A method for predicting drugs that can boost the efficacy of immune checkpoint blockade.

Combination therapy is a promising therapeutic strategy to enhance the efficacy of immune checkpoint blockade (ICB); however, predicting drugs for effective combination is challenging. Here we developed a general data-driven method called CM-Drug for screening compounds that can boost ICB treatment efficacy based on core and minor gene sets identified between responsive and nonresponsive samples in ICB therapy. The CM-Drug method was validated using melanoma and lung cancer mouse models, with combined therapeutic efficacy demonstrated in eight of nine predicted compounds. Among these compounds, taltirelin had the strongest synergistic effect. Mechanistic analysis and experimental verification demonstrated that taltirelin can stimulate CD8+ T cells and is mediated by the induction of thyroid-stimulating hormone. This study provides an effective and general method for predicting and evaluating drugs for combination therapy and identifies candidate compounds for future ICB combination therapy.

miRNASNP-v4: a comprehensive database for miRNA-related SNPs across 17 species.

Single nucleotide polymorphisms (SNPs) within microRNAs (miRNAs) and their target binding sites can influence miRNA biogenesis and target regulation, thereby participating in a variety of diseases and biological processes. Current miRNA-related SNP databases are often species-limited or based on outdated data. Therefore, we updated our miRNASNP database to version 4 by updating data, expanding the species from Homo sapiens to 17 species, and introducing several new features. In miRNASNP-v4, 82 580 SNPs in miRNAs and 24 836 179 SNPs in 3'UTRs of genes across 17 species were identified and their potential effects on miRNA secondary structure and target binding were characterized. In addition, compared to the last release, miRNASNP-v4 includes the following improvements: (i) gene enrichment analysis for gained or lost miRNA target genes; (ii) identification of miRNA-related SNPs associated with drug response and immune infiltration in human cancers; (iii) inclusion of experimentally supported immune-related miRNAs and (iv) online prediction tools for 17 animal species. With the extensive data and user-friendly web interface, miRNASNP-v4 will serve as an invaluable resource for functional studies of SNPs and miRNAs in multiple species. The database is freely accessible at http://gong_lab.hzau.edu.cn/miRNASNP/.

ncRNADrug: a database for validated and predicted ncRNAs associated with drug resistance and targeted by drugs.

Drug resistance is a major barrier in cancer treatment and anticancer drug development. Growing evidence indicates that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in cancer progression, therapy, and drug resistance. Furthermore, ncRNAs have been proven to be promising novel therapeutic targets for cancer treatment. Reversing dysregulated ncRNAs by drugs holds significant potential as an effective therapeutic strategy for overcoming drug resistance. Therefore, we developed ncRNADrug, an integrated and comprehensive resource that records manually curated and computationally predicted ncRNAs associated with drug resistance, ncRNAs targeted by drugs, as well as potential drug combinations for the treatment of resistant cancer. Currently, ncRNADrug collects 29 551 experimentally validated entries involving 9195 ncRNAs (2248 miRNAs, 4145 lncRNAs and 2802 circRNAs) associated with the drug resistance of 266 drugs, and 32 969 entries involving 10 480 ncRNAs (4338 miRNAs, 6087 lncRNAs and 55 circRNAs) targeted by 965 drugs. In addition, ncRNADrug also contains associations between ncRNAs and drugs predicted from ncRNA expression profiles by differential expression analysis. Altogether, ncRNADrug surpasses the existing related databases in both data volume and functionality. It will be a useful resource for drug development and cancer treatment. ncRNADrug is available at http://www.jianglab.cn/ncRNADrug.

ICBcomb: a comprehensive expression database for immune checkpoint blockade combination therapy.

