Regional Functionalization Molecular Design Strategy: A Key to Enhancing the Efficiency of Multi-Resonance OLEDs.

Herein, we propose a regional functionalization molecular design strategy that enables independent control of distinct pivotal parameters through distinct segments of the molecule. Three novel blue emitters A-BN, DA-BN, and A-DBN, have been successfully synthesized by integrating highly rigid and three-dimensional adamantane-containing spirofluorene units into the MR framework. These molecules form two distinctive functional parts: part 1 comprises a boron-nitrogen (BN)-MR framework with adjacent benzene and fluorene units forming a central luminescent core characterized by an exceptionally rigid planar geometry, allowing for narrow FWHM values; part 2 includes peripheral mesitylene, benzene, and adamantyl groups, creating a unique three-dimensional "umbrella-like" conformation to mitigate intermolecular interactions and suppress exciton annihilation. The resulting A-BN, DA-BN, and A-DBN exhibit remarkably narrow FWHM values ranging from 18 to 14 nm and near-unity photoluminescence quantum yields. Particularly, OLEDs based on DA-BN and A-DBN demonstrate outstanding efficiencies of 35.0% and 34.3%, with FWHM values as low as 22 nm and 25 nm, respectively, effectively accomplishing the integration of high color purity and high device performance.

Modulating porous silicon-carbon anode stability: Carbon/silicon carbide semipermeable layer mitigates silicon-fluorine reaction and enhances lithium-ion transport.

Silicon-based material is regarded as one of the most promising anodes for next-generation high-performance lithium-ion batteries (LIBs) due to its high theoretical capacity and low cost. Harnessing silicon carbide's robustness, we designed a novel porous silicon with a sandwich structure of carbon/silicon carbide/Ag-modified porous silicon (Ag-PSi@SiC@C). Different from the conventional SiC interface characterized by a frail connection, a robust dual covalent bond configuration, dependent on SiC and SiOC, has been successfully established. Moreover, the innovative sandwich structure effectively reduces detrimental side reactions on the surface, eases volume expansion, and bolsters the structural integrity of the silicon anode. The incorporation of silver nanoparticles contributes to an improvement in overall electron transport capacity and enhances the kinetics of the overall reaction. Consequently, the Ag-PSi@SiC@C electrode, benefiting from the aforementioned advantages, demonstrates a notably elevated lithium-ion mobility (2.4 * 10-9 cm2·s-1), surpassing that of silicon (5.1 * 10-12 cm2·s-1). The half-cell featuring Ag-PSi@SiC@C as the anode demonstrated robust rate cycling stability at 2.0 A/g, maintaining a capacity of 1321.7 mAh/g, and after 200 cycles, it retained 962.6 mAh/g. Additionally, the full-cell, featuring an Ag-PSi@SiC@C anode and a LiFePO4 (LFP) cathode, exhibits outstanding longevity. Hence, the proposed approach has the potential to unearth novel avenues for the extended exploration of high-performance silicon-carbon anodes for LIBs.

Intracellular calcium dysregulation in heart and brain diseases: Insights from induced pluripotent stem cell studies.

The central nervous system (CNS) plays a role in regulating heart rate and myocardial contractility through sympathetic and parasympathetic nerves, and the heart can impact the functional equilibrium of the CNS through feedback signals. Although heart and brain diseases often coexist and mutually influence each other, the potential links between heart and brain diseases remain unclear due to a lack of reliable models of these relationships. Induced pluripotent stem cells (iPSCs), which can differentiate into multiple functional cell types, stem cell biology and regenerative medicine may offer tools to clarify the mechanisms of these relationships and facilitate screening of effective therapeutic agents. Because calcium ions play essential roles in regulating both the cardiovascular and nervous systems, this review addresses how recent iPSC disease models reveal how dysregulation of intracellular calcium might be a common pathological factor underlying the relationships between heart and brain diseases.

