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Polychlorinated naphthalenes (PCNs) are detrimental to human health and the environment. With the commercial production of PCNs banned, unintentional releases have emerged as a significant environmental source. However, relevant information is still scarce. In this study, provincial emissions for eight PCNs homologues from 37 sources in the Chinese mainland during the period of 1960-2019 were estimated based on a source-specific and time-varying emission factor database. The results showed that the total PCNs emissions in 2019 reached 757.0 kg with Hebei ranked at the top among all the provinces and iron & steel industry as the biggest source. Low-chlorinated PCNs comprised 90% of emissions by mass, while highly chlorinated PCNs dominated in terms of toxicity, highlighting divergent priorities for mitigating emissions and safeguarding human health. The emissions showed an overall upward trend from 1960 to 2019 driven by emission increase from iron & steel industry in terms of source, and from North China and East China in terms of geographic area. Per-capita emissions followed an inverted U-shaped environmental Kuznets curve while emission intensities decreased with increasing per-capita Gross Domestic Product (GDP) following a nearly linear pattern when log-transformed.

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Animals spend a considerable proportion of their life span at rest. However, resting status has often been overlooked when investigating how species respond to environmental conditions. This may induce a large bias in understanding the local adaptation of species across environmental gradients and their vulnerability to potential environmental change. Here, we conducted an empirical study on montane agamid lizards, combined with mechanistic modeling, to compare elevational variations in body temperature and metabolisms (cumulative digestion and maintenance cost) between resting and active status. Our study on three populations of an agamid lizard along an elevational gradient revealed a trend of decreasing body temperature toward higher elevations, the main contributor of which was resting status of the lizards. Using population-specific reaction norms, we predicted greater elevational variation in hourly and cumulative digestion for resting lizards than for active lizards. Climate-change impacts, estimated as the change in cumulative digestion, also show greater elevational variation when resting status is factored into the analysis. Further, our global analysis of 98 agamid species revealed that in about half of their combined distributional range, the contribution of resting status in determining the elevational variation in cumulative digestion and maintenance cost of lizards was greater than the contribution made by a lizard's active status. Our study highlights the importance of considering resting status when investigating how species respond to environmental conditions, especially for those distributed over tropical and subtropical mountain areas.

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Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome, co-opted into the dynamic regulatory network of cellular potency in early embryonic development. In recent studies, resurgent HERVs' transcriptional activity has been frequently observed in many types of human cancers, suggesting their potential functions in the occurrence and progression of malignancy. However, a dedicated web resource for querying the relationship between activation of HERVs and cancer development is lacking. Here, we have constructed a database to explore the sequence information, expression profiles, survival prognosis, and genetic interactions of HERVs in diverse cancer types. Our database currently contains RNA sequencing data of 580 HERVs across 16246 samples, including that of 6478 tumoral and 634 normal tissues, 932 cancer cell lines, as well as 151 early embryonic and 8051 human adult tissues. The primary goal is to provide an easily accessible and user-friendly database for professionals in the fields of bioinformatics, pathology, pharmacology, and related areas, enabling them to efficiently screen the activity of HERVs of interest in normal and cancerous tissues and evaluate the clinical relevance. The ERVcancer database is available at http://kyuanlab.com/ervcancer/.

