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Summary: Physical activity reduces cancer-associated mortality through multiple mechanisms, including tumor immune microenvironment (TIME) reprogramming. However, whether and how physiological interventions promote anti-tumor immunity remain elusive. Here, we report that clinically relevant voluntary exercise promotes muscle-derived extracellular vesicle (EV)-associated miR-29a-3p for tumor extracellular matrix (ECM) inhibition in patients and mouse models, thereby permitting immune cell infiltration and immunotherapy. Mechanistically, an unbiased screening identifies EV-associated miR-29a-3p in response to leisure-time physical activity or voluntary exercise. MiR-29a-3p-containing EVs accumulate in tumors and downregulate collagen composition by targeting COL1A1. Gain- and loss-of-function experiments and cytometry by time of flight (CyTOF) demonstrate that myocyte-secreted miR-29a-3p promotes anti-tumor immunity. Combining immunotherapy with voluntary exercise or miR-29a-3p further enhances anti-tumor efficacy. Clinically, miR-29a-3p correlates with reduced ECM, increased T cell infiltration, and response to immunotherapy. Our work reveals the predictive value of miR-29a-3p for immunotherapy, provides mechanistic insights into exercise-induced anti-cancer immunity, and highlights the potential of voluntary exercise in sensitizing immunotherapy.

Background ICU patients have a high incidence of VTE. The American College of Chest Physicians antithrombotic practice guidelines recommend assessing the risk of VTE in all ICU patients. Although several VTE risk assessment tools exist to evaluate the risk factors among hospitalized patients, there is no validated tool specifically for assessing the risk of VTE in ICU patients. Methods A retrospective corhort study was conducted between June 2018 and October 2022. We obtained data from the electronic medical records of patients with a variety of diagnoses admitted to a mixed ICU. Multivariable logistic regression analysis was used to evaluate the independent risk factors of VTE. Receiver operating characteristic (ROC) curves were used to analyse the predictive accuracy of different tools. Results A total of 566 patients were included, and VTE occurred in 89 patients (15.7%), 62.9% was asymptomatic VTE. A prediction model (the ICU-VTE prediction model) was derived from the independent risk factors identified using multivariate analysis. The ICU-VTE prediction model included eight independent risk factors: history of VTE (3 points), immobilization ≥4 days (3 points), multiple trauma (3 points), age ≥70 years (2 points), platelet count >250 × 10 3 /μL (2 points), central venous catheterization (1 point), invasive mechanical ventilation (1 point), and respiratory failure or heart failure (1 point). Patients with a score of 0–4 points had a low (1.81%) risk of VTE. Patients were at intermediate risk, scoring 5–6 points, and the overall incidence of VTE in the intermediate-risk category was 17.1% (odds ratio [OR], 11.1; 95% confidence interval [CI], 4.2-29.4). Those with a score ≥7 points had a high (44.1%) risk of VTE (OR, 42.6; 95% CI, 16.4-110.3). The area under the curve (AUC) of the ICU-VTE prediction model was 0.838, and the differences in the AUCs were statistically significant between the ICU-VTE prediction model and the other three tools (ICU-VTE score, Z = 3.723, P

Aims: Silicosis is the most common and severe type of pneumoconiosis, imposing a substantial disease burden and economic loss on patients and society. The pathogenesis and key targets of silicosis are not yet clear, and there are currently no effective treatments available. Therefore, we conducted research on mefunidone (MFD), a novel antifibrotic drug, to explore its efficacy and mechanism of action in murine silicosis. Methods: Acute 7-day and chronic 28-day silicosis models were constructed in C57BL/6J mice by the intratracheal instillation of silica and subsequently treated with MFD to assess its therapeutic potential. The effects of MFD on silica-induced inflammation, pyroptosis, and fibrosis were further investigated using immortalized mouse bone marrow-derived macrophages (iBMDMs). Results: In the 7-day silica-exposed mouse models, MFD treatment significantly alleviated pulmonary inflammation and notably reduced macrophage infiltration into the lung tissue. RNA-sequencing analysis of silica-induced iBMDMs followed by gene set enrichment analysis revealed that MFD profoundly influenced cytokine-cytokine receptor interactions, chemokine signaling, and the toll-like receptor signaling pathways. MFD treatment also markedly reduced the secretion of inflammatory cytokines and chemokines from silica-exposed iBMDMs. Moreover, MFD effectively downregulated the activation of the TLR4-NF-κB/MAPK signaling pathway induced by silica and mitigated the upregulation of pyroptosis markers. Additionally, MFD treatment significantly suppressed the activation of fibroblasts and alveolar epithelial cells co-cultured with silica-exposed mouse macrophages. Ultimately, in the 28-day silica-exposed mouse models, MFD administration led to a substantial reduction in the severity of pulmonary fibrosis. Conclusion: MFD mitigates silica-induced pulmonary inflammation and fibrosis in mice by suppressing the TLR4-NF-κB/MAPK signaling pathway and reducing pyroptotic responses in macrophages. MFD could potentially emerge as a novel therapeutic agent for the treatment of silicosis.

Abstract Background The most challenging aspect of rehabilitation is the repurposing of residual functional plasticity in stroke patients. To achieve this, numerous plasticity-based clinical rehabilitation programs have been developed. This study aimed to investigate the effects of motor imagery (MI)-based brain–computer interface (BCI) rehabilitation programs on upper extremity hand function in patients with chronic hemiplegia. Design A 2010 Consolidated Standards for Test Reports (CONSORT)-compliant randomized controlled trial. Methods Forty-six eligible stroke patients with upper limb motor dysfunction participated in the study, six of whom dropped out. The patients were randomly divided into a BCI group and a control group. The BCI group received BCI therapy and conventional rehabilitation therapy, while the control group received conventional rehabilitation only. The Fugl–Meyer Assessment of the Upper Extremity (FMA-UE) score was used as the primary outcome to evaluate upper extremity motor function. Additionally, functional magnetic resonance imaging (fMRI) scans were performed on all patients before and after treatment, in both the resting and task states. We measured the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), z conversion of ALFF (zALFF), and z conversion of ReHo (ReHo) in the resting state. The task state was divided into four tasks: left-hand grasping, right-hand grasping, imagining left-hand grasping, and imagining right-hand grasping. Finally, meaningful differences were assessed using correlation analysis of the clinical assessments and functional measures. Results A total of 40 patients completed the study, 20 in the BCI group and 20 in the control group. Task-related blood-oxygen-level-dependent (BOLD) analysis showed that when performing the motor grasping task with the affected hand, the BCI group exhibited significant activation in the ipsilateral middle cingulate gyrus, precuneus, inferior parietal gyrus, postcentral gyrus, middle frontal gyrus, superior temporal gyrus, and contralateral middle cingulate gyrus. When imagining a grasping task with the affected hand, the BCI group exhibited greater activation in the ipsilateral superior frontal gyrus (medial) and middle frontal gyrus after treatment. However, the activation of the contralateral superior frontal gyrus decreased in the BCI group relative to the control group. Resting-state fMRI revealed increased zALFF in multiple cerebral regions, including the contralateral precentral gyrus and calcarine and the ipsilateral middle occipital gyrus and cuneus, and decreased zALFF in the ipsilateral superior temporal gyrus in the BCI group relative to the control group. Increased zReHo in the ipsilateral cuneus and contralateral calcarine and decreased zReHo in the contralateral middle temporal gyrus, temporal pole, and superior temporal gyrus were observed post-intervention. According to the subsequent correlation analysis, the increase in the FMA-UE score showed a positive correlation with the mean zALFF of the contralateral precentral gyrus (r = 0.425, P