Remediation of phenanthrene contaminated soil by persulphate coupled with Pseudomonas aeruginosa GZ7 based on oxidation prediction model.

Chemical oxidation coupled with microbial remediation has attracted widespread attention for the removal of polycyclic aromatic hydrocarbons (PAHs). Among them, the precise evaluation of the feasible oxidant concentration of PAH-contaminated soil is the key to achieving the goal of soil functional ecological remediation. In this study, phenanthrene (PHE) was used as the target pollutant, and Fe2+-activated persulphate (PS) was used to remediate four types of soils. Linear regression analysis identified the following important factors influencing remediation: PS dosage and soil PHE content for PHE degradation, Fe2+ dosage, hydrolysable nitrogen (HN), and available phosphorus for PS decomposition. A comprehensive model of "soil characteristics-oxidation conditions-remediation effect" with a high predictive accuracy was constructed. Based on model identification, Pseudomonas aeruginosa GZ7, which had high PAHs degrading ability after domestication, was further applied to coupling repair remediation. The results showed that the optimal PS dose was 0.75% (w/w). The response relationship between soil physical, chemical, and biological indicators at the intermediate interface and oxidation conditions was analysed. Coupled remediation effects were clarified using microbial diversity sequencing. The introduction of Pseudomonas aeruginosa GZ7 stimulated the relative abundance of Cohnella, Enterobacter, Paenibacillus, and Bacillus, which can promote material metabolism and energy transformation during remediation.

The use of the self-organizing map (SOM) methodology to study the dissolved organic matter (DOM) in different water body types.

This study investigated the characteristics of dissolved organic matter (DOM) in two distinct water bodies, through the utilization of three-dimensional fluorescence spectroscopy coupled with self-organizing map (SOM) methodology. Specifically, this analysis concentrated on neurons 3, 14, and 17 within the SOM model, identifying notable differences in the DOM compositions of a coal subsidence water body (TX) and the MaChang Reservoir (MC). The humic substance content of DOM TX exceeded that of MC. The origin of DOM in TX was primarily linked to agricultural inputs and rainfall runoff, whereas the DOM in MC was associated with human activities, displaying distinctive autochthonous features and heightened biological activity. Principal component analysis revealed that humic substances dominated the DOM in TX, while the natural DOM in MC was primarily autochthonous. Furthermore, a multiple linear regression model (MLR) determined that external pollution was responsible for 99.11% of variation in the humification index (HIX) of water bodies.

Patient-reported outcomes for the phase 3 FURLONG study of furmonertinib versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer.

Background: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in the FURLONG study. Here we present prespecified secondary endpoints of patient-reported outcomes (PRO). Methods: In this multicentre, double-blind, double-dummy, randomised phase 3 study, patients were 1:1 randomly assigned to receive furmonertinib 80 mg once daily or gefitinib 250 mg once daily. PROs assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and Quality-of-Life Questionnaire Lung Cancer 13 were analysed using a mixed model for repeated measures and time-to-event analyses. A difference in score of 10 points or more was deemed clinically relevant. Findings: Three hundred and fifty-seven patients (furmonertinib group, n = 178; gefitinib group, n = 179) received at least one dose of the study drug, all of whom completed at least one PRO assessment. Statistically significant difference of overall score changes from baseline favoured furmonertinib in physical functioning (between-group difference 2.14 [95% CI 0.25-4.04], p = 0.027), nausea/vomiting (-1.56 [95% CI -2.62 to -0.49], p = 0.004), appetite loss (-2.24 [95% CI -4.26 to -0.23], p = 0.029), diarrhoea (-3.36 [95% CI -5.19 to -1.54], p < 0.001), alopecia (-2.62 [95% CI -4.54 to -0.71], p = 0.007), and pain in other parts (-4.55 [95% CI -7.37 to -1.74], p = 0.002), but not reached clinical relevance. Time to deterioration in physical functioning (hazard ratio 0.63 [95% CI 0.42-0.94], p = 0.021), cognitive functioning (0.73 [95% CI 0.54-0.98], p = 0.034), nausea/vomiting (0.64 [95% CI 0.41-0.99], p = 0.042), appetite loss (0.63 [95% CI 0.43-0.92], p = 0.016), diarrhoea (0.63 [95% CI 0.46-0.85], p = 0.002), dyspnoea (0.72 [95% CI 0.53-0.98], p = 0.034), cough (0.67 [95% CI 0.44-1.00], p = 0.049), dysphagia (0.54 [95% CI 0.35-0.83], p = 0.004), and alopecia (0.62 [95% CI 0.42-0.90], p = 0.012) was longer with furmonertinib versus gefitinib. Interpretation: In patients with locally advanced or metastatic EGFR mutation-positive NSCLC, furmonertinib showed improved scores and delayed deterioration in several functioning and symptoms compared to gefitinib. Funding: Shanghai Allist Pharmaceutical Technology Co., Ltd and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Electric Field Generated at the Millisecond Pulse-Polarized Interface Facilitates the Electrolytic Conversion of SO2 into H2S.

