. On the other hand, Acupuncture, a branch of traditional Chinese medicine, which stimulates the body’s natural healing ability to promote physical and emotional well-being, has reported some significant treatment effects for ONA. Result: The overall result shows that Acupuncture greatly improved patients’ visual acuity, visual field, and visual function in the included study. Acupuncture acting alone showed significant superiority over other treatments for optical nerve atrophy. Acupuncture combined with medication could improve a patient’s condition more rapidly than medications alone. Conclusion: Optic nerve atrophy is a threatening condition to the vision, which is a leading cause of blindness worldwide. Acupuncture has improved the condition of patients with ONA more effectively than other treatment mechanisms in the included study. However, more clinical trials need to be carried out to substantiate stronger evidence of acupuncture for ONA.展开更多
Thermoelectric superlattices are expected to decouple the strong correlation between various thermo-electric parameters,and are an important strategy for excellent thermoelectric performances.The superlattices of(Bi_(...Thermoelectric superlattices are expected to decouple the strong correlation between various thermo-electric parameters,and are an important strategy for excellent thermoelectric performances.The superlattices of(Bi_(2))m(Bi_(2)Te_(3))n homologous series are well-known for low lattice thermal conductivity and intriguing topological surface states.However,the impacts of electronic structure on the thermo-electric performance were still not well-understood in(Bi_(2))m(Bi_(2)Te_(3))n.To cope with this issue,Bi_(2)eBi_(2)Te_(3)superlattice-like films with adjustable Bi_(2)/(Bi_(2)+Bi_(2)Te_(3))molar ratio(R)were successfully fabricated by the molecular beam epitaxy technique.Angle-resolved photoemission spectroscopy measurements com-bined with theoretical calculations revealed the conduction band evolution from single-valley to multi-valley as R≥0.30,leading to intrinsically high carrier effective mass and improved thermoelectric power factor.Also,the superlattice film(R=0.46)with the structure close to Bi_(4)Te_(3)possesses the topological surface state feature around the high symmetry point.As a result of the high effective mass of 3.9 m0 and very high electron density of_(2).31×10^(21)cm^(-3),the film with R=0.46 acquired the highest power factor of 1.49 mW·m^(-1)·K^(-2)at 420 K,outperforming that of other(Bi_(2))m(Bi_(2)Te_(3))n superlattices.This work lays an essential foundation on understanding the electronic structure and further improving thermoelectric performances of(Bi_(2))m(Bi_(2)Te_(3))n homologous series.展开更多
How to engineer single nanocrystal to achieve multiple functions is still a huge challenge.In this work,a novel highly doped rare earth nanocrystal NaErF_(4)@NaGdF_(4)@NaDyF_(4)(Er@Gd@Dy)was designed and fabricated,wh...How to engineer single nanocrystal to achieve multiple functions is still a huge challenge.In this work,a novel highly doped rare earth nanocrystal NaErF_(4)@NaGdF_(4)@NaDyF_(4)(Er@Gd@Dy)was designed and fabricated,which exhibits various performances by itself,including the longitudinal(T1)and transverse relaxation time(T2)double-mode magnetic resonance imaging(MRI),upconversion luminescence and down-shifting luminescence.Upon irradiation of 808 nm near-infrared(NIR)light,the upconverted red light can indirectly activate the photo sensitizer Ce6 conjugated on the surface of nanocrystals for photodynamic therapy(PDT).In vivo experiments demonstrate that the nano materials can eradicate notably primary tumors without obvious systematic toxicity.In addition,the longitudinal and transverse relaxation rates of Er@Gd@Dy are 24.83 and 319.86(mmol/L)^(-1)/s,respectively,which are superior to those of the nanocrystals reported previously.Simultaneously,the nanocrystals have the ability to generate NIR-Ⅱlight located at 1530 nm,favorable in bioimaging in deeper tissues.As a consequence,this new nanoplatform will advance the improvement of multimodal imaging guided tumor diagnosis and treatment.展开更多
Chemodynamic therapy(CDT)as an emerging modality in cancer treatment,its implementation remains a daunting challenge by the lack of smart Fenton catalyst under acidic tumor microenvironments.Herein,we have successfull...Chemodynamic therapy(CDT)as an emerging modality in cancer treatment,its implementation remains a daunting challenge by the lack of smart Fenton catalyst under acidic tumor microenvironments.Herein,we have successfully constructed a Fe_(3)O_(4)@MIL-100 heterojunction by growing Fe-based metal-organic framework(MIL-100)onto the surface of Fe_(3)O_(4) nanoparticles.The as-made heterojunction after encapsu-lating glucose oxidase(termed FMG)is demonstrated as a pH-responsive intelligent Fenton nanosystem with the synergistic effect of starvation therapy(ST).Density functional theory(DFT)calculations reveal that such heterojunction could greatly reduce the energy barrier of the Fenton reaction,which better ex-plains the mechanism of Fenton performance improvement.Moreover,the encapsulated glucose oxidase has successfully activated the ST process,in which its generated H_(2)O_(2) and gluconic acid further improve the CDT efficiency.More O_(2) from the enhanced CDT in turn promotes the enzymatic reaction of glucose oxidase.The Fenton/cascade enzymatic reaction operates in a self-feedback manner as proposed.In vitro and in vivo experiments demonstrate that such intelligent Fenton nanoreactors provide a powerful anti-cancer mechanism for effective tumor ablation with enough safety.This work provides insights into the developments of MOF-based heterojunctions as powerful anticancer treatment nanoreactors.展开更多
