CRISPR-Cas technology has revolutionized our ability to understand and engineer organisms,evolving from a singular Cas9 model to a diverse CRISPR toolbox.A critical bottleneck in developing new Cas proteins is identif...CRISPR-Cas technology has revolutionized our ability to understand and engineer organisms,evolving from a singular Cas9 model to a diverse CRISPR toolbox.A critical bottleneck in developing new Cas proteins is identifying protospacer adjacent motif(PAM)sequences.Due to the limitations of experimental methods,bioinformatics approaches have become essential.However,existing PAM prediction programs are limited by the small number of spacers in CRISPR-Cas systems,resulting in low accuracy.To address this,we develop PAMPHLET,a pipeline that uses homology searches to identify additional spacers,significantly increasing the number of spacers up to 18-fold.PAMPHLET is validated on 20 CRISPR-Cas systems and successfully predicts PAM sequences for 18 protospacers.These predictions are further validated using the DocMF platform,which characterizes protein-DNA recognition patterns via next-generation sequencing.The high consistency between PAMPHLET predictions and DocMF results for Cas proteins demonstrates the potential of PAMPHLET to enhance PAM sequence prediction accuracy,expedite the discovery process,and accelerate the development of CRISPR tools.展开更多
Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during c...Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during cancer treatment.Herein,we develop a concise strategy to prepare pH-responsive nanoparticles via the CaCO3-assisted double emulsion method,thereby enabling effective co-encapsulation of both doxorubicin(DOX),an immunogenic cell death(ICD)inducer,and alkylated NLG919(aNLG919),an inhibitor of indoleamine 2,3-dioxygenase 1(IDO1).The obtained DOX/aNLG919-loaded CaCO3 nanoparticles(DNCaNPs)are able to cause effective ICD of cancer cells and at the same time restrict the production of immunosuppressive kynurenine by inhibiting IDO1.Upon intravenous injection,such DNCaNPs show efficient tumor accumulation,improved tumor penetration of therapeutics and neutralization of acidic TME.As a result,those DNCaNPs can elicit effective anti-tumor immune responses featured in increased density of tumor-infiltrating CD8+cytotoxic T cells as well as depletion of immunosuppressive regulatory T cells(Tregs),thus effectively suppressing the growth of subcutaneous CT26 and orthotopic 4T1 tumors on the Balb/c mice through combined chemotherapy&immunotherapy.This study presents a compendious strategy for construction of pH-responsive nanoparticles,endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.展开更多
The evaluation of therapeutic efficacy is necessary to predict the outcome of patients with metastatic colorectal cancer(CRC). In these patients, there is a critical need for predictive chemosensitivity assays and bio...The evaluation of therapeutic efficacy is necessary to predict the outcome of patients with metastatic colorectal cancer(CRC). In these patients, there is a critical need for predictive chemosensitivity assays and biomarkers to optimize efficacy and minimize toxicity. The introduction of targeted agents has improved the progression-free survival and overall survival of patients with metastatic disease. However, approximately 50% of patients do not show a positive response to chemotherapy and the selection of patients likely to respond to a specific regimen remains challenging. Cell culturebased chemosensitivity tests use autologous viable tumor cells to evaluate susceptibility to specific agents in vitro and predict their direct effects. Adenosine triphosphate-based assays and methyl thiazolyl-diphenyltetrazolium bromide-based assays are used widely as sensitivity tests because of their short assay period, technical simplicity, and the requirement of small amount of specimen. Among protein- and gene-based chemosensitivity assays, assessment of KRAS mutation status predicts the response to epidermal growth factor receptor-targeted therapy in CRC patients. The validation of predictive and prognostic markers enables the selection of therapeutic regimens with optimal efficacy and minimal toxicity for each patient, which has been termed personalized treatment. This review summarizes currently available predictive and prognostic chemosensitivity tests for metastatic CRC.展开更多
Osteoconductive function is remarkably low in bone disease in the absence of bone tissue surrounding the grafting site,or if the bone tissue is in poor condition.Thus,an effective bone graft in terms of both osteocond...Osteoconductive function is remarkably low in bone disease in the absence of bone tissue surrounding the grafting site,or if the bone tissue is in poor condition.Thus,an effective bone graft in terms of both osteoconductivity and osteoinductivity is required for clinical therapy.Recently,the three-dimensional(3D)kagome structure has been shown to be advantageous for bone tissue regeneration due to its mechanical properties.In this study,a polycaprolactone(PCL)kagome-structure scaffold containing a hyaluronic acid(HA)-based hydrogel was fabricated using a 3D printing technique.The retention capacity of the hydrogel in the scaffold was assessed in vivo with a rat calvaria subcutaneous model for 3 weeks,and the results were compared with those obtained with conventional 3D-printed PCL grid-structure scaffolds containing HA-based hydrogel and bulk-type HA-based hydrogel.The retained hydrogel in the kagome-structure scaffold was further evaluated by in vivo imaging system analysis.To further reinforce the osteoinductivity of the kagome-structure scaffold,a PCL kagome-structure scaffold with bone morphogenetic protein-2(BMP-2)containing HA hydrogel was fabricated and implanted in a calvarial defect model of rabbits for 16 weeks.The bone regeneration characteristics were evaluated with hematoxylin and eosin(H&E),Masson’s trichrome staining,and micro-CT image analysis.展开更多
Dear Editor,Breast cancer is now the most frequently diagnosed cancer and is the fifth leading cause of cancer-related death in Chinese women. Therefore, the burden of breast cancer in China is gradually increasing. A...Dear Editor,Breast cancer is now the most frequently diagnosed cancer and is the fifth leading cause of cancer-related death in Chinese women. Therefore, the burden of breast cancer in China is gradually increasing. According to figures released by the Chinese Cancer Center in 2018, the number of newly diagnostic breast cancer is about 278,900 cases, accounting for 16.51%of all women who were diagnosed with the first primary malignant tumors;and 66,000 cases of breast cancer died in 2014 (Chen et al., 2016).展开更多