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BACKGROUND: Pathophysiological mechanisms underlying cognitive impairment in end-stage renal disease (ESRD) remain unclear, with limited studies on the temporal variability of neural activity and its coupling with regional perfusion. PURPOSE: To assess neural activity and neurovascular coupling (NVC) in ESRD patients, evaluate the classification performance of these abnormalities, and explore their relationships with cognitive function. STUDY TYPE: Prospective. POPULATION: Exactly 33 ESRD patients and 35 age, sex, and education matched healthy controls (HCs). FIELD STRENGTH/SEQUENCE: The 3.0T/3D pseudo-continuous arterial spin labeling, resting-state functional MRI, and 3D-T1 weighted structural imaging. ASSESSMENT: Dynamic (dfALFF) and static (sfALFF) fractional amplitude of low-frequency fluctuations and cerebral blood flow (CBF) were assessed. CBF-fALFF correlation coefficients and CBF/fALFF ratio were determined for ESRD patients and HCs. Their ability to distinguish ESRD patients from HCs was evaluated, alongside assessment of cerebral small vessel disease (CSVD) MRI features. All participants underwent blood biochemical and neuropsychological tests to evaluate cognitive decline. STATISTICAL TESTS: Chi-squared test, two-sample t-test, Mann-Whitney U tests, covariance analysis, partial correlation analysis, family-wise error, false discovery rate, Bonferroni correction, area under the receiver operating characteristic curve (AUC) and multivariate pattern analysis. P < 0.05 denoted statistical significance. RESULTS: ESRD patients exhibited higher dfALFF in triangular part of left inferior frontal gyrus (IFGtriang) and left middle temporal gyrus, lower CBF/dfALFF ratio in multiple brain regions, and decreased CBF/sfALFF ratio in bilateral superior temporal gyrus (STG). Compared with CBF/sfALFF ratio, dfALFF, and sfALFF, CBF/dfALFF ratio (AUC = 0.916) achieved the most powerful classification performance in distinguishing ESRD patients from HCs. In ESRD patients, decreased CBF/fALFF ratio correlated with more severe renal impairment, increased CSVD burden, and cognitive decline (0.4 < |r| < 0.6). DATA CONCLUSION: ESRD patients exhibited abnormal dynamic brain activity and impaired NVC, with dynamic features demonstrating superior discriminative capacity and CBF/dfALFF ratio showing powerful classification performance. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

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BACKGROUND: The acute levodopa challenge test (ALCT) is a universal method for evaluating levodopa response (LR). Assessment of Movement Disorder Society's Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) is a key step in ALCT, which is some extent subjective and inconvenience. METHODS: This study developed a machine learning method based on instrumented Timed Up and Go (iTUG) test to evaluate the patients' response to levodopa and compared it with classic ALCT. Forty-two patients with parkinsonism were recruited and administered with levodopa. MDS-UPDRS III and the iTUG were conducted in both OFF-and ON-medication state. Kinematic parameters, signal time and frequency domain features were extracted from sensor data. Two XGBoost models, levodopa response regression (LRR) model and motor symptom evaluation (MSE) model, were trained to predict the levodopa response (LR) of the patients using leave-one-subject-out cross-validation. RESULTS: The LR predicted by the LRR model agreed with that calculated by the classic ALCT (ICC = 0.95). When the LRR model was used to detect patients with a positive LR, the positive predictive value was 0.94. CONCLUSIONS: Machine learning based on wearable sensor data and the iTUG test may be effective and comprehensive for evaluating LR and predicting the benefit of dopaminergic therapy.

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INTRODUCTION: The effects of exposure to particulate matter and frailty, as well as its exposure-response relationship, have not been effectively explored. This study aimed to explore the association between long-term exposure to particulate matter and frailty state and each dimension in Chinese middle-aged and older adults, in addition to the exposure-response relationship. METHODS: The data were obtained from the National Urban Air Quality Real-Time Dissemination Platform and China Health and Retirement Longitudinal Study (CHARLS). Frailty was measured by a frailty index containing 39 indicators. Annual averages of seven pollutants were calculated from hourly monitoring data. We used multilevel regression modeling to explore the association between long-term exposure to particulate matter and frailty. Meanwhile, we explored the exposure-response relationship based on a multilevel generalized summation model. We performed a sensitivity analysis using a multi-pollution model and a quantile-based g-computation (QGC) model. RESULTS: A total of 15,611 participants were included in the analysis. We find that long-term exposure to PM2.5 was associated with an increased risk of pre-frailty and frailty (all p < 0.05). PMc and PM10 exhibited similar associations. The exposure-response relationship between PM2.5 showed a linear relationship, whereas the exposure-response relationship between PM10, PMc showed a nonlinear relationship. Elevated PM2.5 concentrations showed significant positive associations with the number of chronic disease score, IADL score, and functional limitation status score (all p < 0.05). PM10 and PMc showed similar positive correlations. These results remained robust after sensitivity analyses using a multi-pollution model and QGC model. CONCLUSION: Chronic exposure to particulate matter was significantly associated with increased risk of frailty. The exposure-response relationship between PM2.5 concentration and frailty showed a linear relationship, and the exposure-response relationship between PM10 and PMc showed a nonlinear relationship. Exposure to a mixture of pollutants carried a higher risk of frailty than exposure to a single pollutant.