Interfacial electric field holds significant importance in determining both the polar molecular configuration and surface coverage during electrocatalysis. This study introduces a methodology leveraging the varying electric dipole moment of SO2 under distinct interfacial electric field strengths to enhance the selectivity of the SO2 electroreduction process. This approach presented the first attempt to utilize pulsed voltage application to the Au/PTFE membrane electrode for the control of the molecular configuration and coverage of SO2 on the electrode surface. Remarkably, the modulation of pulse duration resulted in a substantial inhibition of the hydrogen evolution reaction (HER) (FEH2 < 3%) under millisecond pulse conditions (ta = 10 ms, tc = 300 ms, Ea = -0.8 V (vs Hg/Hg2SO4), Ec = -1.8 V (vs Hg/Hg2SO4)), concomitant with a noteworthy enhancement in H2S selectivity (FEH2S > 97%). A comprehensive analysis, incorporating in situ Raman spectroscopy, electrochemical quartz crystal microbalance, COMSOL simulations, and DFT calculations, corroborated the increased selectivity of H2S products was primarily associated with the inherently large dipole moment of the SO2 molecule. The enhancement of the interfacial electric field induced by millisecond pulses was instrumental in amplifying SO2 coverage, activating SO2, facilitating the formation of the pivotal intermediate product *SOH, and effectively reducing the reaction energy barrier in the SO2 reduction process. These findings provide novel insights into the influences of ion and molecular transport dynamics, as well as the temporal intricacies of competitive pathways during the SO2 electroreduction process. Moreover, it underscores the intrinsic correlation between the electric dipole moment and surface-molecule interaction of the catalyst.

Smart Bandage Based on a ZIF-8 Triboelectric Nanogenerator for In Situ Real-Time Monitoring of Drug Concentration.

For chronic wounds, frequent replacement of bandages not only increases the likelihood of secondary damage and the risk of cross infection but also wastes medication. Therefore, in situ real-time monitoring of the concentrations of residual drugs in bandages is crucial. Here, we propose a novel strategy that combines a triboelectric nanogenerator (TENG) with medical bandages to develop a smart bandage based on zeolite imidazolate framework TENG. During the process of wound healing, the electrical output of TENG changes with the continuous release of drugs. Based on the correlation between the electrical signal of TENG and drug concentration, the concentration of residual drugs in the bandage can be monitored in real-time in situ, guiding medical staff to replace the bandage at the most appropriate time. The smart bandage based on TENG provides a new strategy for in situ real-time monitoring of drug concentration and also provides an ideal and feasible solution for the field of biomedical drug sensing.

Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical. METHODS: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety. FINDINGS: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1+ PD-1+ CD8+ stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3). CONCLUSIONS: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation. FUNDING: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).