Birth weight(BW)is a key determinant of infant mortality.Previous studies have reported seasonal fluctuation of BW.However,the responsible environmental factors remain disputable.High-altitude environment provides a g...Birth weight(BW)is a key determinant of infant mortality.Previous studies have reported seasonal fluctuation of BW.However,the responsible environmental factors remain disputable.High-altitude environment provides a great opportunity to test the current hypotheses due to its distinctive climate conditions.We collected BW data of~9000 Tibetan singletons born at Lhasa(elevation:3660 m)from 2014 to 2018.Using regression models,we analyzed BW seasonality of highland Tibetans.Multivariate models with meteorological factors as independent variables were employed to examine responsible environmental factors accounting for seasonal variation.We compared BW,low-BW prevalence and sex ratio between high-land and lowland populations,and we observed a significant seasonal pattern of BW in Tibetans,with a peak in winter and a trough in summer.Notably,there is a marked sex-biased pattern of BW seasonality(more striking in males than in females).Sunlight exposure in the 3rd trimester and barometric pressure exposure in the 2nd trimester are significantly correlated with BW,and the latter can be explained by seasonal change of oxygen partial pressure.In particular,due to the male-biased BW seasonality,we found a more serious BW reduction and higher prevalence of low-BW in males,and a skewed sex ratio in highlanders.The infant BW of highland Tibetans has a clear pattern of seasonality.The winter BW is larger than the summer BW,due to the longer sunlight exposure during the late-trimester.Male infants are more sensitive to hypoxia than female infants during the 2nd trimester,leading to more BW reduction and higher mortality.展开更多
Chitosan oligosaccharides(COSs)have been reported to possess a broad range of activities such as antitumor,antioxidant and neuroprotective activities.In this study,the protective efects and mechanisms of peracetylated...Chitosan oligosaccharides(COSs)have been reported to possess a broad range of activities such as antitumor,antioxidant and neuroprotective activities.In this study,the protective efects and mechanisms of peracetylated chitosan oligosaccharides(PACOs)against Aβ-induced cognitive defcits were investigated in Sprague–Dawley(SD)rats.PACOs treatment signifcantly improved the learning and memory function of Alzheimer’s disease(AD)rats and attenuated the neuron cell damage caused by Aβ.PACOs also markedly reduced the levels of lactate dehydrogenase(LDH)and Malondialdehyde(MDA)and decreased the phosphorylation of Tau protein to inhibit oxidative injury and infammatory responses in AD rats.Further studies indicated that PACOs may promote the repair of Aβinduced nerve damage and inhibit neuronal apoptosis mainly through regulating PI3K/Akt/GSK3βsignaling pathway.Consistently,the transcriptome analysis verifed that the diferentially expressed genes(DEGs)were mainly involved in neuron development and the PI3K-Akt signaling pathway.Taken together,peracetylated chitosan oligosaccharides(PACOs)have the potential to be developed into novel anti-AD agents targeting the cellular PI3K/Akt/GSK3βsignaling pathway.展开更多
Self-calibrating luminescent thermometry employing luminescence within the optical transparency windows provides a promising prospect for temperature measurement in the biological fields.In this work,a new Nd^(3+)/Yb^...Self-calibrating luminescent thermometry employing luminescence within the optical transparency windows provides a promising prospect for temperature measurement in the biological fields.In this work,a new Nd^(3+)/Yb^(3+)-codoped metal-organic framework Nd_(0.95)Yb_(0.05)BPTC showing threedimensional anionic network,obtained by reacting ligand[1,1’-biphenyl]-3,3’,5,5’-tetracarboxylic acid(H4BPTC)with Nd^(3+)and Yb^(3+)ions under solvothermal conditions,is reported.Upon 808 nm photoexcitation,Nd_(0.95)Yb_(0.05)BPTC simultaneously emits the characteristic near-infrared luminescence of Nd^(3+)and Yb^(3+)ions based on the efficient energy transfer from Nd^(3+)to Yb^(3+)ions.In addition,the emission intensity ratio of Yb^(3+)and Nd^(3+)shows good exponential-like response to temperature in the physiological range of 293-323 K.The feature properties of Nd_(0.95)Yb_(0.05)BPTC include near-infrared absorption and emission,favorable temperature sensitivity and accurate temperature uncertainty,as well as good chemical stability,making such system useful in biomedical applications.展开更多
The hypoxic nature of solid tumors has severely negative effects on oxygen-based photodynamic therapy.In this study,we used porous Pt nanoparticles as a catalase(CAT)nanozyme,the second near-infrared(NIR-Ⅱ)region pho...The hypoxic nature of solid tumors has severely negative effects on oxygen-based photodynamic therapy.In this study,we used porous Pt nanoparticles as a catalase(CAT)nanozyme,the second near-infrared(NIR-Ⅱ)region photothermal transition agents(PTAs),and carriers of photosensitizer chlorin e6(Ce6)to synthesize a composite nanosystem Pt-Ce6.In this system,Pt-Ce6 can continuously and stably decompose H2O2 into oxygen,thereby alleviating tumor hypoxia and improving the effect of photodynamic therapy(PDT).With 650 nm illumination,the reactive oxygen species(ROS)produced by Ce6 will decrease the mitochondrial membrane potential(MMP,ΔΨm)to release cytochrome c(Cyt-c)from the mitochondria into the cytoplasm,eventually leading to mitochondrial-mediated cellular apoptosis during the PDT process.In addition,Pt-Ce6 has good photothermal stability and high photothermal conversion efficiency(52.62%)in the NIR-II region.In U14 tumor-bearing mice,Pt-Ce6 completely suppressed tumor growth and recurrence under laser irradiation.Thus the nanocomposite shows excellent PDT/photothermal therapy(PTT)synergistic performance in vitro and in vivo.展开更多
