CellMarker 2.0 (http://bio-bigdata.hrbmu.edu.cn/CellMarker or http://117.50.127.228/CellMarker/) is an updated database that provides a manually curated collection of experimentally supported markers ...of various cell types in different tissues of human and mouse. In addition, web tools for analyzing single cell sequencing data are described. We have updated CellMarker 2.0 with more data and several new features, including (i) Appending 36 300 tissue-cell type-maker entries, 474 tissues, 1901 cell types and 4566 markers over the previous version. The current release recruits 26 915 cell markers, 2578 cell types and 656 tissues, resulting in a total of 83 361 tissue-cell type-maker entries. (ii) There is new marker information from 48 sequencing technology sources, including 10X Chromium, Smart-Seq2 and Drop-seq, etc. (iii) Adding 29 types of cell markers, including protein-coding gene lncRNA and processed pseudogene, etc. Additionally, six flexible web tools, including cell annotation, cell clustering, cell malignancy, cell differentiation, cell feature and cell communication, were developed to analysis and visualization of single cell sequencing data. CellMarker 2.0 is a valuable resource for exploring markers of various cell types in different tissues of human and mouse.
Abstract
Lnc2Cancer 2.0 (http://www.bio-bigdata.net/lnc2cancer) is an updated database that provides comprehensive experimentally supported associations between lncRNAs and human cancers. In ...Lnc2Cancer 2.0, we have updated the database with more data and several new features, including (i) exceeding a 4-fold increase over the previous version, recruiting 4989 lncRNA-cancer associations between 1614 lncRNAs and 165 cancer subtypes. (ii) newly adding about 800 experimentally supported circulating, drug-resistant and prognostic-related lncRNAs in various cancers. (iii) appending the regulatory mechanism of lncRNA in cancer, including microRNA (miRNA), transcription factor (TF), variant and methylation regulation. (iv) increasing more than 70 high-throughput experiments (microarray and next-generation sequencing) of lncRNAs in cancers. (v) Scoring the associations between lncRNA and cancer to evaluate the correlations. (vi) updating the annotation information of lncRNAs (version 28) and containing more detailed descriptions for lncRNAs and cancers. Moreover, a newly designed, user-friendly interface was also developed to provide a convenient platform for users. In particular, the functions of browsing data by cancer primary organ, biomarker type and regulatory mechanism, advanced search following several features and filtering the data by LncRNA-Cancer score were enhanced. Lnc2Cancer 2.0 will be a useful resource platform for further understanding the associations between lncRNA and human cancer.
Single-atom catalysts (SACs) supported on two-dimensional (2D) materials are highly attractive for maximizing their catalytic activity. However, graphene based SACs are primarily bonded with nitrogen ...and carbon sites, resulting in poor performance for the oxygen evolution reaction (OER). Herein, we develop a general bimetal-ion adsorption strategy for the synthesis of individually dispersed Ni SACs anchored on the oxygenated sites of ultrathin reduced graphene oxide as efficient OER electrocatalysts. The resultant Ni SACs for OER in alkaline electrolyte exhibit a highly stable overpotential of 328 mV at the current density of 10 mA cm−2, and Tafel slope of 84 mV dec−1 together with long-term durability and negligible degradation for 50 h, which is greatly outperform its counterparts of nitrogen bonded Ni SACs (564 mV, 364 mV dec−1) and Ni(OH)2 nanoparticles anchored on graphene (450 mV, 142 mV dec−1), and most reported Ni based OER electrocatalysts. Furthermore, the extended X-ray absorption fine structure at the Ni K-edge and theoretical simulation reveal that the nickel-oxygen coordination significantly boost OER performance. Therefore, this work will open numerous opportunities for creating novel-type 2D SACs via oxygen–metal bonding as highly robust OER catalysts.
