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The C-C bond cleavage of biomass-derived glycerol to generate value-added C1 products remains challenging owing to its slow kinetics. We propose a surface fluorination strategy to construct dynamic dual hydrogen bonds on a semiconducting BiVO4 photoelectrode to overcome the kinetic limit of the oxidation of glycerol to produce formic acid (FA) in acidic media. Intensive spectroscopic characterizations confirm that double hydrogen bonds are formed by the interaction of the F-Bi-F sites of modified BiVO4 with water molecules, and the unique structure promotes the generation of hydroxyl radicals under light irradiation, which accelerates the kinetics of C-C bond cleavage. Theoretical investigations and infrared adsorption spectroscopy reveal that the double hydrogen bond enhances the C=O adsorption of the key intermediate product 1,3-dihydroxyacetone on the Bi-O sites to initiate the FA pathway. We fabricated a self-powered tandem device with an FA selectivity of 79% at the anode and a solar-to-H2 conversion efficiency of 5.8% at the cathode, and these results are superior to most reported results in acidic electrolytes.

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PURPOSE: To explore the influence of gingival biotype and width of keratinized gingiva on peri-implant bone tissue, soft tissue health, and esthetic outcome of the papilla surrounding single posterior maxillary implants. METHODS: Seventy-eight patients who underwent single posterior maxillary implant surgery from May 2019 to September 2022 were selected, involving the placement of 78 implants. Based on periodontal probing outcomes one month post-restoration, the patients were divided into thin gingival biotype group(n=32) and thick gingival biotype group(n=46). Comparisons were made six months after implant restoration regarding buccal keratinized mucosa width(KMW), peri-implant bone tissue [implant bone loss(IBL)], soft tissue health [modified plaque index (mPLI), modified bleeding index for implants (mBLI), probing pocket depth (PPD)], and esthetic effect of the papilla [papilla index score (PIS), food impaction, gingival margin color satisfaction index (GMCS)]. Statistical analysis was performed with SPSS 27.0 software package. RESULTS: The thick gingival biotype group showed significantly greater keratinized gingival width compared to the thin gingival biotype group (P＜0.05). Spearman correlation analysis revealed a positive correlation between gingival biotype and keratinized gingival width(r=-0.416, P=0.000). For peri-implant bone tissue, bone loss in the thin gingival biotype group was significantly higher than that in the thick gingival biotype group. In soft tissue health, the probing pocket depth for implants in the thin gingival biotype group was significantly less than that in the thick gingival biotype group. In terms of esthetic effect of the papilla, PES score in the thin gingival biotype group was significantly lower than in the thick gingival biotype group(P＜0.05). Pearson correlation analysis showed a negative correlation between gingival biotype and papilla index score, GMCS, bleeding on probing, and PPD, but a positive correlation with food impaction, bone loss and mPLI(P＜0.05). The width of keratinized gingiva was positively correlated with papilla index score, GMCS, bleeding on probing and PPD, but negatively correlated with food impaction, bone loss and mPLI(P＜0.05). There was significantly difference between thin and thick gingival biotype groups for KMW >2 mm(P＜0.05). A significant difference was showed in thick gingival biotype group when KMW ≤2 mm and ＞2 mm(P＜0.05). CONCLUSIONS: Gingival biotype and keratinized mucosa width significantly influence peri-implant bone and soft tissue health as well as esthetic outcome of the papilla around single posterior maxillary implants, offering guidance for predicting the long-term success and esthetic outcomes of implants.