Gastroesophageal reflux disease(GERD)is caused by esophageal dysfunction resulting in reflux of gastric and duodenal contents into the esophagus,which leads to a series of symptoms.[1]The incidence of GERD in East Asi...Gastroesophageal reflux disease(GERD)is caused by esophageal dysfunction resulting in reflux of gastric and duodenal contents into the esophagus,which leads to a series of symptoms.[1]The incidence of GERD in East Asia ranges from 2.5%to 7.8%.[2]Hiatal hernia(HH)refers to the upper part of the stomach protruding into the chest through the esophageal hiatus.HH is closely related to GERD and can play a role in the development and increased incidence of GERD.[3]The surgical treatment of patients with GERD and HH includes HH repair and Nissen,Toupet,or Dor fundoplication(DF).However,post-operative complications have been associated with fundoplication,including dysphagia and abdominal distension,which reduce the benefit of fundoplication.展开更多
A multifunctional, dual-drug carrier platform was successfully constructed. Core-sheU structured NaGdF4：Yb/Er@NaGdF4：Yb@mSiO2-polyethylene glycol （abbreviated as UCNPS） nanopartides loaded with the antiturnor drug...A multifunctional, dual-drug carrier platform was successfully constructed. Core-sheU structured NaGdF4：Yb/Er@NaGdF4：Yb@mSiO2-polyethylene glycol （abbreviated as UCNPS） nanopartides loaded with the antiturnor drug, doxorubicin （DOX） were incorporated into poly（^-caprolactone） （PCL） and gelatin loaded with antiphlogistic drug, indomethacin （MC） to form nanofibrous fabrics （labeled as MC/UCNPS/DOX） via electrospinning process. The resultant multifunctional spinning pieces can be surgically implanted directly at the tumor site of mice as an orthotopic chemotherapy by controlled-release DOX from mesoporous silicon dioxide （SiO2） and upconversion fluorescence/magnetic resonance dual-model imaging through NaGdF4：Yb/Er@NaGdF4：Yb embedded in MCfldCNPS/DOX invivo.展开更多
Estrogen impacts neural development;meanwhile, it has a protective effect on the brain. Bisphenols, primarily bisphenol A (BPA), can exert estrogen-like or estrogen-interfering effects by binding with estrogen recepto...Estrogen impacts neural development;meanwhile, it has a protective effect on the brain. Bisphenols, primarily bisphenol A (BPA), can exert estrogen-like or estrogen-interfering effects by binding with estrogen receptors. Extensive studies have suggested that neurobehavioral problems, such as anxiety and depression, can be caused by exposure to BPA during neural development. Increasing attention has been paid to the effects on learning and memory of BPA exposure at different developmental stages and in adulthood. Further research is required to elucidate whether BPA increases the risk of neurodegenerative diseases and the underlying mechanisms, as well as to assess whether BPA analogs, such as bisphenol S and bisphenol F, influence the nervous system.展开更多
Severe cardiovascular diseases can rapidly lead to death.At present,most studies in the deep learning field using electrocardiogram(ECG)are performed on intra-patient experiments for the classification of coronary art...Severe cardiovascular diseases can rapidly lead to death.At present,most studies in the deep learning field using electrocardiogram(ECG)are performed on intra-patient experiments for the classification of coronary artery disease(CAD),myocardial infarction,and congestive heart failure(CHF).By contrast,actual conditions are inter-patient experiments.In this study,we proposed a deep learning network,namely,CResFormer,with dual feature extraction to improve accuracy in classifying such diseases.First,fixed segmentation of dual-lead ECG signals without preprocessing was used as input data.Second,one-dimensional convolutional layers performed moderate dimensionality reduction to accommodate subsequent feature extraction.Then,ResNet residual network block layers and transformer encoder layers sequentially performed feature extraction to obtain key associated abstract features.Finally,the Softmax function was used for classifications.Notably,the focal loss function is used when dealing with unbalanced datasets.The average accuracy,sensitivity,positive predictive value,and specificity of four classifications of severe cardiovascular diseases are 99.84%,99.68%,99.71%,and 99.90%in intra-patient experiments,respectively,and 97.48%,93.54%,96.30%,and 97.89%in inter-patient experiments,respectively.In addition,the model performs well in unbalanced datasets and shows good noise robustness.Therefore,the model has great application potential in diagnosing CAD,MI,and CHF in the actual clinical environment.展开更多
The accurate delivery of nanoparticles and organic small molecule drugs remains a serious challenge in nanoparticle-based tumor therapy.Dual-targeted therapy combining tumor cell targeting and organelle targeting is a...The accurate delivery of nanoparticles and organic small molecule drugs remains a serious challenge in nanoparticle-based tumor therapy.Dual-targeted therapy combining tumor cell targeting and organelle targeting is an effective solution.Here,an anticancer nanoformulation accurate delivery system was prepared using hyaluronic acid (HA) targeting CD44 receptors on the surface of tumor cells and IR780iodine (IR780) targeting mitochondrial for delivery.The system is based on an ultra-small Janus structured inorganic sensitizer TiO_(2-x)@NaGdF_(4) nanoparticles (TN NPs) prepared by one-step pyrolysis,further loaded with organic small molecule acoustic sensitizer IR780 and mitochondrial hexokinase Ⅱ inhibitor lonidamine (LND),followed by encapsulation of HA.Ultra-small size nanoparticles exhibit strong tissue penetration,tumor inhibition and in vivo metabolism.Under ultrasound radiation,TN NPs and IR780could produce a synergistic effect,effectively increased the efficiency of reactive oxygen species (ROS)production.Meanwhile,the released IR780 could smoothly target the mitochondria,and the ROS produced by IR780 can destroy the mitochondrial structure and disrupt the mitochondrial respiration.LND could inhibit the energy metabolism of tumor cells by reducing the activity of hexokinase Ⅱ (HK Ⅱ),which further accelerates the process of apoptosis.Furthermore,since the Janus structure allows the integration of multifunctional components into a single system,TN NPs can not only serve as an acoustic sensitizer to generate ROS,but the Gd element contained can also act as the nuclear magnetic resonance (MR)imaging contrast agent,suggesting that the nanoformulation can enable imaging-guided diagnosis and therapy.In conclusion,a new scheme to enhance sonodynamic therapy (SDT) and chemotherapy synergistically is proposed here based on ultra-small dual-targeted nanoformulation with Janus structure in the ultrasound radiation environment.展开更多
基金Supported by:the Medicine and Health Scientific Research Projects of Shandong Province,No. 2007HZ065
文摘BACKGROUND： L-3-n-butylphthalide （L-NBP） can inhibit phosphorylation of tau protein and reduce the neurotoxicity of beta-amyloid peptide 1-42 （Aβ1-42）. OBJECTIVE： To observe the neuroprotective effects of L-NBP on caspase-3 and nuclear factor kappa-B （NF- K B） expression in a rat model of Alzheimer＇s disease. DESIGN, TIME AND SETTING： A cell experiment was performed at the Central Laboratory of Provincial Hospital affiliated to Shandong University between January 2008 and August 2008. MATERIALS： L-NBP （purity 〉 98%） was provided by Shijiazhuang Pharma Group NBP Pharmaceutical Company Limited. Aβ1-42, 3-[4,5-dimethylthiazolo-2]-2,5 iphenyltetrazolium bromide （MTT）, and rabbit anti-Caspase-3 polyclonal antibody were provided by Cell Signaling, USA; goat anti-choactase and rabbit anti-NF- kB antibodies were provided by Santa Cruz, USA. METHODS： Primary cultures were generated from rat basal forebrain and hippocampal neurons at 17 or 19 days of gestation. The cells were assigned into five groups： the control group, the Aβ1-42 group （2 μmol/L）, the Aβ1-42 ＋ 0.1 μmol/L L-NBP group, the Aβ1-42 ＋ 1 μ mol/L L-NBP group, and the Aβ1-42 ＋ 10μmol/L L-NBP group. The neurons were treated with Aβ1-42 （2 μmol/L） alone or in combination with L-NBP （0.1, 1, 10 μmol/L） for 48 hours. Cells in the control group were incubated in PBS. MAIN OUTCOME MEASURES： Morphologic changes were evaluated using inverted microscopy, viability using the M-I-I- method, and the changes in caspase-3 and NF- k B expression using Western blot. RESULTS： Induction with Aβ1-42 for 48 hours caused cell death and soma atrophy, and increased caspase-3 and NF- K B expression （P 〈 0.05）. L-NBP blocked these changes in cell morphology, decreased caspase-3 and NF- k B expression （P 〈 0.05）, and improved cell viability, especially at the high dose （P 〈 0.05）. CONCLUSION： AI3^-42 is toxic to basal forebrain and hippocampal primary neurons; L-NBP protects against this toxicity and inhibits the induction of caspase-3 and NF- K B expression.
文摘The purpose of this study was to extract phyco-biliproteins (PBP) from Porphyra yezoensis using an optimized procedure and further establish a large scale process for protein production. According to our previous experiences on the extraction of PBP, salting out methods, e.g. ammonium sulfate precipitation, worked more efficiently than isoelectric precipitation, differential centrifugation or ultrafiltration. Thus, we chose ammonium sulfate to coprecipitate PBP in crude solution. After four times of precipitation followed by one time of high speed centrifugation, the maximum purity of crude phycoerythrin and phycocyanin reached 1.94 (A565/A280) and 0.85 (A615/A280), with a yield of 0.50% and 0.37%, respectively. A total of 0.94 mg phycoerythrin and 0.54 mg phycocyanin with purity of more than 3.2 were obtained from 1 g dried P. yezoensis after additional chromatography. We further scaled up the frozen dried P. yezoensis from 20 g to 400 g, with 1295 mg phycoerythrin and 593 mg phycocyanin obtained.
基金supported by the National Natural Science Foundation(31860497)Natural Science Foundation of Hainan Province(No.2019RC013)and Hainan Provincial Department of Education[Hnjg2019ZD-2].
文摘Receptor-like cytoplasmic kinases(RLCKs),which belong to a large subgroup of receptor-like kinases in plants,play crucial roles in plant development and immunity.However,their functions and regulatory mechanisms in plants remain unclear.Here,we report functional characterization of OsRLCK118 from the OsRLCK34 subgroup in rice(Oryza sativa L.).Expression of OsRLCK118 could be induced by infections with Xanthomonas oryzae pv.oryzae(Xoo)strains PXO68 and PXO99.Silencing of OsRLCK118 altered plant height,flag-leaf angle and second-topleaf angle.Silencing of OsRLCK118 also resulted in increasing susceptibility to Xoo and Magnaporthe oryzae(M.oryzae)in rice plants.OsRLCK118 knock-out plants were more sensitive to bacterial blight whereas OsRLCK118 overexpressor plants exhibited increased disease resistance.Expression levels of pathogenesis-related genes of OsPAL1,OsNH1,OsICS1,OsPR1a,OsPR5 and OsPR10 were reduced in the rlck118 mutant compared to wild-type rice(Dongjin)and knock-out of OsRLCK118 compromised the production of reactive oxygen species.These results suggest that OsRLCK118 may modulate basal resistance to Xoo and M.oryzae,possibly through regulation of ROS burst and hormone mediated defense signaling pathway.