The success of immune checkpoint blockade (ICB) promotes the immunotherapy to be a new pillar in cancer treatment. However, the low response rate of the ICB therapy limits its application. To increase the response rate and enhance efficacy, the ICB combination therapy has emerged and its clinical trials are increasing. Nevertheless, the gene expression profile and its pattern of ICB combination were not comprehensively studied, which limits the understanding of the ICB combination therapy and the identification of new drugs. Here, we constructed ICBcomb (http://bioinfo.life.hust.edu.cn/ICBcomb/), a comprehensive database, by analyzing the human and mouse expression data of the ICB combination therapy and comparing them between groups treated with ICB, other drugs or their combinations. ICBcomb contains 1399 samples across 29 cancer types involving 52 drugs. It provides a user-friendly web interface for demonstrating the results of the available comparisons in the ICB combination therapy datasets with five functional modules: [1, 2] the 'Dataset/Disease' modules for browsing the expression, enrichment and comparison results in each dataset or disease; [3] the 'Gene' module for inputting a gene symbol and displaying its expression and comparison results across datasets/diseases; [4] the 'Gene Set' module for GSVA/GSEA enrichment analysis on the built-in gene sets and the user-input gene sets in different comparisons; [5] the 'Immune Cell' module for immune cell infiltration comparison between different groups by immune cell abundance analysis. The ICBcomb database provides the first resource for gene expression profile and comparison in ICB combination therapy, which may provide clues for discovering the mechanism of effective combination strategies and new combinatory drugs.

GSCA: an integrated platform for gene set cancer analysis at genomic, pharmacogenomic and immunogenomic levels.

Cancer initiation and progression are likely caused by the dysregulation of biological pathways. Gene set analysis (GSA) could improve the signal-to-noise ratio and identify potential biological insights on the gene set level. However, platforms exploring cancer multi-omics data using GSA methods are lacking. In this study, we upgraded our GSCALite to GSCA (gene set cancer analysis, http://bioinfo.life.hust.edu.cn/GSCA) for cancer GSA at genomic, pharmacogenomic and immunogenomic levels. In this improved GSCA, we integrated expression, mutation, drug sensitivity and clinical data from four public data sources for 33 cancer types. We introduced useful features to GSCA, including associations between immune infiltration with gene expression and genomic variations, and associations between gene set expression/mutation and clinical outcomes. GSCA has four main functional modules for cancer GSA to explore, analyze and visualize expression, genomic variations, tumor immune infiltration, drug sensitivity and their associations with clinical outcomes. We used case studies of three gene sets: (i) seven cell cycle genes, (ii) tumor suppressor genes of PI3K pathway and (iii) oncogenes of PI3K pathway to prove the advantage of GSCA over single gene analysis. We found novel associations of gene set expression and mutation with clinical outcomes in different cancer types on gene set level, while on single gene analysis level, they are not significant associations. In conclusion, GSCA is a user-friendly web server and a useful resource for conducting hypothesis tests by using GSA methods at genomic, pharmacogenomic and immunogenomic levels.

PECTIN ACETYLESTERASE12 regulates shoot branching via acetic acid and auxin accumulation in alfalfa shoots.

Shoot branching is an important biological trait affecting alfalfa (Medicago sativa L.) production, but its development is complicated and the mechanism is not fully clear. In the present study, pectin acetylesterase 12 (MsPAE12) and NAM/ATAF/CUC-domain transcription factor gene (MsNAC73) were isolated from alfalfa. MsPAE12 was highly expressed in shoot apexes, and MsNAC73 was found to be a key transcriptional repressor of MsPAE12 by directly binding to salicylic acid (SA) and jasmonic acid (JA) elements in the MsPAE12 promoter. The biological functions of MsPAE12 and MsNAC73 were studied through overexpression (OE) and down-expression (RNAi) of the 2 genes in alfalfa. The numbers of shoot branches increased in MsPAE12-OE lines but decreased in MsPAE12-RNAi and MsNAC73-OE plants, which was negatively related to their indole-3-acetic acid (IAA) accumulation in shoot apexes. Furthermore, the contents of acetic acid (AA) in shoot apexes decreased in MsPAE12-OE plants but increased in MsPAE12-RNAi and MsNAC73-OE plants. The changes of AA contents were positively related to the expression of TRYPTOPHAN AMINOTRANSFERASE 1 (MsTAA1), TRYPTOPHAN AMINOTRANSFERASE-RELATED 2 (MsTAR2), and YUCCA flavin monooxygenase (MsYUCC4) and the contents of tryptophan (Trp), indole-3-pyruvic acid (IPA), and IAA in shoot apexes of MsPAE12-OE, MsPAE12-RNAi, and MsNAC73-OE plants. Exogenous application of AA to wild type (WT) and MsPAE12-OE plants increased Trp, IPA, and IAA contents and decreased branch number. Exogenous IAA suppressed shoot branching in MsPAE12-OE plants, but exogenous IAA inhibitors increased shoot branching in MsPAE12-RNAi plants. These results indicate that the MsNAC73-MsPAE12 module regulates auxin-modulated shoot branching via affecting AA accumulation in shoot apexes of alfalfa.

