Lipid metabolic reprogramming mediated by circulating Nrg4 alleviates metabolic dysfunction-associated steatotic liver disease during the early recovery phase after sleeve gastrectomy.

BACKGROUND: The metabolic benefits of bariatric surgery that contribute to the alleviation of metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. However, the processes and mechanisms underlying the contribution of lipid metabolic reprogramming after bariatric surgery to attenuating MASLD remain elusive. METHODS: A case-control study was designed to evaluate the impact of three of the most common adipokines (Nrg4, leptin, and adiponectin) on hepatic steatosis in the early recovery phase following sleeve gastrectomy (SG). A series of rodent and cell line experiments were subsequently used to determine the role and mechanism of secreted adipokines following SG in the alleviation of MASLD. RESULTS: In morbidly obese patients, an increase in circulating Nrg4 levels is associated with the alleviation of hepatic steatosis in the early recovery phase following SG before remarkable weight loss. The temporal parameters of the mice confirmed that an increase in circulating Nrg4 levels was initially stimulated by SG and contributed to the beneficial effect of SG on hepatic lipid deposition. Moreover, this occurred early following bariatric surgery. Mechanistically, gain- and loss-of-function studies in mice or cell lines revealed that circulating Nrg4 activates ErbB4, which could positively regulate fatty acid oxidation in hepatocytes to reduce intracellular lipid deposition. CONCLUSIONS: This study demonstrated that the rapid effect of SG on hepatic lipid metabolic reprogramming mediated by circulating Nrg4 alleviates MASLD.

CuO (111) Microcrystalline Evoked Indium-Organic Framework for Efficient Electroreduction of CO2 to Formate.

Electrochemical reduction of carbon dioxide (CO2RR) to formate is economically beneficial but suffers from poor selectivity and high overpotential. Herein, enriched microcrystalline copper oxide is introduced on the surface of indium-based metal-organic frameworks. Benefiting from the CuO (111) microcrystalline shell and formed catalytic active In-Cu interfaces, the obtained MIL-68(In)/CuO heterostructure display excellent CO2RR to formate with a Faradaic efficiency (FE) as high as 89.7% at low potential of only -0.7 V vs. RHE in a flow cell. Significantly, the membrane electrode assembly (MEA) cell based on MIL-68(In)/CuO exhibit a remarkable current density of 640.3 mA cm-2 at 3.1 V and can be stably operated for 180 h at 2.7 V with a current density of 200 mA cm-2. The ex/in situ electrochemical investigations reveal that the introduction of CuO increases the formation rate of the carbon dioxide reduction intermediate *HCOO- and inhibits the competitive hydrogen evolution reaction. This work not only provides an in-depth study of the mechanism of the CO2RR pathways on In/Cu composite catalyst but also offers an effective strategy for the interface design of electrocatalytic carbon dioxide reduction reaction.

Development and validation of a machine learning-based predictive model for assessing the 90-day prognostic outcome of patients with spontaneous intracerebral hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (sICH) is associated with significant mortality and morbidity. Predicting the prognosis of patients with sICH remains an important issue, which significantly affects treatment decisions. Utilizing readily available clinical parameters to anticipate the unfavorable prognosis of sICH patients holds notable clinical significance. This study employs five machine learning algorithms to establish a practical platform for the prediction of short-term prognostic outcomes in individuals afflicted with sICH. METHODS: Within the framework of this retrospective analysis, the model underwent training utilizing data gleaned from 413 cases from the training center, with subsequent validation employing data from external validation center. Comprehensive clinical information, laboratory analysis results, and imaging features pertaining to sICH patients were harnessed as training features for machine learning. We developed and validated the model efficacy using all the selected features of the patients using five models: Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), XGboost and LightGBM, respectively. The process of Recursive Feature Elimination (RFE) was executed for optimal feature screening. An internal five-fold cross-validation was employed to pinpoint the most suitable hyperparameters for the model, while an external five-fold cross-validation was implemented to discern the machine learning model demonstrating the superior average performance. Finally, the machine learning model with the best average performance is selected as our final model while using it for external validation. Evaluation of the machine learning model's performance was comprehensively conducted through the utilization of the ROC curve, accuracy, and other relevant indicators. The SHAP diagram was utilized to elucidate the variable importance within the model, culminating in the amalgamation of the above metrics to discern the most succinct features and establish a practical prognostic prediction platform. RESULTS: A total of 413 patients with sICH patients were collected in the training center, of which 180 were patients with poor prognosis. A total of 74 patients with sICH were collected in the external validation center, of which 26 were patients with poor prognosis. Within the training set, the test set AUC values for SVM, LR, RF, XGBoost, and LightGBM models were recorded as 0.87, 0.896, 0.916, 0.885, and 0.912, respectively. The best average performance of the machine learning models in the training set was the RF model (average AUC: 0.906 ± 0.029, P < 0.01). The model still maintains a good performance in the external validation center, with an AUC of 0.817 (95% CI 0.705-0.928). Pertaining to feature importance for short-term prognostic attributes of sICH patients, the NIHSS score reigned supreme, succeeded by AST, Age, white blood cell, and hematoma volume, among others. In culmination, guided by the RF model's variable importance weight and the model's ROC curve insights, the NIHSS score, AST, Age, white blood cell, and hematoma volume were integrated to forge a short-term prognostic prediction platform tailored for sICH patients. CONCLUSION: We constructed a prediction model based on the results of the RF model incorporating five clinically accessible predictors with reliable predictive efficacy for the short-term prognosis of sICH patients. Meanwhile, the performance of the external validation set was also more stable, which can be used for accurate prediction of short-term prognosis of sICH patients.

