Genome-Wide Analysis of C-Repeat Binding Factor Gene Family in Capsicum baccatum and Functional Exploration in Low-Temperature Response.

Capsicum baccatum is a close relative of edible chili peppers (Capsicum annuum) with high economic value. The CBF gene family plays an important role in plant stress resistance physiology. We detected a total of five CBF genes in the C. baccatum genome-wide sequencing data. These genes were scattered irregularly across four chromosomes. The genes were categorized into three groupings according to their evolutionary relationships, with genes in the same category showing comparable principles for motif composition. The 2000 bp upstream of CbCBF contains many resistance-responsive elements, hormone-responsive elements, and transcription factor binding sites. These findings emphasize the crucial functions of these genes in responding to challenging conditions and physiological regulation. Analysis of tissue-specific expression revealed that CbCBF3 exhibited the greatest level of expression among all tissues. Under conditions of low-temperature stress, all CbCBF genes exhibited different levels of responsiveness, with CbCBF3 showing a considerable up-regulation after 0.25 h of cold stress, indicating a high sensitivity to low-temperature response. The importance of the CbCBF3 gene in the cold response of C. baccatum was confirmed by the use of virus-induced gene silencing (VIGS) technology, as well as the prediction of its protein interaction network. To summarize, this study conducts a thorough bioinformatics investigation of the CbCBF gene family, showcases the practicality of employing VIGS technology in C. baccatum, and confirms the significance of the CbCBF3 gene in response to low temperatures. These findings provide significant references for future research on the adaptation of C. baccatum to low temperatures.

ESKtides: a comprehensive database and mining method for ESKAPE phage-derived antimicrobial peptides.

'Superbugs' have received increasing attention from researchers, such as ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.), which directly led to about 1 270 000 death cases in 2019. Recently, phage peptidoglycan hydrolases (PGHs)-derived antimicrobial peptides were proposed as new antibacterial agents against multidrug-resistant bacteria. However, there is still a lack of methods for mining antimicrobial peptides based on phages or phage PGHs. Here, by using a collection of 6809 genomes of ESKAPE isolates and corresponding phages in public databases, based on a unified annotation process of all the genomes, PGHs were systematically identified, from which peptides were mined. As a result, a total of 12 067 248 peptides with high antibacterial activities were respectively determined. A user-friendly tool was developed to predict the phage PGHs-derived antimicrobial peptides from customized genomes, which also allows the calculation of peptide phylogeny, physicochemical properties, and secondary structure. Finally, a user-friendly and intuitive database, ESKtides (http://www.phageonehealth.cn:9000/ESKtides), was designed for data browsing, searching and downloading, which provides a rich peptide library based on ESKAPE prophages and phages. Database URL:  10.1093/database/baae022.

Optimum timing of lung resection surgery following SARS-CoV-2 infection for non-small cell lung cancer.

BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on postoperative recovery of non-small cell lung cancer (NSCLC) is need to be understood, thereby informing the optimal timing of surgical decision-making during the COVID-19 pandemic for NSCLC patients. This study reports the postoperative outcomes of surgical NSCLC patients with preoperative SARS-CoV-2 infection. METHOD: This single-center retrospective cohort study included 241 NSCLC patients who underwent lobectomy or sub-lobectomy between December 1, 2022 and February 14, 2023. Surgical outcomes of patients with preoperative SARS-CoV-2 infection (stratified by the time from diagnosis of SARS-CoV-2 infection to surgery) were compared with those without preoperative SARS-CoV-2 infection. The primary outcomes were total postoperative complications and postoperative pulmonary complications (PPCs), the secondary outcomes included operation time, total postoperative drainage and time, length of hospital stay (LOS), 30-day and 90-day postoperative symptoms. RESULTS: This study included 153 (63.5%) patients with preoperative SARS-CoV-2 infection and 88 (36.5%) patients without previous SARS-CoV-2 infection. In patients with a preoperative SARS-CoV-2 diagnosis, the incidence of total postoperative complications (OR, 3.00; 95% CI, 1.12-8.01; p = 0.028) and PPCs (OR, 4.20; 95% CI, 1.11-15.91; p = 0.035) both increased in patients infected having surgery within 2 weeks compared with non-infection before surgery. However, patients who underwent lung resection more than 2 weeks after SARS-CoV-2 diagnosis had a similar risk of postoperative complications and surgical outcomes with those non-infection before surgery. CONCLUSION: This is the first study to provide evidence regarding the optimum timing of lung resection surgery and assessing early outcomes after surgery in NSCLC patients with SARS-CoV-2 infection. Our study documents that the SARS-CoV-2 infection did not complicate surgical procedures for lung cancer, and suggest that lung surgery should be postponed at least 2 weeks after SARS-CoV-2 infection for NSCLC patients.