Abstract Background Although CDKN2A alteration has been explored as a favorable factor for tumorigenesis in pan-cancers, the association between CDKN2A point mutation (MUT) and intragenic deletion (DEL) and response to immune checkpoint inhibitors (ICIs) is still disputed. This study aims to determine the associations of CDKN2A MUT and DEL with overall survival (OS) and response to immune checkpoint inhibitors treatment (ICIs) among pan-cancers and the clinical features of CDKN2A-altered gastric cancer. Methods This study included 45,000 tumor patients that underwent tumor sequencing across 33 cancer types from four cohorts, the MSK-MetTropism, MSK-IMPACT, OrigiMed2020 and TCGA cohorts. Clinical outcomes and genomic factors associated with response to ICIs, including tumor mutational burden, copy number alteration, neoantigen load, microsatellite instability, tumor immune microenvironment and immune-related gene signatures, were collected in pan-cancer. Clinicopathologic features and outcomes were assessed in gastric cancer. Patients were grouped based on the presence of CDKN2A wild type (WT), CDKN2A MUT, CDKN2A DEL and CDKN2A other alteration (ALT). Results Our research showed that CDKN2A-MUT patients had shorter survival times than CDKN2A-WT patients in the MSK MetTropism and TCGA cohorts, but longer OS in the MSK-IMPACT cohort with ICIs treatment, particularly in patients having metastatic disease. Similar results were observed among pan-cancer patients with CDKN2A DEL and other ALT. Notably, CDKN2A ALT frequency was positively related to tumor-specific objective response rates to ICIs in MSK MetTropism and OrigiMed 2020. Additionally, individuals with esophageal carcinoma or stomach adenocarcinoma who had CDKN2A MUT had poorer OS than patients from the MSK-IMPACT group, but not those with adenocarcinoma. We also found reduced levels of activated NK cells, T cells CD8 and M2 macrophages in tumor tissue from CDKN2A-MUT or DEL pan-cancer patients compared to CDKN2A-WT patients in TCGA cohort. Gastric cancer scRNA-seq data also showed that CDKN2A-ALT cancer contained less CD8 T cells but more exhausted T cells than CDKN2A-WT cancer. A crucial finding of the pathway analysis was the inhibition of three immune-related pathways in the CDKN2A ALT gastric cancer patients, including the interferon alpha response, inflammatory response, and interferon gamma response. Conclusions This study illustrates the CDKN2A MUT and DEL were associated with a poor outcome across cancers. CDKN2A ALT, on the other hand, have the potential to be used as a biomarker for choosing patients for ICI treatment, notably in esophageal carcinoma and stomach adenocarcinoma.

Abstract Nowadays, immunotherapy is one of the most promising anti-tumor therapeutic strategy. Specifically, immune-related targets can be used to predict the efficacy and side effects of immunotherapy and monitor the tumor immune response. In the past few decades, increasing numbers of novel immune biomarkers have been found to participate in certain links of the tumor immunity to contribute to the formation of immunosuppression and have entered clinical trials. Here, we systematically reviewed the oncogenesis and progression of cancer in the view of anti-tumor immunity, particularly in terms of tumor antigen expression (related to tumor immunogenicity) and tumor innate immunity to complement the cancer-immune cycle. From the perspective of integrated management of chronic cancer, we also appraised emerging factors affecting tumor immunity (including metabolic, microbial, and exercise-related markers). We finally summarized the clinical studies and applications based on immune biomarkers. Overall, immune biomarkers participate in promoting the development of more precise and individualized immunotherapy by predicting, monitoring, and regulating tumor immune response. Therefore, targeting immune biomarkers may lead to the development of innovative clinical applications.

Abstract Background Emerging investigations have increasingly highlighted the critical role of tumor-associated macrophages (TAMs) and M2 macrophages in cancer development, progression, and metastasis, marking them as potential targets in various cancer types. The main objective of this research is to discover new biomarkers associated with TAM-M2 macrophages in colorectal cancer (CRC) and to dissect the molecular heterogeneity of CRC by combining single-cell RNA sequencing and bulk RNA-seq data. Methods By utilizing weighted gene co-expression network analysis (WGCNA), we acquired TAM-M2-associated genes by intersecting TAM marker genes obtained from scRNA-seq data with module genes of M2 macrophages derived from bulk RNA-seq data. We employed least absolute shrinkage and selection operator (LASSO) Cox analysis to select predictive biomarkers from these TAM-M2-related genes. Quantitative polymerase chain reaction (qPCR) was employed to validate the mRNA expression levels of the genes identified in the screening. This led to the development of the TAM-M2-related signature (TAMM2RS). We also conducted functional and immune landscape analyses of different risk groups. Results The combination of scRNA-seq and bulk RNA-seq analyses yielded 377 TAM-M2-related genes. DAPK1, NAGK, and TRAF1 emerged as key prognostic genes in CRC, which were identified through LASSO Cox analysis. Utilizing these genes, we constructed and validated the TAMM2RS, demonstrating its effectiveness in predicting survival in CRC patients. Conclusion Our research offers a thorough investigation into the molecular mechanisms associated with TAM-M2 macrophages in CRC and unveils potential therapeutic targets, offering new insights for treatment strategies in colorectal cancer.

Abstract Aims About 20–40% patients with type 2 diabetes mellitus (T2DM) had an increased risk of developing diabetic nephropathy (DN). Dipeptidyl peptidase-4 inhibitors (DPP-4i) were recommended for treatment of T2DM, while the impact of DPP-4i on renal function remained unclear. This study aimed to explore the effect of DPP-4i on renal parameter of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in T2DM. Methods A systematic search was performed across PubMed, Embase and Cochrane Library. A fixed or random-effects model was used for quantitative synthesis according to the heterogeneity, which was assessed with I2 index. Sensitivity analysis and publication bias were performed with standard methods, respectively. Results A total of 17 randomized controlled trials were identified. Administration of DPP-4i produced no significant effect on eGFR (WMD, -0.92 mL/min/1.73m2, 95% CI, -2.04 to 0.19) in diabetic condition. DPP-4i produced a favorable effect on attenuating ACR (WMD, -2.76 mg/g, 95% CI, -5.23 to -0.29) in patients with T2DM. The pooled estimate was stable based on the sensitivity test. No publication bias was observed according to Begg’s and Egger’s tests. Conclusions Treatment with DPP-4i preserved the renal parameter of eGFR in diabetic condition. Available evidences suggested that administration of DPP-4i produced a favorable effect on attenuating ACR in patients with T2DM. International Prospective Register for Systematic Review (PROSPERO) number CRD.42020144642.