Adjuvanted vaccines are recommended for administration through an intramuscular route. The Centers for Disease Control and Prevention (CDC) has recommended the anterolateral thigh using a 22 - 25-G 25-mm (1 inch) need...Adjuvanted vaccines are recommended for administration through an intramuscular route. The Centers for Disease Control and Prevention (CDC) has recommended the anterolateral thigh using a 22 - 25-G 25-mm (1 inch) needle for infants, injected at a 90° into the skin surface, and using a 16 mm (5/8 inch) for newborns. Appropriate needle lengths may differ depending on racial backgrounds. In the present study, the thickness of the epidermis and lengths from the skin surface to the muscle fascia and bone were measured using ultrasonic echograms in order to determine suitable needle lengths for Japanese infants aged 2, 3, 4, 5, 6, and 12 - 15 months old. The thickness of the epidermis was 1.44 - 1.54 mm (95% CI), and the lengths from the skin surface to the muscle fascia and bone were 11.52 - 12.28 mm (95% CI), and 25.66 - 26.93 mm (95% CI), respectively, at the anterolateral thigh. At the center of the deltoid muscle, skin thickness was similar to that at the thigh, furthermore the lengths from the skin surface to the muscle fascia and bone were 8.49 - 9.10 mm (95% CI), and 17.38 - 18.31 mm (95% CI), respectively. The lengths from the skin surface to the muscle fascia and bone were 1 - 2 mm shorter in 2-month-old infants than those in older generations. Therefore, the appropriate needle length for intramuscular injections in Japanese infants was 16 mm (5/8 inch) at any age and sites, and with 25 mm (1 inch) needles at a 90° angle being associated with the risk of over-penetration.展开更多
AIM:To evaluate the feasibility of diagnostic and therapeutic transgastric(TG)peritoneoscopic interventions with a forward-viewing endoscopic ultrasound(FV-EUS).METHODS:This prospective endoscopic experimental study u...AIM:To evaluate the feasibility of diagnostic and therapeutic transgastric(TG)peritoneoscopic interventions with a forward-viewing endoscopic ultrasound(FV-EUS).METHODS:This prospective endoscopic experimental study used an animal model.Combined TG peritoneoscopic interventions and EUS examination of the intraabdominal organs were performed using an FV-EUS on 10 animal models(1 porcine and 9 canine).The procedures carried out include EUS evaluation and endoscopic biopsy of intraperitoneal organs,EUS-guided fine needle aspiration(EUS-FNA),EUS-guided radiofrequency ablation(EUS-RFA),and argon plasma coagulation(APC)for hemostatic control.The animals were kept alive for 7 d,and then necropsy was performed to evaluate results and complications.RESULTS:In all 10 animals,TG peritoneoscopy,followed by endoscopic biopsy for the liver,spleen,abdominal wall,and omentum,was performed successfully.APC helped control minor bleeding.Visualization of intra-abdominal solid organs with real-time EUS was accomplished with ease.Intraperitoneal EUS-FNA was successfully performed on the liver,spleen,and kidney.Similarly,a successful outcome was achieved with EUSRFA of the hepatic parenchyma.No adverse events were recorded during the study.CONCLUSION:Peritoneoscopic natural orifice transluminal endoscopic surgery(NOTES)interventions through FV-EUS were feasible in providing evaluation and performing endoscopic procedures.It promises potential as a platform for future EUS-based NOTES.展开更多
Liquid biopsy,in particular circulating tumor DNA(ctDNA)analysis,has paved the way for a new noninvasive approach to cancer diagnosis,treatment selection and follow-up.As a crucial step in the analysis,the extraction ...Liquid biopsy,in particular circulating tumor DNA(ctDNA)analysis,has paved the way for a new noninvasive approach to cancer diagnosis,treatment selection and follow-up.As a crucial step in the analysis,the extraction of the genetic material from a complex matrix needs to meet specific requirements such as high specificity and low loss of target.Here,we developed a new generation of microfluidic fluidized beds(FBs)that enable the efficient extraction and preconcentration of specific ctDNA sequences from human serum with flow rates up to 15µL/min.We first demonstrated that implementation of a vibration system inducing flow rate fluctuations combined with a mixture of different bead sizes significantly enhanced bead homogeneity,thereby increasing capture efficiency.Taking advantage of this new generation of high-throughput magnetic FBs,we then developed a new method to selectively capture a double-stranded(dsDNA)BRAF mutated DNA sequence in complex matrices such as patient serum.Finally,as proof of concept,ligation chain reaction(LCR)assays were performed to specifically amplify a mutated BRAF sequence,allowing the detection of concentrations as low as 6×104 copies/µL of the mutated DNA sequence in serum.展开更多
Leaf adaxial-abaxial(ad-abaxial)polarity is crucial for leaf morphology and function,but the genetic machinery governing this process remains unclear.To uncover critical genes involved in leaf ad-abaxial patterning,we...Leaf adaxial-abaxial(ad-abaxial)polarity is crucial for leaf morphology and function,but the genetic machinery governing this process remains unclear.To uncover critical genes involved in leaf ad-abaxial patterning,we applied a combination of in silico prediction using machine learning(ML)and experimental analysis.A Random Forest model was trained using genes known to influence ad-abaxial polarity as ground truth.Gene expression data from various tissues and conditions as well as promoter regulation data derived from transcription factor chromatin immunoprecipitation sequencing(ChIP-seq)was used as input,enabling the prediction of novel ad-abaxial polarity-related genes and additional transcription factors.Parallel to this,available and newly-obtained transcriptome data enabled us to identify genes differentially expressed across leaf ad-abaxial sides.Based on these analyses,we obtained a set of 111 novel genes which are involved in leaf ad-abaxial specialization.To explore implications for vegetable crop breeding,we examined the conservation of expression patterns between Arabidopsis and Brassica rapa using single-cell transcriptomics.The results demonstrated the utility of our computational approach for predicting candidate genes in crop species.Our findings expand the understanding of the genetic networks governing leaf ad-abaxial differentiation in agriculturally important vegetables,enhancing comprehension of natural variation impacting leaf morphology and development,with demonstrable breeding applications.展开更多
AIM： To investigate alternative or subordinate pathways involved in colorectal tumorigenesis and tumor growth, possibly determining at-risk populations and predicting responses to treatment. METHODS： Using microarra...AIM： To investigate alternative or subordinate pathways involved in colorectal tumorigenesis and tumor growth, possibly determining at-risk populations and predicting responses to treatment. METHODS： Using microarray gene-expression analysis, we analyzed patterns of gene expression relative to canonical molecular changes and clinicopathological features in 84 sporadic colorectal cancer patients, standardized by tumor location. Subsets of differentially expressed genes were confirmed by real-time reverse-transcript polymerase chain reaction （RT-PCR）. RESULTS： The largest number of genes identified as being differentially expressed was by tumor location, and the next largest number by lymphovascular or neural invasion of tumor cells and by mismatch repair （NMR） defects. Amongst biological processes, the immune response was significantly implicated in entire molecular changes observed during colorectal tumorigenesis （P 〈 0.001）. Amongst 47 differentially expressed genes, seven （PISD, NIBP, BAI2, STOML1, MRPL21, MRPL16, and MKKS） were newly found to correlate with tumorigenesis and tumor growth. Most location-associated molecular changes had distinct effects on gene expression, but the effects of the latter were sometimes contradictory. CONCLUSION： We show that several differentially expressed genes were associated with canonical molecular changes in sporadic colorectal cancers, possibly constituting alternative or subordinate pathways of tumorigenesis. As tumor location was the dominant factor influencing differential gene expression, location-specific analysis may identify location-associated pathways and enhance the accuracy of class prediction.展开更多