The prognostic value of immune escape-related genes in lung adenocarcinoma.

Background: Lung cancer is one of the most common cancers in humans, and lung adenocarcinoma (LUAD) has become the most common histological type of lung cancer. Immune escape promotes progression of LUAD from the early to metastatic late stages and is one of the main obstacles to improving clinical outcomes for immunotherapy targeting immune detection points. Our study aims to explore the immune escape related genes that are abnormally expressed in lung adenocarcinoma, providing assistance in predicting the prognosis of lung adenocarcinoma and targeted. Methods: RNA data and related clinical details of patients with LUAD were obtained from The Cancer Genome Atlas (TCGA) database. Through weighted gene coexpression network analysis (WGCNA), 3112 key genes were screened and intersected with 182 immune escape genes obtained from a previous study to identify the immune escape-related genes (IERGs). The role of IERGs in LUAD was systematically explored through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses, which were used to enrich the relevant pathways of IERGs. The least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analysis were used to identify the key prognostic genes, and a prognostic risk model was constructed. Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data (ESTIMATE) and microenvironment cell populations (MCP) counter methods (which can accurately assess the amount of eight immune cell populations and two stromal cell groups) were used to analyze the tumor immune status of the high and low risk subgroups. The protein expression level of the differentially expressed genes in lung cancer samples was determined by using the Human Protein Atlas (HPA) database. A nomogram was constructed, and the prognostic risk model was verified via the Gene Expression Omnibus (GEO) datasets GSE72094 and GSE30219. Results: Twenty differentially expressed IERGs were obtained. GO analysis of these 20 IERGs revealed that they were mainly associated with the regulation of immune system processes, immune responses, and interferon-γ enrichment in mediating signaling pathways and apoptotic signaling pathways; meanwhile, KEGG analysis revealed that IERGs were associated with necroptosis, antigen processing and presentation, programmed cell death ligand 1 (PD-L1) expression and programmed cell death 1 (PD-1) pathway in tumors, cytokine-cytokine receptor interactions, T helper cell 1 (Th1) and Th2 differentiation, and tumor necrosis factor signaling pathways. Using LASSO and Cox regression analysis, we constructed a four-gene model that could predict the prognosis of patients with LUAD, and the model was validated with a validation cohort. The immunohistochemical results of the HPA database showed that AHSA1 and CEP55 had low expression in normal lung tissue but high expression in lung cancer tissue. Conclusions: We constructed an IERG-based model for predicting the prognosis of LUAD. Among the genes identified, CEP55 and AHSA1 may be potential prognostic and therapeutic targets, and reducing their expression may represent a novel approach in the treatment of LUAD.

Tyrosine Kinase Inhibitor Lenvatinib Causes Cardiotoxicity by Inducing Endoplasmic Reticulum Stress and Apoptosis through Activating ATF6, IRE1α and PERK Signaling Pathways.