Mining-induced landslides are a common form of disaster in the mountainous areas of coal mines. To clarify the deformation and failure patterns of such slopes under the mining action, the particle discrete element method was employed to simulate the destabilization damage process of the anticline coal seam slope under two conditions, single-seam mining and three-seam mining, and analyze the characteristics of crack expansion and rock fragmentation during slope deformation, based on the field investigation of typical mining-controlled landslides. The results show that: 1) In a single-seam condition, an arch-ring type deformation zone is created in the roof area after the coal seam is excavated and evolves into a fallen rock body; while the rock body at the interval of multi-layer excavation will be bent sink collapse, forming a large area of rock fragmentation. 2) Under different excavation conditions, the internal crack evolution and rock fragmentation of the slope are slow at the beginning of the formation of the fall zone and stress redistribution. The stage of roof emergence and rock bending fracture is the main stage of rock fracture and fragmentation. 3) The anti-inclined coal seam mining-controlled mountain failure pattern is mainly manifested as follows: Coal seam mining →Arch-loop-like fall of the roof →Bending and sinking of the internal rock →Pulling and breaking of the trailing edge →Failure of the locking zone at the foot of the slope → Shallow sliding of the fragmented rock. This study provides a new direction for the analysis of the destabilization mechanism of mining-controlled slopes and scientific guidance for the prevention and control of landslide hazards in mining areas.

Abstract Background Immune checkpoint blockade (ICB) has revolutionized the treatment of various cancer types. Despite significant preclinical advancements in understanding mechanisms, identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging. Recent evidence, both preclinical and clinical, underscores the pivotal role of the extracellular matrix (ECM) in modulating immune cell infiltration and behaviors. This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy. Methods We analyzed transcriptomic collagen activity and immune signatures in 649 patients with cancer undergoing ICB therapy. This analysis led to the identification of three distinct immuno‐collagenic subtypes predictive of ICB responses. We validated these subtypes using the transcriptome data from 9,363 cancer patients from The Cancer Genome Atlas (TCGA) dataset and 1,084 in‐house samples. Additionally, novel therapeutic targets were identified based on these established immuno‐collagenic subtypes. Results Our categorization divided tumors into three subtypes: “soft & hot” (low collagen activity and high immune infiltration), “armored & cold” (high collagen activity and low immune infiltration), and “quiescent” (low collagen activity and immune infiltration). Notably, “soft & hot” tumors exhibited the most robust response to ICB therapy across various cancer types. Mechanistically, inhibiting collagen augmented the response to ICB in preclinical models. Furthermore, these subtypes demonstrated associations with immune activity and prognostic predictive potential across multiple cancer types. Additionally, an unbiased approach identified B7 homolog 3 (B7‐H3), an available drug target, as strongly expressed in “armored & cold” tumors, relating with poor prognosis. Conclusion This study introduces histopathology‐based universal immuno‐collagenic subtypes capable of predicting ICB responses across diverse cancer types. These findings offer insights that could contribute to tailoring personalized immunotherapeutic strategies for patients with cancer.

Abstract Background/Objective No previous study has investigated the association between dietary pattern and both general and abdominal obesity risk among adults in Nigeria. This study aimed to evaluate the associations between dietary patterns and the risk of obesity among adult age 18 and above in Ekiti State, Southwestern Nigeria. Methods and study designs A total of 1003 adults were included in this cross-sectional study (males = 558; females = 445). Body mass index (BMI) and waist-to-hip (WHR) were used to assess general and abdominal obesity respectively and they were categorized using WHO recommendation. Partial correlation analyses were performed to assess the associations of dietary patterns with BMI and WHR. Prevalence ratio between dietary pattern and both general and abdominal obesity were calculated using Robust Poisson Regression. Results The prevalence of general obesity among adults was 15.9%, (11.6% among men and 20.2% among women); abdominal obesity was 32.3% (28.9% among males and 44.5% among females). Four dietary patterns were identified; diversified traditional pattern; typical traditional pattern; milk and bread pattern and egg and fish pattern. Diversified traditional pattern was negatively associated with BMI (PR = 0.571, 95%CI: 0.360 ~ 0.905, p = 0.017), and typical traditional pattern was positively associated with BMI (PR = 1.561, 95% CI: 1.043 ~ 2.339, p = 0.031) and WHR in females (PR = 1.849, 95% CI: 1.256 ~ 2.721, p = 0.005). In comparison to those in the lowest quartile, adults with the highest quartile of the typical traditional pattern had a higher risk for abdominal obesity (PR = 1.849, 95%CI = 1.256 ~ 2.721, p = 0.020). Conclusion This study reports an alarming increase in Obesity prevalence among Nigeria adults which is greatly influence by their lifestyle and eating pattern. We found out that a typical traditional food pattern was associated with a higher risk of both general and abdominal obesity, but a diverse traditional food pattern was associated to a reduced risk of general obesity.

Abstract Although most people living with HIV (PLWH) receiving antiretroviral therapy (ART) achieve continuous viral suppression, some show detectable HIV RNA as low-level viremia (LLV) (50–999 copies/mL). Drug resistance mutations (DRMs) in PLWH with LLV is of particular concern as which may lead to treatment failure. In this study, we investigated the prevalence of LLV and LLV-associated DRMs in PLWH in Zhengzhou City, China. Of 3616 ART-experienced PLWH in a long-term follow-up cohort from Jan 2022 to Aug 2023, 120 were identified as having LLV. Of these PLWH with LLV, we obtained partial pol and integrase sequences from 104 (70 from HIV-1 RNA and 34 from proviral DNA) individuals. DRMs were identified in 44 individuals. Subtyping analysis indicated that the top three subtypes were B (48.08%, 50/104), CRF07_BC (31.73%, 33/104), and CRF01_AE (15.38%, 16/104). The proportions of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) associated DRMs were 23.83% (24/104), 35.58% (37/104), 5.77% (6/104), and 3.85% (4/104), respectively, which contributed to an overall prevalence of 42.31% (44/104). When analyzed by individual DRMs, the most common mutation(s) were V184 (18.27%, 19/104), followed by V179 (11.54%, 12/104), K103 (9.62%, 10/104), Y181 (9.62%, 10/104), M41 (7.69%, 8/104), and K65R (7.69%, 8/104). The prevalence of DRMs in ART-experienced PLWH with LLV is high in Zhengzhou City and continuous surveillance can facilitate early intervention and provision of effective treatment.

To explore the preparation, enrichment, and structural analysis of bitter almond antimicrobial peptides, in this experiment, the protein was extracted from the defatted bitter almonds, and the protein was hydrolyzed by enzymes to prepare bitter almond protein antibacterial peptides. The preparation process was optimized, and the resulting peptides' antibacterial activity was detected. The peptides were further purified and enriched. The components with the strongest antibacterial activity were isolated, and their structure was analyzed. The results showed that the papain hydrolysate had the strongest bacteriostatic effect on Gram-positive bacteria, especially Staphylococcus aureus. The optimal conditions for the preparation of bitter almond antibacterial peptides were as follows: The enzymatic hydrolysis temperature was 74℃, the enzyme-to-substrate ratio was 2.5%, and the pH was 7. The protein concentration of the antibacterial peptides was 19.21%, and the minimum inhibitory concentration was 3.13 mg/mL. The antibacterial peptides were isolated and purified by ultrafiltration and gel filtration chromatography (Sephadex G-25). Peptide component A-II-b was screened out to have the strongest inhibitory activity against Staphylococcus aureus. The gel filtration conditions were optimized with a sample concentration of 9.38 mg/mL, an elution rate of 0.68 mL/min, and pure water as the eluent. Under these conditions, the peak area ratio of peptide component A-II-b was 13.15%. The structure of peptide component A-II-b was analyzed by liquid chromatography-mass spectrometry, and the results were imported into the UniProt database and the APD3 database for matching. Seven kinds of bitter almond peptides with potential antibacterial activity with molecular weights of 1500~2500 Da were screened out, including ALPDEVLQNAFRIS, ESWNPRDPQFQWAGVA, VAYWSYNNGEQPLVA, FLDLSNDQNQLDQVPR, GENDNRNQIIRVR, RNLQGENDNRNQIIRVR, and RALPDEVLQNAFRIS. This study promoted the in-depth development and resource reuse of almond active peptides and also provided a theoretical basis for their research and further development and utilization as an antibacterial peptide.