Macrophage migration inhibitory factor(MIF)is a chemokine that plays an essential role in immune system function.Previous studies suggested that MIF protects neurons in ischemic conditions.However,few studies are repo...Macrophage migration inhibitory factor(MIF)is a chemokine that plays an essential role in immune system function.Previous studies suggested that MIF protects neurons in ischemic conditions.However,few studies are reported on the role of MIF in neurological recovery after ischemic stroke.The purpose of this study is to identify the molecular mechanism of neuroprotection mediated by MIF.Human neuroblastoma cells were incubated in Dulbecco’s modified Eagle’s medium under oxygen-glucose deprivation(OGD)for 4 hours and then returned to normal aerobic environment for reperfusion(OGD/R).30 ng/mL MIF recombinant(30 ng/mL)or ISO-1(MIF antagonist;50μM)was administered to human neuroblastoma cells.Then cell cultures were assigned to one of four groups:control,OGD/R,OGD/R with MIF,OGD/R with ISO-1.Cell viability was analyzed using WST-1 assay.Expression levels of brain-derived neurotrophic factor(BDNF),microtubule-associated protein 2(MAP2),Caspase-3,Bcl2,and Bax were detected by western blot assay and immunocytochemistry in each group to measure apoptotic activity.WST-1 assay results revealed that compared to the OGD/R group,cell survival rate was significantly higher in the OGD/R with MIF group and lower in the OGD/R with ISO-1 group.Western blot assay and immunocytochemistry results revealed that expression levels of BDNF,Bcl2,and MAP2 were significantly higher,and expression levels of Caspase-3 and Bax were significantly lower in the MIF group than in the OGD/R group.Expression levels of BDNF,Bcl2,and MAP2 were significantly lower,and expression levels of Caspase-3 and Bax were significantly higher in the ISO-1 group than in the OGD/R group.MIF administration promoted neuronal cell survival and induced high expression levels of BDNF,MAP2,and Bcl2(anti-apoptosis)and low expression levels of Caspase-3 and Bax(pro-apoptosis)in an OGD/R model.These results suggest that MIF administration is effective for inducing expression of BDNF and leads to neuroprotection of neuronal cells against hypoxic injury.展开更多
The neuroprotective function of macrophage migration inhibitory factor(MIF) in ischemic stroke was rarely evaluated.This study aimed to investigate the effects of early treadmill exercise on recovery from ischemic str...The neuroprotective function of macrophage migration inhibitory factor(MIF) in ischemic stroke was rarely evaluated.This study aimed to investigate the effects of early treadmill exercise on recovery from ischemic stroke and to determine whether these effects are associated with the expression levels of MIF and brain-derived neurotrophic factor(BDNF) in the ischemic area.A total of 40 male Sprague-Dawley rats were randomly assigned to the ischemia and exercise group [middle cerebral artery occlusion(MCAO)-Ex,n = 10),ischemia and sedentary group(MCAO-St,n = 10),sham-surgery and exercise group(Sham-Ex,n= 10),or sham-surgery and sedentary group(Sham-St,n = 10).The MCAO-Ex and MCAO-St groups were subjected to MCAO for 60 minutes,whereas the Sham-Ex and Sham-St groups were subjected to an identical operation without MCAO.Rats in the MCAO-Ex and Sham-Ex groups then ran on a treadmill for 30 minutes once a day for 5 consecutive days.After reperfusion,the hanging time tested by the wire hang test was longer and the relative fractional anisotropy determined by MRI was higher in the peri-infarct region of the MCAO-Ex group compared with the MCAO-St group.The expression levels of MIF and BDNF in the peri-infarct region were upregulated in the MCAO-Ex group.Increased MIF and BDNF levels were positively correlated with relative fractional anisotropy changes in the peri-infarct region.There was no significant difference in the levels of MIF and BDNF in the peri-infarct region between the Sham-Ex and Sham-St groups.Our study demonstrated that early exercise(initiated 48 hours after the MCAO) could improve motor and neuronal recovery after ischemic stroke.Furthermore,the increased levels of MIF and BDNF in the peri-infarct region(penumbra) may be one of the mechanisms of enhanced neurological function recovery.All experiments were approved by the Institutional Animal Care and Use Committee in Asan Medical Center in South Korea(2016-12-126).展开更多
Recent observational studies showed that breast-conserving surgery(BCS) resulted in superior survival compared to mastectomy in breast cancer patients. This study compared the clinical outcomes of BCS and mastectomy u...Recent observational studies showed that breast-conserving surgery(BCS) resulted in superior survival compared to mastectomy in breast cancer patients. This study compared the clinical outcomes of BCS and mastectomy using propensity score(PS)matching analysis, which had advantages over conventional methods in reducing bias. Nonmetastatic breast cancer patients who underwent BCS and mastectomy were matched 1:1 based on their PS. We used the Kaplan-Meier method and Cox-regression model to estimate the treatment effects. A total of 2,866 patients with a median follow-up time of 67 months were included in the original study population. Although the mastectomy cohort(N=1,219) had more advanced disease compared to the BCS cohort(N=1,647), LRFS was similar between the two groups(93.8% vs. 92.4%, P>0.05). BCS(vs. mastectomy) was associated with improved DFS(73.8% vs. 58.7%, P<0.01) and CSS(91% vs. 78.2%, P<0.01) in the original population. In the PS-matched population(N=1,668), clinicopathological features were equally distributed between the two cohorts. BCS(vs. mastectomy) was not associated with improved DFS(70.7% vs. 66.9%, P>0.05) or CSS(87.5% vs. 84.9%, P>0.05). We found that PS methods reduce bias when estimating treatment effects using observational data. BCS and mastectomy show equivalent outcomes in nonmetastatic breast cancer patients.展开更多
Objective: To investigate the clinical significance of MET gene amplification in patients with gastric cancer in the palliative setting.Methods: MET amplification was assessed using fluorescence in situ hybridization(...Objective: To investigate the clinical significance of MET gene amplification in patients with gastric cancer in the palliative setting.Methods: MET amplification was assessed using fluorescence in situ hybridization(FISH) in 50 patients and quantitative polymerase chain reaction(qPCR) in 326 patients;259 patients treated with first-line fluoropyrimidine and platinum were included for survival analysis.Results: The results of FISH and qPCR indicated that the c-MET/CEP7 ratio was correlated with gene copy number. The optimal cutoff value for the copy number using qPCR to detect MET gene amplification with FISH was 5(κ=0.778, P<0.001). Twenty-one out of 326 patients(6.4%) were identified as MET amplification with a copy number of >5 detected by qPCR. MET-amplified gastric cancer was associated with an Eastern Cooperative Oncology Group(ECOG) performance status(PS) score of ≥2(33.3% vs. 10.5% P=0.007), peritoneal metastasis(76.2% vs. 46.2%, P=0.008), and elevated bilirubin levels(28.6% vs. 7.3%, P=0.006). The median overall survival(OS) and progression-free survival(PFS) were 11.9 and 5.6 months, respectively. MET-amplified gastric cancer was not associated with survival outcomes [hazard ratio(HR)=0.68, 95% confidence interval(95% CI): 0.35-1.32,P=0.254 for PFS;HR=0.68, 95% CI: 0.35-1.32, P=0.251 for OS].Conclusions: qPCR can be used to detect MET gene amplification. MET amplification was not a predictor of poor prognosis in patients with metastatic or unresectable gastric cancer.展开更多
