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Abstract Objective Ginkgo diterpene lactone meglumine (GDLM) could improve the functional outcome after acute ischemic stroke (AIS). This study aimed to investigate the efficacy of GDLM on the quality of life in patients with AIS in China. Methods This is a post hoc analysis of Efficacy and Safety of Ginkgo Diterpene Lactone Meglumine in Acute Ischemic Stroke trial. The quality of life was measured using the EuroQoL questionnaire, including EQ-5D and EQ visual analogue scale (EQ-VAS). The primary outcomes were changes in EQ-5D and EQ-VAS from baseline to day 14 and day 90 after randomization. Results A total of 3219 patients with completed data on outcomes were enrolled, with median age of 63 years (interquartile range, 55–70) and 2,067 (64.2%) men. GDLM was associated with a significant decrease in scores of ED-5Q components (from 0 [no problem] to 3[extreme problem]), the mean difference between GDLM and placebo group was -0.14 for mobility, -0.11 for usual activities and self-care, -0.09 for pain/discomfort, and -0.34 for anxiety/depression on day 14, respectively. Similar results were observed on day 90. Additionally, there was statistically significant difference of changes in EQ-VAS between the GDLM group and the placebo group from baseline to day 14 (mean difference, 1.70; 95% confidence interval [CI], 0.78–2.62; P = 0.0003) and to day 90 after randomization (mean difference, 3.29; 95% CI, 2.37–4.22; P

This study investigated a screening method for assessing driving ability in participants aged ≥65 years, focusing on physical function, specifically handgrip strength (HGS). Quantitative validation analysis revealed a negative correlation between HGS and age and a weak positive correlation between rate of change in HGS and driving simulator score change. The accident rate was slightly higher among individuals with low HGS, though further validation is necessary. Additionally, qualitative validation highlighted individual differences influenced by exercise frequency and social participation. Consequently, we recommend that evaluation methods consider these individual variations, especially when assessing driving ability in individuals with lower HGS.

Abstract Background The impact of polycyclic aromatic hydrocarbons (PAHs) on lung function has garnered attention, but studies mostly focus on individual effect. This study investigates urinary PAH metabolites as biomarkers of exposure and assesses the relationships between single and combined exposures to nine urinary PAH metabolites and lung function in adults. Methods Data from 4040 adults in the 2007–2012 National Health and Nutrition Examination Survey (NHANES) were analyzed. Weighted generalized linear models estimated the effects of individual PAH metabolites on lung function. Additionally, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were employed to evaluate the combined impacts of multiple PAH metabolites. Results Analyses of individual PAH metabolites revealed negative associations with lung function, excluding forced vital capacity (FVC). The WQS, qgcomp, and BKMR models consistently showed that exposure to multiple PAH metabolites was associated with lung function decrease. WQS indicated that 2-hydroxynaphthalene (2-NAP) was the largest contributor to the reductions in forced expiratory volume in 1 s (FEV1), FVC, peak expiratory flow (PEF), and forced expiratory flow from 25 to 75% of FVC (PEF25-75%). Additionally, 1-hydroxypyrene (1-PYR) was the primary PAH metabolite contributing to the decreases in FEV1/FVC and fractional exhaled nitric oxide (FeNO). The combined effect of urinary PAH metabolites did not affect FVC in the current smokers or FeNO in nonsmokers, but decreased FEV1/FVC in current smokers. Conclusion This study strengthens the negative relationships between multiple PAH metabolites exposure and lung function in adults. Given the limitations of this study, including the lack of knowledge of other exposure pathways and the uncertainty of urinary metabolites, further research is necessary to explore the mechanisms underlying these associations and to address the limitations in exposure assessment.

Hyper-uric acid (UA)-induced kidney injury (HAKI) is caused by the deposition of excess blood UA into the kidneys. We confined molecules of uricase (URI), catalase (CAT), and curcumin (Cur) to a single structure (UC/Cur) while retaining their enzymatic activities via a cross-linking complexation reaction between tannic acid and FeCl3 for treating HAKI. Simultaneously, bovine serum albumin (BSA)-UC/Cur nanoparticles were successfully prepared by interlinking the disulfide bonds of BSA with the enzyme complex via Tris(2-carboxyethyl) phosphine(TCEP) to form sulfhydryl groups. BSA-UC/Cur significantly attenuated MSU-induced NLRP3 inflammasome pathway activation and apoptosis in NRK-52e cells by eliminating UA crystals and intracellular reactive oxygen species. More importantly, treatment with BSA-UC/Cur stabilized blood UA concentrations and lowered proximal tubular protein levels, mitochondrial swelling, and fibrotic areas, renducing the expression of matrix metalloproteinase (MMP)2, MMP9, and NLRP3 while, increasing the expression of tight-junction proteins ZO1 and occludin as well as that of TIMP-1, in HAKI model rats. In addition, BSA-UC/Cur nanoparticles reduced the subpopulation ratios of CD8+ T cells and M1 macrophages and increased those of M2 macrophages and Treg cells. Preliminary in-vivo trials showed that long-term intravenous treatment with BSA-UC/Cur is safe. Therefore, BSA-UC/Cur could be a potential nanotherapeutic agent for HAKI.

Abstract Background Postoperative delirium (POD), an acute and variable disturbance in cognitive function, is an intricate and elusive phenomenon that occurs after cardiac surgery. Despite progress in surgical techniques and perioperative management, POD remains a formidable challenge, imposing a significant burden on patients, caregivers, and healthcare systems. Methods This prospective observational study involved 307 patients who underwent cardiac surgery. Data on the occurrence of delirium, clinical parameters, and postoperative characteristics were collected. A multivariate analysis was performed to assess the relationship between POH and POD. Results Sixty-one patients (21%) developed delirium, with an average onset of approximately 5 days postoperatively and a duration of approximately 6 days. On multivariate analysis, POH was significantly associated with POD, and the adjusted odds ratios indicated that patients with POH were more likely to develop delirium (OR, 5.61; p = 0.006). Advanced age (OR, 1.11; p = 0.002), emergency surgery (OR, 8.31; p = 0.001), and on-pump coronary artery bypass grafting were identified as risk factors of POD. Patients who developed delirium were typically older, more likely to be male, and had higher morbidity rates than those who did not. Conclusion POH is significantly associated with delirium in critically ill patients after cardiac surgery. Surgical complexity and advanced age contribute to the risk of developing POD and poor postoperative outcomes.

Abstract Background Uterine corpus endometrial carcinoma (UCEC) is a prevalent gynecologic malignancy with a favorable prognosis if detected early. However, there is a lack of accurate and reliable early detection tests for UCEC. This study aims to develop a precise and non-invasive diagnostic method for UCEC using circulating cell-free DNA (cfDNA) fragmentomics. Methods Peripheral blood samples were collected from all participants, and cfDNA was extracted for analysis. Low-coverage whole-genome sequencing was performed to obtain cfDNA fragmentomics data. A robust machine learning model was developed using these features to differentiate between UCEC and healthy conditions. Results The cfDNA fragmentomics-based model showed high predictive power for UCEC detection in training (n = 133; AUC 0.991) and validation cohorts (n = 89; AUC 0.994). The model manifested a specificity of 95.5% and a sensitivity of 98.5% in the training cohort, and a specificity of 95.5% and a sensitivity of 97.8% in the validation cohort. Physiological variables and preanalytical procedures had no significant impact on the classifier’s outcomes. In terms of clinical benefit, our model would identify 99% of Chinese UCEC patients at stage I, compared to 21% under standard care, potentially raising the 5-year survival rate from 84 to 95%. Conclusion This study presents a novel approach for the early detection of UCEC using cfDNA fragmentomics and machine learning showing promising sensitivity and specificity. Using this model in clinical practice could significantly improve UCEC management and control, enabling early intervention and better patient outcomes. Further optimization and validation of this approach are warranted to establish its clinical utility.