In this work, CoCrFeNiSix coatings were fabricated by magnetron sputtering at the negative bias voltage ranging from 0 to 100 V. The effect of negative bias voltage on the composition, microstructure and corrosion performance was studied. The results show that all CoCrFeNiSix coatings consisted of amorphous and nanocrystalline FCC phases. However, the ratio of both amorphous/nanocrystalline phases and Si/(Co + Cr + Fe + Ni) atoms decreased with increasing negative bias voltage. Applying negative bias voltage also led to the improved surface quality. Accordingly, the corrosion rate of CoCrFeNiSix coatings in 0.5 mol/L H2SO4 solution exhibited a decreasing trend. Meanwhile, the CoCrFeNiSix coating deposited at 100 V had the lowest passive current density, highest coating resistance and lowest carrier density. This was because that Si competed with Cr to suppress the formation of Cr2O3 in the compact inner layer, and thus the decreasing Si content caused by increasing negative bias voltage led to the improved protection effect of the passive film.

Abstract Objective To analyze the clinical infection characteristics and genetic environments of resistance genes in carbapenem-resistant Citrobacter europaeus using whole-genome sequencing. Methods The susceptibility of two clinical isolates of C. europaeus (WF0003 and WF1643) to 24 antimicrobial agents was assessed using the BD Phoenix™ M50 System and Kirby-Bauer (K-B) disk-diffusion method. Whole-genome sequencing was performed on the Illumina and Nanopore platforms, and ABRicate software was used to predict resistance and virulence genes of carbapenem-resistant C. europaeus. The characteristics of plasmids carrying carbapenem-resistance genes and their genetic environments were analyzed. Single nucleotide polymorphisms were used to construct a phylogenetic tree to analyze the homology of these two C. europaeus strains with ten strains of C. europaeus in the NCBI database. Results The two strains of carbapenem-resistant C. europaeus are resistant to various antimicrobial agents, particularly carbapenems and β-lactams. WF0003 carries bla NDM− 1, which is located on an IncX3 plasmid that has high homology to the pNDM-HN380 plasmid. bla NDM− 1 is located on a truncated Tn125. It differs from Tn125 by the insertion of IS5 in the upstream ISAba125 and the deletion of the downstream ISAba125, which is replaced by IS26. WF1643 carries bla OXA− 48 in a Tn1999 transposon on the IncL/M plasmid, carrying only that single drug resistance gene. Homology analysis of these two strains of C. europaeus with ten C. europaeus strains in the NCBI database revealed that the 12 strains can be classified into three clades, with both WF0003 and WF1643 in the B clade. Conclusion To the best of our knowledge, this is the first study to report an IncX3 plasmid carrying bla NDM− 1 in C. europaeus in China. C. europaeus strains harboring carbapenem-resistance genes are concerning in relation to the spread of antimicrobial resistance, and the presence of carbapenem-resistance genes in C. europaeus should be continuously monitored.

Abstract Semantic segmentation from a three‐dimensional point cloud is vital in autonomous driving, computer vision, and augmented reality. However, current semantic segmentation does not effectively use the point cloud's local geometric features and contextual information, essential for improving segmentation accuracy. A semantic segmentation network that uses local feature fusion and a multilayer attention mechanism is proposed to address these challenges. Specifically, the authors designed a local feature fusion module to encode the geometric and feature information separately, which fully leverages the point cloud's feature perception and geometric structure representation. Furthermore, the authors designed a multilayer attention pooling module consisting of local attention pooling and cascade attention pooling to extract contextual information. Local attention pooling is used to learn local neighbourhood information, and cascade attention pooling captures contextual information from deeper local neighbourhoods. Finally, an enhanced feature representation of important information is obtained by aggregating the features from the two deep attention pooling methods. Extensive experiments on large‐scale point‐cloud datasets Stanford 3D large‐scale indoor spaces and SemanticKITTI indicate that authors network shows excellent advantages over existing representative methods regarding local geometric feature description and global contextual relationships.

Abstract Background The prevalence of burnout among healthcare workers remains chronically high. Former studies have indicated that strength use is a promising approach to reduce burnout. However, relatively little is known about the psychological mechanisms underlying the ability of strength use to reduce burnout, especially among healthcare workers. Aim This study sought to examine the link between strength use and burnout in Chinese healthcare workers, and to explore the mediating roles of beliefs about stress and basic psychological needs satisfaction in that relationship. Methods This study was conducted in two time periods, from September to October 2020 and from February to September 2022. A total of 812 healthcare workers completed a multi-section questionnaire. Results Strength use was negatively associated with burnout and negative stress beliefs, and positively associated with positive stress beliefs, control beliefs, and basic psychological needs satisfaction. Moreover, negative stress beliefs, control beliefs, and basic psychological needs satisfaction fully mediated the relationship between strength use and burnout. Furthermore, effect contrasts revealed that the mediating effect of basic psychological needs satisfaction was stronger than that of negative stress beliefs and control beliefs. Conclusion Our findings revealed that negative stress beliefs, control beliefs, and basic psychological needs satisfaction act as mediators in the association of strength use with burnout. Furthermore, basic psychological needs satisfaction plays a more important mediating role than negative stress beliefs and control beliefs in the strength use–burnout relationship.

The hydrological dynamics and sources of karst tidal springs are difficult to capture and quantify due to fluctuations in their flow velocity. In this study, the Laolongshui (LLS) karst tidal spring in the Maocun underground river basin of Guilin City was taken as an example, with a 2-year continuous monitoring of the electrical conductivity, and water level, as well as water chemical analysis. The results showed the following: (1) discovered the variation pattern of LLS water level in different seasons, the water level fluctuates regularly on a daily scale, with a rise and fall time of 43.6 min after heavy rainfall in the rainy season, while in the dry season, it lasts for about 74–80 h. (2) Four peaks were extracted from the frequency distribution of electrical conductivity, representing the response of springwater under different rainfall conditions. (3) The annual average frequencies of the occurrence of P1, P2, P3, and P4 in terms of time are 53.82, 39.29, 6.18, and 0.72%, respectively. The results provide a new method for analyzing groundwater's source and dynamic changes in karst areas. HIGHLIGHTS Two years of automatic continuous monitoring illustrated the water level fluctuation of a typical karst tidal spring.; Explaining the forming mechanism of karst tidal springs.; The frequency distribution of conductivity quantified the source of karst water.; Providing a fast and low-cost new method for identifying karst water sources.; Enriching groundwater investigation methods and understanding of underground structures.;

Abstract Hydrogen peroxide photosynthesis suffers from insufficient catalytic activity due to the high energy barrier of hydrogen extraction from H2O. Herein, we report that mechanochemically synthesized keto-form anthraquinone covalent organic framework which is able to directly synthesize H2O2 (4784 μmol h−1 g−1 at λ > 400 nm) from oxygen and alkaline water (pH = 13) in the absence of any sacrificial reagents. The strong alkalinity resulted in the formation of OH-(H2O)n clusters in water, which were adsorbed on keto moieties within the framework and then dissociated into O2 and active hydrogen, because the energy barrier of hydrogen extraction was largely lowered. The produced hydrogen reacted with anthraquinone to generate anthrahydroquinone, which was subsequently oxidized by O2 to produce H2O2. This study ultimately sheds light on the importance of hydrogen extraction from H2O for H2O2 photosynthesis and demonstrates that H2O2 synthesis is achievable under alkaline conditions.