Ophiocordyceps sinensis is well known as a traditional Chinese medicine and has widely been used for over 2,000 years to stimulate immune system, decrease blood pressure and to inhibit tumor growth. While miRNAs are i...Ophiocordyceps sinensis is well known as a traditional Chinese medicine and has widely been used for over 2,000 years to stimulate immune system, decrease blood pressure and to inhibit tumor growth. While miRNAs are increasingly recognized for their roles in post-transcriptional regulation of gene expression in animals and plants, miRNAs in fungi were less studied until the discovery of microRNA-like RNA(milRNA). High-throughput sequencing and bioinformatics approaches were used to identify conserved and novel milRNAs in O. sinensis. 40 conserved milRNAs were identified, while 23 pre-miRNA candidates encoding 31 novel milRNAs were predicted. Furthermore, the potential target genes of milRNAs in human were predicted and gene ontology analysis was applied to these genes. Enrichment analysis of GO-represented biological process showed that target genes of both conserved and novel milRNAs are involved in development, metabolic and immune processes, indicating the potential roles of milRNAs of O. sinensis in pharmacological effects as health food and traditional Chinese medicine. This study is the first report on genome-wide analysis of milRNAs in O. sinensis and it provides a useful resource to further study the potential roles of milRNAs as active components of O. sinensis in health food or traditional Chinese medicine.展开更多
Lenses are crucial to light-enabled technologies.Conventional lenses have been perfected to achieve near-diffraction-limited resolution and minimal chromatic aberrations.However,such lenses are bulky and cannot focus ...Lenses are crucial to light-enabled technologies.Conventional lenses have been perfected to achieve near-diffraction-limited resolution and minimal chromatic aberrations.However,such lenses are bulky and cannot focus light into a hotspot smaller than a half-wavelength of light.Pupil filters,initially suggested by Toraldo di Francia,can overcome the resolution constraints of conventional lenses but are not intrinsically chromatically corrected.Here we report single-element planar lenses that not only deliver sub-wavelength focusing,thus beating the diffraction limit of conventional refractive lenses,but also focus light of different colors into the same hotspot.Using the principle of super-oscillations,we designed and fabricated a range of binary dielectric and metallic lenses for visible and infrared parts of the spectrum that are manufactured on silicon wafers,silica substrates and optical fiber tips.Such low-cost,compact lenses could be useful in mobile devices,data storage,surveillance,robotics,space applications,imaging,manufacturing with light and spatially resolved nonlinear microscopies.展开更多
Objective: We aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio(NLR) and myeloidderived suppressor cells(MDSCs) in gastric cancer patients treated with second-line ramucirumab plus paclitaxel...Objective: We aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio(NLR) and myeloidderived suppressor cells(MDSCs) in gastric cancer patients treated with second-line ramucirumab plus paclitaxel.Methods: A total of 116 patients with advanced or metastatic gastric cancer who receive ramucirumab plus paclitaxel were prospectively enrolled. Fresh blood samples were collected before and after treatment, and flow cytometry was performed to assess the proportions of monocytic(m MDSCs) and granulocytic MDSCs(g MDSCs).Results: Median age was 58 years and 71(61.2%) patients were male. A baseline NLR≥2.94 was associated with significantly poorer progression-free survival(PFS) and overall survival(OS) vs. an NLR<2.94(P=0.011 and P=0.002, respectively). In multivariate analysis, an NLR≥2.94 was independently associated with poorer PFS[hazard ratio(HR)=1.58;95% confidence interval(95% CI): 1.01-2.49, P=0.046] and OS(HR=1.77;95% CI:1.04-3.04, P=0.036). While m MDSC counts did not significantly change following two cycles of therapy(P=0.530),g MDSC counts decreased significantly after two treatment cycles(P=0.025) but tended to increase in patients with progressive disease after two treatment cycles(P=0.098). A progressive increase in g MDSC counts(≥44%) was associated with a significantly shorter PFS and OS vs. a g MDSC count increase <44%(P=0.001 and P=0.003,respectively).Conclusions: The baseline NLR may help guide clinical decisions during ramucirumab plus paclitaxel therapy for gastric cancer. Our g MDSC kinetics data warrant further clinical validation and mechanistic investigation.展开更多
Plants play an important role in soil phosphorus nutrition. However, the effect of plants on phosphorus nutrition in soils of the Loess Plateau of China is not well understood. This study was conducted to reveal the r...Plants play an important role in soil phosphorus nutrition. However, the effect of plants on phosphorus nutrition in soils of the Loess Plateau of China is not well understood. This study was conducted to reveal the relationships between plants and phosphorus＇ fractions and availability in the Loess Plateau of China. Twenty-two plant communities were surveyed and soil samples under different plant canopies were collected for the determination of soil properties and inorganic phosphorus fractionation. The results showed that Leguminosae and Lilaceae reduced pH and increased organic matter, cation exchange capacity, total and Olsen phosphorus in soils under their canopies, while Labiatae and Rosaceae increased pH and decreased organic matter, cation exchange capacity, total and Olsen phosphorus in soils under their canopies. The contents of Ca2P, CasP, AI-P and Fe-P were highly related with soil Oisen phosphorus. They were all higher in soils under Leguminosae and Lilaceae and lower in softs under Labiatae and Rosaceae. The results of this study indicate that Leguminosae and Lilaceae improved phosphorus nutrition in soils, yet Labiatae and Rosaceae impeded the improvement of phosphorus nutrition in soils under their canopies, which will be of more help to instruct vegetation restoration in the region and provide information for soil development.展开更多
基金supported by grants from the Foundation for Distinguished Young Talents in Higher Education of Guangdong,China(2024KQNCX157)Our work was also supported in part by the Guangdong Provincial Key Laboratory of Interdisciplinary Research and Application for Data Science,BNU-HKBU United International College(2022B1212010006)+1 种基金in part by the Guangdong Higher Education Upgrading Plan(2021-2025)of“Rushing to the Top,Making Up Shortcomings and Strengthening Special Features”(R0400001-22)Additionally,we acknowledge support from the Zhuhai Basic and Applied Basic ResearchFoundation(2220004002717).
