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With the advantages of eco-friendliness, low cost, and low density, Mg2(Si,Sn) solid solutions are promising candidates for thermoelectric applications. In this work, Sb-doped Mg2Si0.4Sn0.6 bulks were prepared with a combined method of solid-state reaction and high pressure synthesis, followed by spark plasma sintering. Our investigations show that Sb doping optimizes the carrier concentration, while Si/Sn alloying effectively suppresses the lattice thermal conductivity and induces a convergence of the two lowest-lying conduction bands. Additionally, numerous coherent Sn-rich nanoprecipitates are formed within micron-sized grains. All these factors contribute synergistically to improving the thermoelectric properties of Mg2Si0.4Sn0.6. The optimal Mg2(Si0.4Sn0.6)0.985Sb0.015 exhibits a power factor higher than 4 000 μW·m−1·K−2 and a lattice thermal conductivity less than 0.8 W·m−1·K−1 at temperatures higher than 600 K, leading to the highest ZT of 1.61 at 823 K. Current work demonstrates an effective approach to enhancing the thermoelectric performance of n-type Mg2X solid solutions through doping, alloying, and microstructure modification.

Abstract Background Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with MLL rearrangements. Methods qRT-PCR, western blot, and spearman correction analysis were used to validate the regulation of LAMP5-AS1 on LAMP5 expression. In vitro and in vivo experiments were conducted to assess the functional relevance of LAMP5-AS1 in MLL leukemia cell survival. We utilized chromatin isolation by RNA purification (ChIRP) assay, RNA pull-down assay, chromatin immunoprecipitation (ChIP), RNA fluorescence in situ hybridization (FISH), and immunofluorescence to elucidate the relationship among LAMP5-AS1, DOT1L, and the LAMP5 locus. Autophagy regulation by LAMP5-AS1 was evaluated through LC3B puncta, autolysosome observation via transmission electron microscopy (TEM), and mRFP-GFP-LC3 puncta in autophagic flux. Results The study shows the crucial role of LAMP5-AS1 in promoting MLL leukemia cell survival. LAMP5-AS1 acts as a novel autophagic suppressor, safeguarding MLL fusion proteins from autophagic degradation. Knocking down LAMP5-AS1 significantly induced apoptosis in MLL leukemia cell lines and primary cells and extended the survival of mice in vivo. Mechanistically, LAMP5-AS1 recruits the H3K79 histone methyltransferase DOT1L to LAMP5 locus, directly activating LAMP5 expression. Importantly, blockade of LAMP5-AS1-LAMP5 axis can represses MLL fusion proteins by enhancing their degradation. Conclusions The findings underscore the significance of LAMP5-AS1 in MLL leukemia progression through the regulation of the autophagy pathway. Additionally, this study unveils the novel lncRNA-DOT1L-LAMP5 axis as promising therapeutic targets for degrading MLL fusion proteins.

Abstract Background Studies on the factors affecting vault after posterior chamber phakic Implantable Collamer Lens (ICL) have been carried out, but most of them are single-centered and subjective selections of parameters. The present study aimed to systematically analyze the factors for vault. Methods A systematic review of case series, case-control, and cohort studies derived from the articles published in PubMed, the Cochrane Library, Embase, Web of Science, CNKI, CBM, Wanfang and VIP, as well as ClinicalTrials, which were conducted to search for studies on factors of vault using four core terms: phakic intraocular lenses, vault, risk factor and observational study, from January 01, 1997, to February 20, 2023. The included studies were meta-analyzed quantitatively and described qualitatively. Subsequently, meta-regression and subgroup analysis were used. Results We identified 13 studies (1,607 subjects), and 14 factors were considered. Meta-analysis showed that anterior chamber depth (ACD), horizontal corneal white-to-white (hWTW), ICL-size, and age are dual effects of the abnormal vaults; anterior chamber volume (ACV) and lens thickness (LT) are a one-way effect; while axial length (AL), ICL- spherical equivalent (ICL-SE) and Km are insignificant. In addition, descriptive analysis of anterior chamber angle (ACA), horizontal sulcus to sulcus (hSTS), ciliary processes height (T value), crystalline lens rise (CLR), and gender showed that all factors except gender tend to have significant effects on vault. Sensitivity analysis showed stable combined results. Country and design respectively affect the heterogeneity in ACD and ICL-size at low vault, while design affects the heterogeneity in ACD at high vault. No publication bias exists. Conclusions Vault after ICL is related to multiple factors, especially anterior segmental biologic parameters, and they are weighted differently. We hope to provide a reference for the selection and adjustment of ICL.