Regioselective Hydrodeoxygenation of α-Diketones with Phosphites under Visible-Light Catalysis.

Novel regioselective hydrodeoxygenation of α-diketones with phosphites as the deoxygenation reagent was realized via visible-light photoredox catalysis. Broad substrate scope and high functional group compatibility were obtained. Unsymmetric α-diketones were selectively reduced at the carbonyls of higher electrophilicity. This unique regioselectivity compared with available methods makes it a practical complementary approach for the monohydrodeoxygenation of α-diketones.

Integrative analysis of multi-omics data reveals a pseudouridine-related lncRNA signature for prediction of glioma prognosis and chemoradiotherapy sensitivity.

BACKGROUND: Glioblastoma is the most common type of glioma with a high incidence and poor prognosis, and effective medical treatment remains challenging. Pseudouridine (Ψ) is the first post-transcriptional modification discovered and one of the most abundant modifications to RNA. However, the prognostic value of Ψ-related lncRNAs (ΨrLs) for glioma patients has never been systematically evaluated. This study aims to construct a risk model based on ΨrLs signature and to validate the predictive efficiency of the model. METHOD: Transcriptomic data, genomic data, and relevant clinical data of glioma patients were extracted from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). ΨrLs with significant correlation with Ψ-related genes were identified, and univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression were used to further select biomarkers and construct a ΨrLs signature risk model. Then, the expression of lncRNAs of ΨrLs signature in multiple glioma cell lines was detected by qPCR. Further, ROC analysis, stratification analysis, correlation analysis, survival analysis, nomogram, enrichment analysis, immune infiltration analysis, chemoradiotherapy sensitivity analysis, somatic mutation, and recurrent copy number variation (CNV) analysis were used to validate the predictive efficiency of ΨrLs signature in TCGA and CGGA datasets. RESULTS: A four-lncRNA ΨrLs signature (DNAJC27-AS1, GDNF-AS1, ZBTB20-AS4, and DNMBP-AS1) risk model was constructed. By ROC analysis, stratified analysis, correlation analysis, survival analysis, and nomogram, the signature showed satisfactory predictive efficiency. Functional enrichment analysis revealed the differences in immune-related biological processes between high- and low-risk groups. Immune infiltration analysis showed that the high-risk group had lower tumor purity and higher stromal, immune and ESTIMATE scores. Mitoxantrone was identified as effective drug for low-risk group of glioma patients. Key genes in glioma development, including IDH1, EGFR, PTEN, etc., were differentially mutated between risk groups. The main recurrent CNVs in low-risk groups were 19q13.42 deletion and 7q34 amplification; 10q23.31 deletion and 12q14.1 in the high-risk group. CONCLUSIONS: Our study identified a four-lncRNA ΨrLs signature that effectively predicts the prognosis of glioma patients and may serve as a diagnostic tool. Risk scores of glioma patients generated by the signature is associated with immune-related biological processes and chemoradiotherapy sensitivity. These findings may inform the development of more targeted and effective therapies for glioma patients.

Big-sized trees and higher species diversity improve water holding capacities of forests in northeast China.

