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Critical patients of COVID-19 have a dramatically higher case fatality rate than severe cases. [...]it is increasingly urgent to develop early and effective predictors to distinguish critical patients from severe patients. Additionally, lymphocyte count, CRP, LDH, and coagulation indicators (d-dimer, platelet count, PT, and APTT), which were reported to associate with clinical outcome [4, 5], were also included in the random forests model. Despite limited evidence in COVID-19, previous studies demonstrated an important role of VEGF in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) by its properties to increase vascular permeability.

MicroRNAs (miRNAs) are small silencing RNAs with regulatory roles in gene expression. miRNAs interact with Argonaute (AGO) proteins to form effector complexes that cleave target mRNAs or repress translation. Rice (Oryza sativa) encodes four AGO1 homologs (AGO1a, AGO1b, AGO1c, and AGO1d). We used RNA interference (RNAi) to knock down the four AGO1s. The RNAi lines displayed pleiotropic developmental phenotypes and had increased accumulation of miRNA targets. AGO1a, AGO1b, and AGO1c complexes were purified and further characterized. The three AGO1s all have a strong preference for binding small RNAs (sRNAs) with 5' U and have Slicer activity. We cataloged the sRNAs in each AGO1 complex by deep sequencing and found that all three AGO1s predominantly bound known miRNAs. Most of the miRNAs were evenly distributed in the three AGO1 complexes, suggesting a redundant role for the AGO1s. Intriguingly, a subset of miRNAs were specifically incorporated into or excluded from one of the AGO1s, suggesting functional specialization among the AGO1s. Furthermore, we identified rice miRNA targets at a global level. The validated targets include transcription factors that control major stages of development and also genes involved in a variety of physiological processes, indicating a broad regulatory role for miRNAs in rice.

Background Gastric cancer (GC) displays profound molecular heterogeneity, leading to divergent therapeutic responses and prognoses. Programmed cell death (PCD) pathways and the tumor microenvironment (TME) are critical determinants of GC progression, yet their interplay and clinical significance remain insufficiently understood. Methods We conducted integrative multiomics analyses using bulk RNA‐seq data from TCGA‐STAD (426 tumors, 35 normals) and single‐cell RNA‐seq (GSE167297; 4 tumor/normal pairs). PCD‐based molecular subtypes were identified through consensus clustering. Drug sensitivity (pRRophetic), immune infiltration (ESTIMATE/CIBERSORT), and functional enrichment (GSVA/clusterProfiler) were systematically evaluated. A prognostic risk model was established via LASSO‐Cox regression and externally validated in GSE26901. Results Two distinct PCD‐associated subtypes were identified. Cluster 1, characterized by elevated PCD activity, enriched KRAS signaling and interferon response, showed a poorer prognosis; whereas Cluster 2 exhibited favorable survival with activation of E2F and mTORC1 pathways. Cluster 1 demonstrated higher immune and stromal scores but lower tumor purity, along with upregulation of immune checkpoints (PDCD1, CD40LG). Drug sensitivity profiling revealed subtype‐specific vulnerabilities, including heightened sensitivity of Cluster 1 to cJQ1_2172. A nine‐gene prognostic model (5 year AUC = 0.73) robustly predicted survival, with NRP1 identified as an independent risk factor (HR = 1.91, p < 0.05). Conclusions This study delineates the PCD–TME crosstalk underlying GC heterogeneity and proposes a clinically relevant molecular classification and prognostic tool. Our findings highlight subtype‐specific therapeutic vulnerabilities and underscore the potential of targeting PCD pathways to advance precision oncology in GC.

Dual-specificity phosphatase 6 (DUSP6) serves a specific and conserved function on the dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). We previously identified Dusp6 as a regenerative repressor during zebrafish heart regeneration, therefore we propose to investigate the role of this repressor in mammalian cardiac repair. Utilizing a rat strain harboring Dusp6 nonsense mutation, rat neutrophil-cardiomyocyte co-culture, bone marrow transplanted rats and neutrophil-specific Dusp6 knockout mice, we find that Dusp6 deficiency improves cardiac outcomes by predominantly attenuating neutrophil-mediated myocardial damage in acute inflammatory phase after myocardial infarction. Mechanistically, Dusp6 is transcriptionally activated by p38-C/EBPβ signaling and acts as an effector for maintaining p-p38 activity by down-regulating pERK and p38-targeting phosphatases DUSP1/DUSP16. Our findings provide robust animal models and novel insights for neutrophil-mediated cardiac damage and demonstrate the potential of DUSP6 as a therapeutic target for post-MI cardiac remodeling and other relevant inflammatory diseases. Dusp6, an ERK specific phosphatase, was identified as a regenerative repressor during zebrafish heart regeneration. Here, the authors show that Dusp6 deficiency improves post infarctional cardiac repair by predominantly attenuating neutrophil-mediated myocardial damage in mammalian hearts.

The study employed four different models, including the bivariate statistical model Certainty Factor (CF), machine learning models such as Functional Tree (FT), Logistic Model Tree (LMT), Alternating Decision Tree (ADT), and Reduced Error Pruning Tree (REPT), hybrid models based on bagging techniques (Bagging-FT, Bagging-ADT, Bagging-REPT, Bagging-LMT), and various machine learning optimization models, to map landslide susceptibility in Chenggu County with the aim of exploring assessment results that offer greater social value for the study area. The field survey combined with remote sensing technology acquired 181 landslides in Chenggu County. The comprehensive research area currently selects 16 landslide conditioning factors and employs the Certainty Factor (CF) method to examine the relationship between landslides and these factors, aiming to elucidate the mechanisms by which these conditioning factors trigger landslides. Grid search methodology is used to conduct hyper-parametric FT, ADT, LMT and REPT and hybrid models of Bagging algorithm for optimization study to obtain the optimal parameter combination of the model and improve the predictive ability of the model. The CF model, machine learning model and optimization model were constructed, and then the Receiver operating Characteristic (ROC) curves and statistical parameters were compared to verify the model accuracy and generalization ability, and the hybrid model prediction accuracy of Bag-LMT after hyperparametric optimization was the best. The results further validate the importance of optimization of machine learning models in geohazard prediction research.