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Background: Emergency observation unit in China are characterized by a high number of patients, complexity of diseases, and instability of patient conditions, leading to low patient satisfaction. The Kano model is an effective method widely used to identify customer demands and improve service quality to enhance customer satisfaction. However, its application in emergency observation unit has been studied less. This study aims to design a questionnaire based on the Kano model and identify the demands of emergency observation patients to determine priorities for improvements in the emergency observation unit and improve patient satisfaction. Methods: A cross-sectional study was conducted in Guizhou Provincial People's Hospital from March 21st, 2023, to May 20th, 2023. A convenient sampling method was used to recruit 100 patients from the emergency observation unit, who completed a questionnaire designed based on the Kano model to assess their demands for care service. Data were analyzed using IBM SPSS Statistics 28.0 software. The element selection line and sensitivity analysis were used to determine factors for patient service demand improvement. Results: A total of 13 patient service demands for improvement were screened out from 19 service demands, including 1 item of must-be quality (M), 11 item of one-dimensional quality (O), and 1 item of attractive quality (A), These attributes showed significant differences in patients' sociodemographic characteristics. Conclusion: The Kano model is a valuable tool for identifying the characteristics of patients' service demands, and the element screening method can be employed to establish the hierarchy of these demands. These results offer crucial direction for creating forthcoming nursing management initiatives in emergency observation unit.

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BACKGROUND: Breast cancer (BRCA) remains to be among the main causes of cancer-associated mortality in women globally. HGH1 homolog (HGH1) has been reported to be associated with tumor immunity. However, the function of HGH1 in BRCA remains unclear. Therefore, the present study examined the potential role of HGH1 in BRCA. METHODS: The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) were used to obtain RNA-seq data for BRCA. A protein localization of HGH1 was determined by using the Human Protein Atlas (HPA), and immunohistochemistry (IHC) staining revealed an upregulation in the expression of HGH1 in clinical BRCA tissues. Xenograft mice were used to test tumor growth and HGH1 expression in breast cancer cells. The protein interaction information of HGH1 was analyzed using the GeneMANIA website. Based on univariate Cox regression and Kaplan-Meier methods, we evaluated the role of HGH1 in BRCA prognosis. HGH1-related differentially expressed genes were analyzed using GO, KEGG, and GSEA. We also examined the relationship between HGH1 expression, immune checkpoints, and immune infiltration. CCK-8, EdU, and colony formation assays were used to measure cell proliferation, and western blot analysis was used to evaluate HGH1's role in BRCA. RESULTS: IHC results showed that the expression of HGH1 was significantly upregulated in BRCA tissues compared to normal tissues. High levels of HGH1 expression was associated with worse clinical features and a worse prognosis. HGH1 expression was an independent predictor of BRCA outcomes in both univariate and multivariate analyses. Functionally, western blot analysis showed that HGH1 is implicated in cell cycle. As well, knocking down HGH1 significantly reduced BRCA cells' proliferative abilities. Crucially, HGH1 expression levels were positively correlated with Th2 cell infiltration and negatively correlated with Tcm cell infiltration. CONCLUSION: Biomarkers such as HGH1 can reliably predict prognosis in BRCA patients.

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Heparin, a widely studied glycosaminoglycan, plays crucial roles in the regulation of various physiological and pathological processes. Therefore, it's important to develop highly selective and sensitive methods for convenient monitoring of heparin levels in biological systems. We report the design and synthesis of Fe3O4@PDA@MnO2 nanoparticles (FPM-NPs), which exhibit dual enzymatic activities, enabling quantitative detection of heparin. The FPM-NPs feature a unique tri-layer spherical shell structure, possessing both peroxidase-like and oxidase-like activities, and catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence or absence of H2O2. Remarkably, upon co-incubated with heparin, the oxidase activity of FPM-NPs decreases, while the peroxidase activity increases. By leveraging these dual enzymatic properties of FPM-NPs, a highly sensitive and specific colorimetric detection of heparin is achieved, with a detection limit reaching 6.51 nM and a good linear response to quantify heparin ranging 10-800 nM. Additionally, the developed FPM-NPs are successfully applied to measure heparin in fetal bovine serum samples. We also extend this detection method to a paper-based chip, enabling portable detection of heparin through grayscale analysis of mobile phone photographs. The multi-nanozyme-based heparin detection approach provides a new perspective for future research on expanding the application of nanocomposite materials in biomedical detection and analysis.