Abstract Background Camrelizumab plus apatinib have demonstrated robust antitumor activity and safety in patients with advanced cervical cancer (CLAP study; NCT03816553). We herein present the updated long‐term results of the CLAP study and explore potential biomarkers for survival. The outcomes of patients who underwent immune checkpoint inhibitor (ICI) retreatment were also reported. Methods In this phase II trial, eligible patients received camrelizumab 200 mg intravenously every two weeks and apatinib 250 mg orally once daily in 4‐week cycles for up to two years. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Results Between January 21 and August 1, 2019, a total of 45 patients were enrolled. Data were analyzed as of July 31, 2023, representing > 48 months since treatment initiation for all patients. Nine (20.0%) patients completed the 2‐year study. The median duration of response (DOR) was 16.6 months, and 45.0% of patients achieved a DOR of ≥ 24 months. The 12‐month progression‐free survival (PFS) rate was 40.7% (95% confidence interval [CI], 25.2‐55.6), with an 18‐month PFS rate of 37.8% (95% CI, 22.7‐52.8). The median overall survival (OS) was 20.3 months (95% CI, 9.3‐36.9), and the 24‐month OS rate was 47.8% (95% CI, 31.7‐62.3). Age > 50 years, programmed death‐ligand 1 (PD‐L1) combined positive score (CPS) ≥ 1 (versus [vs.] < 1), CPS ≥ 10 (vs. < 1), high tumor mutational burden, and PIK3CA mutations were associated with improved PFS (hazard ratio [HR] < 1) and longer OS (HR < 1). Eight patients who initially responded in the CLAP trial but later experienced disease progression were retreated with ICIs. Among them, 2 (25.0%) achieved a partial response, while 5 (62.5%) had stable disease. Notably, four patients who received retreatment with ICIs survived for more than 45 months. No new safety signals were identified in the present study. Conclusion Long‐term survival follow‐up data demonstrated that camrelizumab plus apatinib has robust, sustained, and durable efficacy in patients with advanced cervical cancer who progress after first‐line platinum‐based chemotherapy. No new safety signals were noted with long‐term treatment.

Abstract Background Triglyceride glucose (TyG) index and its related parameters have been introduced as cost-effective surrogate indicators of insulin resistance, while prospective evidence of their effects on atherosclerotic cardiovascular disease (ASCVD) remained scattered and inconsistent. We aimed to evaluate the association of TyG and its related parameters with new-onset ASCVD, and the predictive capacity were further compared. Method A total of 95,342 ASCVD-free participants were enrolled from the Kailuan study. TyG and its related parameters were defined by fasting blood glucose, triglyceride, body mass index (BMI), waist circumstance (WC) and waist-to-height ratio (WHtR). The primary outcome was incident ASCVD, comprising myocardial infarction (MI) and ischemic stroke (IS). Cox proportional hazard models and restricted cubic spline (RCS) analyses were adopted to investigate the association between each index and ASCVD. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used for comparison of their predictive value for ASCVD. Results During a median follow-up of 15.0 years, 8,031 new cases of ASCVD were identified. The incidence rate of ASCVD increased along with elevated levels of each index, and the relationships were found to be nonlinear in the RCS analyses. The hazard ratio (HR) and 95% confidence interval (95% CI) for ASCVD was 1.39 (1.35, 1.43), 1.46 (1.41, 1.50), 1.50 (1.46, 1.55), and 1.52 (1.48, 1.57) per 1 IQR increase of baseline TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively, and the association were more pronounced for females and younger individuals aged

Abstract Lung cancer is the most common oncological disease worldwide, with non-small cell lung cancer accounting for approximately 85% of lung cancer cases. α-Hederin is a monodesmosidic triterpenoid saponin isolated from the leaves of Hedera helix L. or Nigella sativa and has been extensively studied for its antitumor activity against a variety of tumor cells. It has been suggested that α-Hederin is a potential regulator of autophagy and has high promise for application. However, the specific mechanism and characteristics of α-Hederin in regulating autophagy are not well understood. In this study, we confirmed the potential of α-Hederin application in lung cancer treatment and comprehensively explored the mechanism and characteristics of α-Hederin in regulating autophagy in lung cancer cells. Our results suggest that α-Hederin is an incomplete autophagy inducer that targets mTOR to activate the classical autophagic pathway, inhibits lysosomal acidification without significantly affecting the processes of autophagosome transport, lysosome biogenesis, autophagosome and lysosome fusion, and finally leads to impaired autophagic flux and triggers autophagic damage in NSCLC.

A typical industrial park in the upper reaches of the Yangtze River Economic Belt, which is 70 km from the Chongqing urban center, was used to investigate the occurrence and exposure of harmful volatile organic compounds (VOCs). An exposure risk method and a risk-oriented source apportionment approach were performed to assess the inhalation risks and apportion VOC sources, respectively. The quantitative relationships between risk factors and pollution sources were established, identifying key pathogenic and odorous VOCs. The quantitative emission reduction strategies were developed based on risk thresholds. Residents within the industrial parks face potential health risks due to pathogenic VOCs and nuisance odors, and workers in specific sectors experience two to six times higher risks than those in residential areas. Six risk sources were identified in the industrial park, ranked according to their contribution to VOC concentrations as follows: industrial sewage treatment (IST) (32.59 %), natural gas chemical industry (NGCI) (27.77 %), diesel vehicle exhaust (DVE) (12.04 %), pharmaceutical manufacturing industry (PMI) (11.14 %), chemical raw materials manufacturing (CRMM) (9.96 %), and iron and steel industry (ISI) (6.5 %). Among these, NGCI, IST, and CRMM were the top contributors to pathogenic risks, with contributions of 32.13 %, 29.71 %, and 21.71 % to non-carcinogenic risks, and 18.15 %, 19.87 %, and 27.99 % to carcinogenic risks, respectively. DVE produced significantly higher odor pollution compared to other sources, with intensities that were 3 to 10 times greater. The key pathogenic and odorous VOCs differ by source, resulting in varying control priorities for different VOC species. Reducing emissions from these six sources for 20 high-risk species (e.g., acrolein, 2-chlorotoluene, 1,2-dibromoethane, dichloromethane, and p-diethylbenzene) will simultaneously lower pathogenic and odor risks, with cumulative reduction rates ranging from 4.11 % to 93.75 %. This study provides quantitative control targets for VOCs from a health risk perspective, offering valuable guidance for developing risk management policies in industrial parks.