Abstract Background Whole-genome methylation sequencing of cfDNA is not cost-effective for tumor detection. Here, we introduce reduced representative methylome profiling (RRMP), which employs restriction enzyme for depletion of AT-rich sequence to achieve enrichment and deep sequencing of CG-rich sequences. Methods We first verified the ability of RRMP to enrich CG-rich sequences using tumor cell genomic DNA and analyzed differential methylation regions between tumor cells and normal whole blood cells. We then analyzed cfDNA from 29 breast cancer patients and 27 non-breast cancer individuals to detect breast cancer by building machine learning models. Results RRMP captured 81.9% CpG islands and 75.2% gene promoters when sequenced to 10 billion base pairs, with an enrichment efficiency being comparable to RRBS. RRMP allowed us to assess DNA methylation changes between tumor cells and whole blood cells. Applying our approach to cfDNA from 29 breast cancer patients and 27 non-breast cancer individuals, we developed machine learning models that could discriminate between breast cancer and non-breast cancer controls (AUC = 0.85), suggesting possibilities for truly non-invasive cancer detection. Conclusions We developed a new method to achieve reduced representative methylome profiling of cell-free DNA for tumor detection.

Abstract Background In the global trend of actively promoting the participation of older adults in the digital age, the relevant negative issues featuring potential Internet Addiction (IA) among them has risen to be a new challenge facing the global public health. However, there is a severe lack of related research. This study aimed to gain a comprehensive understanding of the phenomenon and process of IA among the elderly. The purpose of this paper is to introduce factors that may influence IA in the demographic. Methods This study employed qualitative descriptive research methods to investigate older adults’ perceptions and experiences of IA. Semi-structured in-depth personal interviews were conducted between March and June 2023 with 36 senior citizens from urban communities in Chongqing, Southwest China. Data were analyzed via inductive content analysis methods. Results Through data analysis, 2 main categories concerning IA in older adults were identified: risk factors and protective factors. The risk factor categories include 5 individual factors (e.g., Internet as the major avenue for pursuing personal hobbies and interests, etc.), 3 family factors (e.g., household WIFI increasing the risk of prolonged Internet use indoors, etc.), 2 peer factors (e.g., peer recommendation and guidance as catalysts for intensified Internet engagement, etc.), 2 socio-environmental factors (e.g., the widespread daily Internet use spurs offline intolerance, etc.), and 3 Internet platform factors (e.g., the plenitude of online content triggers endless viewing/browsing behaviors, etc.). The category of protective factors encompasses 2 individual factors (e.g., a higher level of perceived risk regarding internet health hazards, etc.) and 2 family factors (e.g., more family commitment, etc.). Conclusions Older adults’ Internet addictive behaviors are shaped by multiple and complex internal and external factors. A higher level of online health risk perception is a key protective factor to effectively avoid the occurrence and deterioration of IA among the aged, a distinct finding from this study. It is believed that the “individual-family-peer-community” synergy strategy is expected to become an essential direction for IA intervention for older adults, in order to promote healthy Internet use among older adults.

Abstract The aberrant activation of the Wnt/β-catenin signaling pathway is closely associated with the development of various carcinomas, especially colorectal cancers (CRCs), where adenomatous colorectal polyposis (APC) mutations are the most frequently observed, which limits the anti-tumor efficiency of inhibitors targeting the upstream of Wnt/β-catenin pathway. The anti-tumor activity of the naturally occurring alkaloid cepharanthine (CEP) extracted from the plant Stephania cepharantha Hayata has been reported in various types of tumors. We previously observed that its derivatives inhibited the Wnt/β-catenin signaling in liver cancer; however, the specific mechanism remains unknown. In this study, we confirmed CEP can effectively inhibit APC-mutant CRC cell lines (SW480, SW620, LoVo) through disturbing of the Wnt/β-catenin signaling and elucidated the underlying mechanisms. Here, we demonstrate that CEP attenuates the Wnt/β-catenin signaling by decreasing the β-catenin, subsequently impeding the proliferation of APC-mutant CRCs. Moreover, CEP induced β-catenin transcription inhibition rather than the instability of β-catenin protein and mRNA contributes to reduction of β-catenin. Taken together, our findings identify CEP as the first β-catenin transcriptional inhibitor in the modulation of Wnt/β-catenin signaling and indicate CEP as a potential therapeutic option for the treatment of APC-mutated CRCs. Graphical Abstract