基金National Natural Science Foundation of China (Grant No. 62374065)Interdisciplinary Research promotion of HUST (No. 2023JCYJ040)+2 种基金Innovation Project of Optics Valley Laboratory (No. OVL2021BG008)Program of Science Technology of Wenzhou City (No. G20210011)financial support from the Innovation and Technology Commission (Grant no. MHP/104/21)。
文摘Lead sulfide quantum dots(PbS QDs) hold unique characteristics, including bandgap tunability, solutionprocessability etc., which make them highly applicable in tandem solar cells(TSCs). In all QD TSCs, its efficiency lags much behind to their single junction counterparts due to the deficient interconnection layer(ICL) and defective subcells. To improve TSCs performance, we developed three kinds of ICL structures based on 1.34 and 0.96 e V PbS QDs subcells. The control, 1,2-ethanedithiol capped PbS QDs(PbS-EDT)/Au/tin dioxide(SnO_(2))/zinc oxide(Zn O), utilized SnO_(2) layer to obtain high surface compactness.However, its energy level mismatch causes incomplete recombination. Bypassing it, the second ICL(PbS-EDT/Au/Zn O) removed SnO_(2) and boosted the power conversion efficiency(PCE) from 5.75% to 8.69%. In the third ICL(PbS-EDT/poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine](PTAA)/Au/Zn O), a thin layer of PTAA can effectively fill fissures on the surface of PbS-EDT and also protect the front cells from solvent penetration. This TSC obtained a PCE of 9.49% with an open circuit voltage of 0.91 V, a short circuit current density of 15.47 m A/cm~2, and a fill factor of 67.7%. To the best of our knowledge, this was the highest PCE achieved by all PbS QD TSCs reported to date. These TSCs maintained stable performance for a long working time under ambient conditions.
基金supported by the National Natural Science Foundationof China,No.30800312 and 30970368the Specialized Research Fund for the Doctoral Program of Higher Education,No.20070269026+1 种基金the Fundamental Research Fund for the Central Universities,No.78210020Innovation Program of Shanghai Municipal Education Commission,No.10ZZ35
文摘NR2B subunits are involved in regulating aging, in particular, age-related learning and memory deficits. We examined 19-month-old NR2B transgenic mice and their littermate controls. First, we detected expression of the NR2B subunit gene, Grin2b, in the neocortex of transgenic mice using real-time PCR. Next, we used microarrays to examine differences in neocortical gene expression. Pathway and signal-net analyses identified multiple pathways altered in the transgenic mice, in-cluding the P53, Jak-STAT, Wnt, and Notch pathways, as well as regulation of the actin cytoskeleton and neuroactive ligand-receptor interactions. Further signal-net analysis highlighted the P53 and insulin-like growth factor pathways as key regulatory pathways. Our results provide new insight into understanding the molecular mechanisms of NR2B regulated age-related memory storage, normal organismal aging and age-related disease.
文摘Objective: Optical Nerve Atrophy is one of the most common causes of blindness worldwide. The condition is linked to several pathologies, which contribute to the damage of the optic nerve. The presence of a tumor on the optic nerve, improper formation of the optic nerve, glaucoma, hereditary and central nervous system diseases, and anterior ischemic optic neuropathy promote deterioration of the optic nerve. The purpose of this review is to examine the efficacy of acupuncture therapy for ONA. Method: Clinical trials (case control-trials), and randomized control trials (RCTs) were assessed to observe the efficacy of acupuncture as well as the safety of acupuncture, needling manipulation, and acupoints selection. The data collected in this research include scientific research papers from China National Knowledge Infrastructure (CNKI), PUBMED library, National Library of Medicine (NLM), EMBASE, Cochrane Library, Chinese Biomedical Literature Database, and other literature library date present. Ophthalmoscope, OCT, pupils test, ocular alignment, nystagmus, and visual acuity check were the diagnostic tools used for ONA in the included study. ONA treatment has been a challenge to ophthalmologists over the past decades. At present, western approaches have no fixed treatment mechanism for the condition. Early diagnosis, the use of magnifying lenses, and reduction of increased fluid around the spinal cord and brain are the multiple disciplinary approaches used in western medicine for ONA. On the other hand, Acupuncture, a branch of traditional Chinese medicine, which stimulates the body’s natural healing ability to promote physical and emotional well-being, has reported some significant treatment effects for ONA. Result: The overall result shows that Acupuncture greatly improved patients’ visual acuity, visual field, and visual function in the included study. Acupuncture acting alone showed significant superiority over other treatments for optical nerve atrophy. Acupuncture combined with medication could improve a patient’s condition more rapidly than medications alone. Conclusion: Optic nerve atrophy is a threatening condition to the vision, which is a leading cause of blindness worldwide. Acupuncture has improved the condition of patients with ONA more effectively than other treatment mechanisms in the included study. However, more clinical trials need to be carried out to substantiate stronger evidence of acupuncture for ONA.
基金Y.J.Ouyang and M.Zhang contributed equally to this work.The work was supported by National Key Research and Development Program of China(Grant No.2021YFA0718700,2019YFA0704900)the National Natural Science Foundation of China(Grant No.92163211)State Key Laboratory of Advanced Technology for Materials Synthesis and Processing of Wsluhan University of Technology(2023-KF-1).
文摘Thermoelectric superlattices are expected to decouple the strong correlation between various thermo-electric parameters,and are an important strategy for excellent thermoelectric performances.The superlattices of(Bi_(2))m(Bi_(2)Te_(3))n homologous series are well-known for low lattice thermal conductivity and intriguing topological surface states.However,the impacts of electronic structure on the thermo-electric performance were still not well-understood in(Bi_(2))m(Bi_(2)Te_(3))n.To cope with this issue,Bi_(2)eBi_(2)Te_(3)superlattice-like films with adjustable Bi_(2)/(Bi_(2)+Bi_(2)Te_(3))molar ratio(R)were successfully fabricated by the molecular beam epitaxy technique.Angle-resolved photoemission spectroscopy measurements com-bined with theoretical calculations revealed the conduction band evolution from single-valley to multi-valley as R≥0.30,leading to intrinsically high carrier effective mass and improved thermoelectric power factor.Also,the superlattice film(R=0.46)with the structure close to Bi_(4)Te_(3)possesses the topological surface state feature around the high symmetry point.As a result of the high effective mass of 3.9 m0 and very high electron density of_(2).31×10^(21)cm^(-3),the film with R=0.46 acquired the highest power factor of 1.49 mW·m^(-1)·K^(-2)at 420 K,outperforming that of other(Bi_(2))m(Bi_(2)Te_(3))n superlattices.This work lays an essential foundation on understanding the electronic structure and further improving thermoelectric performances of(Bi_(2))m(Bi_(2)Te_(3))n homologous series.