AnimalTFDB 4.0: a comprehensive animal transcription factor database updated with variation and expression annotations.

Transcription factors (TFs) are proteins that interact with specific DNA sequences to regulate gene expression and play crucial roles in all kinds of biological processes. To keep up with new data and provide a more comprehensive resource for TF research, we updated the Animal Transcription Factor Database (AnimalTFDB) to version 4.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB4/) with up-to-date data and functions. We refined the TF family rules and prediction pipeline to predict TFs in genome-wide protein sequences from Ensembl. As a result, we predicted 274 633 TF genes and 150 726 transcription cofactor genes in AnimalTFDB 4.0 in 183 animal genomes, which are 86 more species than AnimalTFDB 3.0. Besides double data volume, we also added the following new annotations and functions to the database: (i) variations (including mutations) on TF genes in various human cancers and other diseases; (ii) predicted post-translational modification sites (including phosphorylation, acetylation, methylation and ubiquitination sites) on TFs in 8 species; (iii) TF regulation in autophagy; (iv) comprehensive TF expression annotation for 38 species; (v) exact and batch search functions allow users to search AnimalTFDB flexibly. AnimalTFDB 4.0 is a useful resource for studying TF and transcription regulation, which contains comprehensive annotation and classification of TFs and transcription cofactors.

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/.

Elucidating the Bioinspired Synthesis Process of Magnetosomes-Like Fe3O4 Nanoparticles.

Iron oxide nanoparticles are a kind of important biomedical nanomaterials. Although their industrial-scale production can be realized by the conventional coprecipitation method, the controllability of their size and morphology remains a huge challenge. In this study, a kind of synthetic polypeptide Mms6-28 which mimics the magnetosome protein Mms6 is used for the bioinspired synthesis of Fe3O4 nanoparticles (NPs). Magnetosomes-like Fe3O4 NPs with uniform size, cubooctahedral shape, and smooth crystal surfaces are synthesized via a partial oxidation process. The Mms6-28 polypeptides play an important role by binding with iron ions and forming nucleation templates and are also preferably attached to the [100] and [111] crystal planes to induce the formation of uniform cubooctahedral Fe3O4 NPs. The continuous release and oxidation of Fe2+ from pre-formed Fe2+-rich precursors within the Mms6-28-based template make the reaction much controllable. The study affords new insights into the bioinspired- and bio-synthesis mechanism of magnetosomes.

In Situ TEM Observation of (Cr, Mn, Fe, Co, and Ni)3O4 High-Entropy Spinel Oxide Formation During Calcination at Atomic Scale.

High-entropy oxides (HEOs) are promising anode materials for lithium-ion batteries (LIBs), owing to their stable crystal structure, superionic conductivity, and high capacity. In this study, the (Cr, Mn, Fe, Co, and Ni)3O4 HEO via solid-state reaction is prepared. To improve the synthetic efficiency, it is necessary to understand the formation mechanism. Therefore, a high-resolution transmission electron microscopy (HRTEM) is used to record information during calcination at increasing temperature. The overall formation process included MnO2 and NiO aggregation at 500 °C, followed by (Mn, and Ni)3O4 combined with Co3O4 at 600 °C to form (Mn, Co, and Ni)3O4. At higher temperatures, Fe2O3 and Cr2O3 sequentially combined with (Mn, Co, and Ni)3O4 and formed the (Cr, Mn, Fe, Co, Ni)3O4 at 900 °C. In addition, the valence-state-changing mechanisms and ion arrangements of (Cr, Mn, Fe, Co, and Ni)3O4 are determined using electron energy loss spectroscopy (EELS) and extended X-ray absorption fine structure (EXAFS). This study successfully revealed the formation of HEO at atomic scale. The results provide valuable insights for improving the manufacturing process of (Cr, Mn, Fe, Co, and Ni)3O4 HEOs, which is expected to play a vital role in the development of anode materials for next-generation LIBs.

The MsDHN1-MsPIP2;1-MsmMYB module orchestrates the trade-off between growth and survival of alfalfa in response to drought stress.