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To investigate the value of prognostic nutrition index (PNI) and systemic immunoinflammatory index (SII) for predicting pathological responses of patients with advanced gastric cancer (GC) after neo-adjuvant chemotherapy (NACT). The clinicopathological data of 326 patients with advanced GC who received NACT in Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City) from January 2017 to December 2021 were retrospectively collected. The SII and PNI of patients were calculated. The receiver operating characteristics (ROC) curve was leveraged for getting the optimal cutoff values of SII and PNI. The pathological response of patients after NACT, as obtained from their postoperative pathological examinations, was evaluated based on the tumor regression grade (TRG) criteria. Multivariate regression analysis was employed for identifying factors that led to various pathological responses after NACT in advanced GC patients. The log-rank test was utilized for between-group comparison of patients' survival curves. The SII and PNI were 507.45 and 48.48 respectively, and their levels were divided into high and low groups. Pathological response (TRG 0-1) was observed in 66 cases (20.25%), while non-pathological response (TRG 2-3) was observed in 260 cases (79.75%). The results of multivariate logistic regression analysis showed that tumor diameter < 5 cm, ypT T0-T2, ypN N0, chemotherapy regimen XELOX (capecitabine combined with oxaliplatin), SII < 507.45 (P=0.002), PNI > 48.48 were all independent factors affecting the pathological responses of advanced GC patients after NACT (all P < 0.05). With SII and PNI being included, the AUC was 0.821 (95% CI: 0.765-0.876), and the specificity was 87.90% and the sensitivity was 64.20%. The Kaplan-Meier survival curve analysis showed that NACT patients with tumor diameter < 5 cm, ypT T0-T2, ypN N0, XELOX chemotherapy regimen, SII < 507.45 and SII ≥ 507.45 had a higher survival rate. (P < 0.001). Before treatment, tumor diameter < 5 cm, ypT T0-T2, ypN N0, chemotherapy regimen XELOX, SII < 507.45, PNI > 48.48 were all independent factors affecting the pathological response of advanced GC patients after NACT. Moreover, the inclusion of SII and PNI increased the accuracy of predicting the pathological response of patients after NACT.