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OBJECTIVE: To explore the clinicopathological features and prognosis of TFE3-rearranged renal cell carcinomas (TFE3-rRCC). METHODS: In this retrospective observational study, the data of patients with TFE3-rRCC admitted to Xijing Hospital from January 2010 to October 2023 were collected, encompassing the general information, pathological diagnosis, immunohistochemistry, and the results of FISH detection. The treatment information and survival data of the patients were recorded during the follow-up. RESULTS: A total of 55 patients with TFE3-rRCC were enrolled, among whom 25 were males and 30 were females. TFE3 FISH assay suggested the disruption of the TFE3 gene. Fifty-four patients underwent surgical resection of kidney lesions, while 1 patient did not. By the end of follow-up in December 2023, 3 patients were lost to follow-up, 28 patients remained alive, and 24 patients had died. Among the 52 patients followed up, 31 developed metastases, involving lymph nodes, liver, bone, lung, peritoneum, pleura, adrenal gland, and brain. The 1-year and 5-year survival rates of the patients were 84.6% and 50.6%, respectively. In this study, there were 31 patients with TFE3-rRCC recurrence or metastasis. Median PFS was 7 and 13 months in the VEGFR-TKI and VEGFR-TKI+ ICI groups, respectively. The median OS was 12 months in the VEGFR-TKI treatment group. The median OS data of VEGFR-TKI+ ICI group has not been reached. The ORR and DCR was 25%, 66.7% in the VEGFR-TKI group. The ORR and DCR was 33.3%, 77.8% in the VEGFR-TKI+ ICI group. CONCLUSION: TFE3-rRCC is a rare subtype of malignant renal tumor. The diagnosis mainly relies on pathological morphology, immunohistochemistry, and the detection of TFE3 gene disruption by FISH. In terms of treatment, surgery is the primary approach, and lymph nodes, liver, and bone are the main metastatic sites. VEGFR-TKI+ICI treatment might be an option of recurrent or metastatic TFE3-rRCC.

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With more flexible active sites and intermetal interaction, dual-atom catalysts (DACs) have emerged as a new frontier in various electrocatalytic reactions. Constructing a typical p-d orbital hybridization between p-block and d-block metal atoms may bring new avenues for manipulating the electronic properties and thus boosting the electrocatalytic activities. Herein, we report a distinctive heteronuclear dual-metal atom catalyst with asymmetrical FeSn dual atom sites embedded on a two-dimensional C2N nanosheet (FeSn-C2N), which displays excellent oxygen reduction reaction (ORR) performance with a half-wave potential of 0.914 V in an alkaline electrolyte. Theoretical calculations further unveil the powerful p-d orbital hybridization between p-block stannum and d-block ferrum in FeSn dual atom sites, which triggers electron delocalization and lowers the energy barrier of *OH protonation, consequently enhancing the ORR activity. In addition, the FeSn-C2N-based Zn-air battery provides a high maximum power density (265.5 mW cm-2) and a high specific capacity (754.6 mA h g-1). Consequently, this work validates the immense potential of p-d orbital hybridization along dual-metal atom catalysts and provides new perception into the logical design of heteronuclear DACs.

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Class III peroxidases (CIII PRXs) are plant-specific enzymes with high activity that play key roles in the catalysis of oxidation-reduction reactions. In plants, CIII PRXs can reduce hydrogen peroxide to catalyze oxidation-reduction reactions, thereby affecting plant growth, development, and stress responses. To date, no systematic analysis of the CIII PRX gene family in litchi (Litchi chinensis Sonn.) has been documented, although the genome has been reported. In this study, a total of 77 CIII PRX (designated LcPRX) gene family members were predicted in the litchi genome to provide a reference for candidate genes in the responses to abiotic stresses during litchi growth and development. All of these LcPRX genes had different numbers of highly conserved PRX domains and were unevenly distributed across fifteen chromosomes. They were further clustered into eight clades using a phylogenetic tree, and almost every clade had its own unique gene structure and motif distribution. Collinearity analysis confirmed that there were eleven pairs of duplicate genes among the LcPRX members, and segmental duplication (SD) was the main driving force behind the LcPRX gene expansion. Tissue-specific expression profiles indicated that the expression levels of all the LcPRX family members in different tissues of the litchi tree were significantly divergent. After different abiotic stress treatments, quantitative real-time PCR (qRT-PCR) analysis revealed that the LcPRX genes responded to various stresses and displayed differential expression patterns. Physicochemical properties, transmembrane domains, subcellular localization, secondary structures, and cis-acting elements were also analyzed. These findings provide insights into the characteristics of the LcPRX gene family and give valuable information for further elucidating its molecular function and then enhancing abiotic stress tolerance in litchi through molecular breeding.