Dehydrins and aquaporins play crucial roles in plant growth and stress responses by acting as protector and controlling water transport across membranes, respectively. MsDHN1 (dehydrin) and MsPIP2;1 (aquaporin) were demonstrated to interact with a membrane-anchored MYB protein, MsmMYB (as mMYB) in plasma membrane under normal condition. MsDHN1, MsPIP2;1 and MsDHN1-MsPIP2;1 positively regulated alfalfa tolerance to water deficiency. Water deficiency caused phosphorylation of MsPIP2;1 at Ser 272, which led to release C terminus of mMYB (mMYBΔ83) from plasma membrane and translocate to nucleus, where C terminus of MsDHN1 interacted with mMYBΔ83, and promoted mMYBΔ83 transcriptional activity in response to water deficiency. Overexpression of mMYB and mMYBΔ83 down-regulated the expression of MsCESA3, but up-regulated MsCESA7 expression by directly binding to their promoters, and resulted in high drought tolerance in transgenic hairy roots. These results indicate that the MsDHN1-MsPIP2;1-MsMYB module serves as a key regulator in alfalfa against drought stress.

EVAtool: an optimized reads assignment tool for small ncRNA quantification and its application in extracellular vesicle datasets.

Extracellular vesicles (EVs) carrying various small non-coding RNAs (sncRNAs) play a vital roles in cell communication and diseases. Correct quantification of multiple sncRNA biotypes simultaneously in EVs is a challenge due to the short reads (<30 bp) could be mapped to multiple sncRNA types. To address this question, we developed an optimized reads assignment algorithm (ORAA) to dynamically map multi-mapping reads to the sncRNA type with a higher proportion. We integrated ORAA with reads processing steps into EVAtool Python-package (http://bioinfo.life.hust.edu.cn/EVAtool) to quantify sncRNAs, especially for sncRNA-seq from EV samples. EVAtool allows users to specify interested sncRNA types in advanced mode or use default seven sncRNAs (microRNA, small nucleolar RNA, PIWI-interacting RNAs, small nuclear RNA, ribosomal RNA, transfer RNA and Y RNA). To prove the utilities of EVAtool, we quantified the sncRNA expression profiles for 200 samples from cognitive decline and multiple sclerosis. We found that more than 20% of short reads on average were mapped to multiple sncRNA biotypes in multiple sclerosis. In cognitive decline, the proportion of Y RNA is significantly higher than other sncRNA types. EVAtool is a flexible and extensible tool that would benefit to mine potential biomarkers and functional molecules in EVs.

SMART-SLE: serology monitoring and repeat testing in systemic lupus erythematosus-an analysis of anti-double-stranded DNA monitoring.

OBJECTIVE: Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive. METHODS: Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare. RESULTS: Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009). CONCLUSION: Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.

Chloroplast-targeted late embryogenesis abundant 1 increases alfalfa tolerance to drought and aluminum.

Late embryogenesis-abundant (LEA) proteins are important stress-response proteins that participate in protecting plants against abiotic stresses. Here, we investigated LEA group 3 protein MsLEA1, containing the typically disordered and α-helix structure, via overexpression and RNA interference (RNAi) approaches in alfalfa (Medicago sativa L.) under drought and aluminum (Al) stresses. MsLEA1 was highly expressed in leaves and localized in chloroplasts. Overexpressing MsLEA1 increased alfalfa tolerance to drought and Al stresses, but downregulating MsLEA1 decreased the tolerance. We observed a larger stomatal aperture and a lower water use efficiency in MsLEA1 RNAi lines compared with wild-type plants under drought stress. Photosynthetic rate, Rubisco activity, and superoxide dismutase (SOD) activity increased or decreased in MsLEA1-OE or MsLEA1-RNAi lines, respectively, under drought and Al stress. Copper/zinc SOD (Cu/Zn-SOD), iron SOD (Fe-SOD), and Rubisco large subunit proteins (Ms1770) were identified as binding partners of MsLEA1, which protected chloroplast structure and function under drought and Al stress. These results indicate that MsLEA1 recruits and protects its target proteins (SOD and Ms1770) and increases alfalfa tolerance against drought and Al stresses.

Controllable Fabrication of Multifunctional Micro-thermocouples for Temperature Detection inside Single Suspended Droplets.