High water-holding forests are essential for adapting to drought climates under global warming, and a central issue is which type of forests could conserve more water in the ecosystem. This paper explores how forest structure, plant diversity, and soil physics impact forest water-holding capacities. We investigated 720 sampling plots by measuring water-holding capacities from 1440 soil and litter samples, 8400 leaves, and 1680 branches and surveying 18,054 trees in total (28 species). Water-holding capacities were measured as four soil indices (Maxwc, maximum water-holding capacity; Fcwc, field water-holding capacity; Cpwc, soil capillary water-holding capacity; Ncpwc, non-capillary water-holding capacity), two litter metrics (Maxwcl, maximum water-holding capacity of litters; Ewcl, effective water-holding capacity of litters), and canopy interception (C, the sum of estimated water interception of all branches and leaves of all tree species in the plot). We found that water-holding capacity in the big-sized tree plots was 4-25 % higher in the litters, 54-64 % in the canopy, and 6-37 % in the soils than in the small-sized plots. The higher species richness increased all soil water-holding capacities compared to the lowest richness plot. Higher Simpson and Shannon-Wiener plots had 10-27 % higher Ewcl and C than the lowest plots. Bulk density had the strongest negative relations with Maxwc, Cpwc, and Fcwc, whereas field soil water content positively affected them. Soil physics, forest structure, and plant diversity explained 90.5 %, 5.9 %, and 0.2 % of the water-holding variation, respectively. Tree sizes increased C, Ncpwc, Ewcl directly (p < 0.05), and richness increased Ewcl directly (p < 0.05). However, the direct effects from the uniform angle index (tree distribution evenness) were balanced by their indirect effect from soil physics. Our findings highlighted that the mixed forests with big-sized trees and rich species could effectively improve the water-holding capacities of the ecosystem.

Understanding COVID-19 Vaccine Confidence in People Living with HIV: A pan-Canadian Survey.

Understanding the roots of Covid-19 vaccine hesitancy in at-risk groups, such as persons living with HIV (PLWH), is of utmost importance. We developed a modified Vaccine Hesitancy Scale (VHS) questionnaire using items from the National Advisory Committee on Immunization Acceptability Matrix. To examine factors associated with receiving COVID-19 vaccine and the link between vaccine attitudes and beliefs with vaccine behavior, PLWH were recruited via social media and community-based organizations (February-May 2022). Descriptive statistics were used to summarize results. Total VHS score was generated by adding Likert scale scores and linear regression models used to compare results between participants who received or did not receive COVID-19 vaccines. Logistic regression models were used to identify factors associated with vaccine uptake. A total of 246 PLWH indicated whether they received a COVID-19 vaccine. 89% received ≥ 1 dose. Mean total VHS(SD) for persons having received ≥ 1 COVID-19 vaccine was 17.8(6.2) vs. 35.4(9.4) for participants not having received any COVID-19 vaccine. Persons who received ≥ 1 dose were significantly older than those who had not received any (48.4 ± 13.8 vs. 34.0 ± 7.7 years, p < 0.0001). The majority of participants considered COVID-19 vaccination important for their health(81.3%) and the health of others(84.4%). Multivariate logistic regression revealed the odds of taking ≥ 1dose were increased 2.4-fold [95% CI 1.6, 3.5] with each increase in age of 10 years (p < 0.0001). Sex and ethnicity were not different between groups. In conclusion, PLWH accept COVID-19 vaccines for both altruistic and individual reasons. With evolving recommendations and increasing numbers of booster vaccines, we must re-examine the needs of PLWH regularly.

Iteratively distributed instrumental variable-based pseudo-linear information filter for angle-only tracking.

This paper presents a distributed filtering problem for three-dimensional angle-only target tracking (AOTT) in sensor (i.e., observer) networks. An instrumental variable-based pseudo-linear information filter (IVIF) is firstly derived on the basis of the designed bias-compensated pseudo-linear information filtering, with the help of summation forms of information quantities and bias compensation in a centralized fusion manner. Then, the distributed IVIF (DIVIF) is put forward by using finite-time average consensus to obtain the arithmetic means of defined information quantities and compensated bias in observer networks, which ensures that the filtering result of every observer is consistent with the centralized one. Finally, the iteratively DIVIF is proposed via gradually approaching the true values of relative distance and the corresponding angles between the target and every observer to get the filtering parameters more and more accurately, in order to achieve higher filtering precision. In addition, the computational complexity of the proposed method is also analyzed. The advantages of filtering precision of the proposed method over the existing pseudo-linear Kalman filter and its variants are demonstrated by an AOTT example in observer networks in terms of iteration steps, different levels of process noises and observer's accuracy.

Plant community phylogeny responses to protections and its main drivers in boreal forests, China: General pattern and implications.