文摘CRISPR-Cas technology has revolutionized our ability to understand and engineer organisms,evolving from a singular Cas9 model to a diverse CRISPR toolbox.A critical bottleneck in developing new Cas proteins is identifying protospacer adjacent motif(PAM)sequences.Due to the limitations of experimental methods,bioinformatics approaches have become essential.However,existing PAM prediction programs are limited by the small number of spacers in CRISPR-Cas systems,resulting in low accuracy.To address this,we develop PAMPHLET,a pipeline that uses homology searches to identify additional spacers,significantly increasing the number of spacers up to 18-fold.PAMPHLET is validated on 20 CRISPR-Cas systems and successfully predicts PAM sequences for 18 protospacers.These predictions are further validated using the DocMF platform,which characterizes protein-DNA recognition patterns via next-generation sequencing.The high consistency between PAMPHLET predictions and DocMF results for Cas proteins demonstrates the potential of PAMPHLET to enhance PAM sequence prediction accuracy,expedite the discovery process,and accelerate the development of CRISPR tools.
基金partially supported by the National Natural Science Foundation of China(51802209,22077093,51761145041,51525203)the National Research Programs from Ministry of Science and Technology(MOST)of China(2016YFA0201200)+3 种基金the Natural Science Foundation of Jiangsu Province(BK20180848)the Jiangsu Social Development Project(BE2019658)Collaborative Innovation Center of Suzhou Nano Science and Technologythe 111 Program from the Ministry of Education of China.
文摘Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during cancer treatment.Herein,we develop a concise strategy to prepare pH-responsive nanoparticles via the CaCO3-assisted double emulsion method,thereby enabling effective co-encapsulation of both doxorubicin(DOX),an immunogenic cell death(ICD)inducer,and alkylated NLG919(aNLG919),an inhibitor of indoleamine 2,3-dioxygenase 1(IDO1).The obtained DOX/aNLG919-loaded CaCO3 nanoparticles(DNCaNPs)are able to cause effective ICD of cancer cells and at the same time restrict the production of immunosuppressive kynurenine by inhibiting IDO1.Upon intravenous injection,such DNCaNPs show efficient tumor accumulation,improved tumor penetration of therapeutics and neutralization of acidic TME.As a result,those DNCaNPs can elicit effective anti-tumor immune responses featured in increased density of tumor-infiltrating CD8+cytotoxic T cells as well as depletion of immunosuppressive regulatory T cells(Tregs),thus effectively suppressing the growth of subcutaneous CT26 and orthotopic 4T1 tumors on the Balb/c mice through combined chemotherapy&immunotherapy.This study presents a compendious strategy for construction of pH-responsive nanoparticles,endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.
基金Supported by Grants from Asan Institute for Life Sciences,No.2014-69the National Research Foundation,No.NRF-2013R1A2A1A03070986+1 种基金Ministry of Science,ICT,and Future Planning,the Korea Health 21 RD Project,No.HI06C0868 and No.HI13C1750the Center for Development and Commer-cialization of Anti-Cancer Therapeutics,No.HI10C2014,Ministry of Health and Welfare,South Korea
文摘The evaluation of therapeutic efficacy is necessary to predict the outcome of patients with metastatic colorectal cancer(CRC). In these patients, there is a critical need for predictive chemosensitivity assays and biomarkers to optimize efficacy and minimize toxicity. The introduction of targeted agents has improved the progression-free survival and overall survival of patients with metastatic disease. However, approximately 50% of patients do not show a positive response to chemotherapy and the selection of patients likely to respond to a specific regimen remains challenging. Cell culturebased chemosensitivity tests use autologous viable tumor cells to evaluate susceptibility to specific agents in vitro and predict their direct effects. Adenosine triphosphate-based assays and methyl thiazolyl-diphenyltetrazolium bromide-based assays are used widely as sensitivity tests because of their short assay period, technical simplicity, and the requirement of small amount of specimen. Among protein- and gene-based chemosensitivity assays, assessment of KRAS mutation status predicts the response to epidermal growth factor receptor-targeted therapy in CRC patients. The validation of predictive and prognostic markers enables the selection of therapeutic regimens with optimal efficacy and minimal toxicity for each patient, which has been termed personalized treatment. This review summarizes currently available predictive and prognostic chemosensitivity tests for metastatic CRC.
基金supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),the Ministry of Health&Welfare,Republic of Korea(Grant Number:HI14C2143)the National Research Foundation of Korea(NRF)grant funded by the Korea government(MIST)(NRF-2021R1A2C2009665)。
文摘Osteoconductive function is remarkably low in bone disease in the absence of bone tissue surrounding the grafting site,or if the bone tissue is in poor condition.Thus,an effective bone graft in terms of both osteoconductivity and osteoinductivity is required for clinical therapy.Recently,the three-dimensional(3D)kagome structure has been shown to be advantageous for bone tissue regeneration due to its mechanical properties.In this study,a polycaprolactone(PCL)kagome-structure scaffold containing a hyaluronic acid(HA)-based hydrogel was fabricated using a 3D printing technique.The retention capacity of the hydrogel in the scaffold was assessed in vivo with a rat calvaria subcutaneous model for 3 weeks,and the results were compared with those obtained with conventional 3D-printed PCL grid-structure scaffolds containing HA-based hydrogel and bulk-type HA-based hydrogel.The retained hydrogel in the kagome-structure scaffold was further evaluated by in vivo imaging system analysis.To further reinforce the osteoinductivity of the kagome-structure scaffold,a PCL kagome-structure scaffold with bone morphogenetic protein-2(BMP-2)containing HA hydrogel was fabricated and implanted in a calvarial defect model of rabbits for 16 weeks.The bone regeneration characteristics were evaluated with hematoxylin and eosin(H&E),Masson’s trichrome staining,and micro-CT image analysis.
基金supported by grants from the National Key Research and Development Program of China(2016YFC1302300)the National Natural Science Foundation of China(81621004,81720108029,81930081,91940305)+3 种基金Guangdong Science and Technology Department(2017B030314026)Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR0201001)Guangzhou Science Technology and Innovation Commission(201803040015)partly supported by Fountain-Valley Life Sciences Fund of University of Chinese Academy of Sciences Education Foundation。
文摘Dear Editor,Breast cancer is now the most frequently diagnosed cancer and is the fifth leading cause of cancer-related death in Chinese women. Therefore, the burden of breast cancer in China is gradually increasing. According to figures released by the Chinese Cancer Center in 2018, the number of newly diagnostic breast cancer is about 278,900 cases, accounting for 16.51%of all women who were diagnosed with the first primary malignant tumors;and 66,000 cases of breast cancer died in 2014 (Chen et al., 2016).