DNA from macrophages induces fibrosis and vasculopathy through POLR3A/STING/type I interferon axis in systemic sclerosis.

OBJECTIVE: To clarify the role of RNA polymerase III A (POLR3A)/type I IFN in the pathogenesis of SSc. METHODS: Cytosolic DNA and stimulator of IFN genes (STING) pathway in skin or serum of SSc patients were detected by immunofluorescence, immunohistochemistry and western blotting. DNA from human macrophages was transfected to SSc fibroblasts or human umbilical vein endothelial cells (HUVECs) and then markers of POLR3A/STING pathway were detected by real-time qPCR, western blotting and confocal microscopy. After H151 treatment or knocking down POLR3A/STING, type I IFN response, monocytes adhesion and activation of fibroblasts and HUVECs were evaluated. Regulation of IFN regulatory factor 3 (IRF3) on monocyte chemoattractant protein-1 (MCP-1) was determined by chromatin immunoprecipitation. In bleomycin (BLM)-induced SSc mice, the effect of STING knockout or H151 on vasculopathy and fibrosis was assessed. RESULTS: Cytosolic DNA, colocalization of STING with alpha-smooth muscle actin (α-SMA) or CD31 in the skin, and STING pathway in the serum of SSc patients were increased. Macrophage-derived DNA stimulated the translocation of POLR3A from nucleus to the perinuclear region near STING and activated POLR3A/STING/type I IFN response, monocytes adhesion and MCP-1 expression in fibroblasts/HUVECs and collagen overproduction of fibroblasts. The activated IRF3 bound to the promoter of MCP-1. STING deficiency or H151 administration ameliorated fibrosis and vasculopathy both in vitro and in BLM-induced SSc mice. CONCLUSIONS: SSc presented increased DNA leakage and STING pathway activation. DNA from macrophages induced type I IFN signature of fibroblasts and ECs through POLR3A/STING pathway. Blocking POLR3A/STING axis provides a new therapeutic target for SSc.

Protective effect of spore oil-functionalized nano-selenium system on cisplatin-induced nephrotoxicity by regulating oxidative stress-mediated pathways and activating immune response.