A general bimetal-ion adsorption strategy was successfully developed to synthesize the Ni single atoms anchored on the oxygenated sites of graphene as efficient OER electrocatalysts, which exhibited overpotential of 328 mV and Tafel slope of 84 mV dec−1. Display omitted
Copy number alterations (CNAs) of lincRNAs act as one of important mechanisms in disrupting lincRNA expression which may play critical roles during tumorigenesis in lung adenocarcinoma (LUAD). The ...copy number alterations of lincRNAs can mark the spectrum of cancer progression and may serve as biomarkers for prognosis in LUAD, however it is rarely studied. We analyzed RNASeq data for 488 LUAD patients from TCGA portal and 58 healthy subjects to identify prognostic lincRNAs predictive of patient survival. Computational analysis entailing integration of expression and copy number alteration data revealed five prognostic lincRNAs: RBPMS‐AS1, TDRKH‐AS1, LINC00578, RP11‐470 M17.2 and LINC00941. The copy number alterations in the LINC00578 and RP11‐470 M17.2 genes were positively associated with the longer overall survival of LUAD patients. The CNA in LINC00941 was negatively associated with the longer overall survival. Copy number amplification significantly correlated with increased expression of TDRKH‐AS1, which regulates telomere organization and EZH2‐mediated epigenetic silencing of CDKN1A, CDKN1B and IL24. Decreased survival of LUAD patients was associated with high LINC00941 expression. The LINC00941 regulates the PI3K‐AKT signaling pathway, focal adhesion by influencing potential targets, such as KRAS proto‐oncogene GTPase and VEGFC. These lincRNA‐based prognostic biomarkers may destroy important cancer‐related biological processes contributing to LUAD prognosis. In summary, we demonstrate the prognostic potential of four differentially expressed lincRNAs with copy number alterations (RBPMS‐AS1, TDRKH‐AS1, LINC00578 and RP11‐470 M17.2) that are positively associated with longer overall survival of LUAD patients. One differentially expressed lincRNA LINC00941 with copy number alterations was negatively associated with longer overall survival of LUAD patients.
What's new?
Changes in gene copy number are among the most frequent genetic anomalies occurring in human cancers. The relevance of copy number alterations (CNAs) that occur in noncoding regions, however, remains unclear. Here, investigation of CNAs in long intergenic noncoding RNAs (lincRNAs) in lung adenocarcinoma patients led to the identification of five prognostic lincRNAs. Elevated expression of one of the genes, LINC00941, which regulates PI3K‐AKT signaling and focal adhesion, was negatively associated with lung adenocarcinoma survival. The other four lincRNAs were positively associated with lengthened overall survival. The lincRNA TDRKH‐AS1 contributed to prognosis via regulation of mitochondrial activity and telomere organization.
Acupuncture of the governor vessel and Yangming meridian are widely used in the treatment of acute ischemic stroke (AIS). However, the optimal meridian for acupuncture in the treatment of AIS remains ...uncertain.
This network meta-analysis study aimed to compare the clinical effectiveness of acupuncture at governor vessel and Yangming meridian in the treatment of AIS.
All relevant studies published in CNKI, WANFANG, VIP, Sinomed, Cochrane Library, Web of Science, Pub Med, and Embase before January 13, 2024 were systematically retrieved. The two researchers independently screened the studies and extracted the data. Cochrane ROB tool was used to evaluate the quality of the studies, and Stata 14.0 software was used to conduct a network meta-analysis of neurological deficit score, activities of daily living (ADL), clinical effective rate and Fugl-meyer motor function evaluation (FMA).
A total of 401 studies were obtained, and 17 studies met the inclusion criteria. The surface under the cumulative ranking curve (SUCRA) values of the four outcome indexes were all ranked by "Governor vessel acupuncture + Conventional neurology treatment(GVAc+CT) > Yangming meridian acupuncture + Conventional neurology treatment(YMAc+CT) > Conventional neurology treatment (CT)". Compared to YMAc+CT and CT, GVAc+CT had the best effect in reducing the degree of neurological deficit score (SMD = -0.72, 95%CI = -1.22,-0.21 and SMD = -1.07,95%CI = -1.45,-0.69, respectively) and promoting the recovery of ADL((SMD = 0.59,95%CI = 0.31,0.88 and SMD = 0.96,95%CI = 0.70,1.21, respectively). Compared to CT, GVAc+CT also had a better clinical effective rate in the treatment of AIS (RR = 1.14,95%CI = 1.04,1.25).
Governor vessel acupuncture combined with conventional neurology treatment has the best effect in reducing the degree of neurological deficit score and promoting the recovery of ADL in AIS patientscompared to YMAc+CT and CT. Governor Vessel acupuncture is the most preferable acupoint scheme for clinical acupuncture treatment of AIS.