基金Project supported by the National Natural Science Foundation of China(51872263,52050077,51772142)Taishan Scholars Project(ts20190911)+3 种基金Shandong Natural Science Foundation(ZR2020ZD36)the Zhejiang Natural Science Foundation(LZ19E020001)the Shenzhen Science and Technology Innovation Committee(JCYJ20170412152528921)the Open Funds of the State Key Laboratory of Rare Earth Resource Utilization(RERU2020005)。
文摘How to engineer single nanocrystal to achieve multiple functions is still a huge challenge.In this work,a novel highly doped rare earth nanocrystal NaErF_(4)@NaGdF_(4)@NaDyF_(4)(Er@Gd@Dy)was designed and fabricated,which exhibits various performances by itself,including the longitudinal(T1)and transverse relaxation time(T2)double-mode magnetic resonance imaging(MRI),upconversion luminescence and down-shifting luminescence.Upon irradiation of 808 nm near-infrared(NIR)light,the upconverted red light can indirectly activate the photo sensitizer Ce6 conjugated on the surface of nanocrystals for photodynamic therapy(PDT).In vivo experiments demonstrate that the nano materials can eradicate notably primary tumors without obvious systematic toxicity.In addition,the longitudinal and transverse relaxation rates of Er@Gd@Dy are 24.83 and 319.86(mmol/L)^(-1)/s,respectively,which are superior to those of the nanocrystals reported previously.Simultaneously,the nanocrystals have the ability to generate NIR-Ⅱlight located at 1530 nm,favorable in bioimaging in deeper tissues.As a consequence,this new nanoplatform will advance the improvement of multimodal imaging guided tumor diagnosis and treatment.
基金supported by the Hainan Provincial Key Research and Development Program(No.ZDYF2021SHFZ246)the National Natural Science Foundation of China(Nos.52003069 and 51872263).
文摘Chemodynamic therapy(CDT)as an emerging modality in cancer treatment,its implementation remains a daunting challenge by the lack of smart Fenton catalyst under acidic tumor microenvironments.Herein,we have successfully constructed a Fe_(3)O_(4)@MIL-100 heterojunction by growing Fe-based metal-organic framework(MIL-100)onto the surface of Fe_(3)O_(4) nanoparticles.The as-made heterojunction after encapsu-lating glucose oxidase(termed FMG)is demonstrated as a pH-responsive intelligent Fenton nanosystem with the synergistic effect of starvation therapy(ST).Density functional theory(DFT)calculations reveal that such heterojunction could greatly reduce the energy barrier of the Fenton reaction,which better ex-plains the mechanism of Fenton performance improvement.Moreover,the encapsulated glucose oxidase has successfully activated the ST process,in which its generated H_(2)O_(2) and gluconic acid further improve the CDT efficiency.More O_(2) from the enhanced CDT in turn promotes the enzymatic reaction of glucose oxidase.The Fenton/cascade enzymatic reaction operates in a self-feedback manner as proposed.In vitro and in vivo experiments demonstrate that such intelligent Fenton nanoreactors provide a powerful anti-cancer mechanism for effective tumor ablation with enough safety.This work provides insights into the developments of MOF-based heterojunctions as powerful anticancer treatment nanoreactors.
基金funded by grants from the National Natural Science Foundation of China(NSFC)(91631306 to B.S,3217040584 and 32000390 to Y.H.,32070578 to X.Q and 32170629 to H.Z.)the Youth Innovation Promotion Association of CAS(to Y.H.)+2 种基金the Science and Technology General Program of Yunnan Province(202001AT070110 to Y.H.)the Provincial Natural Science Foundation of Tibet Autonomous Region(XZ2018ZRG-130 to J.L.)Tibetan Fukang Hospital(2017-04 to J.L.).
文摘Birth weight(BW)is a key determinant of infant mortality.Previous studies have reported seasonal fluctuation of BW.However,the responsible environmental factors remain disputable.High-altitude environment provides a great opportunity to test the current hypotheses due to its distinctive climate conditions.We collected BW data of~9000 Tibetan singletons born at Lhasa(elevation:3660 m)from 2014 to 2018.Using regression models,we analyzed BW seasonality of highland Tibetans.Multivariate models with meteorological factors as independent variables were employed to examine responsible environmental factors accounting for seasonal variation.We compared BW,low-BW prevalence and sex ratio between high-land and lowland populations,and we observed a significant seasonal pattern of BW in Tibetans,with a peak in winter and a trough in summer.Notably,there is a marked sex-biased pattern of BW seasonality(more striking in males than in females).Sunlight exposure in the 3rd trimester and barometric pressure exposure in the 2nd trimester are significantly correlated with BW,and the latter can be explained by seasonal change of oxygen partial pressure.In particular,due to the male-biased BW seasonality,we found a more serious BW reduction and higher prevalence of low-BW in males,and a skewed sex ratio in highlanders.The infant BW of highland Tibetans has a clear pattern of seasonality.The winter BW is larger than the summer BW,due to the longer sunlight exposure during the late-trimester.Male infants are more sensitive to hypoxia than female infants during the 2nd trimester,leading to more BW reduction and higher mortality.