In clinical practice, cisplatin is the most commonly used chemotherapy drug to treat a range of malignancies. Severe ROS-regulated nephrotoxicity, however, restricts its applicability. Currently, the main mechanisms leading to cisplatin-induced nephrotoxicity in clinical settings involve hydration or diuresis. However, not all patients can be treated with massive hydration or diuretics. Therefore, it is crucial to develop a treatment modality that can effectively reduce nephrotoxicity through a foodborne route. Selenium has been reported to have strong antioxidant as well as anticancer effects when administered as spore oil. Herein, we established cellular and animal models of cisplatin-induced nephrotoxicity and synthesized spore oil-functionalized nano-selenium (GLSO@SeNPs). We found that GLSO@SeNPs inhibit the mitochondrial apoptotic pathway by maintaining oxidative homeostasis and regulating related signaling pathways (the MAPK, caspase, and AKT signaling pathways). In vivo, GLSO@SeNPs could effectively improve cisplatin-induced renal impairment, effectively maintaining oxidative homeostasis in renal tissues and thus inhibiting the process of renal injury. In addition, GLSO@SeNPs were converted into selenocysteine (SeCys2), which may exert protective effects. Furthermore, GLSO@SeNPs could effectively modulate the ratio of immune cells in kidneys and spleen, reducing the proportions of CD3+CD4+ T cells, CD3+CD8+ T cells, and M1 phenotype macrophages and increasing the proportion of anti-inflammatory regulatory T cells. In summary, in this study, we synthesized food-derived spore oil-functionalized nanomaterials, and we explored the mechanisms by which GLSO@SeNPs inhibit cisplatin-induced nephrotoxicity. Our study provides a basis and rationale for the inhibition of cisplatin-induced nephrotoxicity by food-derived nutrients.

A Quick Simulation Method for Aero-Optical Effects Based on a Density Proxy Model.

Aero-optical effects caused by high-speed flow fields will interfere with the transmission of starlight, reduce the accuracy of optical sensors, and affect the application of celestial navigation on hypersonic vehicles. At present, the research of aero-optical effects relies heavily on the flow field simulation of computational fluid dynamics (CFD), which requires a great deal of computing resources and time, and cannot satisfy the demand of the rapid analysis of aero-optical effects in the engineering design stage. Therefore, a quick simulation method for aero-optical effects based on a density proxy model (DP-AOQS) is proposed in this paper. A proxy model of the turbulent density field is designed to replace the density field in the CFD simulation, and the proxy model is parametrically calibrated to simulate the optical characteristics of the turbulent boundary layer (TBL) in the external flow field of the optical window. The performance of DP-AOQS in the visible light band is verified from the perspectives of density field distribution, optical path difference (OPD), and fuzzy star map. The simulation results show that the method can quickly provide the distortion results of aero-optical effects in different flight conditions on the premise of ensuring the simulation accuracy. The research in this paper provides a new analytical method for the study of aero-optical effects.

Palmar erythema and palmar papules as predictors for dermatomyositis-related acute/subacute interstitial lung disease: a retrospective study.

OBJECTIVES: DM-related acute/subacute interstitial lung disease (A/S-ILD) remains a big therapeutic challenge due to its insidious onset and rapid development. In the present study, we aimed to investigate the association between clinical features of DM and ILD. METHODS: We retrospectively assessed skin manifestations, muscle damage, laboratory tests, concurrent ILD and malignancy in 207 patients with DM and analysed the high-risk factors for ILD. RESULTS: In the 207 DM patients, 153 patients had ILD, in which 131 had chronic ILD (CILD) and 22 had A/S-ILD. The proportions of mechanic's hands, palmar papules and muscle weakness, as well as anti-melanoma differentiation-associated gene 5 (MDA5) antibody and lactic dehydrogenase (LDH), alanine aminotransferase (ALT) and ferritin in the ILD group were significantly higher compared with the non-ILD group. The onset age over 56 years, mechanic's hands and muscle weakness were independent predictive factors for ILD. The proportions of palmar papules, palmar erythema, anti-MDA5 antibody, ALT, aspartate aminotransferase (AST), LDH and ESR in the A/S-ILD group were higher compared with the CILD group. Palmar erythema and palmar papules were independent predictive factors for A/S-ILD. Palmar papules were positively correlated with anti-MDA5 antibody. CONCLUSION: The onset age over 56 years, mechanic's hands or muscle weakness predicted the incidence of DM-related ILD, while palmar erythema or palmar papules could predict potential DM-related A/S-ILD.

Autophagy mediates 2-methoxyestradiol-inhibited scleroderma collagen synthesis and endothelial-to-mesenchymal transition induced by hypoxia.