Abstract Objectives To compare the characteristics of body compositions between metabolic syndrome (MetS) and frailty, and determine the independent and overlapping of MetS and frailty with postoperative complications among older patients with gastric cancer. Design A prospectively observational study. Setting and Participants Two hundred and eighty six older patients from 60 to 80 years undergoing radical gastrectomy for the first time. Measurements MetS was diagnosed by the criteria from the 2020 edition of Chinese guideline for the prevention and treatment of type 2 diabetes mellitus, and frailty was defined by frailty phenotype. An InBody770 impedance analyzer was used to measure body compositions and with 10 fat‐ and muscle‐related indicators being included in this study. Based on the presence of frailty and MetS, patients were divided into the frailty group, MetS group, frailty+MetS group, and normal group, and the body compositions indicators of these groups were compared. Clavien–Dindo classification was used to grade the severity of postoperative complications. Univariate and multivariate regression models were performed to explore the independent and joint association of MetS and frailty with postoperative complications. Results The incidence rate of MetS, frailty, and frailty+MetS being 20.3%, 15.7%, and 4.2% respectively. Compared with the normal group, both fat and muscle compositions were decreased significantly in the frailty group (p 0.05). In contrast, except SVR, the other indicators of the MetS group were higher than the normal group (p 0.05). There was an association of frailty with postoperative total (OR = 3.068, 95% CI: 1.402–6.713) and severe (OR = 9.423, 95% CI: 2.725–32.589) complications, but no association was found of MetS alone. MetS coexisting with frailty was associated with the highest risk of both total (OR = 3.852, 95% CI: 1.020–14.539) and severe (OR = 12.096, 95% CI: 2.183–67.024) complications. Conclusions Both frailty and MetS coexisting with frailty had adverse effects on postoperative complications, which appeared greatly different characteristics in body compositions and therefore reinforced the importance of targeted nutritional or metabolic intervention. Although MetS alone were not significantly associated with postoperative complications, it is essential to focus on the causal relationship and development trend between MetS and frailty to prevent MetS from shifting into frailty, considering the highest risk in their coexistence state.

Background and Purpose Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-HDL-C level and the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence. Methods This study comprised a post hoc analysis of the CHANCE-2 (Ticagrelor or Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial, from which 5,901 patients with complete data on non-HDL-C were included and categorized by median non-HDL-C levels, using a cutoff of 3.5 mmol/L. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days. Results Ticagrelor-aspirin significantly reduced the risk of recurrent stroke in patients with low non-HDL-C (71 [4.8%] vs. 119 [7.7%]; adjusted hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.40–0.74), but not in those with high non-HDL-C (107 [7.3%] vs. 108 [7.6%]; adjusted HR, 0.88; 95% CI, 0.67–1.16), compared with clopidogrel-aspirin (P for interaction=0.010). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin for recurrent stroke decreased as non-HDL-C levels increased. No significant differences in the treatment assignments across the non-HDL-C groups were observed in terms of the rate of severe or moderate bleeding (5 [0.3%] vs. 8 [0.5%] in the low non-HDL-C group; 4 [0.3%] vs. 2 [0.1%] in the high non-HDL-C group; P for interaction=0.425). Conclusion CHANCE-2 participants with low non-HDL-C levels received more clinical benefit from ticagrelor-aspirin versus clopidogrel-aspirin compared to those with high non-HDL-C, following minor ischemic stroke or transient ischemic attack.

Abstract Objective To construct a nutrition support program for middle-aged and elderly patients with acute decompensated heart failure (ADHF) during hospitalization. Methods Based on the JBI Evidence-Based Health Care Model as the theoretical framework, the best evidence was extracted through literature analysis and a preliminary nutrition support plan for middle-aged and elderly ADHF patients during hospitalization was formed. Two rounds of expert opinion consultation were conducted using the Delphi method. The indicators were modified, supplemented and reduced according to the expert’s scoring and feedback, and the expert scoring was calculated. Results The response rates of the experts in the two rounds of consultation were 86.7% and 100%, respectively, and the coefficient of variation (CV) for each round was between 0.00% and 29.67% (all

Abstract Genomic alterations that activate Fibroblast Growth Factor Receptor 2 (FGFR2) are common in intrahepatic cholangiocarcinoma (ICC) and confer sensitivity to FGFR inhibition. However, the depth and duration of response is often limited. Here, we conduct integrative transcriptomics, metabolomics, and phosphoproteomics analysis of patient-derived models to define pathways downstream of oncogenic FGFR2 signaling that fuel ICC growth and to uncover compensatory mechanisms associated with pathway inhibition. We find that FGFR2-mediated activation of Nuclear factor-κB (NF-κB) maintains a highly glycolytic phenotype. Conversely, FGFR inhibition blocks glucose uptake and glycolysis while inciting adaptive changes, including switching fuel source utilization favoring fatty acid oxidation and increasing mitochondrial fusion and autophagy. Accordingly, FGFR inhibitor efficacy is potentiated by combined mitochondrial targeting, an effect enhanced in xenograft models by intermittent fasting. Thus, we show that oncogenic FGFR2 signaling drives NF-κB-dependent glycolysis in ICC and that metabolic reprogramming in response to FGFR inhibition confers new targetable vulnerabilities.

Metatronic circuits extend the concept of subwavelength-scaled lumped circuitry from electronics to optics and photonics, providing a distinctive design paradigm for versatile optical nanocircuits. Here, based on the design of optical nanocircuits using metatronics concept, we introduce a general approach for dispersion synthesis with metasurface to achieve high-selectivity filtering response. We theoretically and numerically demonstrate how to achieve basic circuit lumped elements in metatronics by tailoring the dispersion of metasurface at the frequency of interest. Then, following the Butterworth filter design method, the meticulously designed metasurface, acting as lumped elements, are properly stacked to achieve a near-rectangular filtering response. Compared to the conventional designs, the proposed approach can simultaneously combine high selectivity with the theoretically widest out-of-band rejection in a considerably simple and time-efficient manner of circuit assembly, similar to electronic circuits, without extensive numerical simulations and complex structures. This dispersion synthesis approach provides exciting possibilities for high-performance metasurface design and future integrated circuits and chips.

An integrated computer software system for macromolecular crystallography (MX) data collection at the BL02U1 and BL10U2 beamlines of the Shanghai Synchrotron Radiation Facility is described. The system, Finback, implements a set of features designed for the automated MX beamlines, and is marked with a user-friendly web-based graphical user interface (GUI) for interactive data collection. The Finback client GUI can run on modern browsers and has been developed using several modern web technologies including WebSocket, WebGL, WebWorker and WebAssembly. Finback supports multiple concurrent sessions, so on-site and remote users can access the beamline simultaneously. Finback also cooperates with the deployed experimental data and information management system, the relevant experimental parameters and results are automatically deposited to a database.