BACKGROUND: Lenvatinib is a tyrosine kinase inhibitor that can improve progression-free survival in patients with thyroid cancer and hepatocellular carcinoma. However, it is limited by adverse cardiovascular events, including hypertension and cardiac dysfunction. Activation of endoplasmic reticulum stress is involved in cardiomyocyte apoptosis. OBJECTIVE: This study aimed to confirm whether the cardiotoxicity of lenvatinib is associated with endoplasmic reticulum stress by targeting the activating transcription factor 6 (ATF6), inositol- requiring enzyme 1α (IRE1α) and protein kinase RNA-like ER kinase (PERK) signaling pathways. METHODS: Male C57/BL6 mice were intragastric administration with 30 mg/kg/day lenvatinib. Electrocardiography (ECG) and echocardiography were used to detect arrhythmias and cardiac function. Neonatal rat cardiomyocytes were treated with lenvatinib for 48h. Cell counting kit (CCK8), 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFHDA), Hoechst 33258 and dihydrorhodamine 123 were respectively used for evaluating cell viability, the level of reactive oxygen species (ROS), nuclear morphological changes and mitochondrial membrane potential (MMP) level. RESULTS: Lenvatinib remarkably decreased the posterior wall thickness of left ventricle during diastole and systole but caused little decrease to the left ventricular ejection fraction (LVEF, %). Furthermore, lenvatinib greatly prolonged the corrected QT interval (QTc) and altered the morphology of cardiomyocytes. No dramatic difference in fibrosis was found in mouse cardiac slices. Lenvatinib upregulates apoptosis-related protein expression. In addition, lenvatinib increased ERS-related protein expression (GRP78, CHOP, and ATF6) and enhanced PERK phosphorylation. In neonatal rat cardiac myocytes, lenvatinib markedly decreased the viability of cardiomyocytes and induced apoptosis. Furthermore, ROS production increased and MMP decreased. Similar to the mice experiment, lenvatinib caused upregulation of apoptosis-related and ERS-related proteins and increased the phosphorylation levels of PERK and IRE1α. CONCLUSION: Lenvatinib-induced cardiotoxicity is associated with ERS-induced apoptosis by targeting the ATF6, IRE1α, and PERK signaling pathways.

Efficacy and safety of sintilimab in combination with chemotherapy for recurrent extensive-stage small cell lung cancer: a real-world retrospective study.

Background: Immune checkpoint inhibitors (ICIs) no longer are approved for second-line or later treatment of extensive-stage small cell lung cancer (ES-SCLC), and have not been studied in combination with chemotherapy. Exploring the efficacy and safety of second-line or later immunotherapy for ES-SCLC is an urgent clinical question that needs to be addressed, and combination therapies are an important research direction. This study intended to investigate the efficacy and safety of the sintilimab in combination with chemotherapy as a second-line and beyond treatment option for ES-SCLC. Methods: Medical records of patients who received treatment with sintilimab in combination with chemotherapy or chemotherapy alone as a second-line or beyond therapy were retrospectively analyzed. The study evaluated efficacy and safety. Indicators of efficacy included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Safety indicators included adverse events (AEs). Results: This cohort comprised of 46 patients: 24 in the sintilimab combination chemotherapy group and 22 in the chemotherapy group. Chemotherapy received by both groups was either albumin-bound paclitaxel or irinotecan. Compared with the chemotherapy group, the sintilimab combination chemotherapy group had higher ORR and DCR (ORR: 37.5% vs. 9.1%, P=0.04; DCR: 75.0% vs. 40.9%, P=0.04), and significantly prolonged PFS and OS [median PFS (mPFS): 5.07 vs. 2.45 months, P=0.006; median OS (mOS): 14.43 vs. 10.34 months, P=0.009]. Also, there was no significant increase in the incidence of AEs in the sintilimab combination chemotherapy group, which was well tolerated by patients. Conclusions: Sintilimab in combination with chemotherapy is superior to single-agent chemotherapeutic treatment as second-line or later therapy in ES-SCLC patients who have not received prior immunotherapy. These results need to be confirmed in future clinical trials.

The impact of digital finance on young People's health insurance participation decisions in China.