Microdroplets have recently emerged as an exciting technological platform for wide applications. In this work, we developed a controllable fabrication approach to novel tungsten-platinum micro-thermocouples that function not only as a sensitive temperature sensor but also as a flexible suspender for individual microdroplet studies. The controllable fabrication hinges on the formation of tungsten tip apex nodes to make junctions with platinum, which was achieved through a unique combinational strategy, involving gradient coating with a complete insulating layer and subsequent targeted removal by tip electroporation. Benefiting from its coaxial structure, microspherical contact node end, hydrophobic surface, and thermoelectric performance, the as-fabricated micro-thermocouple was successfully employed for the microdroplet suspension and in situ temperature detection throughout the droplet evaporation cycle. It was observed that the temperature inside the suspended microdroplets was lower than that of the external environment, and there existed temperature discontinuity during droplet evaporation. By integrating the capabilities of temperature monitoring and droplet manipulation into a single micro-thermocouple, this work demonstrates its versatility and promising applications in expanded sensing for single microdroplets and other microsystems.

Targeting cytohesin-1 suppresses acute myeloid leukemia progression and overcomes resistance to ABT-199.

Adhesion molecules play essential roles in the homeostatic regulation and malignant transformation of hematopoietic cells. The dysregulated expression of adhesion molecules in leukemic cells accelerates disease progression and the development of drug resistance. Thus, targeting adhesion molecules represents an attractive anti-leukemic therapeutic strategy. In this study, we investigated the prognostic role and functional significance of cytohesin-1 (CYTH1) in acute myeloid leukemia (AML). Analysis of AML patient data from the GEPIA and BloodSpot databases revealed that CYTH1 was significantly overexpressed in AML and independently correlated with prognosis. Functional assays using AML cell lines and an AML xenograft mouse model confirmed that CYTH1 depletion significantly inhibited the adhesion, migration, homing, and engraftment of leukemic cells, delaying disease progression and prolonging animal survival. The CYTH1 inhibitor SecinH3 exerted in vitro and in vivo anti-leukemic effects by disrupting leukemic adhesion and survival programs. In line with the CYTH1 knockdown results, targeting CYTH1 by SecinH3 suppressed integrin-associated adhesion signaling by reducing ITGB2 expression. SecinH3 treatment efficiently induced the apoptosis and inhibited the growth of a panel of AML cell lines (MOLM-13, MV4-11 and THP-1) with mixed-lineage leukemia gene rearrangement, partly by reducing the expression of the anti-apoptotic protein MCL1. Moreover, we showed that SecinH3 synergized with the BCL2-selective inhibitor ABT-199 (venetoclax) to inhibit the proliferation and promote the apoptosis of ABT-199-resistant leukemic cells. Taken together, our results not only shed light on the role of CYTH1 in cell-adhesion-mediated leukemogenesis but also propose a novel combination treatment strategy for AML.

Lethal pulmonary thromboembolism in mice induced by intravenous human umbilical cord mesenchymal stem cell-derived large extracellular vesicles in a dose- and tissue factor-dependent manner.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a potential risk of thromboembolism, an issue that remains insufficiently explored. In this study, we systematically investigated the procoagulant activity of large EVs derived from human umbilical cord MSCs (UC-EVs) both in vitro and in vivo. UC-EVs were isolated from cell culture supernatants. Mice were injected with UC-EVs (0.125, 0.25, 0.5, 1, 2, 4 µg/g body weight) in 100 µL PBS via the tail vein. Behavior and mortality were monitored for 30 min after injection. We showed that these UC-EVs activated coagulation in a dose- and tissue factor-dependent manner. UC-EVs-induced coagulation in vitro could be inhibited by addition of tissue factor pathway inhibitor. Notably, intravenous administration of high doses of the UC-EVs (1 µg/g body weight or higher) led to rapid mortality due to multiple thrombus formations in lung tissue, platelets, and fibrinogen depletion, and prolonged prothrombin and activated partial thromboplastin times. Importantly, we demonstrated that pulmonary thromboembolism induced by the UC-EVs could be prevented by either reducing the infusion rate or by pre-injection of heparin, a known anticoagulant. In conclusion, this study elucidates the procoagulant characteristics and mechanisms of large UC-EVs, details the associated coagulation risk during intravenous delivery, sets a safe upper limit for intravenous dose, and offers effective strategies to prevent such mortal risks when high doses of large UC-EVs are needed for optimal therapeutic effects, with implications for the development and application of large UC-EV-based as well as other MSC-EV-based therapies.

EVAtlas: a comprehensive database for ncRNA expression in human extracellular vesicles.