Abstract Objective The molecular mechanism of the protective effect of Cordyceps cicadae polysaccharides (CCPs) on renal tubulointerstitial fibrosis in diabetic nephropathy (DN) is still unclear. This study aims to further understand the molecular mechanisms behind the therapeutic benefits of CCP on diabetic nephropathy. Methods Mice were randomly assigned into six groups (n = 8). Cordyceps cicadae polysaccharide dissolved in 5% dimethyl sulfoxide was administered by gavage for 12 consecutive weeks. The CCP doses were divided into low, medium, and high, 75, 150, and 300 mg/kg/day, respectively. The efficacy of CCP was determined by assessing the renal function and histological alterations in diabetic db/db mice. The degree of glomerular mesangial dilatation and sclerosis was evaluated using semiquantitative markers. Cell viability, apoptosis, epithelial–mesenchymal transition (EMT), inflammation, oxidative stress, and mitochondrial reactive oxygen species (ROS) in high glucose (HG)‐cultured MPC5 podocytes were determined. The interaction of miR‐30a‐3p and tripartite motif‐containing protein 16 (TRIM16) was examined by luciferase reporter assay. Western blotting, reverse transcription‐polymerase chain reaction, and immunofluorescence were used to analyze gene and protein expressions. Results The in vivo findings illustrated that CCP may protect mice with type 2 diabetes from inflammation and oxidative damage (P

With the rapid development of seed research, understanding the external structure and characteristics of plants has become essential. Seed coat thickness plays a key role in assessing seed quality in seed reproduction, storage, processing, and research. However, traditional manual measurement methods are labor-intensive, subjective bias, and measurement errors. To solve this problem , we propose an efficient and universal deep learning method, FSUNet. Base on the UNet model, FSUNet introduces a new Full-Scale Information Fusion module (FSIF), adopting 7 × 7 depth-wise separable convolutions and point convolutions to capture remote information, and designs the MConv module. The FSUNet model has 5.109 M parameters, only 14.79% of the UNet model. This research validated the method with a self-constructed corn seed coat segmentation dataset. FSUNet achieved segmentation results of 69.37%, 67.80%, 83.85%, and 85.40% on the self-constructed dataset and the three public datasets, respectively, which are 0.24%, 1.95%, 1.51%, and 0.73% higher than those of the UNet model. Compared to other recent lightweight models like CMUNext, FSUNet shows significant advantages. In addition, we also provide a seed coat thickness measurement algorithm that can obtain stable and accurate measurement results. Through our method, the measurement efficiency and accuracy of seed coat thickness can be significantly improved, providing strong tools and technical support for plant seed research.

Papain-like protease (PLpro) is an attractive anti-coronavirus target. The development of PLpro inhibitors, however, is hampered by the limitations of the existing PLpro assay and the scarcity of validated active compounds. We developed a novel in-cell PLpro assay based on BRET and used it to evaluate and discover SARS-CoV-2 PLpro inhibitors. The developed assay demonstrated remarkable sensitivity for detecting the reduction of intracellular PLpro activity while presenting high reliability and performance for inhibitor evaluation and high-throughput screening. Using this assay, three protease inhibitors were identified as novel PLpro inhibitors that are structurally disparate from those previously known. Subsequent enzymatic assays and ligand-protein interaction analysis based on molecular docking revealed that ceritinib directly inhibited PLpro, showing high geometric complementarity with the substrate-binding pocket in PLpro, whereas CA-074 methyl ester underwent intracellular hydrolysis, exposing a free carboxyhydroxyl group essential for hydrogen bonding with G266 in the BL2 groove, resulting in PLpro inhibition.

Background Recent Mendelian randomization and meta‐analysis highlight the relevance of MCP‐1 (monocyte chemoattractant protein‐1) in stroke. We aimed to investigate the associations between MCP‐1 and clinical outcomes in patients with ischemic stroke or transient ischemic attack and test whether inflammation mediates or jointly contributes to the relationships. Methods and Results A total of 10 700 patients from the Third China National Stroke Registry study were included. Multivariable Cox regression was used for recurrent stroke and all‐cause death, and logistic regression was used for poor functional outcome. Mediation analyses were performed to clarify whether inflammation mediates the associations. After adjusting for potential confounders, low MCP‐1 level (

With the increase in the number of microgrids in the same distribution area usually belong to different subjects of interest, forming a multi-subject game pattern. Considering the interests of distribution networks and microgrids, a distribution network-multi-microgrid master–slave game model is established by selecting distribution networks as game masters and microgrids as game slaves. A master–slave game equilibrium algorithm based on a Kriging metamodel is proposed. The method replaces the microgrid energy internal management model with a proposed Kriging metamodel. In the iterative optimization process, the particle swarm optimization algorithm is used to generate new sampling points and modify the model in a targeted way so as to quickly and accurately obtain the transaction price and output plan of each microgrid. The algorithm does not need all the parameters of the microgrid, which both achieves the purpose of protecting the privacy of the microgrid and avoids a large number of calls to the lower optimization model, effectively reducing the amount of computation and improving the efficiency of the solution. The results show that the overall operating costs of the three microgrids used in the case study are reduced by 1.4%, 4.6%, and 1.6%, respectively, which effectively balances the interests of multiple parties in the microgrid system; the revenue of the distribution network is increased by 50.6%.

Background: The development of effective inhibitors that can inhibit amyloid β (Aβ) peptides aggregation and promote neurite outgrowth is crucial for the possible treatment of Alzheimer’s disease (AD). Lobaria (Schreb.) Hoffm., a traditional Chinese medicine used in Himalaya region for inflammatory diseases, contains depsides/depsidones (DEPs) such as gyrophoric acid, norstictic acid, and stictic acid known for their anti-cancer and anti-inflammation properties.Methods:Lobaria extracts were analyzed using HPLC to identify DEPs and establish standards. The inhibitory effects of Lobaria on Aβ42 fibrillization and depolymerization were assessed using various approaches with biophysical and cellular methods. The neuroprotective activity of Lobaria extracts and its DEPs aganist Aβ-mediated cytotoxicity was also evaluated.Results: Norstictic and stictic acid were found in the water extract, while norstictic, stictic, and gyrophoric acid were detected in the ethanol extract of Lobaria. Both extracts, and their DEPs effectively inhibited Aβ42 fibrillation and disaggregate mature Aβ42 fibrils. Notably, the ethanol extract showed superior inhibitory effect compared to the water extract, with gyrophoric acid being the most effective DEPs. Additionally, herbal extract-treated Aβ42 aggregation species significantly protected neuronal cells from Aβ42-induced cell damage and promoted neurite outgrowth.Conclusion: This study is the first to investigate the effect of Lobaria on Aβ42 and neuronal cell in AD. Given that Lobaria is commonly used in ethnic medicine and food with good safety records, our findings propose that Lobaria extracts and DEPs have potential as neuroprotective and therapeutic agents for AD patients.

To explore the mechanism of the refinement and toughening of Nb-Si-based composites with different Y contents, Nb-16Si-20Ti-2ZrC-(0, 0.05, 0.1, 0.5) Y composites were prepared by arc melting. The results show that Y has a positive effect on the shift of the eutectic point and promotes it moving to the low Si side. Adding 0.1 at.% Y refines the Nbss phase from 38.7 to 11.2 μm. Y2O3 forms due to the strong affinity of Y to O. The edge-to-edge model predicted that there was no phase relationship between Y2O3 and Nbss and primary γ-(Nb,X)5Si3, which was verified by TEM. Y refines the Nbss and the Nbss/γ-(Nb,X)5Si3 cluster with compositional supercooling. As Y content increased, the fracture toughness at room temperature increased and decreased. When the Y content was 0.1 %, the KQ value reached 17.2 MPa·m1/2. The internal oxygen consumption of Y and the refinement of Nbss lead to the toughness improvement of the Nbss phase, promoting the formation of a large number of dimples. Microcracks form in the fine γ-(Nb,X)5Si3 of eutectoid cluster, which hinder the primary crack growth and enhance the ambient fracture toughness. These findings are of great significance for the further development of high-performance Nb-Si-based matrix composites.