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The pursuit of high efficacy C-C coupling during the electrochemical CO2 reduction reaction remains a tremendous challenge owing to the high energy barrier of CO2 activation and insufficient coverage of the desired intermediates on catalytic sites. Inspired by the concept of capture-coupled CO2 activation, we fabricated quinone-grafted carbon nanofibers via an in situ oxidative carbonylation strategy. The quinone functionality of carbon nanofibers promotes the capture of CO2 followed by activation. At a current density of 400 mA cm-2, the Faradaic efficiency of ethylene reached 62.9 %, and a partial current density of 295 mA cm-2 was achieved on the quinone-rich carbon nanofibers. The results of in situ spectroscopy and theoretical calculations indicated that the remarkable selectivity enhancement in ethylene originates from the quinone structure, rather than the electronic properties of Cu particles. The interaction of quinone with CO2 increases the local *CO coverage and simultaneously hinders the co-adsorption of *H on Cu sites, which greatly reduces the energy barrier for C-C coupling and restrains subsequent *CO protonation. The modulation strategy involving specific oxygenated structure, as an independent degree of freedom, guides the design of functionalized carbon materials for tailoring the selectivity of desired products during the CO2 capture and reduction.

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The electrocatalytic synthesis of high-value-added urea by activating N2 and CO2 is a green synthesis technology that has achieved carbon neutrality. However, the chemical adsorption and C-N coupling ability of N2 and CO2 on the surface of the catalyst are generally poor, greatly limiting the improvement of electrocatalytic activity and selectivity in electrocatalytic urea synthesis. Herein, novel hierarchical mesoporous CeO2/Co3O4 heterostructures are fabricated, and at an ultralow applied voltage of -0.2 V, the urea yield rate reaches 5.81 mmol g-1 h-1, with a corresponding Faraday efficiency of 30.05%. The hierarchical mesoporous material effectively reduces the mass transfer resistance of reactants and intermediates, making it easier for them to access active centers. The emerging space-charge regions at the heterointerface generate local electrophilic and nucleophilic regions, facilitating CO2 targeted adsorption in the electrophilic region and activation to produce *CO intermediates and N2 targeted adsorption in the nucleophilic region and activation to generate *N ═ N* intermediates. Then, the electrons in the σ orbitals of *N ═ N* intermediates can be easily accepted by the empty eg orbitals of Co3+ in CeO2/Co3O4, which presents a low-spin state (LS: t2g6eg0). Subsequently, *CO couples with *N ═ N* to produce the key intermediate *NCON*. Interestingly, it was discovered through in situ Raman spectroscopy that the CeO2/Co3O4 catalyst has a reversible spinel structure before and after the electrocatalytic reaction, which is due to the surface reconstruction of the catalyst during the electrocatalytic reaction process, producing amorphous active cobalt oxides, which is beneficial for improving electrocatalytic activity.

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Background: The tertiary lymphatic structure (TLS) is an important component of the tumor immune microenvironment and has important significance in patient prognosis and response to immune therapy. However, the underlying mechanism of TLS in soft tissue sarcoma remains unclear. Methods: A total of 256 RNAseq and 7 single-cell sequencing samples were collected from TCGA-SARC and GSE212527 cohorts. Based on published TLS-related gene sets, four TLS scores were established by GSVA algorithm. The immune cell infiltration was calculated via TIMER2.0 and "MCPcounter" algorithms. In addition, the univariate, LASSO, and multivariate-Cox analyses were used to select TLS-related and prognosis-significant hub genes. Single-cell sequencing dataset, clinical immunohistochemical, and cell experiments were utilized to validate the hub genes. Results: In this study, four TLS-related scores were identified, and the total-gene TLS score more accurately reflected the infiltration level of TLS in STS. We further established two hub genes (DUSP9 and TNFSF14) prognosis markers and risk scores associated with soft tissue sarcoma prognosis and immune therapy response. Flow cytometry analysis showed that the amount of CD3, CD8, CD19, and CD11c positive immune cell infiltration in the tumor tissue dedifferentiated liposarcoma patients was significantly higher than that of liposarcoma patients. Cytological experiments showed that soft tissue sarcoma cell lines overexpressing TNFSF14 could inhibit the proliferation and migration of sarcoma cells. Conclusion: This study systematically explored the TLS and related genes from the perspectives of bioinformatics, clinical features and cytology experiments. The total-gene TLS score, risk score and TNFSF14 hub gene may be useful biomarkers for predicting the prognosis and immunotherapy efficacy of soft tissue sarcoma.