OBJECTIVES: To investigate whether autophagy mediates 2-methoxyestradiol (2-ME)-inhibited hypoxia-induced fibrosis and endothelial-to-mesenchymal transition (endoMT) in SSc. METHODS: Autophagy in the skin of SSc patients was assessed by transmission electron microscopy. SSc skin fibroblasts and human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic (1% O2) conditions with 2-ME or autophagy inhibitor. Collagen I and connective tissue growth factor (CTGF) in fibroblasts and vascular endothelial (VE)-cadherin, CD31, vimentin and α-smooth muscle actin (α-SMA) in HUVECs were examined by western blotting. Autophagic markers were evaluated by confocal microscopy and immunofluorescence. RESULTS: SSc skins presented increased autolysosomes, LC3-II, collagen I and CTGF. Hypoxia-challenged fibroblasts and HUVECs formed more autophagosomes and autolysosomes, with increased LC3 and decreased P62. Meanwhile, hypoxia increased collagen I and CTGF in fibroblasts and increased vimentin and α-SMA but decreased VE-cadherin and CD31 in HUVECs. Bafilomycin A1 increased LC3-II and P62 in fibroblasts and HUVECs and decreased collagen I and CTGF in fibroblasts and vimentin and α-SMA in HUVECs, while upregulating VE-cadherin and CD31. 3-methyladenine decreased autophagy and fibrosis in fibroblasts and endothelial-to-mesenchymal transition in HUVECs. 2-ME-treated HUVECs showed more autophagosomes and fewer autolysosomes while 2-ME-treated fibroblasts showed fewer of both. Moreover, 2-ME decreased LC3-II and increased P62 in fibroblasts and increased both in HUVECs. Inhibition of autophagy by 2-ME showed the same effect with bafilomycin A1 on fibroblast collagen synthesis as well as endothelial and mesenchymal markers in HUVECs. CONCLUSION: Autophagy mediated hypoxia-induced fibroblast collagen synthesis and endoMT in SSc, which could be reversed by 2-ME.

2-Methoxyestradiol inhibits hypoxia-induced scleroderma fibroblast collagen synthesis by phosphatidylinositol 3-kinase/Akt/mTOR signalling.

Objectives: To investigate the mechanism of 2-methoxyestradiol (2-ME) in inhibiting hypoxia-induced collagen synthesis of fibroblasts in SSc. Methods: The expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and connective tissue growth factor (CTGF) in skin specimens derived from SSc patients and healthy volunteers were examined by immunohistochemistry. HIF-1α was knocked down by lentiviral transduction, and SSc dermal fibroblasts cultured under normoxic (21% O2) or hypoxic (1% O2) condition were treated with PI3K inhibitor LY294002, rapamycin or 2-ME (25 µM). The protein levels of HIF-1α, CTGF, collagen I, p-Akt and p-mTOR were examined by western blotting or immunofluorescence. Apoptosis and cell cycle of fibroblasts were assessed by flow cytometry and by measuring caspase 3 activity, and cell proliferation was evaluated by Cell Counting Kit-8. Results: The expressions of HIF-1α and CTGF were increased in skins of SSc patients compared with healthy controls. Hypoxia up-regulated the protein levels of HIF-1α, CTGF and collagen I in SSc fibroblasts. In contrast, 2-ME inhibited PI3K/Akt/mTOR pathway and down-regulated protein levels of HIF-1α, CTGF and collagen I. Knockdown of HIF-1α reduced expressions of CTGF and collagen I, which were further down-regulated by 2-ME intervention. Moreover, 2-ME promoted the apoptosis and inhibited the proliferation of SSc fibroblasts by arresting the cell cycle at the G2/M phase. Conclusion: 2-ME reduced the production of CTGF and collagen I in SSc fibroblasts induced by hypoxia through PI3K/Akt/mTOR/HIF-1α signalling and inhibited the proliferation of fibroblasts. These findings suggested that 2-ME could be employed as a promising antifibrotic therapy for SSc.

The Level of Expectations Regarding Aging Among Older Adults: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically review the level of expectations regarding aging (ERA) among older adults. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Adults aged 60 years and older in any setting. METHODS: We searched 11 databases for cross-sectional studies that reported ERA scores among older adults using the ERA survey from inception to May 1, 2022, without language restrictions. Two researchers independently selected studies, extracted data, and assessed quality. The mean scores and standard deviations of the ERA survey and its subscales were pooled using the Stata software (version 17.0). RESULTS: Twelve studies with 3664 participants were included in this study. The pooled mean scores of overall ERA were 37.85 (95% CI, 33.54-42.16). Specifically, the pooled scores for expectations regarding physical health, mental health, and cognitive function were 31.67 (95% CI, 27.42-35.92), 43.69 (95% CI, 38.99-48.39), and 33.28 (95% CI, 29.56-37.00), respectively. No statistically significant differences between groups were observed in any subgroup analysis. CONCLUSIONS AND IMPLICATIONS: The level of ERA among older adults is relatively low, particularly concerning cognitive function and physical health dimensions. These findings may provide a valuable reference for public health professionals and policymakers to intervene and manage the health problems of older adults.

