Neural stem cell-derived exosomes regulate cell proliferation,migration,and cell death of brain microvascular endothelial cells via the miR-9/Hes1 axis under hypoxia

Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 axis.However,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain unknown.Therefore,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 axis.Methods:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs.Results:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions.The overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic conditions.Moreover,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death.Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death.Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice.Meanwhile,EXO treatment improved cerebrovascular alterations.Conclusion:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions.Therefore,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.

Quantifying the natural growth rate of hepatocellular carcinoma:A real-world retrospective study in southwestern China

BACKGROUND In recent years,approximately half of the newly diagnosed cases and mortalities attributed to hepatocellular carcinoma(HCC)have been reported in China.Despite the high incidence of HCC,there remains a paucity of data regarding the natural growth pattern and the determination of optimal surveillance intervals specific to the Chinese population.AIM To quantify the natural tumor growth pattern of HCC in regional China.METHODS A retrospective analysis was performed on patients from a single institution in Southwest China who had undergone two or more serial dynamic computed tomography or magnetic resonance imaging scans between 2014 and 2020,without having received any anti-cancer therapy.Tumor growth was assessed using tumor volume doubling time(TVDT)and tumor growth rate(TGR),with volumes measured manually by experienced radiologists.Simple univariate linear regression and descriptive analysis were applied to explore associations between growth rates and clinical factors.RESULTS This study identifies the median TVDT for HCC as 163.4 d,interquartile range(IQR)72.1 to 302.3 d,with a daily TGR of 0.42%(IQR 0.206%-0.97%).HCC growth patterns reveal that about one-third of tumors grow indolently with TVDT exceeding 270 d,another one-third of tumors exhibit rapid growth with TVDT under 90 d,and the remaining tumors show intermediate growth rates,with TVDT ranging between 3 to 9 months.CONCLUSION The identified TGRs support biannual surveillance and follow-up for HCC patients in certain regions of China.Given the observed heterogeneity in HCC growth,further investigation is warranted.

Differences in the predictive value of red cell distribution width for the mortality of patients with heart failure due to various heart diseases

Background Increased red blood cell distribution width （RDW） is associated with adverse outcomes in patients with heart failure （HF）. The objective of this study was to compare the differences in the predictive value of RDW in patients with HF due to different causes. Methods We retrospectively investigated 1,021 HF patients from October 2009 to December 2011 at Fuwai Hospital （Beijing, China）. HF in these patients was caused by three diseases; coronary heart disease （CHD）, dilated cardiomyopathy （DCM） and valvular heart disease （VHD）. Patients were followed-up for 21 ~ 9 months. Results The RDW, mortality and survival duration were significantly different among the three groups. Kaplan-Meier analysis showed that the cumulative survival decreased significantly with increased RDW in patients with HF caused by CHD and DCM, but not in those with HF patients caused by VHD. In a multivariable model, RDW was identified as an independent predictor for the mortality of HF patients with CHD （P 〈 0.001, HR 1.315, 95% CI 1.122-1.543）. The group with higher N-terminal pro-brain natriuretic peptide （NT-proBNP） and higher RDW than median had the lowest cumulative survival in patients with HF due to CHD, but not in patients with HF due to DCM. Conclusions RDW is a prognostic indicator for patients with HF caused by CHD and DCM; thus, RDW adds important information to NT-proBNP in CHD caused HF patients.