Background: The digital finance era has reshaped young people's lifestyles, risk perceptions and insurance participation decisions. Modern youth have to constantly seek for rational social security support and construct individual protection barriers to adapt to new lifestyles and social structures. China's multi-tiered, universal health insurance system is urgently needed to satisfy young people's flexible needs and rational decision-making. Methods: Based on the micro data from 2011 ~ 2021 Chinese General Social Survey (CGSS), this paper uses macro data from Digital Inclusive Finance Index (DIFI) matching to construct probit and m-logit model to assess the impact of the development of digital finance on Chinese youth whether or not to participate in health insurance, and how they choose the concrete type of health insurance. Results: (1) Baseline regression results shows that digital finance has a significant positive effect on Chinese youth's health insurance participation decisions, and has different effects on choices within health insurance types. Strong support for the conclusions is provided by endogeneity and robustness tests. (2) The results of the heterogeneity analysis reveal that the marginal effect of digital finance on young people's health insurance decisions shows urban-rural differences, divergence in levels of self-rated health. (3) The mechanism analysis results suggest that there are two mechanism paths of digital finance on youth health insurance decisions: the household income effect and the subjective well-being effect, and two moderating effects: employment type and family structure. Conclusion: Highlighting the positive value that digital finance brings to the perception of youth insurance participation and the construction of social security systems, it needs to pay close attention to the dynamic changes in employment security and family structure through data, and explore the socio-psychological fluctuation and demand for social security among modern youth. To provide a way forward to achieve the integration of the health insurance system in China and solve the current problem of health insurance equity.

Effect of a comprehensive geriatric assessment nursing intervention model on older patients with diabetes and hypertension.

BACKGROUND: The Comprehensive Geriatric Assessment (CGA) was introduced late in China and is primarily used for investigating and evaluating health problems in older adults in outpatient and community settings. However, there are few reports on its application in hospitalized patients, especially older patients with diabetes and hypertension. AIM: To explore the nursing effect of CGA in hospitalized older patients with diabetes and hypertension. METHODS: We performed a retrospective single-center analysis of patients with comorbid diabetes mellitus and hypertension who were hospitalized and treated in the Jiangyin Hospital of Traditional Chinese Medicine between September 2020 and June 2022. Among the 80 patients included, 40 received CGA nursing interventions (study group), while the remaining 40 received routine nursing care (control group). The study group's comprehensive approach included creating personalized CGA profiles, multidisciplinary assessments, and targeted interventions in areas, such as nutrition, medication adherence, exercise, and mental health. However, the control group received standard nursing care, including general and medical history collection, fall prevention measures, and regular patient monitoring. After 6 months of nursing care implementation, we evaluated the effectiveness of the interventions, including assessments of blood glucose levels fasting blood glucose, 2-h postprandial blood glucose, and glycated hemoglobin, type A1c (HbA1c); blood pressure indicators such as diastolic blood pressure (DBP) and systolic blood pressure (SBP); quality of life as measured by the 36-item Short Form Survey (SF-36) questionnaire; and treatment adherence. RESULTS: After 6 months, the nursing outcomes indicated that patients who underwent CGA nursing interventions experienced a significant decrease in blood glucose indicators, such as fasting blood glucose, 2-h postprandial blood glucose, and HbA1c, as well as blood pressure indicators, including DBP and SBP, compared with the control group (P < 0.05). Quality of life assessments, including physical health, emotion, physical function, overall health, and mental health, showed marked improvements compared to the control group (P < 0.05). In the study group, 38 patients adhered to the clinical treatment requirements, whereas only 32 in the control group adhered to the clinical treatment requirements. The probability of treatment adherence among patients receiving CGA nursing interventions was higher than that among patients receiving standard care (95% vs 80%, P < 0.05). CONCLUSION: The CGA nursing intervention significantly improved glycemic control, blood pressure management, and quality of life in hospitalized older patients with diabetes and hypertension, compared to routine care.

Full Electron Delocalization across the Cluster in 1,12-bisBMes2-p-carborane Radical Anion.

Conjugation between three-dimensional (3D) carboranes and the attached substituents is commonly believed to be very weak. In this paper, we report that reducing 1,12-bis(BMes2)-p-carborane (B2pCab) with one electron gives a radical anion with a centrosymmetric semiquinoidal structure. This radical anion shows extensive electron delocalization between the two boron centers over the p-carborane bridge due to the overlap of carborane lowest unoccupied molecular orbital (LUMO) and the BMes2 LUMO. Unlike dianions of other C2B10H12 carboranes, which rearrange to a nido-form, two-electron reduction of B2pCab leads to a rearrangement into a basket-shaped intermediate.

Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.

BACKGROUND: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS. METHODS: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were administered intravenously every 3 weeks. The co-primary endpoints were OS and PFS assessed by the independent review committee. FINDINGS: As of April 30, 2022, the median OS was significantly longer in the camrelizumab-chemotherapy group compared to the placebo-chemotherapy group (15.6 [95% confidence interval (CI): 14.0-18.4] vs. 12.6 months [95% CI 11.2-13.8]; hazard ratio [HR]: 0.70 [95% CI 0.58-0.84]; one-sided p < 0.0001), with 3-year OS rates of 25.6% and 12.8% in the two groups, respectively. The 2-year PFS rates were 20.4% in the camrelizumab-chemotherapy group and 3.4% in the placebo-chemotherapy group. Adverse events were consistent with those reported in the interim analysis. Higher PD-L1 expression correlated with extended OS, and multivariate analysis identified sex and prior history of radiotherapy as independent indicators of OS. CONCLUSIONS: The sustained and significant improvement in efficacy with camrelizumab-chemotherapy compared to placebo-chemotherapy, along with the absence of accumulating or delayed toxicities, supports the long-term use of camrelizumab-chemotherapy as a standard therapy in untreated advanced/metastatic ESCC. FUNDING: This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Efficacy and safety of electroacupuncture for insomnia: A systematic review and meta-analysis.

BACKGROUND: Electroacupuncture is often used to treat insomnia. OBJECTIVE: To evaluate the efficacy and safety of electroacupuncture for insomnia. SEARCH STRATEGY: Databases including PubMed, Cochrane Library, Embase, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Data and VIP Full-text e-Journals Database were searched up to January 15, 2023. INCLUSION CRITERIA: Randomized clinical trials were included if they compared the clinical efficacy and safety of electroacupuncture with sham acupuncture, no treatment or usual care (UC) and general acupuncture. DATA EXTRACTION AND ANALYSIS: The full texts of the studies were reviewed to remove ineligible literature. The extracted data included authors, publication year, diagnostic criteria, sample size, population characteristics, interventions and outcomes. The above steps were performed independently by two reviewers and the data were cross-checked. Stata15.0 software was used to analyze the extracted outcome data. For continuous data (Pittsburgh Sleep Quality Index [PSQI] score and Insomnia Severity Index score), weighted mean difference (WMD) was calculated and 95% confidence interval (CI) was reported when the same scale was applied. For dichotomous variables (clinical response rate and adverse events), a meta-analysis was performed using risk ratio (RR) as the effect indicator. RESULTS: Thirty-one trials with 2226 subjects were included. The meta-analysis suggested that electroacupuncture was more effective in improving insomnia compared with the control group (sham acupuncture, no treatment, UC and general acupuncture) (RR = 1.21; 95% CI: [1.16, 1.27]), significantly reducing the PSQI score in insomnia patients after treatment and at follow-up (WMD = -3.23; 95% CI: [-4.29, -2.17]; P < 0.001). There was no significant difference in the incidence of adverse events between the EA and control groups (sham acupuncture and no treatment or UC. RR = 1.48; 95% CI: [0.91, 2.40]; P = 0.117). In addition, the regression results revealed that receiving electroacupuncture for seven to nine weeks provided the best efficacy (P < 0.05). CONCLUSION: Electroacupuncture can significantly promote better sleep quality in insomnia patients and is suitable for the treatment of various types of insomnia. However, the articles included were single-center trials with small sample sizes, and some articles were of poor quality. Therefore, further research is still needed to confirm these findings. Please cite this article as: Xu HY, Wu LN, Zhang Y, Ba T, Zhao XF. Efficacy and safety of electroacupuncture for insomnia: A systematic review and meta-analysis. J Integr Med. 2024; Epub ahead of print.

Lymphocytes in Patients with Chronic Active Epstein-Barr Virus Disease Exhibited Elevated PD-1/PD-L1 Expression and a Prevailing Th2 Immune Response.