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Background: The link between glymphatic system function in the brain and alterations in white-matter microstructure among individuals with major depressive disorder (MDD) remains unclear. This study aimed to examine the assessment of glymphatic system function in patients with MDD using the diffusion tensor imaging along the perivascular space (DTI-ALPS) index and to evaluate its association with cerebral-white-matter abnormalities and neuropsychological scores. Methods: From February 2023 to November 2023, this cross-sectional study recruited 35 patients with MDD from the Psychosomatic Diseases Department of the First Affiliated Hospital of Dalian Medical University. In this time period, 23 healthy controls (HCs) were enlisted from the community and matched with the MDD cohort in terms of years of education, gender, and age. All participants underwent magnetic resonance imaging, depression, anxiety, and cognitive assessments. The tract-based spatial statistics (TBSS) analyzed DTI parameters and identified significant clusters. Automated fiber quantification (AFQ) was used to automatically identify fiber bundles with statistical differences. Mann-Whitney tests or two-sample t-tests were used for comparisons. Interobserver consistency of the DTI-ALPS measurements was evaluated using the interclass correlation coefficient (ICC). Partial correlation analyses and linear regression analyses were used to examine relationships. A comparison of the DTI-ALPS index was made between the two groups. Correlations among diffusion characteristics, neuropsychological scores, and the DTI-ALPS index were analyzed. Results: Compared to HCs, patients with MDD exhibited a lower DTI-ALPS score (P=0.001). According to using linear regression analysis, the ALPS index was found to be an independent predictor of the Hamilton Depression Rating Scale [B=-25.32; P=0.001; 95% confidence interval (CI): -40.35 to -11.55], Hamilton Anxiety Rating Scale (B=-33.48; P=0.003; 95% CI: -55.38 to -11.24), and Montreal Cognitive Assessment total score (B=8.59; P=0.008; 95% CI: 2.38 to 14.79). According to the TBSS analysis, there were clusters of increased axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) in patients with MDD as compared to HCs (all P values <0.05). A lower DTI-ALPS score was correlated with higher AD (r=-0.592; P<0.001), MD (cluster 1: r=-0.567, P=0.001; cluster 2: r=-0.581, P<0.001), and RD (r=-0.491; P=0.004) values. AFQ analysis identified the significantly different diffusion indicators in the left cingulum bundle (CB_L), left inferior longitudinal fasciculus (ILF_L), and left uncinate fasciculus (UF_L) between the two groups (all false discovery rate P values <0.05). DTI-ALPS score was negatively correlated with the AD value of CB_L (r=-0.304; P=0.024), ILF_L (r=-0.35; P=0.008), and UF_L (r=-0.354; P=0.008) in AFQ tract-level analysis. In point-wise analysis, the MD value of CB_L at nodes 33 to 36 was negatively correlated with DTI-ALPS score (r ranging from -0.504 to -0.535; P<0.01). Conclusions: Our results indicated a decrease in DTI-ALPS index score in patients with MDD. DTI-ALPS score was associated with depression, anxiety, declined cognitive ability, and white-matter microstructural abnormalities and may thus be a promising biomarker for the partial evaluation of glymphatic system function in patients with MDD.

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We investigate the temperature tunable dual quasi-bound states in the continuum (qBICs) in a silicon/vanadium dioxide (Si/VO2) hybrid metasurface with Q-factor being as large as 9.3 × 106 and 2.8 × 107 by breaking the in-plane C2 symmetry. The far-field scattering of multipoles and near-field distributions confirm that the toroidal dipole and magnetic quadrupole dominate the dual qBICs resonance. The high performance of slow light with ultralarge group index exceeding 5.6 × 105 and the inverse quadratic law between the group index and asymmetric parameter are achieved. By temperature tuning of the VO2 thin film at the sub-10 K scale, a modulation depth of 90% and the ON/OFF ratio exceeding 12.8 dB are obtained. The proposed temperature tunable dual qBICs have potential applications in the fields of tunable slow light, temperature switches, and sensors.

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Metformin (MET) is currently the first-line treatment for type 2 diabetes mellitus (T2DM). However, overdose and long-term use of MET may induce a serious liver injury. What's worse, diagnosis of MET-induced liver injury remains challenging in clinic. Although several probes have been reported for imaging MET-induced liver injury utilizing upregulated hepatic H2S as a biomarker, they are still at risk of nonspecific activation in complex physiological environments and rely on light excitation with limited imaging depth. Herein, we rationally designed and developed a dual-locked probe, DPA-H2S, for precise imaging of MET-induced liver injury by H2S-activated sonoafterglow luminescence. DPA-H2S is a small molecule consisting of a sonosensitizer protoporphyrin IX (PpIX) and an afterglow substrate that is dual-locked with a H2S-responsive 2,4-dinitrobenzene group and a 1O2-responsive electron-rich double bond. When employing DPA-H2S for imaging of MET-induced liver injury in vivo, since the PpIX moiety can produce 1O2 in situ at the liver site under focused ultrasound (US) irradiation, the two locks of DPA-H2S can be specifically activated by the highly upregulated H2S at the liver injury sites and the in situ generated 1O2, respectively. Thus, the sonoafterglow signal of DPA-H2S is significantly turned on, enabling precise imaging of the MET-induced liver injury. In vitro results showed that, through H2S-activated sonoafterglow luminescence, DPA-H2S was capable of imaging H2S with good sensitivity and high selectivity and realized deep tissue imaging (∼20 mm, signal-to-background ratio (SBR) = 3.4). Furthermore, we successfully applied DPA-H2S for precise in vivo imaging of MET-induced liver injury. We anticipate that our dual-locked probe, DPA-H2S, may serve as a promising tool in assisting the diagnosis of MET-induced liver injury in clinics and informing the clinical utilization of MET in the near future.