Sclerotinia rot is a serious disease that occurs on Zephyranthes candida. A thorough understanding of the pathogenic fungal species and understanding the biological characteristics are important for controlling sclerotinia. Fungal strains were isolated from the diseased leaves of Z. candida through tissue isolation. Koch’s hypothesis screened pathogenic strains by pathogenicity of healthy leaves, including re-isolation and identification. A multigene phylogenetic tree was constructed by extracting genomic DNA from pathogenic strains and measuring the nucleotide sequences at four sites, including the internal transcribed spacer (ITS), RNA polymerase II second largest subunit (RPB2), glyceraldehyde-3-phosphate dehydrogenase (G3PDH), and heat shock protein 60 (HSP60). Morphological characteristics of the fungal structures were evaluated through microscopic analysis. The growth of pathogens was observed and recorded under different pH, different temperatures, different carbon sources and different nitrogen sources to clarify their biological characteristics. Representative strains D7, D13, X4, and X15 infected Z. candida and caused sclerotinia rot. At the beginning of the culture, white flocculent fungal hyphae appeared on the potato dextrose agar (PDA) medium, and black spherical to irregular-shaped sclerotia appeared at the edge of the colony after 7 days. The diameter of the sclerotia was 2.4–8.6 mm and 0.4–0.9 mm, respectively. One sclerotium was able to germinate from 1 to 5 apothecia. Ascus were cylindrical or spindle-shaped, with a size of 110.0–120.0 × 9.2–11.6 μm. One ascus contained eight colorless, oval ascospores, with a size of 8.4–12.0 × 4.5–5.5 μm. Based on the phylogenetic tree constructed with the gene sequences for ITS, G3PDH, HSP60, and RPB2, D7 and D13 shared 99% homology with sclerotinia sclerotiorum, whereas X4 and X15 shared 99% homology with sclerotinia minor. S. sclerotiorum growth was more suitable when the culture temperature was 15°C–25°C, pH 5.0, carbon source was maltose and nitrogen source was yeast powder. S. minor growth was more suitable when the culture temperature was 15°C, pH 5.0, the carbon source was glucose, and the nitrogen source was yeast powder. The results identified the pathogens as S. sclerotiorum and S. minor. To the best of our knowledge, this is the first report of S. sclerotiorum and S. minor causing sclerotinia rot on Z. candida. We herein aimed to identify the causal agent of sclerotinia rot of Z. candida in China based on morphological characteristics, molecular identification, and pathogenicity tests. Performed the experiments on the biological characteristics, to understand the law of disease occurrence. We also evaluated methods for the effective control of this disease. Our findings provide support for further studies on the pathogenesis mechanism of sclerotinia rot.

ABSTRACT Naphthoquine is a promising candidate for antimalarial combination therapy. Its combination with artemisinin has demonstrated excellent efficacy in clinical trials conducted across various malaria-endemic areas. A co-formulated combination of naphthoquine and azithromycin has also shown high clinical efficacy for malaria prophylaxis in Southeast Asia. Developing new combination therapies using naphthoquine will provide additional arsenal responses to the growing threat of artemisinin resistance. Furthermore, due to its long half-life, the possible interaction of naphthoquine with other drugs also needs attention. However, studies on its pharmacodynamic interactions with other drugs are still limited. In this study, the in vitro interactions of naphthoquine with ivermectin, atovaquone, curcumin, and ketotifen were evaluated in the asexual stage of Plasmodium falciparum 3D7. By using the combination index analysis and the SYBR Green I-based fluorescence assay, different interaction patterns of selected drugs with naphthoquine were revealed. Curcumin showed a slight but significant synergistic interaction with naphthoquine at lower effect levels, and no antagonism was observed across the full range of effect levels for all tested ratios. Atovaquone showed a potency decline when combined with naphthoquine. For ivermectin, a significant antagonism with naphthoquine was observed at a broad range of effect levels below 75% inhibition, although no significant interaction was observed at higher effect levels. Ketotifen interacted with naphthoquine similar to ivermectin, but significant antagonism was observed for only one tested ratio. These findings should be helpful to the development of new naphthoquine-based combination therapy and the clinically reasonable application of naphthoquine-containing therapies.IMPORTANCEPharmacodynamic interaction between antimalarials is not only crucial for the development of new antimalarial combination therapies but also important for the appropriate clinical use of antimalarials. The significant synergism between curcumin and naphthoquine observed in this study suggests the potential value for further development of new antimalarial combination therapy. The finding of a decline in atovaquone potency in the presence of naphthoquine alerts to a possible risk of treatment or prophylaxis failure for atovaquone–proguanil following naphthoquine-containing therapies. The observation of antagonism between naphthoquine and ivermectin raised a need for concern about the applicability of naphthoquine-containing therapy in malaria-endemic areas with ivermectin mass drug administration deployed. Considering the role of atovaquone–proguanil as a major alternative when first-line artemisinin-based combination therapy is ineffective and the wide implementation of ivermectin mass drug administration in malaria-endemic countries, the above findings will be important for the appropriate clinical application of antimalarials involving naphthoquine-containing therapies.

Background: Compliance to sublingual immunotherapy (SLIT) is generally low, resulting in reduced short- and long-term clinical efficacy. Compliance is a critical factor determining the success of allergic rhinitis (AR) treatment. Objective: To analyze the compliance of patients with house dust mite (HDM)-induced AR to SLIT and the impact of coronavirus disease 2019 (COVID-19) on compliance. Methods: The clinical data of 3117 patients with HDM-induced AR who started SLIT between July 2018 and April 2022 were retrospectively reviewed. We assessed the reasons for non-compliance and the changes in non-compliance during the COVID-19 pandemic compared to the pre-pandemic period. Results: Of 3117 patients, 507 (16.27%) patients (ages, 5–67 years) were identified as non-compliant. The most common reason for non-compliance was poor efficacy (27.22%). The non-compliance rate was highest during 24–36 months of SLIT (28.13%, 153/544), followed by 12–24 months (7.02%, 91/1296). Non-compliance was significantly higher in adolescents/adults than in children (P = 0.000). Although the generalized linear model analysis indicated that compliance was affected by the COVID-19 pandemic during 3–6 months of SLIT, the overall compliance to SLIT was not significantly affected by the pandemic, according to the Kaplan-Meier survival analysis. Conclusions: The non-compliance rate of SLIT in this study was low, and poor efficacy was the most common reason for non-compliance. The compliance of adolescents/adults was lower than that of children. The COVID-19 pandemic did not significantly impact compliance to SLIT, which is an appropriate strategy for the home treatment of AR patients during major public health events.

Objectives In recent years, economic toxicity has significantly affected the physical and mental health as well as the quality of life of patients with colorectal cancer. However, this issue has not garnered adequate attention from healthcare professionals. This study aims to investigate the experiences of economic toxicity and coping strategies among patients with colorectal cancer fistula. The findings are intended to inform the development of suitable and effective intervention programmes to address economic toxicity within this patient population.Design A descriptive phenomenological approach was employed in this qualitative research, using a semistructured method for data collection and analysis of interview data. Traditional content analysis methods were applied, encompassing coding, categorisation and theme distillation. Data analysis continued until thematic saturation was achieved, with no new themes emerging.Setting Nanjing Medical University Lianyungang Clinical Medical College.Participants A total of 21 patients with colorectal cancer fistula were selected as interview subjects through purposive sampling. The selection took place from May 2022 to May 2023, involving patients during their stay at a tertiary hospital in Lianyungang city, Jiangsu province, China.Results In total, three pieces and eight subthemes were distilled: subjective feelings (worries about treatment costs, concerns about uncertainty about the future, worries about daily life), coping styles (coping alone, unwillingness to help, prepurchased insurance, dealing with illness, giving up treatment, inability to afford costs) and needs and aspirations (need for health policies, need for social support).Conclusions Patients with colorectal cancer fistulae experience economic toxicity, leading to significant impairment in both physical and mental health. Despite employing various coping strategies, healthcare professionals must prioritise addressing the economic toxicity issue in patients. Implementing rational and effective interventions can greatly assist patients in effectively managing economic toxicity.