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T-cell receptor (TCR) recognition of antigens is fundamental to the adaptive immune response. With the expansion of experimental techniques, a substantial database of matched TCR-antigen pairs has emerged, presenting opportunities for computational prediction models. However, accurately forecasting the binding affinities of unseen antigen-TCR pairs remains a major challenge. Here, we present convolutional-self-attention TCR (CATCR), a novel framework tailored to enhance the prediction of epitope and TCR interactions. Our approach utilizes convolutional neural networks to extract peptide features from residue contact matrices, as generated by OpenFold, and a transformer to encode segment-based coded sequences. We introduce CATCR-D, a discriminator that can assess binding by analyzing the structural and sequence features of epitopes and CDR3-ß regions. Additionally, the framework comprises CATCR-G, a generative module designed for CDR3-ß sequences, which applies the pretrained encoder to deduce epitope characteristics and a transformer decoder for predicting matching CDR3-ß sequences. CATCR-D achieved an AUROC of 0.89 on previously unseen epitope-TCR pairs and outperformed four benchmark models by a margin of 17.4%. CATCR-G has demonstrated high precision, recall and F1 scores, surpassing 95% in bidirectional encoder representations from transformers score assessments. Our results indicate that CATCR is an effective tool for predicting unseen epitope-TCR interactions. Incorporating structural insights enhances our understanding of the general rules governing TCR-epitope recognition significantly. The ability to predict TCRs for novel epitopes using structural and sequence information is promising, and broadening the repository of experimental TCR-epitope data could further improve the precision of epitope-TCR binding predictions.

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East Asian continental outflows with PM2.5, O3, and other species may determine the baseline conditions and affect the air quality in downwind areas via long-range transport (LRT). To gain insight into the impact and spatiotemporal characteristics of airborne pollutants in East Asian continental outflows, a versatile multicopter drone sounding platform was used to simultaneously observe PM2.5, O3, CO2, and meteorological variables (temperature, specific humidity, pressure, and wind vector) above the northern tip of Taiwan, Cape Fuiguei, which often encounters continental outflows during winter monsoon periods. By coordinating hourly high-spatial-resolution profiles provided by drone soundings, WRF/CMAQ model air quality predictions, HYSPLIT-simulated backward trajectories, and MERRA-2 reanalysis data, we analyzed two prominent phenomena of airborne pollutants in continental outflows to better understand their physical/chemical characteristics. First, we found that pollutants were well mixed within a sounding height of 500 m when continental outflows passed through and completely enveloped Cape Fuiguei. Eddies induced by significant fluctuations in wind speeds coupled with minimal temperature inversion and LRT facilitated vertical mixing, possibly resulting in high homogeneity of pollutants within the outflow layer. Second, the drone soundings indicated exceptionally high O3 concentrations (70-100 ppbv) but relatively low concentrations of PM2.5 (10-20 µg/m3), CO2 (420-425 ppmv), and VOCs in some air masses. The low levels of PM2.5, CO2, and VOCs ruled out photochemistry as the cause of the formation of high-level O3. Further coordination of spatiotemporal data with air mass trajectories and O3 cross sections provided by MERRA-2 suggested that the high O3 concentrations could be attributed to stratospheric intrusion and advection via continental outflows. High-level O3 concentrations persisted in the lower troposphere, even reaching the surface, suggesting that stratospheric intrusion O3 may be involved in the rising trend in O3 concentrations in parts of East Asia in recent years in addition to surface photochemical factors.

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Background: Lipid metabolism disorders lead to lipotoxicity. The hyperlipidemia-induced early stage of renal injury mainly manifests as podocyte damage. CD36 mediates fatty acid uptake and the subsequent accumulation of toxic lipid metabolites, resulting in podocyte lipotoxicity. Methods: Male Sprague-Dawley rats were divided into two groups: the normal control group and the high-fat diet group (HFD). Podocytes were cultured and treated with palmitic acid (PA) and sulfo-N-succinimidyl oleate (SSO). Protein expression was measured by immunofluorescence and western blot analysis. Boron-dipyrromethene staining and Oil Red O staining was used to analyze fatty acid accumulation. Results: Podocyte foot process (FP) effacement and marked proteinuria occurred in the HFD group. CD36 protein expression was upregulated in the HFD group and in PA-treated podocytes. PA-treated podocytes showed increased fatty acid accumulation, reactive oxygen species (ROS) production, and actin cytoskeleton rearrangement. However, pretreatment with the CD36 inhibitor SSO decreased lipid accumulation and ROS production and alleviated actin cytoskeleton rearrangement in podocytes. The antioxidant N-acetylcysteine suppressed PA-induced podocyte FP effacement and ROS generation. Conclusions: CD36 participated in fatty acid-induced FP effacement in podocytes via oxidative stress, and CD36 inhibitors may be helpful for early treatment of kidney injury.