HOIL‐1, a component of the linear ubiquitin chain assembly complex (LUBAC), ubiquitylates serine and threonine residues in proteins by esterification. Here, we report that mice expressing an E3 ...ligase‐inactive HOIL‐1C458S mutant accumulate polyglucosan in brain, heart and other organs, indicating that HOIL‐1’s E3 ligase activity is essential to prevent these toxic polysaccharide deposits from accumulating. We found that HOIL‐1 monoubiquitylates glycogen and α1:4‐linked maltoheptaose in vitro and identify the C6 hydroxyl moiety of glucose as the site of ester‐linked ubiquitylation. The monoubiquitylation of maltoheptaose was accelerated > 100‐fold by the interaction of Met1‐linked or Lys63‐linked ubiquitin oligomers with the RBR domain of HOIL‐1. HOIL‐1 also transferred pre‐formed ubiquitin oligomers to maltoheptaose en bloc, producing polyubiquitylated maltoheptaose in one catalytic step. The Sharpin and HOIP components of LUBAC, but not HOIL‐1, bound to unbranched and infrequently branched glucose polymers in vitro, but not to highly branched mammalian glycogen, suggesting a potential function in targeting HOIL‐1 to unbranched glucosaccharides in cells. We suggest that monoubiquitylation of unbranched glucosaccharides may initiate their removal from cells, preventing precipitation as polyglucosan.
Synopsis
Mutations in the linear ubiquitin chain assembly complex (LUBAC) component HOIL‐1, which can ubiquitylate hydroxyl side chains in polypeptides, are linked to toxic polyglucosan accumulation. Demonstration of glucosaccharide ubiquitylation by the HOIL‐1 E3 ligase suggests its involvement in a quality control mechanism that removes unbranched glycogen to prevent its precipitation as toxic polyglucosan deposits.
HOIL‐1 in vitro monoubiquitylates the unbranched α1:4‐linked glucosaccharide maltoheptaose at the C6‐hydroxyl moiety of glucose.
HOIL‐1‐catalysed monoubiquitylation of maltoheptaose is accelerated > 100‐fold by Met1‐linked or Lys63‐linked ubiquitin oligomers, which interact with the RBR domain of HOIL‐1.
LUBAC components Sharpin and HOIP bind to unbranched and infrequently branched glucose polymers in vitro, but not to highly branched mammalian glycogen.
Mice expressing an E3 ligase‐inactive mutant of HOIL‐1 accumulate polyglucosan in brain and other organs.
Linear ubiquitin chain assembly complex (LUBAC) targeting and ubiquitin attachment to unbranched glucose polymers may prevent formation of toxic polyglucosan deposits in cells.
RNA N6-methyladenosine (m6A) regulators play essential roles in diverse biological processes, including immune responses. Mounting evidence suggests that their dysregulation is intricately linked to ...numerous diseases. However, the role of m6A-associated genes in carotid atherosclerosis and their relationship with aging and immune cells remain unclear. Analyze the expression profiles of m6A-related genes in carotid atherosclerosis-related datasets. Based on the expression patterns of m6A-related genes, perform consistent clustering analysis of carotid atherosclerosis samples and investigate associated immune cell infiltration patterns and aging characteristics. Develop an m6A prediction model specific to carotid atherosclerosis and analyze the relationships between immune cells infiltration and aging features. The m6A methylation modification level exhibited a substantial decrease in early-stage carotid atherosclerosis samples compared to late-stage carotid atherosclerosis samples. Subsequently, two distinct m6A subtypes were defined through consensus clustering analysis, with the lower m6A modification level group showing associations with heightened immune cell infiltration and increased expression of aging-related genes. A model composed of five m6A-related genes was formulated, and the results indicated that this model possesses effective predictive and therapeutic capabilities for carotid atherosclerosis. Furthermore, the downregulation of YTHDC1 expression resulted in elevated expression of inflammatory factors and a decrease in the expression of the aging-related gene RGN. Single-cell data analysis suggests that the reduced expression of YTHDC1 may decrease the degradation of inflammation-related factors in macrophages, leading to a highly inflammatory state in the carotid artery wall. Furthermore, the sustained release of inflammatory factors may increase the expression of the aging-related gene RGN in vascular smooth muscle cells, further exacerbating the progression of atherosclerosis. A reduced level of m6A methylation modification could enhance inflammation and expedite cellular aging, thereby contributing to the development of carotid atherosclerosis.