基金This work was supported by National Natural Science Foundation of China(31500646,81874320,and 81672585)Shandong Major Science and Technology Project(2021ZDSYS22)+2 种基金the Promotive Research Fund for Excellent Young and Middle-aged Scientists of Shandong Province(BS2015YY040)Qingdao Science and Technology Development project(15-9-1-67-JCH)Youth Research Fund of Afliated Hospital of Qingdao University(QDFYQN202101003).
文摘Chitosan oligosaccharides(COSs)have been reported to possess a broad range of activities such as antitumor,antioxidant and neuroprotective activities.In this study,the protective efects and mechanisms of peracetylated chitosan oligosaccharides(PACOs)against Aβ-induced cognitive defcits were investigated in Sprague–Dawley(SD)rats.PACOs treatment signifcantly improved the learning and memory function of Alzheimer’s disease(AD)rats and attenuated the neuron cell damage caused by Aβ.PACOs also markedly reduced the levels of lactate dehydrogenase(LDH)and Malondialdehyde(MDA)and decreased the phosphorylation of Tau protein to inhibit oxidative injury and infammatory responses in AD rats.Further studies indicated that PACOs may promote the repair of Aβinduced nerve damage and inhibit neuronal apoptosis mainly through regulating PI3K/Akt/GSK3βsignaling pathway.Consistently,the transcriptome analysis verifed that the diferentially expressed genes(DEGs)were mainly involved in neuron development and the PI3K-Akt signaling pathway.Taken together,peracetylated chitosan oligosaccharides(PACOs)have the potential to be developed into novel anti-AD agents targeting the cellular PI3K/Akt/GSK3βsignaling pathway.
基金Project supported by the National Natural Science Foundation of China(51802284,51872263)Zhejiang Provincial Natural Science Foundation of China(LY20E020007,LZ19E020001)。
文摘Self-calibrating luminescent thermometry employing luminescence within the optical transparency windows provides a promising prospect for temperature measurement in the biological fields.In this work,a new Nd^(3+)/Yb^(3+)-codoped metal-organic framework Nd_(0.95)Yb_(0.05)BPTC showing threedimensional anionic network,obtained by reacting ligand[1,1’-biphenyl]-3,3’,5,5’-tetracarboxylic acid(H4BPTC)with Nd^(3+)and Yb^(3+)ions under solvothermal conditions,is reported.Upon 808 nm photoexcitation,Nd_(0.95)Yb_(0.05)BPTC simultaneously emits the characteristic near-infrared luminescence of Nd^(3+)and Yb^(3+)ions based on the efficient energy transfer from Nd^(3+)to Yb^(3+)ions.In addition,the emission intensity ratio of Yb^(3+)and Nd^(3+)shows good exponential-like response to temperature in the physiological range of 293-323 K.The feature properties of Nd_(0.95)Yb_(0.05)BPTC include near-infrared absorption and emission,favorable temperature sensitivity and accurate temperature uncertainty,as well as good chemical stability,making such system useful in biomedical applications.
基金the National Natural Science Foundation of China(51872263 and 31970755)Zhejiang Provincial Natural Science Foundation(LZ19E020001 and LQ18B010002)。
文摘The hypoxic nature of solid tumors has severely negative effects on oxygen-based photodynamic therapy.In this study,we used porous Pt nanoparticles as a catalase(CAT)nanozyme,the second near-infrared(NIR-Ⅱ)region photothermal transition agents(PTAs),and carriers of photosensitizer chlorin e6(Ce6)to synthesize a composite nanosystem Pt-Ce6.In this system,Pt-Ce6 can continuously and stably decompose H2O2 into oxygen,thereby alleviating tumor hypoxia and improving the effect of photodynamic therapy(PDT).With 650 nm illumination,the reactive oxygen species(ROS)produced by Ce6 will decrease the mitochondrial membrane potential(MMP,ΔΨm)to release cytochrome c(Cyt-c)from the mitochondria into the cytoplasm,eventually leading to mitochondrial-mediated cellular apoptosis during the PDT process.In addition,Pt-Ce6 has good photothermal stability and high photothermal conversion efficiency(52.62%)in the NIR-II region.In U14 tumor-bearing mice,Pt-Ce6 completely suppressed tumor growth and recurrence under laser irradiation.Thus the nanocomposite shows excellent PDT/photothermal therapy(PTT)synergistic performance in vitro and in vivo.
基金supported by the Medical Science and Technology Research Program of Henan Province(Nos.2018020042 and LHGJ20190226).
文摘Gastroesophageal reflux disease(GERD)is caused by esophageal dysfunction resulting in reflux of gastric and duodenal contents into the esophagus,which leads to a series of symptoms.[1]The incidence of GERD in East Asia ranges from 2.5%to 7.8%.[2]Hiatal hernia(HH)refers to the upper part of the stomach protruding into the chest through the esophageal hiatus.HH is closely related to GERD and can play a role in the development and increased incidence of GERD.[3]The surgical treatment of patients with GERD and HH includes HH repair and Nissen,Toupet,or Dor fundoplication(DF).However,post-operative complications have been associated with fundoplication,including dysphagia and abdominal distension,which reduce the benefit of fundoplication.
基金This project is financially supported by the National Natural Science Foundation of China （NSFC, Nos. 51332008, 51372243, 51422209, and 51202239）, the National Basic Research Program of China （No. 2014CB643803）.