Abstract Heart failure is the prevalent complication of acute myocardial infarction. We aim to identify a biomarker for heart failure post-acute myocardial infarction. This observational study includes 1062 and 1043 patients with acute myocardial infarction in the discovery and validation cohorts, respectively. The outcomes are in-hospital and long-term heart failure events. S100A8/A9 is screened out through proteomic analysis, and elevated circulating S100A8/A9 is independently associated with heart failure in discovery and validation cohorts. Furthermore, the predictive value of S100A8/A9 is superior to the traditional biomarkers, and the addition of S100A8/A9 improves the risk estimation using traditional risk factors. We finally report causal effect of S100A8/A9 on heart failure in three independent cohorts using Mendelian randomization approach. Here, we show that S100A8/A9 is a predictor and potentially causal medicator for heart failure post-acute myocardial infarction.

Abstract Traditional eye drops are administered via topical instillation. However, frequent dosing is needed due to their relatively rapid precorneal removal and low ocular bioavailability. To address these issues, stearoyl L-carnitine-modified nanoemulsions (SC-NEs) were fabricated. The physicochemical properties of SC-NEs in terms of size, morphology, zeta potential, encapsulation efficiency, and in vitro drug release behavior were characterized. The cellular uptake and mechanisms of SC-NEs were comprehensively studied in human corneal epithelial cells and the stearoyl L-carnitine ratio in SC-NEs was optimized. The optimized SC-NEs could target the novel organic cation/carnitine transporter 2 (OCTN2) and amino acid transporter B (0 +) (ATB0,+) on the corneal epithelium, which led to superior corneal permeation, ocular surface retention ability, ocular bioavailability. Furthermore, SC-NEs showed excellent in vivo anti-inflammatory efficacy in a rabbit model of endotoxin-induced uveitis. The ocular safety test indicated that the SC-NEs were biocompatible. In general, the current study demonstrated that OCTN2 and ATB0,+-targeted nanoemulsions were promising ophthalmologic drug delivery systems that can improve ocular drug bioavailability and boost the therapeutic effects of drugs for eye diseases. Graphical Abstract

Abstract While phonon anharmonicity affects lattice thermal conductivity intrinsically and is difficult to be modified, controllable lattice defects routinely function only by scattering phonons extrinsically. Here, through a comprehensive study of crystal structure and lattice dynamics of Zintl-type Sr(Cu,Ag,Zn)Sb thermoelectric compounds using neutron scattering techniques and theoretical simulations, we show that the role of vacancies in suppressing lattice thermal conductivity could extend beyond defect scattering. The vacancies in Sr2ZnSb2 significantly enhance lattice anharmonicity, causing a giant softening and broadening of the entire phonon spectrum and, together with defect scattering, leading to a ~ 86% decrease in the maximum lattice thermal conductivity compared to SrCuSb. We show that this huge lattice change arises from charge density reconstruction, which undermines both interlayer and intralayer atomic bonding strength in the hierarchical structure. These microscopic insights demonstrate a promise of artificially tailoring phonon anharmonicity through lattice defect engineering to manipulate lattice thermal conductivity in the design of energy conversion materials.

Abstract Proteins containing a ubiquitin regulatory X (UBX) domain are cofactors of Cell Division Cycle 48 (CDC48) and function in protein quality control. However, whether and how UBX-containing proteins participate in host–microbe interactions remain unclear. Here we show that MoNLE1, an effector from the fungal pathogen Magnaporthe oryzae, is a core virulence factor that suppresses rice immunity by specifically interfering with OsPUX8B.2. The UBX domain of OsPUX8B.2 is required for its binding to OsATG8 and OsCDC48-6 and controls its 26 S proteasome–dependent stability. OsPUX8B.2 and OsCDC48-6 positively regulate plant immunity against blast fungus, while the high-temperature tolerance heat-shock protein OsBHT, a putative cytoplasmic substrate of OsPUX8B.2–OsCDC48-6, negatively regulates defense against blast infection. MoNLE1 promotes the nuclear migration and degradation of OsPUX8B.2 and disturbs its association with OsBHT. Given the high conservation of MoNLE1 among fungal isolates, plants with broad and durable blast resistance might be generated by engineering intracellular proteins resistant to MoNLE1.

Abstract Background Neuroblastoma (NB), a type of solid tumor in children, has a poor prognosis. Few blood biomarkers can accurately predict the prognosis, including recurrence and survival, in children with NB. In this study, we found that the serum total cholesterol (Tchol) level was associated with the prognosis of patients through a retrospective study. Methods Multivariate Cox regression model was used to identify the independent risk factors in the children with NB. Kaplan–Meier method was used to analyze the correlation between the common biomarkers, including the serum Tchol level, and the prognosis of the patients. ROC curves were used to predict the accuracy of the International Neuroblastoma Staging System (INSS) stage and Children’s Oncology Group (COG) risk stratification after adding the serum Tchol level. Results Compared with the other patients, serum Tchol level was significantly increased in the relapsed and died patients (P

Abstract Background The objective of this research was to elucidate the association between the length of infertility and the outcomes of intrauterine insemination (IUI) in women of varying ages - a topic that has been the subject of investigation for numerous years, yet lacks a definitive consensus. Methods A retrospective cohort investigation involving 5268 IUI cycles was undertaken at the Reproductive Medicine Center of Nanjing Drum Tower Hospital from 2016 to 2022. Utilizing the smooth fitting curve along with threshold and saturation effect analysis, the correlation between infertility duration and IUI clinical pregnancy rates was discerned. Moreover, patients were bifurcated into two cohorts based on their respective infertility durations. A secondary examination was also performed employing propensity-score matching to mitigate the impact of confounding variables. Subsequent threshold and saturation effect analysis was carried out across various subgroups, segmented on the basis of age differentiation. Results When the duration of infertility was more than 5 years, the clinical pregnancy rate decreased with the increase of infertility duration (aOR: 0.894, 95%CI: 0.817–0.991, p = 0.043). The multivariate regression analysis suggested that longer duration of infertility (≥ 5 years) was significantly correlated with the lower clinical pregnancy rate (aOR: 0.782, 95% CI: 0.643–0.950, p = 0.01). After the propensity-score matching, the clinical pregnancy rate of women with longer infertility duration were also higher. When the duration of infertility was more than 5 years, the clinical pregnancy rate of women younger than 35 years old decreased with the increase of infertility duration (aOR: 0.906, 95%CI: 0.800–0.998, p = 0.043). Conclusions The clinical pregnancy rate and live birth rate of IUI in young women (

Abstract Evidence has revealed that DDOST plays an important role in cancer development and progression. However, there are no reports on functions of DDOST in cervical tumorigenesis. Hence, we investigated the relationship of DDOST with prognosis, mutation, promoter methylation, immune cell infiltration, and drug sensitivity using bioinformatics techniques. Our results demonstrated that DDOST was significantly upregulated in a variety of tumor types and correlated with poor prognosis, including cervical cancer. Cox regression analysis dissected that high DDOST expression was associated with poor survival in cervical cancer patients. Immune infiltration analysis defined that DDOST was negatively correlated with CD8 T cells and NK cells. Strikingly, the sensitivity to multiple drugs was negatively correlated with the expression of DDOST. Therefore, our findings uncovered that DDOST could play an essential role in the tumor microenvironment and tumor immune regulation in cervical cancer, which indicated that DDOST could be a useful biomarker for prognosis and a potential therapeutic target for cancer treatment.