Nintedanib Mitigates Radiation-Induced Pulmonary Fibrosis by Suppressing Epithelial Cell Inflammatory Response and Inhibiting Fibroblast-to-Myofibroblast Transition.

Radiation-induced pulmonary fibrosis (RIPF) represents a serious complication observed in individuals undergoing thoracic radiation therapy. Currently, effective interventions for RIPF are unavailable. Prior research has demonstrated that nintedanib, a Food and Drug Administration (FDA)-approved anti-fibrotic agent for idiopathic pulmonary fibrosis, exerts therapeutic effects on chronic fibrosing interstitial lung disease. This research aimed to investigate the anti-fibrotic influences of nintedanib on RIPF and reveal the fundamental mechanisms. To assess its therapeutic impact, a mouse model of RIPF was established. The process involved nintedanib administration at various time points, both prior to and following thoracic radiation. In the RIPF mouse model, an assessment was conducted on survival rates, body weight, computed tomography features, histological parameters, and changes in gene expression. In vitro experiments were performed to discover the mechanism underlying the therapeutic impact of nintedanib on RIPF. Treatment with nintedanib, administered either two days prior or four weeks after thoracic radiation, significantly alleviated lung pathological changes, suppressed collagen deposition, and improved the overall health status of the mice. Additionally, nintedanib demonstrated significant mitigation of radiation-induced inflammatory responses in epithelial cells by inhibiting the PI3K/AKT and MAPK signaling pathways. Furthermore, nintedanib substantially inhibited fibroblast-to-myofibroblast transition by suppressing the TGF-ß/Smad and PI3K/AKT/mTOR signaling pathways. These findings suggest that nintedanib exerts preventive and therapeutic effects on RIPF by modulating multiple targets instead of a single anti-fibrotic pathway and encourage the further clinical trials to determine the efficacy of nintedanib in patients with RIPF.

STX4 as a potential biomarker for predicting prognosis and guiding clinical treatment decisions in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) represents a frequent subtype of kidney cancer, with the prognosis remaining poor for individuals with metastatic disease. Given its resistance to both radiation and chemotherapy, targeted therapies and immunotherapies have emerged as critical for effective ccRCC treatment. Within this context, the SNARE protein STX4, which is associated with malignant cancer cell migration, provides a promising focus. The underlying mechanism, however, requires further illumination. Furthermore, the influence of STX4 on the ccRCC tumor microenvironment remains to be determined. In our research, we utilized multiple databases and immunohistochemical staining to confirm differential STX4 expression and its prognostic implications. We evaluated the potential tumor-promoting function of STX4 in ccRCC cell lines through molecular studies. Additionally, we conducted functional enrichment analysis to delve deeper into the underlying mechanisms and performed immune infiltration and drug sensitivity analyses to assess the potential of STX4 as a prognostic biomarker and therapeutic target. Our study reveals that STX4 contributes to cancer progression by enhancing AKT expression and stimulating the activation of VEGF signaling pathways. Additionally, STX4 further fosters CD8+ T-cell infiltration and diminishes the percentage of CAFs and M2-TAMs. Our findings suggest that patients presenting higher STX4 levels may exhibit enhanced responsiveness to immunotherapy and higher sensitivity to the medications axitinib and everolimus. Finally, we propose STX4 expression assessment as a novel approach to predict patient response to respective immunotherapies and targeted treatments, hence potentially improving patient outcomes.

FeCoNi molybdenum-based oxides for efficient electrocatalytic oxygen evolution reaction.