Abstract Maintaining energy balance and economical operation is significant for energy hub (EH) which serves as the central component. Implementing real‐time regulation for heating and cooling equipment within the EH is challenging due to their slow response time in response to the stochastic fluctuation in renewable energy sources and demands while the opposite is true for electric energy storage equipment (EST), a conventional single timescale energy management strategy is no longer sufficient to take into account the operating characteristics of all equipment. With this motivation, this study proposes a deep reinforcement learning based two‐timescale energy management strategy for EH, which controls heating & cooling equipment on a long timescale of 1 h, and EST on a short timescale of 15 min. The actions of the EST are modelled as discrete to reduce the action spaces, and the discrete‐continuous hybrid action sequential TD3 model is proposed to address the problem of handling both discrete and continuous actions in long timescale policy. A joint training approach based on the centralized training framework is proposed to learn multiple levels of policies in parallel. The case studies demonstrate that the proposed strategy reduces the economic cost and carbon emissions by 1%, and 0.5% compared to the single time‐scale strategy respectively.

To reduce the negative effects of pectin and hemicellulose in the cell wall of feijoa fruit on fruit juice quality, and improve the juice yield, the effects of the enzyme ratio (hemicellulose and pectinase), the enzyme amount, temperature, and time on the juice yield and soluble solids of "Unique U-100" feijoa fruit juice were investigated. Based on single factor experiment, response surface methodology was further used to optimize the optimal technological parameters of enzymatic hydrolysis of feijoa fruit juice. The results showed that under the conditions of the ratio of the compound enzyme (hemicellulase/pectinase) of 2.14:1, enzyme amount of 19.6 g/L, enzymolysis temperature of 56.8 ℃, and enzymolysis time of 92 min, the juice yield of feijoa fruit was the highest, which was 79.5%, with a relative error of 5.67% compared to the predicted value of model. The soluble solid content in fruit juice was 15.7%, with a relative error of 0.83% compared to the predicted value of the model. In addition, compared to the directly squeezed fruit juice, the enzymatically hydrolyzed fruit juice showed higher clarity, total phenolic content (24.4 mg GAE/100 g), and VC content (2.42 mg/100 g). Therefore, this study optimized the process of pectinase and hemicellulase complex enzymatic hydrolysis for the preparation of feijoa fruit, which improved the juice yield and nutritional quality and provided a theoretical basis for the further processing of feijoa fruit juice.

Mirror therapy is proposed to enhance post-stroke awareness of the affected limb and mental ability, but convincing evidence on the perceptuo-motor processes is insufficient. In this study, we aimed to investigate the longitudinal effect of mirror therapy on limb perception and early motor processes in stroke patients using the hand mental rotation (HMR) task with both behavioral and electrophysiological evidence. Fifty stroke patients were randomly assigned to a mirror therapy group (MG, N =25) or a conventional treatment group (CG, N =25). Before and after 4-week intervention, the HMR task was performed, and its behavioral performance and EEG characteristics were measured and correlated with clinical outcomes. Behavioral analysis showed that enhanced accuracy of the HMR task, correlating with greater improvement in upper extremity motor function, was only observed in the MG. The ERD/ERS and brain network analysis revealed significant group differences in brain activation and local network metrics in the ipsilesional hemisphere during the preparation and execution of mental rotation while processing the affected hand stimuli. Specifically, the MG showed enhanced ipsilesional parietal ERD in the $\alpha $ (8-13 Hz) and $\beta 1$ (13-20 Hz) bands, along with increased ipsilesional centroparietal nodal strength and betweenness centrality, which were cross-correlated. The results indicate the potential of long-term mirror therapy for promoting perceptuo-motor processes, facilitating visuospatial perception, and improving motor preparation and mental ability of the affected limb, thereby contributing to post-stroke recovery.