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BACKGROUND: Jinwei decoction can enhance the anti-inflammatory effect of glucocorticoid (GC) on chronic obstructive pulmonary disease (COPD) by restoring the activity of human histone deacetylase-2 (HDAC2). However the upstream mechanism of Jinwei decoction on HDAC2 expression is not clear. OBJECTIVE: To explore the target of Jinwei decoction to enhance the anti-inflammatory effect of GC on COPD through microRNA155-5p (miR-155-5p) by network pharmacology and experimental verification. METHODS: The TCMSP database was used to screen active ingredients and target genes of Jinwei decoction, and miRWalk2.0 was used to predict downstream target genes of miR-155-5p. COPD-related genes were identified by searching GeneCards, Grugbank and OMIM databases; Venny 2.1 was used to screen intersection genes; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of intersection genes were analyzed by R software. Protein-protein interactions (PPIs) were analyzed by Cytoscape 3.7.2 software to identify core genes. Finally, interactions between main compounds and potential targets were verified by molecular docking. A COPD cell model was established by 5% cigarette smoke extract (CSE)- induced bronchial epithelial cell (BEAS-2B), and the results of network pharmacology were verified by in vitro experiments. RESULTS: Two hundred thirty-one active ingredients, 352 Jinwei decoction drug targets, 5949 miR-155-5p target genes, 8286 COPD target genes, and 127 intersection genes were identified. Twelve core proteins of PPI networks may be involved. GO enrichment analysis showed that regulation of membrane potential， response to steroid hormone, and histone modification were involved; KEGG pathway enrichment analysis concentrated in the PI3K-Akt, mitogen-activated protein kinase (MAPK), HIF-1, and other signaling pathways. The molecular docking results showed that quercetin, luteolin and stigmasterol have higher affinity with PTGS2, HIF1A and AKT1. The results of cell experiments revealed that Jinwei decoction not only enhances the anti- inflammatory effect of GC in the COPD cell model but also reverses the high expression of miR-155-5p、PI3k、Akt, and low expression of HDAC2, thereby inhibiting the inflammatory response of COPD. CONCLUSION: Jinwei decoction can regulate HDAC2 activity and enhance the anti-inflammatory effect of GC on COPD by modulating miR-155-5p. Its mechanism of action may be related to its effect on the PI3K-Akt through miR-155-5p.

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The sluggish kinetics of hydrogen evolution reaction (HER) via water reduction limits the efficiency of alkaline water electrolysis. The HER kinetics is not only intimately related to the catalyst surface structure but also relevant to the cation identity of the electrolyte. The cation dependence also relies on the surface electronic structure and applied potential, but this interrelated effect and its underlying mechanism awaits elucidation. Herein, differently-charged molybdenum sulfide (MoSx) cluster supports ([Mo3S13]2- and [Mo3S7]4+) are utilized to hybridize with the identical metallic Ru centers. The specific electrostatic interaction between MoSx clusters and Ru precursors induces different Ru valences of the hybrids, with a higher valence state for Ru/Mo3S13 endowing a higher activity. The Ru/Mo3S13 and Ru/Mo3S7 exhibited drastically-different cation dependence, in which the charged support determines the local accumulation of cations and resulting water structures. The more negatively-charged Mo3S13 support induces the facile accumulation of cations, especially for less-hydrated K+ cations. The water activation capability by Ru valences and cation accumulation from the support effect in-together determine the cation-dependent alkaline HER activity. This work not only enriches the understanding about the cation-dependent HER mechanism but also shines a light on the rational optimization strategy of electrode/electrolyte interfaces.