The search for highly efficient and inexpensive electrocatalysts is crucial to the advancement of environmentally friendly and sustainable energy sources. Here, adopting a one-step hydrothermal method, we have effectively fabricated a self-supported multi-metal molybdenum-based oxide (FeCoNi-MoO4) on nickel foam (NF). In addition to changing the catalyst's microstructure, the introducing of Fe and Co, enhanced its active center count, improved its electronic structure, and in turn reduced the difficulty for high-valence Ni and Fe species to form, which accelerates the oxygen evolution reaction (OER) kinetics by promoting the development of the actual active materials, NiOOH and FeOOH. FeCoNi-MoO4 has outstanding OER performance, requiring just 204 mV overpotentials at 10 mA cm-2 and 271 mV at 100 mA cm-2. Its exceptional OER kinetics at both low and high currents are indicated by a Tafel slope of 50.6 mV dec-1, which is attributed to the combined effect of its multi-metal composition and a higher number of active sites. Moreover, the FeCoNi-MoO4 electrode was operated continuously for over 48 h. Furthermore, the density functional theory (DFT) results demonstrated that the introducing of Fe and Co, which quickens the rate of electron transfer during the electrocatalytic process, improves the ability of oxygen intermediate species to adsorb, and ultimately lowers the overpotential, is responsible for the increased electrocatalytic activity of FeCoNi-MoO4. This work offers hope for further developments in the sector by proposing an efficient approach for creating multi-active electrocatalysts that are stable, economical, and efficient.

ATM inhibition enhance immunotherapy by activating STING signaling and augmenting MHC Class I.

Accumulating evidence supports the concept that DNA damage response targeted therapies can improve antitumor immune response by increasing the immunogenicity of tumor cells and improving the tumor immune microenvironment. Ataxia telangiectasia mutated (ATM) is a core component of the DNA repair system. Although the ATM gene has a significant mutation rate in many human cancers, including colorectal, prostate, lung, and breast, it remains understudied compared with other DDR-involved molecules such as PARP and ATR. Here, we found that either gene knockout or drug intervention, ATM inhibition activated the cGAS/STING pathway and augmented MHC class I in CRC cells, and these effects could be amplified by radiation. Furthermore, we found that MHC class I upregulation induced by ATM inhibition is dependent on the activation of the NFκB/IRF1/NLRC5 pathway and independent of STING. Animal experiments have shown increasing infiltration and cytotoxic function of T cells and better survival in ATM-deficient tumors. This work indicated that ATM nonsense mutation predicted the clinical benefits of radiotherapy combined with immune checkpoint blockade for patients with CRC. It also provides a molecular mechanism rationale for ATM-targeted agents for patients with CRC.

Mass spectrometry-based proteomic landscape of rice reveals a post-transcriptional regulatory role of N6-methyladenosine.

Rice is one of the most important staple food and model species in plant biology, yet its quantitative proteomes are largely uncharacterized. Here we quantify the relative protein levels of over 15,000 genes across major rice tissues using a tandem mass tag strategy followed by intensive fractionation and mass spectrometry. We identify tissue-specific and tissue-enriched proteins that are linked to the functional specificity of individual tissues. Proteogenomic comparison of rice and Arabidopsis reveals conserved proteome expression, which differs from mammals in that there is a strong separation of species rather than tissues. Notably, profiling of N6-methyladenosine (m6A) across the rice major tissues shows that m6A at untranslated regions is negatively correlated with protein abundance and contributes to the discordance between RNA and protein levels. We also demonstrate that our data are valuable for identifying novel genes required for regulating m6A methylation. Taken together, this study provides a paradigm for further research into rice proteogenome.

Efficacy and safety of patients with chronic kidney disease undergoing left atrial appendage closure for atrial fibrillation.

BACKGROUND: The relative safety and efficacy of left atrial appendage closure (LAAC) for atrial fibrillation (AF) in patients with chronic kidney disease (CKD) have not been well defined. To evaluate the results in this cohort, we conducted a systematic review and meta-analysis of observational studies. METHODS: We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to January 2023 for all relevant studies. Our inclusion criteria were met by twelve observational studies that included 61324 patients altogether. RESULTS: Compared with no CKD group, in-hospital mortality (OR: 2.84, 95% CI: 2.12-3.81, p<0.01, I2 = 0%), acute kidney injury (AKI) (OR: 4.39,95% CI:4.00-4.83, P<0.01, I2 = 3%), major bleeding events (OR: 1.44, 95% CI: 1.29-1.60, p<0.01 I2 = 0%), and pericardial effusion/tamponade (OR 1.30; 95% CI 1.13-1.51, p < 0.01; I2 = 0%) were more common in the CKD group, especially in patients with end-stage renal disease (ESRD). No significant difference was observed in the occurrence of stroke (OR: 1.24, 95% CI: 0.86-1.78, P = 0.25, I2 = 0%), LAAC success rates (OR: 1.02, 95% CI: 0.33-3.16, p = 0.97, I2 = 58%) and vascular access complications (OR: 1.13, 95% CI: 0.91-1.39, p = 0.28, I2 = 0%) between the two groups. During the follow-up, there was no difference in the risk of stroke between the two groups. CONCLUSIONS: CKD patients who receive LAAC have a greater risk of in-hospital mortality, AKI, pericardial effusion/tamponade, and major bleeding events than those without CKD, especially in patients with ESRD. No significant difference in the risk of stroke was found in the long-term follow-up after LAAC between the two groups, demonstrating a similar efficacy of LAAC to prevent stroke in CKD patients.