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Ligand engineering is crucial for tuning the structural and optoelectronic properties of perovskite nanocrystals (NCs), which also improves their stability. In contrast to the typically used long-chain alkylamine ligands, we successfully introduced an aromatic 1-(p-tolyl)ethylamine (PTEA) ligand to synthesize the CsPbX3 (X = Br or I) NCs. The CsPbI3 and CsPbBr3 NCs demonstrated long carrier lifetimes of ∼877 and 49 ns, respectively, as well as high photoluminescence quantum yields (PLQYs) of ∼99% and 95%, respectively. Furthermore, such NCs realized excellent long-term stability in an ambient atmosphere without obvious degradation over one month. All of these properties were better than the properties of NCs coated with the conventional alkylamine ligands. The high performance of these NCs was discussed with the effective surface passivation by PTEA. Our finding suggests a facile and effective ligand (PTEA) for modulating perovskites, achieving enhancement of both the carrier lifetime and the PLQY.

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HSP70 protein, as an important member of the heat shock protein (HSP) family, plays an important role in plant growth, development, and response to biotic and abiotic stresses. In order to explore the role of HSP70 gene family members in Litchi chinensis under low temperature, high temperature, drought, and salt stress, bioinformatics methods were used to identify the HSP70 gene family members within the entire L. chinensis genome. The expression of these genes under various abiotic stresses was then detected using quantitative real-time PCR (qRT-PCR). The results showed that the LcHSP70 gene family consisted of 18 members, which were unevenly distributed across ten L. chinensis chromosomes. The LcHSP70 protein contained 479-851 amino acids, with isoelectric points ranging from 5.07 to 6.95, and molecular weights from 52.44 kDa to 94.07 kDa. The predicted subcellular localization showed that LcHSP70 protein was present in the nucleus, cytoplasm, endoplasmic reticulum, mitochondria, and chloroplast. Phylogenetic analysis divided the LcHSP70 proteins into five subgroups, namely Ⅰ, Ⅱ, Ⅲ, Ⅳ, and Ⅵ. The promoter regions of the LcHSP70 genes contained various cis-acting elements related to plant growth, development, hormone response, and stress response. Moreover, the expression of LcHSP70 genes displayed distint tissue-specific expression level, categorized into universal expression and specific expression. From the selected 6 LcHSP70 genes (i.e., LcHSP70-1, LcHSP70-5, LcHSP70-10, LcHSP70-14, LcHSP70-16, and LcHSP70-18), their relative expression levels were assessed under different abiotic stresses using qRT-PCR. The results indicated that the gene family members exhibited diverse responses to low temperature, high temperature, drought, and salt stress, with significant variations in their expression levels across different time periods. These results provide a foundation for further exploration of the function of the LcHSP70 gene family.