BackgroundCancer has emerged as a considerable global health concern, contributing substantially to both morbidity and mortality. Recognizing the urgent need to enhance the overall well-being and quality of life (QOL) of cancer patients, a growing number of researchers have started using online mindfulness-based interventions (MBIs) in oncology. However, the effectiveness and optimal implementation methods of these interventions remain unknown. ObjectiveThis study evaluates the effectiveness of online MBIs, encompassing both app- and website-based MBIs, for patients with cancer and provides insights into the potential implementation and sustainability of these interventions in real-world settings. MethodsSearches were conducted across 8 electronic databases, including the Cochrane Library, Web of Science, PubMed, Embase, SinoMed, CINAHL Complete, Scopus, and PsycINFO, until December 30, 2022. Randomized controlled trials involving cancer patients aged ≥18 years and using app- and website-based MBIs compared to standard care were included. Nonrandomized studies, interventions targeting health professionals or caregivers, and studies lacking sufficient data were excluded. Two independent authors screened articles, extracted data using standardized forms, and assessed the risk of bias in the studies using the Cochrane Bias Risk Assessment Tool. Meta-analyses were performed using Review Manager (version 5.4; The Cochrane Collaboration) and the meta package in R (R Foundation for Statistical Computing). Standardized mean differences (SMDs) were used to determine the effects of interventions. The Reach, Effectiveness, Adoption, Implementation, and Maintenance framework was used to assess the potential implementation and sustainability of these interventions in real-world settings. ResultsAmong 4349 articles screened, 15 (0.34%) were included. The total population comprised 1613 participants, of which 870 (53.9%) were in the experimental conditions and 743 (46.1%) were in the control conditions. The results of the meta-analysis showed that compared with the control group, the QOL (SMD 0.37, 95% CI 0.18-0.57; P

Abstract Background Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood. Methods Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single‐cell RNA‐sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single‐cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations. Results There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone‐lysine N‐methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto‐oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues. Conclusions We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti‐inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications. Highlights Single‐cell RNA‐sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A‐mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.

Context: Salvia miltiorrhiza (SM) is a commonly used herb in traditional Chinese medicine (TCM) and has been used in the treatment of pancreatic cancer to relieve the symptom of “blood stasis and toxin accumulation.” Tanshinones (Tan), the main lipophilic constituents extracted from the roots and rhizomes of SM, have been reported to possess anticancer functions in several cancers. But the mechanism of how the active components work in pancreatic cancer still need to be clarified. Objective: In this study, we aimed to investigate the therapeutic potential of Tan in pancreatic cancer and elucidate the underlying mechanisms. Materials and Methods: The viabilities of PANC-1 and Bxpc-3 cells were determined by MTT assay, after treatment with various concentrations of Tan. The apoptotic cells were quantified by annexin V-FITC/PI staining and DAPI staining assays. The expression of relative proteins was used western blotting. Tumor growth was assessed by subcutaneously inoculating cells into C57BL/6 mice. Results: Our experiments discovered that Tan effectively suppressed pancreatic cancer cell proliferation and promoted apoptosis. Mechanistically, we propose that Tan enhances intracellular ROS levels by activating the AKT/FOXO3/SOD2 signaling pathway, ultimately leading to apoptosis in pancreatic cancer cells. In vivo assay showed the antitumor effect of Tan. Conclusion: Tan, a natural compound from Salvia miltiorrhiza , was found to effectively suppress pancreatic cancer cell proliferation and promote apoptosis both in vitro and in vivo. Mechanistically, we propose a positive feedback loop mechanism. These findings provide valuable insights into the molecular pathways driving pancreatic cancer progression.

Introduction: This study aimed to investigate the safety and efficacy of neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitors (ICIs) in patients with locally advanced rectal cancer (LARC). Patients diagnosed with LARC and treated with programmed cell death protein-1 (PD-1) inhibitors were recruited. Methods: Four different treatment strategies were employed in this study: plan A [long-course radiotherapy + PD-1 inhibitor/capecitabine + PD-1 inhibitor/XELOX+ total mesorectal excision (TME)], plan B (long-course radiotherapy + capecitabine + PD-1 inhibitor/XELOX + TME), plan C (short-course radiotherapy + PD-1 inhibitor/XELOX + TME), and plan D (PD-1 inhibitor/XELOX + short-course radiotherapy + TME). The basic information about patients, pathological indicators, adverse events, and efficacy indexes of treatment plans were analyzed. Results: 96.8 % of patients were mismatch repair proficient (pMMR) and only 2 patients belonged to mismatch repair deficient (dMMR). The 2 patients with dMMR showed a pathological complete response (pCR) rate of 100 %, while the pCR rate of pMMR patients was 43.3 %. The overall tumor descending rate reached 79 %, and the anus-retained rate was 88.7 % in all LARC patients. Plan A exhibited the highest pCR rate of 60 %, and plan C had the highest tumor descending rate and anal preservation rate. Radiation enteritis was the most common adverse event in LARC patients after neoadjuvant therapy, and its incidence was the highest in Plan A. Conclusion: Neoadjuvant chemoradiotherapy combined with ICIs demonstrated favorable efficacy and safety in treating LARC patients.

Abstract Soft composite solids are made of inclusions dispersed within soft matrices. They are ubiquitous in nature and form the basis of many biological tissues. In the field of materials science, synthetic soft composites are promising candidates for building various engineering devices due to their highly programmable features. However, when the volume fraction of the inclusions increases, predicting the mechanical properties of these materials poses a significant challenge for the classical theories of composite mechanics. The difficulty arises from the inherently disordered, multi-scale interactions between the inclusions and the matrix. To address this challenge, we systematically investigated the mechanics of densely filled soft elastomers containing stiff microspheres. We experimentally demonstrate how the strain-stiffening response of the soft composites is governed by the critical scalings in the vicinity of a shear-jamming transition of the included particles. The proposed criticality framework quantitatively connects the overall mechanics of a soft composite with the elasticity of the matrix and the particles, and captures the diverse mechanical responses observed across a wide range of material parameters. The findings uncover a novel design paradigm of composite mechanics that relies on engineering the jamming properties of the embedded inclusions.