Effects of a mindfulness-based interventions on stress, burnout in nurses: a systematic review and meta-analysis.

Background: Stress in the healthcare environment causes negative effects in nurses such as burnout, anxiety, and depression. The COVID-19 pandemic has resulted in increased pressure on medical staff globally, highlighting the potential benefits of mindfulness-based interventions in reducing nurses' stress levels. Despite numerous studies exploring the effect of mindfulness-based training on nurses, the results remain inconclusive. Objective: To systematically evaluate the impact of mindfulness training on nurse's performance and increase the certainty of existing evidence. Methods: This study searched various databases, including EBSCO, Embase, Web of Science, PubMed, ProQuest, Scopus, Cochrane Online Library, Wanfang, SinoMed, CNKI, and VIP, for randomized controlled trials on the impact of mindfulness-based interventions for nurses up until 02 December 2022. Two investigators independently screened and extracted data from the articles, while also assessing the risk of bias. The data was analyzed using RevMan 5.4 software. Results: This review identified 15 studies out of the 2,171 records retrieved, consisting of a total of 1,165 participants who were randomized. Post-intervention analysis provided very-low certainty evidence of moderate effectiveness of mindfulness-based training in reducing stress [standardized mean difference (SMD) = -0.81; 95% confidence interval (CI) = -1.11 to -0.52], with no significant effect on anxiety (SMD = -0.30; 95% CI = -0.72 to 0.13) or depression (SMD = -0.24; 95% CI = -0.55 to 0.07). However, the training was effective in reducing burnout, as demonstrated by the lower scores for emotional exhaustion (SMD = -4.27; 95% CI = -5.94 to -2.59) and depersonalization (SMD = -2.89; 95% CI = -4.24 to -1.54) and higher scores for personal accomplishment (SMD = 2.81; 95% CI = 0.12 to 5.50). There was a sustained improvement in stress levels in the short-term (≤3 months), with delayed benefits for burnout. However, only two studies were available for later follow-ups, and there was no significant evidence of long-term effects. Conclusion: Mindfulness-based training may be a viable intervention for improving the psychological wellbeing of nurses, including reducing stress, burnout. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023387081.

S-Species-Evoked High-Valence Ni2+ δ of the Evolved ß-Ni(OH)2 Electrode for Selective Oxidation of 5-Hydroxymethylfurfural.

An efficient NiSx -modified ß-Ni(OH)2 electrode is reported for the selective oxidation reaction of 5-hydroxymethylfurfural (HMFOR) with excellent electrocatalytic 5-hydroxymethylfurfural (HMF) selectivity (99.4%), conversion (97.7%), and Faradaic efficiency (98.3%). The decoration of NiSx will evoke high-valence Ni2+ δ species in the reconstructed ß-Ni(OH)2 electrode, which are the real active species for HMFOR. The generated NiSx /Ni(OH)O modulates the proton-coupled electron-transfer (PCET) process of HMFOR, where the electrocatalytically generated Ni(OH)O can effectively trap the protons from the CHO end in HMF to realize electron transfer. The oxygen evolution reaction (OER) competes with the HMFOR when NiSx /Ni(OH)O continues to accumulate, to generate the NiSx /NiOx (OH)y intermediate. Density functional theory (DFT) calculations and experimental results verify that the adsorption energy of HMF can be optimized through the increased NiSx composition for more efficient capture of protons and electrons in the HMFOR.