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The application of immune checkpoint inhibitors (ICIs) has changed the treatment of advanced hepatocellular carcinoma. Transcatheter arterial chemoembolization (TACE) is a first-line treatment for intermediate hepatocellular carcinoma. Serving as a local treatment modality that can induce immunogenic cell death, the efficacy and safety of combined use with ICI have not been evaluated. Although there have been prospective studies aimed at evaluating the efficacy and safety of ICI combined with TACE in BCLC stage B HCC patients, there are few reports on the evaluation of BCLC stage C patients with distant metastasis or portal vein cancer thrombus. Data of unresectable hepatocellular carcinoma patients received PD-1 inhibitor and TACE were collected in Xijing Hospital from June 2019 to December 2022. The tumor response was evaluated according to the Solid Tumor Modified Response Evaluation Standard (mRECIST), including complete response (CR), partial response (PR), disease stability (SD), disease progression (PD), objective response rate (ORR), and disease control rate (DCR). The progression-free survival (PFS) and overall survival (OS) were used to estimate therapy efficacy. The treatment-related adverse events were evaluated based on National Cancer Institute Common Adverse Event Evaluation Criteria (CTCAE) version 5.0. A total of 42 patients with unresectable hepatocellular carcinoma were included in this study, including 34 males (80.5%) and 8 females (19.5%). The average age is 54.5 years, ranging from 34 to 72. The median follow-up time was 12.3 months, with an ORR of 42.9% and a DCR of 90.5% as of the follow-up time. The median PFS is 7.5 months (95% CI: 5.76-9.23), and the median OS has not yet been reached; 6-month PFS was 62.2%. Safety analysis showed that 41 (97.6%) patients experienced treatment-related adverse reactions, mainly including elevated AST and ALT, fever, elevated bilirubin, hypothyroidism, nausea, abdominal pain, and rash. 40 patients had grade 1/2 adverse reactions, and only one patient had grade 3 adverse reactions, manifested as intolerable rash, nausea, and vomiting. Treatment is terminated when symptomatic treatment and drug suspension cannot be alleviated. In this study, thre patients with unresectable hepatocellular carcinoma were treated with PD-1 inhibitor combined with TACE to achieve good tumor reduction effect and underwent liver cancer resection surgery. For patients with unresectable hepatocellular carcinoma, whether in BCLC stage B or stage C, effective systemic therapy (PD-1 inhibitor) combined with local therapy (TACE) can achieve a high rate of tumor regression and objective response. Some patients may even pursue surgical treatment opportunities, and the treatment-related adverse reactions are controllable, which is expected to provide new options for extending the survival of unresectable hepatocellular carcinoma patients.

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The MADS-box protein is an important transcription factor in plants and plays an important role in regulating the plant abiotic stress response. In this study, a total of 94 MADS-box genes were predicted in the litchi genome, and these genes were widely distributed on all the chromosomes. The LcMADS-box gene family was divided into six subgroups (Mα, Mß, Mγ, Mδ, MIKC, and UN) based on their phylogenetical relationships with Arabidopsis, and the closely linked subgroups exhibited more similarity in terms of motif distribution and intron/exon numbers. Transcriptome analysis indicated that LcMADS-box gene expression varied in different tissues, which can be divided into universal expression and specific expression. Furthermore, we further validated that LcMADS-box genes can exhibit different responses to various stresses using quantitative real-time PCR (qRT-PCR). Moreover, physicochemical properties, subcellular localization, collinearity, and cis-acting elements were also analyzed. The findings of this study provide valuable insights into the MADS-box gene family in litchi, specifically in relation to stress response. The identification of hormone-related and stress-responsive cis-acting elements in the MADS-box gene promoters suggests their involvement in stress signaling pathways. This study contributes to the understanding of stress tolerance mechanisms in litchi and highlights potential regulatory mechanisms underlying stress responses.

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Hydrogels, recognized for their biocompatibility, are extensively employed in the realm of wearable devices. Nevertheless, their application is often constrained by their low mechanical robustness, rendering them susceptible to damage during operation. The restoration of their load-bearing and sensory functionalities post-damage represents a captivating yet underexplored domain. Conventional repair techniques, reliant on hydrogen bonding or van der Waals forces, falter in the face of hydrogels' high water content. In this study, a novel composite adhesive gel (SGG), integrating sodium alginate, guar gum, and graphene oxide, was engineered to mend impaired hydrogels. Furthermore, an optimized repair approach, utilizing a cross-shaped sectional (CSS) enhancement strategy, was devised to reinstate the hydrogels' load and sensory capabilities. Investigations revealed that the SGG adhesive infiltrated the hydrogel, establishing an intermediary gel stratum, subsequently solidifying to mend the material through topological adhesion. This process reestablished the continuity of the polymer network and the aqueous phase within the hydrogel. Following the application of the CSS augmentation method, the peak tensile strain of the remediated hydrogel exceeded 200 %, with the uppermost observable adhesive energy touching 2526 J/m2. In addition, the ability to respond to strain was significantly rejuvenated, suggesting an effective methodology for the rehabilitation of wearable technology.