Highlights Through facial basicity adjustment, kinetically favorable ZnxNi1-xO@CF electrode was formed with a high density hierarchical structure and three dimensional open pores. The optimal Zn-doping ratio in ZnxNi1-xO@CF has excellent sodium storage and desalination performance (128.9 mg g-1). The mechanism of Na+ intercalation process was studied by electrochemical quartz crystal microbalance with dissipation monitoring in situ test and the activation mechanism of redox-inert Zn-doping on electrode materials was reported.

Exploring new prototypes for a given chemical composition is of great importance and interest to several disciplines. As a famous semiconducting binary compound, InSe usually exhibits a two-dimensional layered structure with decent physical and mechanical properties. However, it is less noticed that InSe can also adopt a monoclinic structure, denoted as mcl-InSe. The synthesis of such a phase usually requires high-pressure conditions, and the knowledge is quite scarce on its chemical bonding, lattice dynamics, and thermal transport. Here in this work, by developing a facile method combining mechanical alloying and spark plasma sintering, we successfully synthesize mcl-InSe bulks with well-crystallized nanograins. The chemical bonding of mcl-InSe is understood as compared with layered InSe via charge analysis. Low cut-off frequencies of acoustic phonons and several low-lying optical modes are demonstrated. Noticeably, mcl-InSe exhibits a low room-temperature thermal conductivity of 0.6 W·m−1·K−1, which is smaller than that of other materials in the In–Se system and many other selenides. Low-temperature thermal analyses corroborate the role of nanograin boundaries and low-frequency optical phonons in scattering acoustic phonons. This work provides new insights into the non-common prototype of the InSe binary compound with potential applications in thermoelectrics or thermal insulation.

The cyclic oxidation and topologically close-packed (TCP) phase precipitation behaviors of β-(Ni, Pt)Al coatings with different Pt/Al ratios at 1150 °C were investigated. In the initial oxidation stage, coatings with different Pt/Al ratios exhibited comparable high-temperature oxidation resistance, likely due to a similar level of Al absorption. Subsequently, oxide spallation was common for coatings with lower Pt/Al ratios due to the formation of fine-grained alumina and a “sandwich” structure (a multilayer porous structure) oxide scale. For coatings with higher Pt/Al ratios, severe rumpling occurred, and numerous cracks formed in the oxide scale. However, sufficient Al concentration in the outer zone and the improved deformation tolerance of the oxide scale enhanced the spallation resistance of the thermally grown oxide (TGO). Furthermore, a higher Pt/Al ratio promotes uphill diffusion of Al, which reduces its migration into the substrate, thereby diminishing TCP precipitation. Coatings with the same Pt/Al ratios but higher Pt and Al contents further reduced TCP precipitation after oxidation. This improvement is attributed to the initially lower Al concentration in these coatings' secondary reaction zone (SRZ) and their greater thickness.

Composite body armor made of brittle ceramic and tough laminate can protect human body from penetration while reducing weight. However, there is a lack of a simple and comprehensive method for assessing ballistic impact response and blunt injury. In this study, the three-dimensional Digital Image Correlation technique was used to investigate the back-face response of ceramic/ultra-high-molecular-weight-polyethylene laminate composite body armor impacted by a 7.62 mm rifle bullet. Blunt injury assessment was conducted by Bullet Coefficient (BC) and Abbreviated Injury Scale (AIS) criteria. Firstly, the ceramic tile exhibited transverse and radial cracks; the laminate showed thin layers separation, bullet holes and pits, kink, sheared, and torn morphology. Secondly, the bulge button face showed a transition from circular to rectangular shape, and the shear strain distribution exhibited an L-shaped pattern. Thirdly, at the moment of maximum bulge kinetic energy, approximately 8.73 % of bullet kinetic energy converted into total bulge kinetic energy, in which the x- and y-directional kinetic energy accounted for 29.66 %. Fourthly, the BC values decreased as the gap between armor and the human body increased, and the corresponding AIS decreased from 4 to 0. Finally, a Smooth Particle Hydrodynamics and Finite Element Method (SPH-FEM) coupled numerical model was applied to simulate the occurrence of ceramic cracks and laminate damage. This study proposed a quantitative evaluation of ballistic performance and blunt injury of body armor based on the back-face morphology. The results provide quantitative evidence to research the impact mechanism and offer methods for assessing human blunt injury behind the armor.

Ovarian cancer (OC) is recognized as the most lethal type of gynecological malignancy, making treatment options challenging. Discovering novel therapeutic targets will benefit OC patients. This study aimed to reveal the mechanism by which SRSF9 regulates OC progression. Cell proliferation was determined via CCK-8 assays, whereas cell migration and invasion were monitored via Transwell assays. Western blotting and qPCR assays were used to detect protein and mRNA alterations. RNA pull-down, RNA immunoprecipitation (RIP), and actinomycin D experiments were performed to investigate the relationships between SRSF9 and USP22. Co-IP was used to validate the interaction between USP22 and ZEB1. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were used to verify the regulatory effect of ZEB1 on the transcription of SRSF9. Subcutaneous xenograft models were established to evaluate the impact of SRSF9 on tumor development. Knockdown of SRSF9 significantly suppressed the proliferation, invasion, migration, tumorigenicity, and epithelial‒mesenchymal transition (EMT) of OC cells. SRSF9 can bind to USP22 mRNA, increasing its stability. Moreover, the overexpression of USP22 reversed the impact of SRSF9 silencing on malignant phenotypes. USP22 can mediate the deubiquitination of ZEB1, thereby enhancing the progression of OC. Furthermore, ZEB1 upregulated SRSF9 expression through transcriptional activation, thus establishing a positive feedback loop. SRSF9 enhanced the malignant characteristics of OC through a positive feedback loop of SRSF9/USP22/ZEB1. This functional circuit may help in the development of novel therapeutic approaches for treating OC.