Patterns of the phylogenetic structure have been broadly applied to predict community assembly processes. However, the distribution pattern of evolutionary diversity and its drivers under nature conservation are still poorly understood in boreal forests. Here, we investigated 1738 sampling plots and subplots from distinct protection intensities (PIs) zones in five representative National Nature Reserves (NNRs). Multiple comparisons, redundancy analysis, and linear mixed model were performed to identify the changes in community phylogeny across different PIs and NNRs and the drivers for these variations. Our results showed considerable plant community phylogeny variations in different NNRs. As indicated by SesMPD (standardized mean pairwise distance) and SesMNTD (standardized the mean nearest taxon distance), trees, shrubs, and herbs presented overdispersed, clustered, and random distribution patterns, respectively, in different PIs. Protection resulted in the phylogenetic structure between the nearest species of trees showing a more overdispersed pattern (p < 0.05). Protection decreased the phylogenetically clustered degree between the nearest species of shrubs (p > 0.05), while the herbs still maintained a random pattern. Community traits explained the most to phylogeny variation of different communities (24 %-71 %, p < 0.01), followed by geoclimatic factors (2 %-24 %) and conservation processes (1 %-21 %). The higher mean annual precipitation and under branch height at the lower latitude area accompanied the higher SesMPD and SesMNTD. The higher PIs attended with higher tree SesMPD, and the longer protection time resulted in higher shrub PSR (phylogenetic species richness) and PSV (phylogenetic species variability). Including the location of NNRs, community traits, and years of protection, rather than only emphasizing PI itself, could optimize community phylogenetic structure and preserve the evolutionary potential of biodiversity.

lncRNASNP v3: an updated database for functional variants in long non-coding RNAs.

Long non-coding RNAs (lncRNAs) act as versatile regulators of many biological processes and play vital roles in various diseases. lncRNASNP is dedicated to providing a comprehensive repository of single nucleotide polymorphisms (SNPs) and somatic mutations in lncRNAs and their impacts on lncRNA structure and function. Since the last release in 2018, there has been a huge increase in the number of variants and lncRNAs. Thus, we updated the lncRNASNP to version 3 by expanding the species to eight eukaryotic species (human, chimpanzee, pig, mouse, rat, chicken, zebrafish, and fruitfly), updating the data and adding several new features. SNPs in lncRNASNP have increased from 11 181 387 to 67 513 785. The human mutations have increased from 1 174 768 to 2 387 685, including 1 031 639 TCGA mutations and 1 356 046 CosmicNCVs. Compared with the last release, updated and new features in lncRNASNP v3 include (i) SNPs in lncRNAs and their impacts on lncRNAs for eight species, (ii) SNP effects on miRNA-lncRNA interactions for eight species, (iii) lncRNA expression profiles for six species, (iv) disease & GWAS-associated lncRNAs and variants, (v) experimental & predicted lncRNAs and drug target associations and (vi) SNP effects on lncRNA expression (eQTL) across tumor & normal tissues. The lncRNASNP v3 is freely available at http://gong_lab.hzau.edu.cn/lncRNASNP3/.

A glycosylation-related gene signature predicts prognosis, immune microenvironment infiltration, and drug sensitivity in glioma.

Glioma represents the most common primary cancer of the central nervous system in adults. Glycosylation is a prevalent post-translational modification that occurs in eukaryotic cells, leading to a wide array of modifications on proteins. We obtained the clinical information, bulk RNA-seq data, and single-cell RNA sequencing (scRNA-seq) from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gene Expression Omnibus (GEO), and Repository of Molecular Brain Neoplasia Data (Rembrandt) databases. RNA sequencing data for normal brain tissues were accessed from the Genotype-Tissue Expression (GTEx) database. Then, the glycosylation genes that were differentially expressed were identified and further subjected to variable selection using a least absolute shrinkage and selection operator (LASSO)-regularized Cox model. We further conducted enrichment analysis, qPCR, nomogram, and single-cell transcriptome to detect the glycosylation signature. Drug sensitivity analysis was also conducted. A five-gene glycosylation signature (CHPF2, PYGL, GALNT13, EXT2, and COLGALT2) classified patients into low- or high-risk groups. Survival analysis, qPCR, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group. Furthermore, GSEA and immune infiltration analysis indicated that the glycosylation signature has the potential to predict the immune response in glioma. In addition, four drugs (crizotinib, lapatinib, nilotinib, and topotecan) showed different responses between the two risk groups. Glioma cells had been classified into seven lines based on single-cell expression profiles. The five-gene glycosylation signature can accurately predict the prognosis of glioma and may offer additional guidance for immunotherapy.

Erratum: Biomineralized Bimetallic Oxide Nanotheranostics for Multimodal Imaging-Guided Combination Therapy: Erratum.

[This corrects the article DOI: 10.7150/thno.40715.].