Abstract Disulfidptosis, a novel form of regulated cell death, occurs due to the aberrant accumulation of intracellular cystine and other disulfides. Moreover, targeting disulfidptosis could identify promising approaches for cancer treatment. Long non-coding RNAs (lncRNAs) are known to be critically implicated in clear cell renal cell carcinoma (ccRCC) development. Currently, the involvement of disulfidptosis-related lncRNAs in ccRCC is yet to be elucidated. This study primarily dealt with identifying and validating a disulfidptosis-related lncRNAs-based signature for predicting the prognosis and immune landscape of individuals with ccRCC. Clinical and RNA sequencing data of ccRCC samples were accessed from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was conducted for the identification of the disulfidptosis-related lncRNAs. Additionally, univariate Cox regression analysis, Least Absolute Shrinkage and Selection Operator Cox regression, and stepwise multivariate Cox analysis were executed to develop a novel risk prognostic model. The prognosis-predictive capacity of the model was then assessed using an integrated method. Variation in biological function was noted using GO, KEGG, and GSEA. Additionally, immune cell infiltration, the tumor mutational burden (TMB), and tumor immune dysfunction and exclusion (TIDE) scores were calculated to investigate differences in the immune landscape. Finally, the expression of hub disulfidptosis-related lncRNAs was validated using qPCR. We established a novel signature comprised of eight lncRNAs that were associated with disulfidptosis (SPINT1-AS1, AL121944.1, AC131009.3, AC104088.3, AL035071.1, LINC00886, AL035587.2, and AC007743.1). Kaplan–Meier and receiver operating characteristic curves demonstrated the acceptable predictive potency of the model. The nomogram and C-index confirmed the strong correlation between the risk signature and clinical decision-making. Furthermore, immune cell infiltration analysis and ssGSEA revealed significantly different immune statuses among risk groups. TMB analysis revealed the link between the high-risk group and high TMB. It is worth noting that the cumulative effect of the patients belonging to the high-risk group and having elevated TMB led to decreased patient survival times. The high-risk group depicted greater TIDE scores in contrast with the low-risk group, indicating greater potential for immune escape. Finally, qPCR validated the hub disulfidptosis-related lncRNAs in cell lines. The established novel signature holds potential regarding the prognosis prediction of individuals with ccRCC as well as predicting their responses to immunotherapy.

Abstract Neointimal hyperplasia is a pathological vascular remodeling caused by abnormal proliferation and migration of subintimal vascular smooth muscle cells (VSMCs) following intimal injury. There is increasing evidence that tRNA-derived small RNA (tsRNA) plays an important role in vascular remodeling. The purpose of this study is to search for tsRNAs signature of neointima formation and to explore their potential functions. The balloon injury model of rat common carotid artery was replicated to induce intimal hyperplasia, and the differentially expressed tsRNAs (DE-tsRNAs) in arteries with intimal hyperplasia were screened by small RNA sequencing and tsRNA library. A total of 24 DE-tsRNAs were found in the vessels with intimal hyperplasia by small RNA sequencing. In vitro, tRF-Glu-CTC inhibited the expression of fibromodulin (FMOD) in VSMCs, which is a negative modulator of TGF-β1 activity. tRF-Glu-CTC also increased VSMC proliferation and migration. In vivo experiments showed that inhibition of tRF-Glu-CTC expression after balloon injury of rat carotid artery can reduce the neointimal area. In conclusion, tRF-Glu-CTC expression is increased after vascular injury and inhibits FMOD expression in VSMCs, which influences neointima formation. On the other hand, reducing the expression of tRF-Glu-CTC after vascular injury may be a potential approach to prevent vascular stenosis.

Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease. Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases, including Parkinson’s and Huntington’s diseases, however, the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated. In the current study, the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated. Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy. In addition, Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro, and suppress amyloid-beta-induced pathology such as paralysis, in a transgenic Caenorhabditis elegans in vivo model. Moreover, genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent. Most importantly, Citri Reticulatae Semen extract was confirmed to improve cognitive impairment, neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice. As revealed by both in vitro and in vivo models, these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.

Abstract Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device’s soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.

Abstract Background High cardiovascular health (CVH) was associated with lower risk of cardiovascular disease (CVD) and longer life expectancy. However, whether life years lived without CVD could increase faster than or at least at the same pace as total lifespan remains unknown. We aimed to explore the associations of CVH status with total life expectancy and life years lived with and without CVD among middle-aged and elderly men and women. Methods We included 65,587 participants aged ≥ 45 years from Kailuan study, who were recruited during June 2006 to October 2007. CVH was scored and classified (low [0–49 points], moderate [50–79 points] and high [80–100 points]) with Life’s Essential 8, incorporating evaluations of health behaviors and factors. All-cause mortality and incident non-fatal CVD were recorded from baseline to December 31, 2020. The multi-state life table was adopted to explore the associations of CVH status with total life expectancy and life years lived with and without CVD. Results Six thousand fifty eight cases of incident non-fatal CVD and 10,580 cases of deaths were identified. Men aged 45 years with low, moderate, and high CVH had a life expectancy of 33.0, 36.5 and 38.5 years, of which 7.8 (23.6%), 6.0 (16.3%) and 3.7 years (9.6%) were spent with CVD. For women, the corresponding life expectancy was 36.6, 43.6 and 48.6 years, and the remaining life years lived with CVD were 7.8 (21.3%), 6.0 (13.7%) and 4.5 years (9.3%), respectively. The benefits of high CVH were persistent across lifespan from age 45 to 85 years and consistent when CVH was evaluated with health behaviors and factors alone. Conclusions High CVH compared with low CVH was associated with longer total life expectancy and fewer years spent with CVD, indicating that promoting CVH is of great importance for CVD prevention and healthy ageing in China.

Abstract Background The risk of cardiovascular disease (CVD) depended on the magnitude and exposure duration of insulin resistance (IR). This study aimed to investigate the associations of cumulative metabolic score for IR (cumMETS-IR) with incident CVD, and to further explore the modulated effects of time course of METS-IR accumulation. Methods We enrolled 47,270 participants without CVD and underwent three examinations during 2006–2010 from the Kailuan study. CumMETS-IR from 2006 to 2010 were calculated as the mean values of METS-IR between consecutive examinations multiplying by time intervals between visits. Time course of METS-IR accumulation was calculated as the slope of METS-IR versus time. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD risk were calculated with multivariable-adjusted Cox regressions. Results During a median follow-up of 10.99 years, we identified 3184 cases of incident CVD. The risk of incident CVD increased with increasing cumMETS-IR (HR, 1.77; 95% CI 1.58–1.98 for the Q4 versus Q1 group), exposure duration (HR, 1.60; 95% CI 1.45–1.77 for 6 years versus 0 years), and cumulative burden (HR, 1.49; 95% CI 1.37–1.61 for burden ≥ 0 versus

Abstract Background Hospice and Palliative Care (HPC) is in high demand in China; however, the country is facing the shortage of qualified HPC nurses. A well-suited competence framework is needed to promote HPC human resource development. Nevertheless, existing unstandardized single-structured frameworks may not be sufficient to meet this need. This study aimed at constructing a comprehensive multi-structured HPC competence framework for nurses. Methods This study employed a mixed-method approach, including a systematic review and qualitative interview for HPC competence profile extraction, a two-round Delphi survey to determine the competences for the framework, and a cross-sectional study for framework structure exploration. The competence profiles were extracted from publications from academic databases and interviews recruiting nurses working in the HPC field. The research team synthesized profiles and transferred them to competences utilizing existing competence dictionaries. These synthesized competences were then subjected to Delphi expert panels to determine the framework elements. The study analyzed theoretical structure of the framework through exploratory factor analysis (EFA) based on a cross-sectional study receiving 491 valid questionnaires. Results The systematic review involved 30 publications from 10 countries between 1995 and 2021, while 13 nurses from three hospitals were interviewed. In total, 87 and 48 competence profiles were respectively extracted from systematic review and interview and later synthesized into 32 competences. After the Delphi survey, 25 competences were incorporated into the HPC competence framework for nurses. The EFA found a two-factor structure, with factor 1 comprising 18 competences namely Basic Competences; factor 2 concluding 7 competences namely Developmental Competences. Conclusions The two-factor HPC competence framework provided valuable insights into the need and directions of Chinese HPC nurses’ development.