Combining radiation and the ATR inhibitor berzosertib activates STING signaling and enhances immunotherapy via inhibiting SHP1 function in colorectal cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown a moderate response in colorectal cancer (CRC) with deficient mismatch repair (dMMR) functions and poor response in patients with proficient MMR (pMMR). pMMR tumors are generally immunogenically "cold", emphasizing combination strategies to turn the "cold" tumor "hot" to enhance the efficacy of ICIs. ATR inhibitors (ATRi) have been proven to cooperate with radiation to promote antitumor immunity, but it is unclear whether ATRi could facilitate the efficacy of IR and ICI combinations in CRCs. This study aimed to investigate the efficacy of combining ATRi, irradiation (IR), and anti-PD-L1 antibodies in CRC mouse models with different microsatellite statuses. METHODS: The efficacy of combining ATRi, IR, and anti-PD-L1 antibodies was evaluated in CRC tumors. The tumor microenvironment and transcriptome signatures were investigated under different treatment regimens. The mechanisms were explored via cell viability assay, flow cytometry, immunofluorescence, immunoblotting, co-immunoprecipitation, and real-time quantitative PCR in multiple murine and human CRC cell lines. RESULTS: Combining ATRi berzosertib and IR enhanced CD8+ T cell infiltration and enhanced the efficacy of anti-PD-L1 therapy in mouse CRC models with different microsatellite statuses. The mechanistic study demonstrated that IR + ATRi could activate both the canonical cGAS-STING-pTBK1/pIRF3 axis by increasing cytosolic double-stranded DNA levels and the non-canonical STING signaling by attenuating SHP1-mediated inhibition of the TRAF6-STING-p65 axis, via promoting SUMOylation of SHP1 at lysine 127. By boosting the STING signaling, IR + ATRi induced type I interferon-related gene expression and strong innate immune activation and reinvigorated the cold tumor microenvironment, thus facilitating immunotherapy. CONCLUSIONS: The combination of ATRi and IR could facilitate anti-PD-L1 therapy by promoting STING signaling in CRC models with different microsatellite statuses. The new combination strategy raised by our study is worth investigating in the management of CRC.

[Impact of pesticide use on the density of Anopheles anthropophagus and malaria incidence].

OBJECTIVE: To investigate the impact of the application of chemical pesticides on the distribution of Anopheles anthropophagus in rice fields and the malaria incidence. METHOD: Twenty-four villages from 16 counties in the provinces of Zhejiang, Sichuan and Guangxi were chosen for the surveys in the period of 1983-1987. For the survey of An. anthropophagus, indoor human bait trapping until midnight and catching the mosquitoes in all the nets in early morning were carried out to get the density and population ratio of the mosquitoes. Historical data on Anopheles spp., malaria incidence, acreage of the single or double season cropping of rice and on the quantity of chemical pesticide used in rice fields were collected from the study areas. RESULTS: In Hang-jia-hu region of Zhejiang Province, double season rice cropping was performed at that time, the quantity of pesticides used in 1973 was 45 kg/hm2, which was as high as 50 times than that in the 1950s. The density of An. anthropophagus decreased yearly, no An. anthropophagus could be found at 11 survey points in late 1980s. The malaria incidence dropped to less than 1 per 10000. In Leshan and Yibin areas of Sichuan Province, the major cultivation was single cropping, pesticides were applied in paddy fields since 1960s, and the average quantity of pesticides used was 8.6 kg/hm2 during 1970s-1980s. No significant difference on the density of An. anthropophagus was revealed between 1980s (86.2%) and 1960s (82.2%) (chi2=0.63, P>0.05). After mid-1980s, pesticide use gradually increased, and reached to 18.18 kg/hm2 in average in the years after 2000. The density of An. anthropophagus decreased, no An. anthropophagus was found in 2010 in the area surveyed and no malaria cases were reported as well. With double season cropping in Huanjiang County of Guangxi, the pesticide amount consumed was 1.79kg/hm2, 25.13 kg/hm2 and 7.68 kg/hm2 in paddy fields in 1960s, 1970s, and 1980s, respectively. The proportion of An. anthropophagus in anophelines was 52%(1 747/3 392) in the beginning of the 1980s. After the year 2000, the average pesticide use increased to 20.38 kg/hm2 in paddy fields. It was difficult to find An. anthropophagus in human dwellings after 2008. The average annual malaria incidence dropped to 0.14 per 10 000. CONCLUSION: Change of farming activities and especially use of chemical pesticides in high quantity at the rice fields undermine the breeding environments of An. anthropophagus, greatly reduce the mosquito population and therefore the malaria incidence.