文摘Adjuvanted vaccines are recommended for administration through an intramuscular route. The Centers for Disease Control and Prevention (CDC) has recommended the anterolateral thigh using a 22 - 25-G 25-mm (1 inch) needle for infants, injected at a 90° into the skin surface, and using a 16 mm (5/8 inch) for newborns. Appropriate needle lengths may differ depending on racial backgrounds. In the present study, the thickness of the epidermis and lengths from the skin surface to the muscle fascia and bone were measured using ultrasonic echograms in order to determine suitable needle lengths for Japanese infants aged 2, 3, 4, 5, 6, and 12 - 15 months old. The thickness of the epidermis was 1.44 - 1.54 mm (95% CI), and the lengths from the skin surface to the muscle fascia and bone were 11.52 - 12.28 mm (95% CI), and 25.66 - 26.93 mm (95% CI), respectively, at the anterolateral thigh. At the center of the deltoid muscle, skin thickness was similar to that at the thigh, furthermore the lengths from the skin surface to the muscle fascia and bone were 8.49 - 9.10 mm (95% CI), and 17.38 - 18.31 mm (95% CI), respectively. The lengths from the skin surface to the muscle fascia and bone were 1 - 2 mm shorter in 2-month-old infants than those in older generations. Therefore, the appropriate needle length for intramuscular injections in Japanese infants was 16 mm (5/8 inch) at any age and sites, and with 25 mm (1 inch) needles at a 90° angle being associated with the risk of over-penetration.
文摘AIM:To evaluate the feasibility of diagnostic and therapeutic transgastric(TG)peritoneoscopic interventions with a forward-viewing endoscopic ultrasound(FV-EUS).METHODS:This prospective endoscopic experimental study used an animal model.Combined TG peritoneoscopic interventions and EUS examination of the intraabdominal organs were performed using an FV-EUS on 10 animal models(1 porcine and 9 canine).The procedures carried out include EUS evaluation and endoscopic biopsy of intraperitoneal organs,EUS-guided fine needle aspiration(EUS-FNA),EUS-guided radiofrequency ablation(EUS-RFA),and argon plasma coagulation(APC)for hemostatic control.The animals were kept alive for 7 d,and then necropsy was performed to evaluate results and complications.RESULTS:In all 10 animals,TG peritoneoscopy,followed by endoscopic biopsy for the liver,spleen,abdominal wall,and omentum,was performed successfully.APC helped control minor bleeding.Visualization of intra-abdominal solid organs with real-time EUS was accomplished with ease.Intraperitoneal EUS-FNA was successfully performed on the liver,spleen,and kidney.Similarly,a successful outcome was achieved with EUSRFA of the hepatic parenchyma.No adverse events were recorded during the study.CONCLUSION:Peritoneoscopic natural orifice transluminal endoscopic surgery(NOTES)interventions through FV-EUS were feasible in providing evaluation and performing endoscopic procedures.It promises potential as a platform for future EUS-based NOTES.
基金supported by the European Union Horizon 2020 under Grant 737212:CATCH-U-DNA,Capturing Non-Amplified Tumor Circulating DNA with Ultrasound Hydrodynamicssupported by a PhD grant from ENS Paris-Saclay(L.Alexandre)+1 种基金We would also like to acknowledge the financial support of the CNRS,the Institute Curiereceived the support of“Institut Pierre-Gilles de Gennes”(laboratoire d’excellence,“Investissements d’avenir”program ANR-10-IDEX-0001-02 PSL,ANR-10-EQPX-34 and ANR-10-LABX-31).
文摘Liquid biopsy,in particular circulating tumor DNA(ctDNA)analysis,has paved the way for a new noninvasive approach to cancer diagnosis,treatment selection and follow-up.As a crucial step in the analysis,the extraction of the genetic material from a complex matrix needs to meet specific requirements such as high specificity and low loss of target.Here,we developed a new generation of microfluidic fluidized beds(FBs)that enable the efficient extraction and preconcentration of specific ctDNA sequences from human serum with flow rates up to 15µL/min.We first demonstrated that implementation of a vibration system inducing flow rate fluctuations combined with a mixture of different bead sizes significantly enhanced bead homogeneity,thereby increasing capture efficiency.Taking advantage of this new generation of high-throughput magnetic FBs,we then developed a new method to selectively capture a double-stranded(dsDNA)BRAF mutated DNA sequence in complex matrices such as patient serum.Finally,as proof of concept,ligation chain reaction(LCR)assays were performed to specifically amplify a mutated BRAF sequence,allowing the detection of concentrations as low as 6×104 copies/µL of the mutated DNA sequence in serum.
基金supported by the National Key Research and Development Program of China (Grant No.2022YFF1003003)the Central Public-interest Scientific Institution Basal Research Fund (Grant No.Y2023PT16)+1 种基金the Agricultural Science and Technology Innovation Program (ASTIP)supported by China Scholarship Council (Grant No.202103250097)。
文摘Leaf adaxial-abaxial(ad-abaxial)polarity is crucial for leaf morphology and function,but the genetic machinery governing this process remains unclear.To uncover critical genes involved in leaf ad-abaxial patterning,we applied a combination of in silico prediction using machine learning(ML)and experimental analysis.A Random Forest model was trained using genes known to influence ad-abaxial polarity as ground truth.Gene expression data from various tissues and conditions as well as promoter regulation data derived from transcription factor chromatin immunoprecipitation sequencing(ChIP-seq)was used as input,enabling the prediction of novel ad-abaxial polarity-related genes and additional transcription factors.Parallel to this,available and newly-obtained transcriptome data enabled us to identify genes differentially expressed across leaf ad-abaxial sides.Based on these analyses,we obtained a set of 111 novel genes which are involved in leaf ad-abaxial specialization.To explore implications for vegetable crop breeding,we examined the conservation of expression patterns between Arabidopsis and Brassica rapa using single-cell transcriptomics.The results demonstrated the utility of our computational approach for predicting candidate genes in crop species.Our findings expand the understanding of the genetic networks governing leaf ad-abaxial differentiation in agriculturally important vegetables,enhancing comprehension of natural variation impacting leaf morphology and development,with demonstrable breeding applications.