Dynamic alternative polyadenylation during iPSC differentiation into cardiomyocytes.

Alternative polyadenylation (APA) is an important post-transcription regulatory mechanism widely occurring in eukaryotes and has been associated with special traits/diseases by several studies. However, the dynamic roles and patterns of APA in cell differentiation remain largely unknown. Here, we systematically characterized the APA profiles during the differentiation of induced pluripotent stem cells (iPSCs) to cardiomyocytes by the previously published RNA-seq data across 16 time points. We identified 950 differential APA events and found five dynamic APA patterns with fuzzy c-means clustering analysis. Among them, 3'UTR progressive lengthening is the main APA pattern over time, the genes of which are enriched in cell cycle and mRNA metabolic process pathways. By constructing the linear mixed-effects model, we also indicated that TIA1 plays an important role in regulating APA events with this pattern, including genes essential to cardiac function. Additionally, APA and polyA machinery activity with another pattern can immediately respond to developmental signal-mediated stimuli at the early differentiation stage and result in a sharp shortening of the 3'UTR. Finally, a miRNA-APA network is constructed and several hub miRNAs potentially regulating cardiomyocyte differentiation are detected. Our results show the complex APA mechanisms during the differentiation of iPSCs into cardiomyocytes and provide further insights for the understanding of APA regulation and cell differentiation.

Systematic analysis of the effects of genetic variants on chromatin accessibility to decipher functional variants in non-coding regions.

Genome-wide association study (GWAS) has identified thousands of single nucleotide polymorphisms (SNPs) associated with complex diseases and traits. However, deciphering the functions of these SNPs still faces challenges. Recent studies have shown that SNPs could alter chromatin accessibility and result in differences in tumor susceptibility between individuals. Therefore, systematically analyzing the effects of SNPs on chromatin accessibility could help decipher the functions of SNPs, especially those in non-coding regions. Using data from The Cancer Genome Atlas (TCGA), chromatin accessibility quantitative trait locus (caQTL) analysis was conducted to estimate the associations between genetic variants and chromatin accessibility. We analyzed caQTLs in 23 human cancer types and identified 9,478 caQTLs in breast carcinoma (BRCA). In BRCA, these caQTLs tend to alter the binding affinity of transcription factors, and open chromatin regions regulated by these caQTLs are enriched in regulatory elements. By integrating with eQTL data, we identified 141 caQTLs showing a strong signal for colocalization with eQTLs. We also identified 173 caQTLs in genome-wide association studies (GWAS) loci and inferred several possible target genes of these caQTLs. By performing survival analysis, we found that ~10% caQTLs potentially influence the prognosis of patients. To facilitate access to relevant data, we developed a user-friendly data portal, BCaQTL (http://gong_lab.hzau.edu.cn/caqtl_database), for data searching and downloading. Our work may facilitate fine-map regulatory mechanisms underlying risk loci of cancer and discover the biomarkers or therapeutic targets for cancer prognosis. The BCaQTL database will be an important resource for genetic and epigenetic studies.

Comparison of protective effects of alprostadil with Salvia miltiorrhiza against myocardial ischemia-reperfusion injury in rats.

OBJECTIVES: Our study aimed to investigate the effects of alprostadil and Salvia miltiorrhiza extract on myocardial ischemia-reperfusion injury (IRI) and related underlying molecular mechanisms. METHODS: A myocardial IRI model was established in Wistar rats via surgical ligation of the left anterior descending coronary artery followed by loosening of the occlusion. The rats were divided into four groups: saline, sham, alprostadil, and S. miltiorrhiza. Rats in the saline and sham groups were injected with normal saline by tail vein once daily for 10 consecutive days. Rats in the S. miltiorrhiza and alprostadil groups were injected with S. miltiorrhiza extract (20 µg/kg) or alprostadil. Histological differences in myocardial tissues between rats in the sham group and in the myocardial IRI model were observed by hematoxylin and eosin staining. India ink perfusion was used to quantify the number of capillary microvessels. Real-time quantitative reverse transcription polymerase chain reaction was used to determine serum expression levels of soluble intercellular adhesion molecule (sICAM), soluble vascular adhesion molecule (sVCAM), CD11b and CD18. RESULTS: The alprostadil and S. miltiorrhiza groups had significantly higher numbers of microvessels than the saline group. Serum sICAM and sVCAM expression was significantly reduced in the alprostadil and S. miltiorrhiza groups. Meanwhile, sICAM and sVCAM in the alprostadil group were markedly lower than in the S. miltiorrhiza group. Moreover, the alprostadil group had markedly lower mRNA expression of CD11b and CD18, which were clearly lower than in the S. miltiorrhiza group. CONCLUSION: Alprostadil may have cardioprotective effects for myocardial IRI, with down-regulated expression of sICAM, sVCAM, CD11b, and CD18.