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The transition metal-catalyzed asymmetric hydro-functionalization of 1,3-dienes has been well explored, but most reactions focus on electron-neutral substrates in an intermolecular manner. Here we first demonstrate that readily available 2,4-dienyl hydrazones and oximes can be efficiently utilized in the hydro-cyclization reaction under co-catalysis of a Brønsted acid and a chiral palladium complex, furnishing multifunctional dihydropyrazones and dihydroisoxazoles, respectively. Diverse substitution patterns for both types of electron-deficient diene compounds are tolerated, and corresponding heterocycles were generally constructed with moderate to excellent enantioselectivity, which can be elaborated to access products with higher molecular complexity and diversity. Control experiments and density functional theory calculations support that α-regioselective protonation of dienyl substrates by acid and concurrent π-Lewis base activation of Pd0 complex is energetically favoured in the formation of active π-allylpalladium intermediates, and an outer-sphere allylic amination or etherification mode is adopted to deliver the observed cyclized products enantioselectively.

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Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition regarded as a major risk factor for colitis-associated cancer. However, the underlying mechanisms of IBD remain unclear. First, five GSE data sets available in GEO were used to perform 'batch correction' and Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs). Candidate molecules were identified using CytoHubba, and their diagnostic effectiveness was predicted. The CIBERSORT algorithm evaluated the immune cell infiltration in the intestinal epithelial tissues of patients with IBD and controls. Immune cell infiltration in the IBD and control groups was determined using the least absolute shrinkage selection operator algorithm and Cox regression analysis. Finally, a total of 51 DEGs were screened, and nine hub genes were identified using CytoHubba and Cytoscape. GSE87466 and GSE193677 were used as extra data set to validate the expression of the nine hub genes. CD4-naïve T cells, gamma-delta T cells, M1 macrophages and resting dendritic cells (DCs) are the main immune cell infiltrates in patients with IBD. Signal transducer and activator of transcription 1, CCR5 and integrin subunit beta 2 (ITGB2) were significantly upregulated in the IBD mouse model, and suppression of ITGB2 expression alleviated IBD inflammation in mice. Additionally, the expression of ITGB2 was upregulated in IBD-associated colorectal cancer (CRC). The silence of ITGB2 suppressed cell proliferation and tumour growth in vitro and in vivo. ITGB2 resting DCs may provide a therapeutic strategy for IBD, and ITGB2 may be a potential diagnostic marker for IBD-associated CRC.

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Previous studies have demonstrated that the combination of photodynamic therapy, photothermal therapy and chemotherapy is highly effective in treating hepatocellular carcinoma (HCC). However, the clinical application of this approach has been hindered by the lack of efficient and low-toxicity drug delivery platforms. To address this issue, we developed a novel biomimetic nanocarrier platform named ZID@RM, which utilizes ZIF8 functional nanoparticles encapsulated with macrophage membrane and loaded with indocyanine green and doxorubicin. The bionic nanocarrier platform has good biocompatibility, reducing the risk of rapid clearance by macrophages and improving the targeting ability for HCC cells. Under the dual regulation of acidity and infrared light, ZID@RM stimulated the generation of abundant reactive oxygen species within HCC cells, induced tumor cell pyroptosis and promoted the release of damage-associated molecular patterns to induce immune responses. In the future, this technology platform has the potential to provide personalized and improved healthcare by using patients' own macrophage membranes to create an efficient drug delivery system for tumor therapy.Graphical abstract Scheme 1 Schematic representation of the synthesis of a biomimetic nanomedicine delivery platform (ZID@RM) and its application in tumor imaging-guided combination therapy.

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Molecular tunneling junctions based on self-assembled monolayers (SAMs) have demonstrated rectifying characteristics at the nanoscale that can hardly be achieved using traditional approaches. However, defects in SAMs result in high leakage when applying bias. The poor performance of molecular diodes compared to silicon or thin-film devices limits their further development. In this study, we show that incorporating "mixed backbones" with flexible-rigid structures into molecular junctions can dynamically block tunneling currents, which is difficult to realize using non-molecular technology. Our idea is achieved by the interaction between interfacial dipole moments and electric field, triggering structured packing in SAMs. Efficient blocking of leakage by more than an order of magnitude leads to a significant enhancement of the rectification ratio to the initial value. The rearrangement of supramolecular structures has also been verified through electrochemistry and electroluminescence measurements. Moreover, the enhanced rectification is extended to various challenging environments, including endurance measurements, bending of electrodes, and rough electrodes, thus demonstrating the feasibility of the dynamic behavior of molecules for practical electronic applications.