Biosensors are attractive tools for detecting molecules and small particles, as they can produce rapid, sensitive, and specific signals [...]

Abstract A cavity‐magnonic system composed of a superconducting microwave resonator coupled to a magnon mode hosted by the organic‐based ferrimagnet vanadium tetracyanoethylene (V[TCNE]x) is demonstrated. This work is motivated by the challenge of scalably integrating a low‐damping magnetic system with planar superconducting circuits. V[TCNE]x has ultra‐low intrinsic damping, can be grown at low processing temperatures on arbitrary substrates, and can be patterned via electron beam lithography. The devices operate in the strong coupling regime, with a cooperativity exceeding 1000 for coupling between the Kittel mode and the resonator mode at T≈0.4 K, suitable for scalable quantum circuit integration. Higher‐order magnon modes are also observed with much narrower linewidths than the Kittel mode. This work paves the way for high‐cooperativity hybrid quantum devices in which magnonic circuits can be designed and fabricated as easily as electrical wires.

BackgroundThere is evidence of an association between the gut microbiota and progression of stroke. However, the relationship between gut microbial metabolites, specifically bile acids (BAs), and post-ischemic stroke disability and poor functional outcomes remains unexplored.MethodsPatients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in the Third China National Stroke Registry were grouped according to total bile acid (TBA) quartile on admission. Association of TBA with disability and poor functional outcomes were evaluated using logistic regression models and restricted cubic splines.ResultsData for 9,536 patients were included. After adjusting for confounders, the risks of disability and poor functional outcomes were significantly lower in the highest TBA quartile than in the lowest TBA quartile at the 3-month follow-up, with respective odds ratios (ORs) of 0.65 (95% confidence interval [CI] 0.55–0.78; p

ABSTRACTRickettsia rickettsii (R. rickettsii), the causative agent of Rocky Mountain spotted fever (RMSF), is the most pathogenic member among Rickettsia spp. Previous studies have shown that tripartite motif-containing 56 (TRIM56) E3 ligase-induced ubiquitination of STING is important for cytosolic DNA sensing and type I interferon production to induce anti-DNA viral immunity, but whether it affects intracellular replication of R. rickettsii remains uncharacterized. Here, we investigated the effect of TRIM56 on HeLa and THP-1 cells infected with R. rickettsii. We found that the expression of TRIM56 was upregulated in the R. rickettsii-infected cells, and the overexpression of TRIM56 inhibited the intracellular replication of R. rickettsii, while R. rickettsii replication was enhanced in the TRIM56-silenced host cells with the reduced phosphorylation of IRF3 and STING and the increased production of interferon-β. In addition, the mutation of the TRIM56 E3 ligase catalytic site impairs the inhibitory function against R. rickettsii in HeLa cells. Altogether, our study discovers that TRIM56 is a host restriction factor of R. rickettsii by regulating the cGAS-STING-mediated signaling pathway. This study gives new evidence for the role of TRIM56 in the innate immune response against intracellular bacterial infection and provides new therapeutic targets for RMSF.IMPORTANCEGiven that Rickettsia rickettsii (R. rickettsii) is the most pathogenic member within the Rickettsia genus and serves as the causative agent of Rocky Mountain spotted fever, there is a growing need to explore host targets. In this study, we examined the impact of host TRIM56 on R. rickettsii infection in HeLa and THP-1 cells. We observed a significant upregulation of TRIM56 expression in R. rickettsii-infected cells. Remarkably, the overexpression of TRIM56 inhibited the intracellular replication of R. rickettsii, while silencing TRIM56 enhanced bacterial replication accompanied by reduced phosphorylation of IRF3 and STING, along with increased interferon-β production. Notably, the mutation of the TRIM56’s E3 ligase catalytic site did not impede R. rickettsii replication in HeLa cells. Collectively, our findings provide novel insights into the role of TRIM56 as a host restriction factor against R. rickettsii through the modulation of the cGAS-STING signaling pathway.

Abstract Background Epidemiological studies have demonstrated an association between red blood cell distribution width (RDW) and the prognosis of pneumonia-associated diseases. However, prognostic value of RDW in patients with ventilator-associated pneumonia (VAP) has yet to be investigated. This study aimed to explore the association between RDW and in-hospital mortality in VAP patients and explore predictive value of RDW for VAP patients. Methods This retrospective cohort study included 1,543 VAP patients from the Medical Information Mart for Intensive Care IV database 2008-2019. The primary outcome was considered to 30-day in-hospital mortality of VAP patients in this study. Non-high RDW level group was defined as

Abstract Background Preeclampsia (PE) is a new-onset pregnancy-specific disorder with a high prevalence that leads to over 70 000 maternal and 500 000 foetal fatalities worldwide each year. The level of chemerin, a newly identified adipokine, is increased in diabetic and obese patients. Currently, there are several studies describing the relationship between maternal circulating chemerin levels and PE. Therefore, this study aimed to assess their association in pooled samples. Methods Four databases were systematically searched to identify potential studies that reported circulating chemerin levels in PE and normal pregnancy groups. Standardized mean differences (SMDs), 95% confidence intervals (CIs), and 95% prediction intervals (PIs) were calculated using a random-effects meta-analysis. The probability of heterogeneity was also investigated by sensitivity analysis, subgroup analysis, and meta-regression. Results Thirteen studies in 11 articles with a total of 860 PE patients and 1309 women with normal pregnancies met the inclusion criteria. The results of the meta-analysis revealed that circulating chemerin, which levels in PE patients were considerably higher than those in controls (SMD = 1.39, 95% CI: 1.02, 1.77, 95% PI: -0.07, 2.86). Moreover, sensitivity analysis determined that the outcomes of the overall pooled results were not affected after the elimination of any study. Notably, subgroup analysis demonstrated a similar expression pattern irrespective of geographic location, severity, timing of sampling, and sample size. Last, there were no factors that significantly impacted the overall estimate, according to meta-regression. Conclusions This meta-analysis is the first to assess circulating chemerin levels in PE patients. The findings indicate that circulating chemerin levels may be a potential marker to diagnose PE.

Abstract Background Cashmere has long been used as the raw material for wool textiles. The diameter of the cashmere fibre determines its quality and economic value. However, the regulatory role of noncoding RNAs (ncRNAs) in cashmere fineness remains unclear, especially regarding the interaction between ncRNAs and coding RNAs. Results Transcriptome sequencing was used to identify the expression profiles of long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) in the skin tissues of Jiangnan cashmere goats with different cashmere fineness levels. Integration analysis of ncRNA and coding RNA was performed in combination with previous research results. The results showed that 16,437 lncRNAs, 2234 circRNAs, and 1322 miRNAs were identified in 8 skin samples of cashmere goats. A total of 403 differentially expressed (DE) lncRNAs, 62 DE circRNAs and 30 DE miRNAs were identified in the skin tissues of the fine groups (Fe) and coarse groups (Ce). We predicted the target gene of DE lncRNA, the target gene of DE miRNA and the host gene of DE circRNA. Based on functional annotation and enrichment analysis of target genes, we found that DE lncRNAs could be involved in regulating the fineness traits of cashmere. The most potential lncRNAs were MSTRG.42054.1, MSTRG.18602.3, and MSTRG.2199.13. Conclusions The data from this study enriched the cashmere goat noncoding RNA database and helped to supplement the annotation of the goat genome. The results provided a new direction for the breeding of cashmere characters.