Extracellular vesicles (EVs) packing various molecules play vital roles in intercellular communication. Non-coding RNAs (ncRNAs) are important functional molecules and biomarkers in EVs. A comprehensive investigation of ncRNAs expression in EVs under different conditions is a fundamental step for functional discovery and application of EVs. Here, we curated 2030 small RNA-seq datasets for human EVs (1506 sEV and 524 lEV) in 24 conditions and over 40 diseases. We performed a unified reads dynamic assignment algorithm (RDAA) considering mismatch and multi-mapping reads to quantify the expression profiles of seven ncRNA types (miRNA, snoRNA, piRNA, snRNA, rRNA, tRNA and Y RNA). We constructed EVAtlas (http://bioinfo.life.hust.edu.cn/EVAtlas), a comprehensive database for ncRNA expression in EVs with four functional modules: (i) browse and compare the distribution of ncRNAs in EVs from 24 conditions and eight sources (plasma, serum, saliva, urine, sperm, breast milk, primary cell and cell line); (ii) prioritize candidate ncRNAs in condition related tissues based on their expression; (iii) explore the specifically expressed ncRNAs in EVs from 24 conditions; (iv) investigate ncRNA functions, related drugs, target genes and EVs isolation methods. EVAtlas contains the most comprehensive ncRNA expression in EVs and will be a key resource in this field.

Factors influencing postoperative visual improvement in 208 patients with tuberculum sellae meningiomas.

OBJECTIVE: Tuberculum sellae meningiomas (TSMs) usually compress the optic nerve and optic chiasma, thus affecting vision. Surgery is an effective means to remove tumors and improve visual outcomes. On a larger scale, this study attempted to further explore and confirm the factors related to postoperative visual outcomes to guide the treatment of TSMs. METHODS: Data were obtained from 208 patients with TSMs who underwent surgery at our institution between January 2010 and August 2022. Demographics, ophthalmologic examination results, imaging data, extent of resection, radiotherapy status, and surgical approaches were included in the analysis. Univariate and multivariate logistic regressions were used to assess the factors that could lead to favorable visual outcomes. RESULTS: The median follow-up duration was 63 months, and gross total resection (GTR) was achieved in 174 (83.7%) patients. According to our multivariate logistic regression analysis, age < 60 years (odds ratio [OR] = 0.310; P = 0.007), duration of preoperative visual symptoms (DPVS) < 10 months (OR = 0.495; P = 0.039), tumor size ≤ 27 mm (OR = 0.337; P = 0.002), GTR (OR = 3.834; P = 0.006), and a tumor vertical-to-horizontal dimensional ratio < 1 (OR = 2.593; P = 0.006) were found to be significant independent predictors of favorable visual outcomes. CONCLUSION: Age, DPVS, tumor size, GTR, and the tumor vertical-to-horizontal dimensional ratio were found to be powerful predictors of favorable visual outcomes. This study may help guide decisions regarding the treatment of TSMs.

Effect of intravenous different drugs on the prevention of restlessness during recovery period of pediatric laparoscopic surgery: a randomized control trial.

PURPOSE: To explored the impact of dexmedetomidine and esketamine in mitigating restlessness during the postoperative recovery phase following laparoscopic surgery in children. METHODS: 102 individuals aged 1 to 7 years experiencing laparoscopic surgery were randomly allocated into three groups, each accepting 1 µg/kg of dexmedetomidine, 0.3 mg/kg of esketamine, or saline immediately at the end of carbon dioxide pneumoperitoneum. Emergence agitation (EA) occurrence was assessed by PAED scale and 5-point agitation scale. Pain was judged using Face, Legs, Activity, Cry, and Consolability (FLACC) scale. The recovery time, extubation time, and post-anesthesia care unit (PACU) stay time were recorded for all three groups. RESULTS: Patients administered 1 µg/kg of dexmedetomidine (8.8%) and individuals given 0.3 mg/kg of esketamine (11.8%) showed lower incidences of emergence agitation compared to those receiving saline (35.5%; P = 0.009). There was no statistically significant difference in the time to discharge from the PACU among the three groups of patients (P > 0.05). The recovery time and extubation time were notably extended in the dexmedetomidine group (40.88 ± 12.95 min, 42.50 ± 13.38 min) when compared to the saline group (32.56 ± 13.05 min, 33.29 ± 11.30 min; P = 0.009, P = 0.010). CONCLUSION: Following CO2 pneumoperitoneum in pediatric laparoscopic surgeries, the intravenous administration of 1 µg/kg dexmedetomidine or 0.3 mg/kg esketamine effectively lowers EA occurrence without extending PACU time.