Mesenchymal stem cells (MSCs) have been widely used in the treatment of various inflammatory diseases. The inadequate understanding of MSCs and their heterogeneity can impact the immune environment, which may be the cause of the good outcomes of MSCs-based therapy that cannot always be achieved. Recently, stem cells from human exfoliated deciduous teeth (SHED) showed great potential in inflammatory and autoimmune diseases due to their immature properties compared with MSCs. In our study, single-cell RNA sequencing (scRNA-seq) revealed that SHED in a low differentiation state (S7) exhibited the powerful ability to recruit multiple immune cells. In contrast, SHED in a relatively high differentiation state (S1) may hold a solid ability to secret many factors with paracrine signaling capacity. The analysis result shows that SHED has more robust immunomodulatory properties than human bone marrow-derived mesenchymal stem cells (hBMSCs) or human umbilical cord-derived mesenchymal stem cells (hUCMSCs). When co-cultured with PBMCs, SHED can enhance the proliferation of Treg and down-regulate TNF-α in vitro. SHED may have some advantages in the treatment of inflammatory and autoimmune diseases.

microRNAs （miRNAs） play important roles in the regulation of gene expression. In Arabidopsis, mature miRNAs are processed from primary miRNA transcripts （pri-miRNAs） by nuclear HYL1/SE/DCL1 complexes that form Dicing bodies （D-bodies）. Here we report that an RNA-binding protein MOS2 binds to pri-miRNAs and is involved in efficient processing of pri-miRNAs. MOS2 does not interact with HYL1, SE, and DCL1 and is not localized in D- bodies. Interestingly, in the absence of MOS2, the recruitment of pri-miRNAs by HYL1 is greatly reduced and the localization of HYL1 in D-bodies is compromised. These data suggest that MOS2 promotes pri-miRNA processing through facilitating the recruitment of pri-miRNAs by the Dicing complexes.

The coronavirus disease 2019 pandemic has stimulated intensive research interest in its transmission pathways and infection factors, e.g., socioeconomic and demographic characteristics, climatology, baseline health conditions or pre-existing diseases, and government policies. Meanwhile, some empirical studies suggested that built environment attributes may be associated with the transmission mechanism and infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, no review has been conducted to explore the effect of built environment characteristics on the infection risk. This research gap prevents government officials and urban planners from creating effective urban design guidelines to contain SARS-CoV-2 infections and face future pandemic challenges. This review summarizes evidence from 25 empirical studies and provides an overview of the effect of built environment on SARS-CoV-2 infection risk. Virus infection risk was positively associated with the density of commercial facilities, roads, and schools and with public transit accessibility, whereas it was negatively associated with the availability of green spaces. This review recommends several directions for future studies, namely using longitudinal research design and individual-level data, considering multilevel factors and extending to diversified geographic areas.

Previous studies showed tacrolimus monotherapy and dual therapy with tacrolimus and prednisone as effective treatment modalities in managing membranous nephropathy. However, few studies have compared these therapeutic regimens. The patients were divided into two groups based on the treatment regimen: (1) tacrolimus and prednisone dual therapy (T + P group, n = 67) treatment group; and (2) tacrolimus monotherapy (T group, n = 65) or the control group. Propensity matching method and subgroup analysis to eliminate the bias in the relationship between the treatment regimen and the outcomes. The mean remission times were 20.33 ± 2.75 weeks at T group and 9.50 ± 1.81 weeks at T + P group. The T group had a remission rates of 73.33, 76.66 and 66.66% at 12weeks, 24weeks and 48weeks, while the T + P group had a remission rate of 81.66, 86.66, 91.66%; At the follow-up of 48 weeks, the relapse rate for the T group was 21.66%, and that for the T + P group was 5%. The anti-PLA2R ab is positive and therapy may be the independent risk factors for predicting remission. Tacrolimus and low-dose prednisone dual therapy is efficacious in managing MN and lowers the recurrence rate in clinical practice.

The simultaneous achievement of chiral multiple‐resonance thermally activated delayed fluorescence (MR‐TADF) emitters with narrowband and circularly polarized electroluminescence (CPEL) poses a challenge. Herein, a MR‐TADF emitter, Spiro‐BNCz, embedding spirofluorene structure was developed and chiral separated, whose emission peaks at 528 nm in toluene with Commission Internationale de L'Eclairage coordinates of (0.26, 0.69). The conjugation extension caused by embedding sulfur substituted spirofluorene on B/N framework shortens the singlet‐triplet energy gap and increases spin‐orbital coupling matrix element. Therefore, a fast reverse intersystem crossing rate constant of 2.8 × 106 s−1 and a high photoluminescence efficiency of 92% in film were achieved. The organic light‐emitting diode (OLED) exhibits a maximum external quantum efficiency of 32.3%. Particularly, the circularly polarized OLEDs based on Spiro‐BNCz enantiomers show symmetric CPEL with dissymmetry factors (|gEL|) ≈ 10−3. The integration of chiral S‐substituted spirofluorene structure and B/N skeleton has proven to be an effective approach for achieving pure‐green emission and symmetric CPL. The corresponding CP‐OLEDs demonstrate a remarkable EQE of 32.3% and symmetric CPEL with gEL factors approximately on the order of 10‐3.