Abstract Background There is inconclusive evidence to suggest that the expression of programmed cell death ligand 1 (PD-L1) is a putative predictor of response to EGFR-TKI therapy in advanced ...EGFR-mutant non-small cell lung cancer (NSCLC). We evaluated the heterogeneity in PD-L1 expression in the primary lung site and metastatic lymph nodes to analyze the association between PD-L1 expression and response for patients treated with EGFR-TKI. Methods This study reviewed 184 advanced NSCLC patients with EGFR mutations who received first-generation EGFR-TKI as first-line treatment from 2020 to 2021 at Shanghai Chest Hospital. The patients were divided into the primary lung site group ( n = 100) and the metastatic lymph nodes group ( n = 84) according to the biopsy site. The patients in each group were divided into TPS < 1%, TPS 1–49%, and TPS ≥ 50% groups according to PD-L1 expression. Results The median PFS was 7 (95% CI: 5.7–8.3) months, and the median OS was 26 (95% CI: 23.5–28.5) months for all patients. No correlation existed between PFS or OS and PD-L1 expression. The median PFS in the primary lung site group was 11 months (95% CI: 9.6–12.4) in the TPS < 1% group, 8 months (95% CI: 6.6–9.4) in TPS 1–49% group, and 4 months (95% CI: 3.2–4.8) in TPS ≥ 50% group, with statistically significant differences ( p = 0.000). The median OS of the TPS < 1% group and TPS ≥ 50% group showed a statistically significant difference ( p = 0.008) in the primary lung site group. In contrast, PD-L1 expression in the lymph nodes of EGFR-mutant patients was unrelated to PFS or OS after EGFR-TKI therapy. Conclusion PD-L1 expression from the primary lung site might predict clinical benefit from EGFR-TKI, whereas PD-L1 from metastatic lymph nodes did not. Trial registration : This retrospective study was approved by the Ethics Committee of Shanghai Chest Hospital (ID: IS23060) and performed following the Helsinki Declaration of 1964 (revised 2008).
NMR studies of large proteins have gathered much interest in recent years, especially after methyl-transverse relaxation optimized spectroscopy was successfully applied to systems as large as ~1 MDa ...in molecular weight. However, to fully take advantage of these spectra, there is a need for convenient and robust methods for making resonance assignments rapidly. Here, we present an improved version of our program MAP-XS (methyl assignment prediction from X-ray structure) for the automatic assignment of methyl peaks, based on nuclear Overhauser effects (NOE) correlations and chemical shifts together with available structures. No manual analysis of the NOE data is needed in this new version, which helps to further accelerate the assignment process. A refined algorithm as well as more efficient sampling produces results from single runs of MAP-XSII using unanalyzed NOE data are comparable to those achieved by the old version using manually curated data with every NOE peak correctly attributed to the two related methyl peaks; in addition, checking the results from multiple parallel runs against each other provides an effective mechanism for getting rid of the wrong assignments while keeping the correct ones, which significantly improves the reliability of final assignments. The new program is tested against three different proteins and delivers ~95 % correct assignments; positive results are also achieved for tests using different cut-off distances for NOEs, structures of lower resolutions, and ambiguous residue types.
To systematically evaluate the effectiveness and potential underlying mechanisms of acupuncture in the treatment of experimental model of migraine in rats.
Nine electronic databases, including CNKI ...(China National Knowledge Infrastructure), WanFang, VIP (Chinese Scientific Journals Database), Sinomed, PubMed, Cochrane Library, Web of Science and EBSCO, were searched for randomized experimental studies on migraine in rats involving acupuncture intervention. The search period ranged from inception to June 2022. The methodological quality was assessed using the SYRCLE's risk of bias tool for animal studies. Data were analyzed using the Revman 5.3 software.
A total of 13 studies were included in this analysis. Findings from the available experimental studies documented that acupuncture significantly reduced behavior scores of rats with migraine (MD = -15.01, 95%CI = -18.01, -12.01, P<0.00001) and downregulated the expression of calcitonin gene-related peptide (CGRP) (MD = -16.14, 95%CI = -21.45, -10.83, P<0.00001), substance P (SP) (MD = -11.47, 95%CI = -15.97, -6.98, P<0.00001) and nitric oxide (NO) (MD = -3.02, 95%CI = -3.79, -2.26, P<0.00001) in serum, and stimulatory G protein (Gsa) (MD = -62.90, 95%CI = -69.88, -55.92, P<0.00001) in brainstem. Acupuncture also significantly increased the content of inhibitory G protein (Gia) (MD = 24.01, 95%CI = 20.10, 27.92, P<0.00001) in brainstem and 50% paw withdrawal threshold (50%PWT) (MD = 1.96, 95%CI = 1.15, 2.77, P<0.00001).
Acupuncture can effectively improve the behavioral performance of rates with migraine, and its mechanism of action might involve the inhibition of meningeal vasodilation and inflammatory factors, and the reduction of neurogenic inflammation.
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