Depressive disorder has been known to be associated with high variability in resting-state electroencephalography (EEG) signals. However, this phenomenon is often ignored in stimulus-related brain activities. This study proposed a new method to explore the EEG variability evoked by transcranial magnetic stimulation (TMS, TMS-EEG) in depressive disorder (DE) patients. The TMS-EEG data were collected from 34 DE patients and 36 healthy controls (HC). The maximum eigenvalue of the real binary correlation matrix, calculated between different trials using cross-correlation and surrogate methods, was extracted to assess trial-by-trial variability (TTV) of TMS-EEG. The new method was found to more sensitive and reliable than the standard deviation method. DE patients exhibited significantly smaller TTV in Gamma band and greater TTV in Delta band than HC. Furthermore, the HAMD-17 scores were negatively correlated with TTV values in Gamma band. This study represented the first investigation into the TTV in TMS-EEG data and revealed abnormal values in DE patients. Those findings enhance our understanding of TMS-EEG technology and provide valuable insights for studying the characteristics of DE.

Automated ventricular function analysis can enhance healthcare consistency and accessibility, particularly in resource-limited settings. Current segmentation methods trained on adult heart ultrasounds struggle to accurately outline the irregular shape of the left ventricle owing to their limited exploration of border features. HFE-Mamba is introduced for left ventricle segmentation with shape awareness in order to address the existing challenge. Therefore, this proposal introduces the High-Frequency Enhancement Block (HFEB), enhancing the high-frequency component of left ventricles, particularly the boundary area in pediatric echocardiograms. Moreover, this also facilitates the investigation of target boundary specifics while extracting features. The incorporation of newly suggested vision mamba layers into encoder and decoder branches enhances the model’s computational and memory efficiency while capturing global dependencies. Tests conducted on two publicly available datasets indicate the superior predictive accuracy of the HFE-Mamba model in identifying target shapes.

Objective To systematically evaluate the safety and efficacy of intraoperative cell salvage (IOCS) for placenta previa women undergoing cesarean section. Methods The PubMed, Web of Science, Embase, the Cochrane Library of clinical trials, China National Knowledge Infrastructure (CNKI) and Wan Fang databases were searched from inception to September 2022. The standardized mean differences (SMDs) or relative risk (RR) and 95% confidence intervals (CIs) and prediction intervals (PIs) regarding the comparison between the IOCS and allogeneic blood transfusion (ABT) groups were analyzed using R software Version 4.1.2 and Stata Version 12.0. Results Five RCTs and ten retrospective cohort studies were included in this meta-analysis. Analysis of cohort studies showed that compared with the ABT group, women with placenta previa who underwent IOCS had generally higher postoperative hemoglobin (Hb) (SMD, 0.626; 95% CI: 0.103 to 1.149; 95% PI: -1.320 to 2.572) and hematocrit (Hct) (SMD, 0.617; 95% CI: 0.130 to 1.104; 95% PI: -1.084 to 2.317) levels. In RCTs, we observed that placenta previa women undergoing IOCS were almost 72.7% less likely to suffer from adverse events AEs than the ABT group (RR, 0.273; 95% CI, 0.082 to 0.904). The difference in postoperative prothrombin time (PT), activated prothrombin time (APTT), fibrinogen (Fib) concentration, blood urea nitrogen (BUN) and creatinine (Cr) between the IOCS and ABT group did not reach statistical significance. Conclusion Women with placenta previa who undergo IOCS have higher postoperative Hb and Hct concentrations compared to those treated with ABT. IOCS has no major effects on postoperative coagulation parameters and renal function parameters. IOCS is associated with a significantly lower risk of transfusion-related AEs among women undergoing cesarean section.

With development of integrated energy systems and energy markets, transactive energy has received increasing attention from society and academia, and realization of energy distribution and integrated demand response through market transactions has become a current research hotspot. Research on optimized operation of a distributed energy station as a regional energy supply center is of great significance for improving flexibility and reliability of the system. Based on retail-side energy trading market, this study first establishes a framework of combined electric and heating energy markets and analyses a double auction market mechanism model of interconnected distributed energy stations. This study establishes a mechanism model of energy market participants, and establishes the electric heating combined market-clearing model to maximize global surplus considering multi-energy storage. Finally, in the case study, a typical user energy consumption scenario in winter is selected, showing market-clearing results and demand response effects on a typical day. Impact of transmission line constraints, energy supply equipment capacity, and other factors on clearing results and global surplus are compared and analyzed, verifying the effects of the proposed method on improving global surplus, enhancing interests of market participants and realizing coordination and optimal allocation of both supply and demand resources through energy complementarity between regions.