Correlation of fibrinogen level and absorbance change in both PT and APTT clotting curves on BCSXP

Objective： To investigate the correlation of fibrinogen level and absorbance change in both PT and APTT clotting curves on BCSXP Analyzer. Methods：A serial of standard fibrinogen and 250 patient plasma samples with different qualities（normal, hemolysis, icterus, and lipemia） were run on BCSXP for assays PT, APTT and Fibrinogen. The absorbance change（DeltaA） from baseline to plateau in clotting curve was retrieved and analyzed on its correlation with the Fibrinogen result. Influence of plasma quality and PT/ APTT result on this correlation was also studied respectively. Results：Both PT-DeltaA and APTT-DeltaA showed good linear regres- sion with fibrinogen level in the sample, with R2 close to 0.90 in both standard and patient samples. Hemolysis（H）, itcterus（I） and lipemia（L） of the sample with valid clotting curves were found to have no significant difference in this correlation from normal（N） sample（R2： 0.83H, 0.92I, 0.81L and 0.79N in PT; 0.89H, 0.95l, 0.91L and 0.89N in APTT） in either PT or APTT curve. PT or APTT result also has little impact on this correlation（0.71 in range 7 - 10 sec, 0.56 inl0 - 20 sec, and 0.70 in 20 sec-; R2 in APTT： 0.88 in 20-30 sec, 0.92 in 30-40 sec, and 0.95 in 40 sec-）. Conclusion：The absorbance change in either PT or APTT clotting curve correlates well with the fibrinogen level in plasma, which is independent of plasma quality PT or APTT results. The absorbance change can be used as an alternative way to roughly estimate fibrinogen level in either PT or APTT clotting curve when the result of clauss-based fibrinogen measurement is not available.

Prognostic value of neutrophil-to-lymphocyte ratio in gastric cancer patients undergoing neoadjuvant chemotherapy:A systematic review and meta-analysis

BACKGROUND In recent studies,accumulating evidence has revealed a strong association between the inflammatory response and the prognosis of many tumors.There is a certain correlation of neutrophil-to-lymphocyte ratio(NLR)with the prognosis in gastric cancer(GC)patients undergoing neoadjuvant chemotherapy(NAC).However,the existing research results have remained controversial.AIM To explore the relationship between NLR ratio and prognosis of GC patients receiving NAC.METHODS A thorough systematic search was performed in databases such as PubMed,Embase,Web of Science,and Cochrane Library,the search is available until February 29,2024,and studies exploring the interaction of NLR with clinical outcomes were collected.Relevant studies meeting pre-defined inclusion and exclusion criteria were carefully chosen.The outcomes included progression-free survival(PFS),relapse-free survival,disease-free survival(DFS),and overall survival(OS).The hazard ratio(HR)and its corresponding 95%confidence interval(CI)were utilized for estimation.RESULTS Our analysis encompassed 852 patients and incorporated data from 12 cohort studies.The comprehensive analysis revealed a significant association of high NLR with reduced OS(HR=1.76;95%CI:1.22-2.54,P=0.003),relapsefree survival(HR=3.73;95%CI:1.74-7.96,P=0.0007),and PFS(HR=2.32;95%CI:1.42-3.81,P=0.0008)in patients.However,this correlation in disease-free survival was not significant.NLR demonstrated its crucial role in effectively predicting the OS of GC patients undergoing NAC at different detection times,ages,regions,and NLR thresholds.CONCLUSION In GC patients receiving NAC,an elevated NLR is strongly associated with reduced OS and PFS.NLR has become an effective biomarker for patient prognosis evaluation,providing valuable insights for the treatment strategies of NAC in GC patients.

Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas

Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Intracellular RNA Labeling Technologies for the Analysis of RNA Biology

As a cornerstone of the central dogma of molecular biology,RNA plays vital roles in living organisms.Over the past few decades,many RNA labeling technologies have been developed to elucidate the biological function of RNA.These technologies have signifi-cantly advanced our understanding of RNA secondary structure,localization,and turnover.Additionally,taking advantage of these innovative RNA labeling approaches,plenty of tool kits have been devised for the regulation of RNA-related biological process,such as gene expression and gene editing.In this review,we primarily focus on an array of intracellular RNA labeling methods,encom-passing chemical probes-based labeling,metabolic labeling,and proximity-dependent labeling.We also provide a brief overview of their applications in the research of RNA biology.Finally,the perspectives of RNA labeling are also discussed.