基金Supported by The Basic Research Program of the Korea Science & Engineering Foundation,No.R01-2006-000-10021-0the Korea Health 21 R&D Project,Ministry of Health & Welfare No.A062254
文摘AIM： To investigate alternative or subordinate pathways involved in colorectal tumorigenesis and tumor growth, possibly determining at-risk populations and predicting responses to treatment. METHODS： Using microarray gene-expression analysis, we analyzed patterns of gene expression relative to canonical molecular changes and clinicopathological features in 84 sporadic colorectal cancer patients, standardized by tumor location. Subsets of differentially expressed genes were confirmed by real-time reverse-transcript polymerase chain reaction （RT-PCR）. RESULTS： The largest number of genes identified as being differentially expressed was by tumor location, and the next largest number by lymphovascular or neural invasion of tumor cells and by mismatch repair （NMR） defects. Amongst biological processes, the immune response was significantly implicated in entire molecular changes observed during colorectal tumorigenesis （P 〈 0.001）. Amongst 47 differentially expressed genes, seven （PISD, NIBP, BAI2, STOML1, MRPL21, MRPL16, and MKKS） were newly found to correlate with tumorigenesis and tumor growth. Most location-associated molecular changes had distinct effects on gene expression, but the effects of the latter were sometimes contradictory. CONCLUSION： We show that several differentially expressed genes were associated with canonical molecular changes in sporadic colorectal cancers, possibly constituting alternative or subordinate pathways of tumorigenesis. As tumor location was the dominant factor influencing differential gene expression, location-specific analysis may identify location-associated pathways and enhance the accuracy of class prediction.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,No.2016R1A2B4012772(to DYK)
文摘Macrophage migration inhibitory factor(MIF)is a chemokine that plays an essential role in immune system function.Previous studies suggested that MIF protects neurons in ischemic conditions.However,few studies are reported on the role of MIF in neurological recovery after ischemic stroke.The purpose of this study is to identify the molecular mechanism of neuroprotection mediated by MIF.Human neuroblastoma cells were incubated in Dulbecco’s modified Eagle’s medium under oxygen-glucose deprivation(OGD)for 4 hours and then returned to normal aerobic environment for reperfusion(OGD/R).30 ng/mL MIF recombinant(30 ng/mL)or ISO-1(MIF antagonist;50μM)was administered to human neuroblastoma cells.Then cell cultures were assigned to one of four groups:control,OGD/R,OGD/R with MIF,OGD/R with ISO-1.Cell viability was analyzed using WST-1 assay.Expression levels of brain-derived neurotrophic factor(BDNF),microtubule-associated protein 2(MAP2),Caspase-3,Bcl2,and Bax were detected by western blot assay and immunocytochemistry in each group to measure apoptotic activity.WST-1 assay results revealed that compared to the OGD/R group,cell survival rate was significantly higher in the OGD/R with MIF group and lower in the OGD/R with ISO-1 group.Western blot assay and immunocytochemistry results revealed that expression levels of BDNF,Bcl2,and MAP2 were significantly higher,and expression levels of Caspase-3 and Bax were significantly lower in the MIF group than in the OGD/R group.Expression levels of BDNF,Bcl2,and MAP2 were significantly lower,and expression levels of Caspase-3 and Bax were significantly higher in the ISO-1 group than in the OGD/R group.MIF administration promoted neuronal cell survival and induced high expression levels of BDNF,MAP2,and Bcl2(anti-apoptosis)and low expression levels of Caspase-3 and Bax(pro-apoptosis)in an OGD/R model.These results suggest that MIF administration is effective for inducing expression of BDNF and leads to neuroprotection of neuronal cells against hypoxic injury.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education,No.2016R1A2B4012772(to DYK)
文摘The neuroprotective function of macrophage migration inhibitory factor(MIF) in ischemic stroke was rarely evaluated.This study aimed to investigate the effects of early treadmill exercise on recovery from ischemic stroke and to determine whether these effects are associated with the expression levels of MIF and brain-derived neurotrophic factor(BDNF) in the ischemic area.A total of 40 male Sprague-Dawley rats were randomly assigned to the ischemia and exercise group [middle cerebral artery occlusion(MCAO)-Ex,n = 10),ischemia and sedentary group(MCAO-St,n = 10),sham-surgery and exercise group(Sham-Ex,n= 10),or sham-surgery and sedentary group(Sham-St,n = 10).The MCAO-Ex and MCAO-St groups were subjected to MCAO for 60 minutes,whereas the Sham-Ex and Sham-St groups were subjected to an identical operation without MCAO.Rats in the MCAO-Ex and Sham-Ex groups then ran on a treadmill for 30 minutes once a day for 5 consecutive days.After reperfusion,the hanging time tested by the wire hang test was longer and the relative fractional anisotropy determined by MRI was higher in the peri-infarct region of the MCAO-Ex group compared with the MCAO-St group.The expression levels of MIF and BDNF in the peri-infarct region were upregulated in the MCAO-Ex group.Increased MIF and BDNF levels were positively correlated with relative fractional anisotropy changes in the peri-infarct region.There was no significant difference in the levels of MIF and BDNF in the peri-infarct region between the Sham-Ex and Sham-St groups.Our study demonstrated that early exercise(initiated 48 hours after the MCAO) could improve motor and neuronal recovery after ischemic stroke.Furthermore,the increased levels of MIF and BDNF in the peri-infarct region(penumbra) may be one of the mechanisms of enhanced neurological function recovery.All experiments were approved by the Institutional Animal Care and Use Committee in Asan Medical Center in South Korea(2016-12-126).
基金supported by grants from the National Key Research and Development Program of China (2016YFC1302300)the National Natural Science Foundation of China (81720108029, 81621004, 81490750)+2 种基金Guangdong Science and Technology Department (2016B030229004)Guangzhou Science Technology and Innovation Commission (201803040015)supported by FountainValley Life Sciences Fund of University of Chinese Academy of Sciences Education Foundation
文摘Recent observational studies showed that breast-conserving surgery(BCS) resulted in superior survival compared to mastectomy in breast cancer patients. This study compared the clinical outcomes of BCS and mastectomy using propensity score(PS)matching analysis, which had advantages over conventional methods in reducing bias. Nonmetastatic breast cancer patients who underwent BCS and mastectomy were matched 1:1 based on their PS. We used the Kaplan-Meier method and Cox-regression model to estimate the treatment effects. A total of 2,866 patients with a median follow-up time of 67 months were included in the original study population. Although the mastectomy cohort(N=1,219) had more advanced disease compared to the BCS cohort(N=1,647), LRFS was similar between the two groups(93.8% vs. 92.4%, P>0.05). BCS(vs. mastectomy) was associated with improved DFS(73.8% vs. 58.7%, P<0.01) and CSS(91% vs. 78.2%, P<0.01) in the original population. In the PS-matched population(N=1,668), clinicopathological features were equally distributed between the two cohorts. BCS(vs. mastectomy) was not associated with improved DFS(70.7% vs. 66.9%, P>0.05) or CSS(87.5% vs. 84.9%, P>0.05). We found that PS methods reduce bias when estimating treatment effects using observational data. BCS and mastectomy show equivalent outcomes in nonmetastatic breast cancer patients.