Abstract Background The synthetic liver X receptor ligand (LXR) T0901317 (T0) has been reported to attenuate atherosclerosis (AS) without hyperglyceridemia due to innovative drug combination or nano-sized drug delivery. Given the key roles of mangiferin (MGF) in lipid metabolism and atherogenesis, it is critical to investigate progression of atherosclerotic lesion after combined treatment of MGF and T0. Methods Atherosclerotic plaque formation and hepatic lipid accumulation were compared in Apoe −/− mice among T0 and/or MGF treatment. The in vitro functions of MGF and T0 were analyzed by Oil-red O staining, cholesterol efflux assay, transmission electron microscopy and western blot analyses with or without acetylated low density lipoprotein. Results The combination therapy are effective regulators for atherosclerotic plaque formation in Apoe −/− mice, due to upregulation of ABCA1 and ABCG1 induced by LXR activation. Subsequently, we identified autophagy promoted by MGF and T0 treatment establishes a positive feedback loop that increases cholesterol efflux, resulted from LXRα activation. Under atherogenic conditions, the autophagy inhibitor CQ abolished the enhancement effect on cholesterol outflow of MGF and T0. Mechanically, MGF and T0 promotes LXRα and mTOR/AMPK signaling cascade in macrophage, and promotes AMPK signaling cascade in hepatocyte, leading to lipid metabolic homeostasis. Conclusions Altogether, our findings reveal that MGF and T0 engages in AS therapy without side effects by activating AMPK-dependent autophagy to promote macrophage cholesterol efflux, and MGF might serve as a natural compound to assist T0 in AS via targeting autophagy.

Abstract Atomic and close-to-atom scale manufacturing is a promising avenue toward single-photon emitters, single-electron transistors, single-atom memory, and quantum-bit devices for future communication, computation, and sensing applications. Laser manufacturing is outstanding to this end for ease of beam manipulation, batch production, and no requirement for photomasks. It is, however, suffering from optical diffraction limits. Herein, we report a spatial resolution improved to the quantum limit by exploiting a threshold tracing and lock-in method, whereby the two-order gap between atomic point defect complexes and optical diffraction limit is surpassed, and a feature size of

Abstract Introduction Gestational trophoblastic neoplasia (GTN) with intracardiac metastasis is rare, and here we reported a patient with intracardiac metastasis of high-risk and refractory gestational choriocarcinoma and reviewed relevant literatures. Case presentation A 37-year-old woman presented with vaginal bleeding and high level of β-human chorionic gonadotropin (β-hCG) at 199,060 (mIU/mL). It was clinically diagnosed with gestational choriocarcinoma. The patient initially received eight cycles of chemotherapy but unsatisfactory response was observed, and the level of β-hCG still ranged between 5000 and 10,000. Then there was found intracardiac masses in the right atrium (2.6*1.7 cm), anterior chordae tendineae of the tricuspid valve (1.4*0.7 cm) and the right ventricle (4.1*2.9 cm) by ultrasonic cardiogram (UCG). PET/CT highly suspected the intracardiac metastasis of choriocarcinoma (SUVmax = 9.3) and no disease was found in the lung and pelvis. The patient undertook complete intracardiac masses resection. The pathology confirmed the intracardiac metastasis of disease. After a week of operation, the UCG found a 5.4*4.2 cm mass in the right atrium again. Considering the poor prognosis, the patient received palliative care and eventually died of disease progression. Conclusion Intracardiac metastasis of GTN is an aggressive sign of disease. Patients can benefit from chemotherapy and surgery. Future investigation of PD-1 immunotherapy combines with chemotherapy are expected to improve the prognosis in this group of patients.