Development of heart failure risk prediction models based on a multi-marker approach using random forest algorithms

Background:The early identification of heart failure(HF)risk may favorably affect outcomes,and the combination of multiple biomarkers may provide a more comprehensive and valuable means for improving the risk of stratification.This study was conducted to assess the importance of individual cardiac biomarkers creatine kinase MB isoenzyme(CK-MB),B-type natriuretic peptide(BNP),galectin-3(Gal-3)and soluble suppression of tumorigenicity-2(sST2)for HF diagnosis,and the predictive performance of the combination of these four biomarkers was analyzed using random forest algorithms.Methods:A total of 193 participants(80 patients with HF and 113 age-and gender-matched healthy controls)were included from June 2017 to December 2017.The correlation and regression analysis were conducted between cardiac biomarkers and echocardiographic parameters.The accuracy and importance of these predictor variables were assessed using random forest algorithms.Results:Patients with HF exhibited significantly higher levels of CK-MB,BNP,Gal-3,and sST2.BNP exhibited a good independent predictive capacity for HF(AUC 0.956).However,CK-MB,sST2,and Gal-3 exhibited a modest diagnostic performance for HF,with an AUC of 0.709,0.711,and 0.777,respectively.BNP was the most important variable,with a remarkably higher mean decrease accuracy and Gini.Furthermore,there was a general increase in predictive performance using the multi-marker model,and the sensitivity,specificity was 91.5%and 96.7%,respectively.Conclusion:The random forest algorithm provides a robust method to assess the accuracy and importance of predictor variables.The combination of CK-MB,BNP,Gal-3,and sST2 achieves improvement in prediction accuracy for HF.

Surgical outcome after complete repair of tetralogy of Fallot with absent pulmonary valve: comparison between bovine jugular vein-valved conduit and monocusp-valve patch

Background The prognosis of tetralogy of Fallot with absent pulmonary valve (TOF/APV) without operation is poor. We evaluated the surgical outcome of TOF/APV in a single center. Methods Twenty-two TOF/APV patients underwent complete surgical correction in our hospital. Right ventricular outflow tract reconstruction was performed using bovine jugular vein (BJV)-valved conduit implantation (n=10), homograft-valved conduit implantation (n=2), or monocusp-valve patch (n=10). Health-related quality of life (QOL) was evaluated during follow-up. Results The overall survival at 5 and 10 years was 86.4±7.3% (confidence interval 69.4–97.2%). The survival rates were significantly different between patients with and without bronchial stenosis (40 and 100%, P=0.0003, log-rank test). The survival of patients aged>6 months was higher than those≤6 months (100 vs. 40%, P=0.0003, log-rank test). Patients with BJV-valved conduits had higher systolic gradients from the right ventricle to the pulmonary artery (RV–PA) compared to those with monocusp-valve patches. BJV-valved conduit implantation was a risk factor for post-operative pulmonary-valve stenosis. The QOL score for patients with BJV-valved conduits was lower than those with monocusp-valve patches (P<0.05). No reoperation was performed during follow-up. Conclusions Bronchial stenosis and lower age (≤6 months) were the main factors influencing post-operative survival. The use of a BJV-valved conduit was a main reason for RV–PA restenosis;thus, the use of a BJV-valved conduit may increase the need for repeat intervention and decrease the post-operative quality of life.

Age-dependent changes of total and differential white blood cell counts in children