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BACKGROUND: Tumor cells frequently suffer from endoplasmic reticulum (ER) stress. Previous studies have extensively elucidated the role of tumorous unfolded protein response in melanoma cells, whereas the effect on tumor immunology and the underlying mechanism remain elusive. METHODS: Bioinformatics, biochemical assays and pre-clinical mice model were employed to demonstrate the role of tumorous inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) in anti-tumor immunity and the underlying mechanism. RESULTS: We firstly found that IRE1α signaling activation was positively associated with the feature of tumor-infiltrating lymphocytes. Then, pharmacological ER stress induction by HA15 exerted prominent anti-tumor effect in immunocompetent mice and was highly dependent on CD8+T cells, paralleled with the reshape of immune cells in tumor microenvironment via tumorous IRE1α-XBP1 signal. Subsequently, tumorous IRE1α facilitated the expression and secretion of multiple chemokines and cytokines via XBP1-NF-κB axis, leading to increased infiltration and anti-tumor capacity of CD8+T cells. Ultimately, pharmacological induction of tumorous ER stress by HA15 brought potentiated therapeutic effect along with anti-PD-1 antibody on melanoma in vivo. CONCLUSIONS: Tumorous IRE1α facilitates CD8+T cells-dependent anti-tumor immunity and improves immunotherapy efficacy by regulating chemokines and cytokines via XBP1-NF-κB axis. The combination of ER stress inducer and anti-PD-1 antibody could be promising for increasing the efficacy of melanoma immunotherapy.

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Objective To observe the incidence of pericardial tamponade(PT)after left atrial appendage closure(LAAC)in patients with non-valvular atrial fibrillation(NVAF),and to explore its related factors and outcomes.Methods NVAF patients who were hospitalized and treated with LAAC in Department of Cardiology of our hospital from August 2014 to March 2023 were selected for the study.The general clinical data,preoperative transthoracic echocardiography and transesophageal echocardiography data,results of routine preoperative laboratory tests,intraoperative data and follow-up data of the patients were collected through the hospital medical record management system.The enrolled patients were classified into the non-PT group(n=8)and the PT group(n =1184)according to whether PT occurred after LAAC or not.The incidence of PT,related risk factors and outcomes were statistically analyzed.Results This study included 639 males(53.6%)and 553 females(46.4%),with an average age of 68.1±9.65 years.The CHA2 DS2-VASc score was 4.51±1.72,and the HAS-BLED score was 3.36±1.09.PT occurred in 8 cases(0.67%),among them,6 cases occurred 1 to 33 h after LAAC,and 2 cases occurred on day 19 and day 27 after LAAC.As for the results of transesophageal echocardiography(TEE)and LAA angiography,compared with the non-PT group,the PT group had the significantly larger maximum caliber of the LAA(P=0.025,P=0.015),smaller maximum depth of the LAA(P=0.028,P=0.031),and lower success rate of one-time placement of the occluder(P=0.031);The occluder compression rate of the PT group was significantly greater than that of the non-PT group(P=0.046).Multivariate analysis showed that larger maximum diameter of LAA,smaller average effective depth of LAA and larger compression rate of occluder were the main risk factors for PT.All the 8 PT patients were cured by stopping antithrombotic drugs,pericardiocentesis or surgical drainage.During a mean follow-up of 39±27 months,there were no device-related thrombosis(DRT),ischemic stroke,systemic embolism and other complications in the PT group.Conclusion The incidence of PT after LAAC is low,which is related to the large diameter of LAA,the relatively insufficient depth of the LAA and the large compression rate of the occlude.PT can be cured by stopping antithrombotic drugs and pericardiocentesis/surgical drainage.

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Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

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Objective To analyze the metabolic changes of myocardial tissue in rats under acute exposure to macleaya cordata by gas chromatography mass spectrometry(GC-MS),explore forensic identifications of its characteristic metabolites,and verify its toxicological mechanism in poisoning cases.Methods The rats in the exposure group were given 382 mg/kg macleaya extract solution by gavage,and the rats in the control group were given the same dose of solvent.The myocardial samples were analyzed by GC-MS,and pattern recognition was conducted through partial least squares discriminant analysis(PLSDA).The differential metabolites with characteristic changes were identified by variable importance projection(VIP value＞1)and Student's t test(P＜0.01).Results Compared with the control group,21 potential characteristic metabolites were identified.Through KEGG pathway enrichment analysis,it was found that these metabolites were mainly involved in the pathways of glycine,serine and threonine metabolism;pyruvate metabolism and glycerolipid metabolism.Conclusion Through the study of myocardial metabolism in rats exposed to macleaya cordata,we found the information on metabolites closely related to poisoning,which provides new insight and reference for studies on the mechanisms of macleaya cordata poisoning in the field of forensic medicine.