Construction and Validation of a Necroptosis-Related lncRNA Signature in Prognosis and Immune Microenvironment for Glioma.

Background: Glioma is the most common primary brain tumor, representing approximately 80.8% of malignant tumors. Necroptosis triggers and enhances antitumor immunity and is expected to be a new target for tumor immunotherapy. The effectiveness of necroptosis-related lncRNAs as potential therapeutic targets for glioma has not been elucidated. Methods: We acquired RNA-seq data sets from LGG and GBM samples, and the corresponding clinical characteristic information is from TCGA. Normal brain tissue data is from GTEX. Based on TCGA and GTEx, we used univariate Cox regression to sort out survival-related lncRNAs. Lasso regression models were then built. Then, we performed a separate Kaplan-Meier analysis of the lncRNAs used for modeling. We validated different risk groups via OS, DFS, enrichment analysis, comprehensive immune analysis, and drug sensitivity. Results: We constructed a 12 prognostic lncRNAs model after bioinformatic analysis. Subsequently, the risk score of every glioma patient was calculated based on correlation coefficients and expression levels, and the patients were split into low- and high-risk groups according to the median value of the risk score. A nomogram was established for every glioma patient to predict prognosis. Besides, we found significant differences in OS, DFS, immune infiltration and checkpoints, and immune therapy between different risk subgroups. Conclusion: Predictive models of 12 necroptosis-related lncRNAs can facilitate the assessment of the prognosis and molecular characteristics of glioma patients and improve treatment modalities.

Glycoprotein B Antibodies Completely Neutralize EBV Infection of B Cells.

The Epstein-Barr virus (EBV) is the first reported oncogenic herpesvirus that establishes persistent infection in B lymphocytes in 95% of adults worldwide. Glycoprotein B (gB) plays a predominant role in the fusion of the viral envelope with the host cell membrane. Hence, it is of great significance to isolate gB-specific fusion-inhibiting neutralizing antibodies (NAbs). AMMO5 is the only gB NAb but fails to antagonize B-cell infection. It is essential to isolate potent NAbs that can completely block EBV infection of B cells. Using hybridoma technology and neutralization assay, we isolate two gB NAbs 8A9 and 8C12 that are capable of completely neutralizing B-cell infection in vitro. In addition, 8A9 shows cross-reactivity with rhesus lymphocryptovirus (rhLCV) gB. Competitive binding experiments demonstrate that 8A9 and 8C12 recognize novel epitopes that are different from the AMMO5 epitope. The epitopes of 8A9 and 8C12 are mapped to gB D-II, and the AMMO5 epitope is located precisely at gB aa 410-419. We find that 8A9 and 8C12 significantly inhibit gB-derived membrane fusion using a virus-free fusion assay. In summary, this study identifies two gB-specific NAbs that potently block EBV infection of B cells. Our work highlights the importance of gB D-II as a predominant neutralizing epitope, and aids in the rational design of therapeutics or vaccines based on gB.

Oesophageal reconstruction with a reversed gastric conduit for a complex oesophageal cancer patient: a case report.

BACKGROUND: The gastric conduit is the best replacement organ for oesophageal reconstruction, but a reversed gastric conduit (RGC) is rare. Oesophageal reconstruction for oesophageal cancer patients with a previous history of complicated gastrointestinal surgery is rather difficult. Here, we report a case in which oesophageal reconstruction was successfully managed using RGC based solely on the left gastroepiploic artery supply. CASE PRESENTATION: A 69-year-old man with oesophageal cancer had a history of endoscopic intestinal polypectomy and pylorus-preserving pancreaticoduodenectomy (PPPD). The right gastroepiploic artery and right gastric artery had been completely severed. The only supply artery that could be used for the gastric conduit was just the left gastroepiploic artery. Because of the complex history of abdominal surgery, we had no choice but to use the RGC to complete the oesophageal reconstruction, in which the gastric conduit was passed reversely through the hiatus to the oesophageal bed and layered end-to-side manual intrathoracic anastomosis with the esophagus. The patient had transient feeding problems with postoperative delayed thoracic stomach emptying but no anastomotic stenosis or thoracic stomach fistula. He was satisfied with his life and had no long-term complications. There was no significant effect on gut physiological function, and RGC could work normally. CONCLUSIONS: Oesophageal reconstruction with RGC is a feasible procedure for complex oesophageal carcinoma that can simplify complicated surgical procedures, has less influence on gut function, is less invasive, and is safe.