Background:Total and differential white blood cell counts are important for the diagnostic evaluation of suspected diseases.To facilitate the interpretation of total and differential white blood cell counts in pediatric patients,the present study investigated agedependent changes in total and differential white blood cell counts in healthy reference children.Methods:Data were obtained from the Pediatric Reference Intervals in China study(PRINCE),which aims to establish and verify pediatric reference intervals for Chinese children based on a nationwide multicenter cross-sectional study from January 2017 to December 2018.Quantile curves were calculated using the generalized additive models for location,shape,and scale method.The 2.5th,50th,and 97.5th quantile curves were calculated for both total and differential white blood counts.Percents of stacked area charts were used to demonstrate the proportions of differential white blood cells.All statistical analyses were performed using R software.Results:Both 50th and 97.5th quantiles of total white blood cell count and monocyte count were highest at birth,then rapidly decreased in the first 6 months of life;relatively slow reduction continued until 2 years of age.The lymphocyte count was low during infancy and increased to its highest level at 6 months of age;it then exhibited moderate and continuous reduction until approximately 9 years of age.The pattern of neutrophil count changed with age in a manner opposite to that of lymphocyte count.Besides,there were two inter-sections of lymphocyte count and neutrophil count during infancy and at approximately 5 years of age,based on locally weighted regression(LOESS)analysis.There were no apparent age-related changes in eosinophil or basophil counts.Conclusion:These data regarding age-related changes in total and differential white blood cell counts can be used to assess the health of pediatric patients and guide clinical decisions.

Diversity and independent evolutionary profiling of rodent-borne viruses in Hainan,a tropical island of China

The risk of emerging infectious diseases(EID)is increasing globally.More than 60%of EIDs worldwide are caused by animal-borne pathogens.This study aimed to characterize the virome,analyze the phylogenetic evolution,and determine the diversity of rodent-borne viruses in Hainan Province,China.We collected 682 anal and throat samples from rodents,combined them into 28 pools according to their species and location,and processed them for next-generation sequencing and bioinformatics analysis.The diverse viral contigs closely related to mammals were assigned to 22 viral families.Molecular clues of the important rodent-borne viruses were further identified by polymerase chain reaction for phylogenetic analysis and annotation of genetic characteristics such as arenavirus,coronavirus,astrovirus,pestivirus,parvovirus,and papillomavirus.We identified pestivirus and bocavirus in Leopoldoms edwardsi from Huangjinjiaoling,and bocavirus in Rattus andamanensis from the national nature reserves of Bangxi with low amino acid identity to known pathogens are proposed as the novel species,and their rodent hosts have not been previously reported to carry these viruses.These results expand our knowledge of viral classification and host range and suggest that there are highly diverse,undiscovered viruses that have evolved independently in their unique wildlife hosts in inaccessible areas.

Solitary fibrous tumor of the prostate:a case report and 5-year follow-up

Dear Editor, Solitary fibrous tumors (SFTs) originating from the prostate are extremely rare. The prognosis of patients with SFTs who undergo surgical treatment is good, but aggressive SFTs can recur, so patients should be closely followed up.1 Here, we report a 46-year-old male patient with prostatic SFT who was followed up for 5 years after surgical treatment. This study was approved by the Ethics Committee of Lanzhou University Second Hospital (Lanzhou, China). The patient provided written informed consent.

Transition-Metal-Free Allylic Defluorination Cross-Electrophile Coupling Employing Rongalite

Comprehensive Summary The conversion of CF3-alkenes to gem-difluoroalkenes using reductive cross-coupling strategy has received much attention in recent years,however,the use of green and readily available reducing salt to mediate these reactions remains to be explored.In this work,a concise construction of gem-difluoroalkenes,which requires neither a catalyst nor a metal reducing agent,was established.Rongalite,a safe and inexpensive industrial product,was employed as both a radical initiator and reductant.This procedure was compatible with both linear and cyclic diaryliodonium salts,enabling a wide variety of substrates(>70 examples).The utility of this approach was demonstrated through gram-scale synthesis and efficient late-stage functionalizations of anti-inflammatory drugs.

Sequencing-based methods for single-cell multi-omics studies

Single-cell multi-omics technologies have thrived in recent years.The combined studies of different modalities in single cells have enabled comprehensive insights into the complex functional networks of vital biomacromolecules,thus paving the way for a thorough understanding of cell biology and pathology.In this review,we focus on the advances of single-cell multi-omics technologies utilizing sequencing strategies and propose potential perspectives.