Deep neural networks have made remarkable contributions in many fields such as computer vision and natural language processing. However, due to their complex internal structures, for a long time, there is a lack of trust in deep neural networks, particularly in the domains like healthcare, finance, traffic safety, etc. To explain the internal mechanism of deep neural networks, a series of interpretable models, which mainly focus on enhancing the interpretability of deep learning models, has been proposed. This study pursues to data interpretability by analyzing the significance of image features with the goal of mining essential information contained in various visual features. Super-pixel segmentation is firstly applied to divide the image into several coherent visual feature regions, and these regions are subsequently overwritten by certain marks. Next, image occlusion is realized by modifying the pixel values of these feature regions according to the marks. Finally, we conduct comparative analytics of the classification results between the original data and occluded data to scrutinize the importance of key visual features. A collection of experimental studies is conducted and the results consistently demonstrate that the proposed method enables to observe the classifier’s dependence on different features, offering a new perspective on interpretability rooted in data analytics.

Currently, commercial cellular public networks such as 4G/5G have been widely deployed in China. In addition to serving general public customers, they are extensively used in the electric power industry for electricity information acquisition and distribution automation telemetry, as well as other non-control-related businesses. Simultaneously, power grid companies are actively studying and deploying electric power wireless private networks for bearing high-security control-related businesses such as distribution grid dispatching and distributed energy control. Electric power wireless private networks utilize dedicated spectrum resources, which operate on narrow individual carrier channels with numerous carriers in a discrete manner. These spectral characteristics indicate that electric power wireless private networks require unique system designs that are different from those of commercial cellular networks. Although some proposals have been proposed in relevant research, a unified and mature technical specification for electric power wireless private networks has not yet been established. This paper introduces the development history of electric power wireless private networks and power grid business requirements, with a specific emphasis on system design and key technologies, including frame structure and numerology, massive discrete carrier aggregation, spectrum sensing, security and isolation. We presented a comprehensive analysis and suggestions for these key technologies. Finally, we discuss future research on technological evolution. This study offers indications for an electric power wireless private network ecosystem.

Social dysfunction is a risk factor for several neuropsychiatric illnesses. Previous studies have shown that the lateral septum (LS)-related pathway plays a critical role in mediating social behaviors. However, the role of the connections between the LS and its downstream brain regions in social behaviors remains unclear. In this study, we conducted a three-chamber test using electrophysiological and chemogenetic approaches in mice to determine how LS projections to ventral CA1 (vCA1) influence sociability. Our results showed that gamma-aminobutyric acid (GABA)-ergic neurons were activated following social experience, and that social behaviors were enhanced by chemogenetic modulation of these neurons. Moreover, LS GABAergic neurons extended their functional neural connections via vCA1 glutamatergic pyramidal neurons, and regulating LSGABA→vCA1Glu neural projections affected social behaviors, which were impeded by suppressing LS-projecting vCA1 neuronal activity or inhibiting GABAA receptors in vCA1. These findings support the hypothesis that LS inputs to the vCA1 can control social preferences and social novelty behaviors. These findings provide new insights regarding the neural circuits that regulate sociability.

Abstract Type 2 diabetes (T2D)-related fragility fractures represent an increasingly tough medical challenge, and the current treatment options are limited. Mechanical loading is essential for maintaining bone integrity, although bone mechano-responsiveness in T2D remains poorly characterized. Herein, we report that exogenous cyclic loading-induced improvements in bone architecture and strength are compromised in both genetically spontaneous and experimentally-induced T2D mice. T2D-induced reduction in bone mechano-responsiveness is directly associated with the weakened Ca2+ oscillatory dynamics of osteocytes, although not those of osteoblasts, which is dependent on PPARα-mediated specific reduction in osteocytic SERCA2 pump expression. Treatment with the SERCA2 agonist istaroxime was demonstrated to improve T2D bone mechano-responsiveness by rescuing osteocyte Ca2+ dynamics and the associated regulation of osteoblasts and osteoclasts. Moreover, T2D-induced deterioration of bone mechano-responsiveness is blunted in mice with osteocytic SERCA2 overexpression. Collectively, our study provides mechanistic insights into T2D-mediated deterioration of bone mechano-responsiveness and identifies a promising countermeasure against T2D-associated fragility fractures.