Hirudin Regulates Vascular Function in Chronic Renal Failure through Modulating Macrophage Polarization.

Excessive inflammation is responsible for arteriovenous fistula (AVF) failure, which determines the therapeutic effect of chronic renal failure (CRF). Macrophage polarization is of great significance in the inflammatory response. Hirudin (Hiru) has been reported to possess a definite anti-inflammatory effect. This study is to uncover the impacts of Hiru on classically (M1)/alternatively (M2) macrophage polarization in the CRF rat model and rat vascular smooth muscle cells (VSMCs). After the CRF rat model was administrated with different concentrations of Hiru, blood urea nitrogen (BUN) and serum creatinine (Scr) levels were tested. H&E staining was to detect vascular injury, and IHC assay was to analyze inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) expressions in vascular tissues. Levels of inflammatory factors were examined by ELISA. Besides, western blot was to estimate the levels of marker proteins related to macrophage, proliferation, and apoptosis. CCK-8 was to measure cell viability. We discovered that Hiru alleviated renal function injury and vascular injury, exacerbated VSMC hyperplasia, and stimulated the differentiation and activation of M1 macrophage towards M2 macrophage in vivo. Moreover, after treatment with lipopolysaccharide (LPS)/IFN-gamma (IFN-γ), the increased M1/M2 ratio and enhanced levels of inflammatory factors were observed. Furthermore, Hiru boosted the proliferation and ameliorated the inflammatory response and apoptosis of rat VSMCs during the process of coincubation of M1-conditioned medium (CM). Collectively, Hiru played a protective role against vascular injury in CRF directly or through its influence on M1 macrophage polarization and inflammation.

Pyroptosis-Related Gene Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Glioma.

Objective: Gliomas are the most common primary tumors in the central nervous system with a bad prognosis. Pyroptosis, an inflammatory form of regulated cell death, plays a vital role in the progression and occurrence of tumors. However, the value of pyroptosis related genes (PRGs) in glioma remains poorly understood. This study aims to construct a PRGs signature risk model and explore the correlation with clinical characteristics, prognosis, tumor microenviroment (TME), and immune checkpoints. Methods: RNA sequencing profiles and the relevant clinical data were obtained from the Chinese Glioma Genome Atlas (CGGA), the Cancer Genome Atlas (TCGA), the Repository of Molecular Brain Neoplasia Data (REMBRANDT), and the Genotype-Tissue Expression Project (GTEx-Brain). Then, the differentially expressed pyroptosis related genes (PRGs) were identified, and the least absolute shrinkage and selection operator (LASSO) and mutiCox regression model was generated using the TCGA-train dataset. Then the expression of mRNA and protein levels of PRGs signature was detected through qPCR and human protein atlas (HPA). Further, the predictive ability of the PRGs-signature, prognostic analysis, and stratification analysis were utilized and validated using TCGA-test, CGGA, and REMBRANDT datasets. Subsequently, we constructed the nomogram by combining the PRGs signature and other key clinical features. Moreover, we used gene set enrichment analysis (GSEA), GO, KEGG, the tumor immune dysfunction and exclusion (TIDE) single-sample GSEA (ssGSEA), and Immunophenoscore (IPS) to determine the relationship between PRGs and TME, immune infiltration, and predict the response of immune therapy in glioma. Results: A four-gene PRGs signature (CASP4, CASP9, GSDMC, IL1A) was identified and stratified patients into low- or high-risk group. Survival analysis, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group than in the low-risk group. Correlation analysis showed that the risk score was correlated with poor disease features. Furthermore, GSEA and immune infiltrating and IPS analysis showed that the PRGs signature could potentially predict the TME, immune infiltration, and immune response in glioma. Conclusion: The newly identified four-gene PRGs signature is effective in diagnosis and could robustly predict the prognosis of glioma, and its impact on the TME and immune cell infiltrations may provide further guidance for immunotherapy.