基金supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (No. HI12C1785)
文摘Objective: To investigate the clinical significance of MET gene amplification in patients with gastric cancer in the palliative setting.Methods: MET amplification was assessed using fluorescence in situ hybridization(FISH) in 50 patients and quantitative polymerase chain reaction(qPCR) in 326 patients;259 patients treated with first-line fluoropyrimidine and platinum were included for survival analysis.Results: The results of FISH and qPCR indicated that the c-MET/CEP7 ratio was correlated with gene copy number. The optimal cutoff value for the copy number using qPCR to detect MET gene amplification with FISH was 5(κ=0.778, P<0.001). Twenty-one out of 326 patients(6.4%) were identified as MET amplification with a copy number of >5 detected by qPCR. MET-amplified gastric cancer was associated with an Eastern Cooperative Oncology Group(ECOG) performance status(PS) score of ≥2(33.3% vs. 10.5% P=0.007), peritoneal metastasis(76.2% vs. 46.2%, P=0.008), and elevated bilirubin levels(28.6% vs. 7.3%, P=0.006). The median overall survival(OS) and progression-free survival(PFS) were 11.9 and 5.6 months, respectively. MET-amplified gastric cancer was not associated with survival outcomes [hazard ratio(HR)=0.68, 95% confidence interval(95% CI): 0.35-1.32,P=0.254 for PFS;HR=0.68, 95% CI: 0.35-1.32, P=0.251 for OS].Conclusions: qPCR can be used to detect MET gene amplification. MET amplification was not a predictor of poor prognosis in patients with metastatic or unresectable gastric cancer.
基金supported by the National Basic Research Program of China (2014CB542300)the National Natural Science Foundation of China (81602697)+1 种基金the Natural Science Foundation of Jiangsu Province (BE2016737) the Fundamental Research Funds for the Central Universities (020814380070)
文摘Ophiocordyceps sinensis is well known as a traditional Chinese medicine and has widely been used for over 2,000 years to stimulate immune system, decrease blood pressure and to inhibit tumor growth. While miRNAs are increasingly recognized for their roles in post-transcriptional regulation of gene expression in animals and plants, miRNAs in fungi were less studied until the discovery of microRNA-like RNA(milRNA). High-throughput sequencing and bioinformatics approaches were used to identify conserved and novel milRNAs in O. sinensis. 40 conserved milRNAs were identified, while 23 pre-miRNA candidates encoding 31 novel milRNAs were predicted. Furthermore, the potential target genes of milRNAs in human were predicted and gene ontology analysis was applied to these genes. Enrichment analysis of GO-represented biological process showed that target genes of both conserved and novel milRNAs are involved in development, metabolic and immune processes, indicating the potential roles of milRNAs of O. sinensis in pharmacological effects as health food and traditional Chinese medicine. This study is the first report on genome-wide analysis of milRNAs in O. sinensis and it provides a useful resource to further study the potential roles of milRNAs as active components of O. sinensis in health food or traditional Chinese medicine.
基金supported by the Agency for Science,Technology and Research(A*STAR)of Singapore(Grants 122-360-0009)the Singapore Ministry of Education(Grant MOE2011-T3-1-005)+1 种基金the Engineering and Physical Sciences Research Council UK(Grants EP/F040644/1 and EP/M009122/1)the University of Southampton Enterprise Fund.
文摘Lenses are crucial to light-enabled technologies.Conventional lenses have been perfected to achieve near-diffraction-limited resolution and minimal chromatic aberrations.However,such lenses are bulky and cannot focus light into a hotspot smaller than a half-wavelength of light.Pupil filters,initially suggested by Toraldo di Francia,can overcome the resolution constraints of conventional lenses but are not intrinsically chromatically corrected.Here we report single-element planar lenses that not only deliver sub-wavelength focusing,thus beating the diffraction limit of conventional refractive lenses,but also focus light of different colors into the same hotspot.Using the principle of super-oscillations,we designed and fabricated a range of binary dielectric and metallic lenses for visible and infrared parts of the spectrum that are manufactured on silicon wafers,silica substrates and optical fiber tips.Such low-cost,compact lenses could be useful in mobile devices,data storage,surveillance,robotics,space applications,imaging,manufacturing with light and spatially resolved nonlinear microscopies.
文摘Objective: We aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio(NLR) and myeloidderived suppressor cells(MDSCs) in gastric cancer patients treated with second-line ramucirumab plus paclitaxel.Methods: A total of 116 patients with advanced or metastatic gastric cancer who receive ramucirumab plus paclitaxel were prospectively enrolled. Fresh blood samples were collected before and after treatment, and flow cytometry was performed to assess the proportions of monocytic(m MDSCs) and granulocytic MDSCs(g MDSCs).Results: Median age was 58 years and 71(61.2%) patients were male. A baseline NLR≥2.94 was associated with significantly poorer progression-free survival(PFS) and overall survival(OS) vs. an NLR<2.94(P=0.011 and P=0.002, respectively). In multivariate analysis, an NLR≥2.94 was independently associated with poorer PFS[hazard ratio(HR)=1.58;95% confidence interval(95% CI): 1.01-2.49, P=0.046] and OS(HR=1.77;95% CI:1.04-3.04, P=0.036). While m MDSC counts did not significantly change following two cycles of therapy(P=0.530),g MDSC counts decreased significantly after two treatment cycles(P=0.025) but tended to increase in patients with progressive disease after two treatment cycles(P=0.098). A progressive increase in g MDSC counts(≥44%) was associated with a significantly shorter PFS and OS vs. a g MDSC count increase <44%(P=0.001 and P=0.003,respectively).Conclusions: The baseline NLR may help guide clinical decisions during ramucirumab plus paclitaxel therapy for gastric cancer. Our g MDSC kinetics data warrant further clinical validation and mechanistic investigation.
基金supported by the National Key Basic Research Special Foundation Project(2007CB106803)National Natural Science Foundation(40801111, 41001137)One hundred-Talent Plan of Chinese Academy of Sciences,the CAS/SAFEA International Partnership Program for Creative Research Teams,and the Program for Youthful Talents in Northwest A and F University
文摘Plants play an important role in soil phosphorus nutrition. However, the effect of plants on phosphorus nutrition in soils of the Loess Plateau of China is not well understood. This study was conducted to reveal the relationships between plants and phosphorus＇ fractions and availability in the Loess Plateau of China. Twenty-two plant communities were surveyed and soil samples under different plant canopies were collected for the determination of soil properties and inorganic phosphorus fractionation. The results showed that Leguminosae and Lilaceae reduced pH and increased organic matter, cation exchange capacity, total and Olsen phosphorus in soils under their canopies, while Labiatae and Rosaceae increased pH and decreased organic matter, cation exchange capacity, total and Olsen phosphorus in soils under their canopies. The contents of Ca2P, CasP, AI-P and Fe-P were highly related with soil Oisen phosphorus. They were all higher in soils under Leguminosae and Lilaceae and lower in softs under Labiatae and Rosaceae. The results of this study indicate that Leguminosae and Lilaceae improved phosphorus nutrition in soils, yet Labiatae and Rosaceae impeded the improvement of phosphorus nutrition in soils under their canopies, which will be of more help to instruct vegetation restoration in the region and provide information for soil development.