Background And Objectives: Chronic active Epstein-Barr virus disease (CAEBV) is a proliferative disease of EBV+ T or natural killer (NK) cells with an unclear pathogenesis. This study aimed to examine the frequency and exhaustion levels of lymphocyte subsets in patients with CAEBV to further investigate the pathogenesis. Methods: Using flow cytometry, we detected the frequency, expression levels of programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1), and EBV infection status of peripheral T subsets and NK cells in patients with CAEBV and healthy individuals. Results: 24 patients and 15 healthy individuals were enrolled in this study. Patients showed notably higher expression levels of PD-1 and PD-L1 in peripheral T subsets and NK cells compared to healthy individuals (P < 0.05). EBV+ lymphocytes exhibited significantly higher PD-L1 expression levels than EBV- lymphocytes. Additionally, the frequency of effector memory T (Tem) cells was significantly increased in patients, and the PD-L1 expression level was positively correlated with the EBV load. Besides, helper T cell 2 (Th2) immune bias, also favoring EBV amplification, was found in patients, including increased Th2 cell frequency, enhanced response capacity, and elevated serum levels of associated cytokines. The distribution and PD-1 expression levels of peripheral T subsets returned to normal in patients who responded to PD-1 blockade therapy. Conclusions: The up-regulation of the PD-1/PD-L1 pathway of peripheral T and NK cells and Th2 immune predominance jointly promoted EBV replication and the development of CAEBV. PD-1 blockade therapy reduced the PD-1 expression level of lymphocytes and helped normalize the distribution of the T subsets.

Marine aquaculture can deliver 40% lower carbon footprints than freshwater aquaculture based on feed, energy and biogeochemical cycles.

Freshwater aquaculture is an increasingly important source of blue foods but produces substantial methane and nitrous oxide emissions. Marine aquaculture, also known as mariculture, is a smaller sector with a large growth potential, but its climate impacts are challenging to accurately quantify. Here we assess the greenhouse gas emissions from mariculture's aquatic environment in global potentially suitable areas at 10 km resolution on the basis of marine biogeochemical cycles, greenhouse gas measurements from research cruises and satellite-observed net primary productivity. Mariculture's aquatic emissions intensities are estimated to be 1-6 g CH4 kg-1 carcass weight and 0.05-0.2 g N2O kg-1 carcass weight, >98% and >80% lower than freshwater systems. Using a life-cycle assessment approach, we show that mariculture's carbon footprints are ~40% lower than those of freshwater aquaculture based on feed, energy use and the aquatic environment emissions. Adoption of mariculture alongside freshwater aquaculture production could offer considerable climate benefits to meet future dietary protein and nutritional needs.

Mitochondrial calcium uniporter knockdown in hippocampal neurons alleviates anxious and depressive behavior in the 3XTG Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive and degenerative disorder accompanied by emotional disturbance, especially anxiety and depression. More and more evidence shows that the imbalance of mitochondrial Ca2+ (mCa2+) homeostasis has a close connection with the pathogenesis of anxiety and depression. The Mitochondrial Calcium Uniporter (MCU), a key channel of mCa2+ uptake, induces the imbalance of mCa2+ homeostasis and may be a therapeutic target for anxiety and depression of AD. In the present study, we revealed for the first time that MCU knockdown in hippocampal neurons alleviated anxious and depressive behaviors of APP/PS1/tau mice through elevated plus-maze (EPM), elevated zero maze (EZM), sucrose preference test (SPT) and tail suspension test (TST). Western blot analysis results demonstrated that MCU knockdown in hippocampal neurons increased levels of glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (vGAT) and GABAA receptor α1 (GABRA1) and activated the PKA-CREB-BDNF signaling pathway. This study indicates that MCU inhibition has the potential to be developed as a novel therapy for anxiety and depression in AD.