This study was set to study the anti-proliferative effects of secoxyloganin in MDA-MB-231 breast cancer cells. The MTT cell viability assay results demonstrated that secoxyloganin significantly (p

In this study, we investigated the growth performance and early sex differentiation in Chinese longsnout catfish (Leiocassis longirostris), and further systematically evaluated its feminization by oral administration of various doses and treatment durations of 17β-estradiol (E2). Under the same breeding condition, the growth rate of male Chinese longsnout catfish was 20.8 % and 33.9 % faster than that of the female sibling at one- and two-year-old, respectively. The ovarian cavity began forming on 15 dph and completed by 21 dph, while the primary oocytes were at chromatin-nucleolus stage by 33 dph and at the peri-nucleolus stage oocytes by 65 dph. In presumptive testis, the seminiferous lobule appeared on 15 dph and the efferent duct anlage presented on 53 dph. Subsequently, germ cells entered into mitosis and formed the spermatogonia at 69 dph. Compared with the control group (no E2 diet), the fries treated with E2 at 10, 50, 100 or 150 mg/kg diet from 10 to 90 dph were 100 % female by morphology and histology observation. However, the growth and survival rate rapidly decreased as the E2 dosage rose. Furthermore, fries treated with10 mg/kg E2 during 15–85 dph, 20–80 dph, 25–75 dph, 30–70 dph, 35–65 dph and 40–60 dph were explored. 3.33 ± 3.33 % and 45.55 ± 5.09 % sex reversal ratio was identified in 30–70 dph and 35–65 dph group, respectively. All female populations were observed in 15–85 dph, 20–80 dph and 25–75 dph groups, despite slow development of ovary among them compared with the control group. Additionally, the growth performance of fries in 25–75 dph group was closest to that of the control group, while their serum E2 and 11-KT levels were consistent with XX females. Transcriptomic analyses were performed to assess gene expression difference among the XX females, XY males and feminized XY females, and most DEGs were shared between XY male vs XX female and XY male vs XY female. In addition, qRT-PCR validation of 12 DEGs associated with gonadal differentiation were consistent with RNA-Seq analysis (r=0.942, P

As the most aggressive and metastatic subtype of breast cancer, clinical demands of triple negative breast cancer (TNBC) have far not been met. Heat shock protein 60 (HSP60) is over expressed in tumor cells and impair the efficacy of photothermal therapy. In this work, a conjugate composed of self-designed peptide targeting HSP60 and gold nanorods was constructed, referred to as AuNR-P17. Results showed that AuNR-P17 was able to simultaneously down regulate the level of HSP60 and locate in the mitochondria where HSP60 is enriched in the tumor cells of TNBC, which also impeded the interaction between HSP60 and integrin α3, thereby reducing the tumor cells' heat tolerance and metastatic capabilities. At the same time, AuNR-P17 induced remarkable mitochondrial apoptosis when exposed to the laser irradiation of 808 nm. The dual functions of AuNR-P17 led to the decrement of BCL-2 and the activation of p53 and cleaved caspase-3. The danger associated molecular patterns (DAMPs) generated from the mitochondrial apoptosis elicited strong and long-term specific immune responses against TNBC in vivo and ultimately inhibited the tumor metastasis and recurrence with significantly prolonged survival (>100 days) on TNBC mice. In conclusion, this study demonstrated HSP60 a promising potential therapeutic target for triple negative breast cancer and exhibited powerful capacity of AuNR-P17 in photothermal immune therapy.

Background Irisin, as a myokine, plays a protective role against cardiovascular disease, including myocardial infarction, atherosclerosis and hypertension. However, whether irisin attenuates salt-sensitive hypertension and the related underlying mechanisms is unknown.Methods Male Dahl salt-resistant (DSR) and Dahl salt-sensitive (DSS) (12 weeks) rats were fed a high salt diet (8% NaCl) with or without irisin treatment by intraperitoneal injection for 8 weeks.Results Compared with DSR rats, DSS rats showed higher systolic blood pressure (SBP), impaired natriuresis and diuresis and renal dysfunction. In addition, it was accompanied by downregulation of renal p-AMPKα and upregulation of renal RAC1 and nuclear mineralocorticoid receptor (MR). Irisin intervention could significantly up-regulated renal p-AMPKα level and down-regulated renal RAC1-MR signal, thereby improving renal sodium excretion and renal function, and ultimately reducing blood pressure in DSS rats. Ex vivo treatment with irisin reduced the expression of RAC1 and nuclear MR in primary renal distal convoluted tubule cells from DSS rats and the effects of irisin were abolished by cotreatment of compound C (AMPK inhibitor), indicating that the regulation of RAC1-MR signals by irisin depended on the activation of AMPK.Conclusions Irisin administration lowered salt-sensitive hypertension through regulating RAC1-MR signaling via activation of AMPK, which may be a promising therapeutic approach for salt-sensitive hypertension.

Background The primary objective was to examine the association between the lactate/albumin ratio (LAR) and the prognosis of patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT).Methods Utilizing the Medical Information Mart for Intensive Care IV (MIMIC-IV, v2.0) database, we categorized 703 adult AKI patients undergoing CRRT into survival and non-survival groups based on 28-day mortality. Patients were further grouped by LAR tertiles: low (< 0.692), moderate (0.692-1.641), and high (> 1.641). Restricted cubic splines (RCS), Least Absolute Shrinkage and Selection Operator (LASSO) regression, inverse probability treatment weighting (IPTW), and Kaplan-Meier curves were employed.Results In our study, the patients had a mortality rate of 50.07% within 28 days and 62.87% within 360 days. RCS analysis revealed a non-linear correlation between LAR and the risk of mortality at both 28 and 360 days. Cox regression analysis, which was adjusted for nine variables identified by LASSO, confirmed that a high LAR (>1.641) served as an independent predictor of mortality at these specific time points (p 1.641) was found to be an autonomous predictor of mortality at both 28 and 360 days in critically ill patients with AKI undergoing CRRT.

Introduction: A strong association was previously established between body mass index (BMI) and female reproductive system tumors; however, the causal relationship is unclear. We conducted a Mendelian randomization (MR) study to further explore this association. Methods: Genetic information for BMI was retrieved from a published genome-wide association study involving 339,224 participants. Genetic associations with five common female reproductive system tumors were obtained from the FinnGen, UK Biobank studies, and other large consortia. Results: Genetic predisposition towards BMI exhibits a significant association with multiple tumors of the female reproductive system. Specifically, for every 1-unit increase in BMI log-transformed odds ratio (OR). The OR fluctuations overall for patients with breast cancer ranged from 0.661 to 0.996 (95% confidence interval [CI],0.544-1.000, P

Abstract The multi‐component strategy has proven effective in advancing the performance of organic photovoltaics (OPVs), enhancing photocurrent and fill factor through spectral complementarity and morphology optimization. However, the open‐circuit voltage (VOC) mechanism in multi‐component systems lacks systematic investigation. In this study, we explore the influence of alloy‐like phases on energy level distribution and energy loss mechanisms in multi‐component OPVs. Appropriate modulation of donor alloy‐like phases maintains the original intermolecular stacking, enhances component compatibility, reduces acceptor aggregation, and improves acceptor phase purity, mitigating non‐radiative recombination losses. Additionally, suitable alloy‐like phase modulation elevates charge transfer (CT) states, reducing the gap between CT and local exciton state, lowering reorganization energy, and alleviating radiative recombination loss below the bandgap. Through synergistic optimization (layer‐by‐layer method with solid additive), ternary devices based on Y6 acceptor achieve a notable 19.41% power conversion efficiency, offering new insights for the analysis of the energy loss of the multi‐component OPVs.

Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied by local and systemic bone loss. FcγRs, especially FcγRIIa (hFcγRIIa), have been implicated in the pathogenesis of RA. However, the contribution of hFcγRIIa to bone loss has not been fully elucidated. In the present study, we demonstrated the double-edged sword role of hFcγRIIa on osteoclast differentiation through investigations involving hFcγRIIa-transgenic (hFcγRIIa-Tg) mice. Our findings reveal that hFcγRIIa-Tg mice, previously shown to exhibit heightened susceptibility to collagen-induced arthritis (CIA), displayed increased osteoporosis during CIA or at advanced ages (40 weeks), accompanied by heightened in vivo osteoclast differentiation. Notably, bone marrow cells from hFcγRIIa-Tg mice exhibited enhanced efficiency in differentiating into osteoclasts and bone resorption in vitro compared to wild-type mice when stimulated with receptor activators of NF-κB ligand (RANKL). Additionally, hFcγRIIa-Tg mice exhibited augmented sensitivity to RANKL-induced bone loss in vivo, highlighting the osteoclast-promoting role of hFcγRIIa. Mechanistically, bone marrow cells from hFcγRIIa-Tg mice displayed heightened Syk self-activation, leading to mTOR-pS6 pathway activation, thereby promoting RANKL-driven osteoclast differentiation. Intriguingly, while hFcγRIIa crosslinking hindered RANKL-induced osteoclast differentiation, it activated the kinase cAbl, subsequently triggering STAT5 activation and inhibiting the expression of osteoclast-associated genes. This study provides novel insights into hFcγRIIa-mediated osteoclast biology, suggesting promising therapeutic targets for managing bone remodeling disorders.

Abstract Wearing face masks is the best way to stop the spread of respiratory infections. However, if masks are not sterilized, changing them too frequently can actually increase the risk of cross‐contamination. Herein, the construction of an antipathogen photocatalytic mask with carbon vacancy‐modified carbon nitride nanosheets (g‐C3N4‐VC Ns) coated on the non‐woven fabrics of the out layer of the mask, offering effective and long‐term protection against damaging pathogens when exposed to light is reported. The introduced carbon vacancies are found capable of creating energy‐disordered sites and inducing energetic electric force to overcome the Coulomb interactions between electron‐hole pairs, thus promoting the electron‐hole separation to achieve a high generation of reactive oxygen species (ROS). Thanks to its high activity in generating ROS upon exposure to light, the as‐prepared photocatalytic mask shows high pathogen sterilization performance. This, in turn, prolongs the mask's protective lifetime, decreases the need for regular replacement, and decreases medical waste production. The work demonstrated here opens new viewpoints in designing pathogens biocidal protective devices for health protection, offering significant promise in specific environment self‐protection.

High glycogen in oysters contributes to their flavor, quality, and hardiness, making it a crucial target trait for breeding purposes. Until now, the upstream regulatory mechanism for glycogen synthesis has remained unclear. Protein phosphatase-1 regulatory subunit 3 (PPP1R3) is a member of a family that directs the protein phosphatase-1 (PP1) to glycogen, resulting in the activation of glycogen synthase (GS) and the inactivation of glycogen phosphorylase (GP). However, their functions in molluscan species have remained unclear until now. In our study, we verified the function of the PP1α/PPP1R3D pathways in the glycogen metabolism process in Crassostrea gigas. Initially, we conducted a phylogenetic analysis and identified two PP1 and PPP1R3 members in molluscan species, emphasizing copy number variations in eukaryotic animals. Additionally, we identified distinct substitutions of conserved motifs specific to bivalves, Cephalopoda, or Gastropods, revealing functional diversity in PP1 and PPP1R3. Our primary focus was on PP1α/PPP1R3D in the oyster C.gigas, detected in the muscle glycogen fraction of bivalve species, with mRNA expression showing a positive correlation with glycogen content. By manipulating CgPPP1R3D expression in oysters through adenovirus-mediated overexpression or siRNA-mediated downregulation, we established a direct positive correlation between CgPPP1R3D expression levels and glycogen content. Colocation analysis confirmed protein interactions between CgPP1α and CgPPP1R3D. Furthermore, to elucidate the correlation between gene expression and glycogen accumulation, we conducted an association analysis and identified a cluster of significant SNP loci upstream of CgPPP1R3D significantly related to glycogen content. The high polymorphism observed may be linked to differential expressions of CgPPP1R3D in oyster individuals with high and low glycogen levels. These findings serve as a crucial reference for enhancing glycogen traits in molluscan species.

A comprehensive evaluation of the relationship between the densities of various cell types in the breast cancer tumor microenvironment and patient prognosis is currently lacking. Additionally, the absence of a large patch-level whole slide imaging (WSI) dataset of breast cancer with annotated cell types hinders the ability of artificial intelligence to evaluate cell density in breast cancer WSI. We first employed Lasso-Cox regression to build a breast cancer prognosis assessment model based on cell density in a population study. Pathology experts manually annotated a dataset containing over 70,000 patches and used transfer learning based on ResNet152 to develop an artificial intelligence model for identifying different cell types in these patches. The results showed that significant prognostic differences were observed among breast cancer patients stratified by cell density score (P = 0.0018), with the cell density score identified as an independent prognostic factor for breast cancer patients (P < 0.05). In the validation cohort, the predictive performance for overall survival (OS) was satisfactory, with area under the curve (AUC) values of 0.893 (OS) at 1-year, 0.823 (OS) at 3-year, and 0.861 (OS) at 5-year intervals. We trained a robust model based on ResNet152, achieving over 99% classification accuracy for different cell types in patches. These achievements offer new public resources and tools for personalized treatment and prognosis assessment.

Background Oxylipin metabolism plays an essential role in glioma progression and immune modulation in the tumor microenvironment. Lipid metabolic reprogramming has been linked to macrophage remodeling, while the understanding of oxylipins and their catalyzed enzymes lipoxygenases in the regulation of glioma-associated microglia/macrophages (GAMs) remains largely unexplored.Methods To explore the pathophysiological relevance of oxylipin in human glioma, we performed Ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) analysis in human glioma and non-tumor brain tissues. To comprehensively investigate the role of arachidonate lipoxygenase 5 (ALOX5) in glioma, we performed in vivo bioluminescent imaging, immunofluorescence staining and flow cytometry analysis on tumors from orthotopic glioma-bearing mice. We developed an ALOX5-targeted nanobody, and tested its anti-glioma efficacy of combination therapy with α-programmed cell death protein-1 (PD-1).Results In this study, we found that ALOX5 and its oxylipin 5-hydroxyeicosatetraenoic acid (5-HETE) are upregulated in glioma, accumulating programmed death-ligand 1 (PD-L1)+ M2-GAMs and orchestrating an immunosuppressive tumor microenvironment. Mechanistically, 5-HETE derived from ALOX5-overexpressing glioma cells, promotes GAMs migration, PD-L1 expression, and M2 polarization by facilitating nuclear translocation of nuclear factor erythroid 2-related factor 2. Additionally, a nanobody targeting ALOX5 is developed that markedly suppresses 5-HETE efflux from glioma cells, attenuates M2 polarization of GAMs, and consequently ameliorates glioma progression. Furthermore, the combination therapy of the ALOX5-targeted nanobody plus α-PD-1 exhibits superior anti-glioma efficacy.Conclusions Our findings reveal a pivotal role of the ALOX5/5-HETE axis in regulating GAMs and highlight the ALOX5-targeted nanobody as a potential therapeutic agent, which could potentiate immune checkpoint therapy for glioma.