文摘A multifunctional, dual-drug carrier platform was successfully constructed. Core-sheU structured NaGdF4：Yb/Er@NaGdF4：Yb@mSiO2-polyethylene glycol （abbreviated as UCNPS） nanopartides loaded with the antiturnor drug, doxorubicin （DOX） were incorporated into poly（^-caprolactone） （PCL） and gelatin loaded with antiphlogistic drug, indomethacin （MC） to form nanofibrous fabrics （labeled as MC/UCNPS/DOX） via electrospinning process. The resultant multifunctional spinning pieces can be surgically implanted directly at the tumor site of mice as an orthotopic chemotherapy by controlled-release DOX from mesoporous silicon dioxide （SiO2） and upconversion fluorescence/magnetic resonance dual-model imaging through NaGdF4：Yb/Er@NaGdF4：Yb embedded in MCfldCNPS/DOX invivo.
基金supported by a grant from the National Natural Science Foundation of China(No.21577095).
文摘Estrogen impacts neural development;meanwhile, it has a protective effect on the brain. Bisphenols, primarily bisphenol A (BPA), can exert estrogen-like or estrogen-interfering effects by binding with estrogen receptors. Extensive studies have suggested that neurobehavioral problems, such as anxiety and depression, can be caused by exposure to BPA during neural development. Increasing attention has been paid to the effects on learning and memory of BPA exposure at different developmental stages and in adulthood. Further research is required to elucidate whether BPA increases the risk of neurodegenerative diseases and the underlying mechanisms, as well as to assess whether BPA analogs, such as bisphenol S and bisphenol F, influence the nervous system.
基金This paper was supported by the National Major Scientific Research Instrument Development Project(No.62027819)the General Project of National Natural Science Foundation of China(No.62076177)Shanxi Province Key Technology and Generic Technology R&D Project(No.2020XXX007).
文摘Severe cardiovascular diseases can rapidly lead to death.At present,most studies in the deep learning field using electrocardiogram(ECG)are performed on intra-patient experiments for the classification of coronary artery disease(CAD),myocardial infarction,and congestive heart failure(CHF).By contrast,actual conditions are inter-patient experiments.In this study,we proposed a deep learning network,namely,CResFormer,with dual feature extraction to improve accuracy in classifying such diseases.First,fixed segmentation of dual-lead ECG signals without preprocessing was used as input data.Second,one-dimensional convolutional layers performed moderate dimensionality reduction to accommodate subsequent feature extraction.Then,ResNet residual network block layers and transformer encoder layers sequentially performed feature extraction to obtain key associated abstract features.Finally,the Softmax function was used for classifications.Notably,the focal loss function is used when dealing with unbalanced datasets.The average accuracy,sensitivity,positive predictive value,and specificity of four classifications of severe cardiovascular diseases are 99.84%,99.68%,99.71%,and 99.90%in intra-patient experiments,respectively,and 97.48%,93.54%,96.30%,and 97.89%in inter-patient experiments,respectively.In addition,the model performs well in unbalanced datasets and shows good noise robustness.Therefore,the model has great application potential in diagnosing CAD,MI,and CHF in the actual clinical environment.
基金financially supported by the National Natural Science Foundation of China (Nos. 52250077, 52272156, 51872263 and 52202175)Taishan Scholars Project (No. ts20190911)+1 种基金Shandong Natural Science Foundation (No. ZR2020ZD36)Guangdong Basic and Applied Basic Research Foundation (No. 2022A1515010461)。
文摘The accurate delivery of nanoparticles and organic small molecule drugs remains a serious challenge in nanoparticle-based tumor therapy.Dual-targeted therapy combining tumor cell targeting and organelle targeting is an effective solution.Here,an anticancer nanoformulation accurate delivery system was prepared using hyaluronic acid (HA) targeting CD44 receptors on the surface of tumor cells and IR780iodine (IR780) targeting mitochondrial for delivery.The system is based on an ultra-small Janus structured inorganic sensitizer TiO_(2-x)@NaGdF_(4) nanoparticles (TN NPs) prepared by one-step pyrolysis,further loaded with organic small molecule acoustic sensitizer IR780 and mitochondrial hexokinase Ⅱ inhibitor lonidamine (LND),followed by encapsulation of HA.Ultra-small size nanoparticles exhibit strong tissue penetration,tumor inhibition and in vivo metabolism.Under ultrasound radiation,TN NPs and IR780could produce a synergistic effect,effectively increased the efficiency of reactive oxygen species (ROS)production.Meanwhile,the released IR780 could smoothly target the mitochondria,and the ROS produced by IR780 can destroy the mitochondrial structure and disrupt the mitochondrial respiration.LND could inhibit the energy metabolism of tumor cells by reducing the activity of hexokinase Ⅱ (HK Ⅱ),which further accelerates the process of apoptosis.Furthermore,since the Janus structure allows the integration of multifunctional components into a single system,TN NPs can not only serve as an acoustic sensitizer to generate ROS,but the Gd element contained can also act as the nuclear magnetic resonance (MR)imaging contrast agent,suggesting that the nanoformulation can enable imaging-guided diagnosis and therapy.In conclusion,a new scheme to enhance sonodynamic therapy (SDT) and chemotherapy synergistically is proposed here based on ultra-small dual-targeted nanoformulation with Janus structure in the ultrasound radiation environment.
基金supported by the Yunnan Digitalization,Development and Application of Biotic Resource(202002AA100007)the National Natural Science Foundation of China(82222064,81973147,82001986,and 82073569)+6 种基金Shandong Medical and Health Technology Development Project(202005010068)Shandong University Distinguished Young Scholarsthe Outstanding Youth Science Foundation of Yunnan Basic Research Project(202001AW070021,and 202101AW070001)the Reserve Talent Project for Young and Middle-Aged Academic and Technical Leaders(2012005AC160023)the Key Science Foundation of Yunnan Basic Research(202101AS070040)the Innovative Research Team of Yunnan Province(202005AE160002)the Science Foundation of Yunnan Basic Research(202201AT070010)。