Abstract Background Frailty contributes to adverse outcomes in older adults and places a heavy burden on healthcare resources. Dysphagia is associated with frailty, but the mechanisms by which dysphagia affects frailty in older adults are unclear. This study aimed to investigate a serial mediating effect of self-perceived oral health and self-reported nutritional status in the relationship between dysphagia and frailty among hospitalized older patients in China. Methods This cross-sectional study included 1200 patients aged ≥ 65 years in the Department of Geriatrics, Shaanxi Provincial People’s Hospital. A structured face-to-face interview was used to survey the following questionnaires: General Information Questionnaire, Tilburg Frailty Indicators (TFI), Eating Assessment Tool-10 (EAT-10), 30mL Water Swallow Test (WST), Geriatric Oral Health Assessment Index (GOHAI), and Short-Form Mini-Nutritional Assessment (MNA-SF). A total of 980 participants with complete data were included in the analysis. Statistical analysis was performed using SPSS 26.0 and Amos 28.0 software. Spearman’s correlation analysis was used for correlation analysis of study variables. The results of the multivariate linear regression analysis for frailty were used as covariates in the mediation analysis, and the structural equation model (SEM) was used to analyze the mediating effects among the study variables. Results Dysphagia, self-perceived oral health, self-reported nutritional status, and frailty were significantly correlated (P

Recently, ordinary residential users’ tolerance for power outages has dropped much by the flourishing economy. To further improve the power supply reliability, a scheme of seamless closed-loop load transfer was proposed based on series compensation technology. For its field application, two points should be considered: 1) For the efficient utilization, the device is designed with high mobility. But its mobility is limited due to its power requirements and the usage of magnetic components. 2) The mobility leads to variable nodes interconnected each time, which puts forward high requirements for the control strategy. The following are proposed: 1) Proposing a novel control strategy based on online impedance estimation method to ensure the effectiveness of the mobile prototype in variable scenarios. 2) Employing modular design and series-parallel mode to reduce the individual cabinet’s volume, while utilizing the short-term overload capacity of magnetic components to augment the power density. A mobile prototype is developed, and test results prove the effectiveness of the control strategy and the engineering feasibility of the prototype.

Abstract Background Immunotherapy targeting PD-1/PD-L1 has revolutionized the treatment of extensive-stage small cell lung cancer (ES-SCLC). However, clinical trials suggest differential efficacy of anti-PD-1 agents and anti-PD-L1 agents in first-line treatment of ES-SCLC. This retrospective multicenter study aimed to compare the efficacy and safety of anti-PD-1 agents versus anti-PD-L1 agents in first-line treatment of ES-SCLC in real-world practice. Methods Patients with pathologically or cytologically confirmed ES-SCLC treated with platinum plus etoposide combined with anti-PD-1 or PD-L1 agents as first-line treatment in different centers of PLA General Hospital between January 2017 and October 2021 were included for this study. Survival outcomes and safety were compared between patients receiving anti-PD-1 and PD-L1 agents. Results Of the total 154 included patients, 68 received anti-PD-1 agents plus chemotherapy (PD-1 group), and 86 received anti-PD-L1 agents plus chemotherapy (PD-L1 group). Progression-free survival (PFS) and overall survival (OS) in the entire cohort were 7.6 months (95% confidence interval [CI]: 6.5–8.2 months) and 17.4 months (95% CI: 15.3–19.3 months), respectively. Median PFS and OS were comparable between the PD-1 group and PD-L1 group (PFS: 7.6 months vs. 8.3 months, HR = 1.13, 95% CI: 0.79–1.62, p = 0.415; OS: 26.9 months vs. 25.6 months, HR = 0.96, 95% CI: 0.63–1.47, p = 0.859. The objective response rate and disease control rate were comparable between the two groups: 79.4% vs. 79.1% and 92.6% vs. 94.2%, respectively. The 6-month, 12-month, and 18-month PFS and OS rates were slightly higher in the PD-L1 group than in the PD-1 group, while the 24-month PFS rate was slightly higher in the PD-1 group than in the PD-L1 group. Stratified analysis showed that locoregional thoracic radiotherapy and normal lactate dehydrogenase level were independent predictors of better OS in ES-SCLC patients treated with first-line chemotherapy plus ICI. Adverse events were not significantly different between the two groups. Conclusions Anti-PD-1 agents and anti-PD-L1 agents combined with chemotherapy as first-line treatment for ES-SCLC are comparably effective and well tolerated.

Abstract The authors aim to assess the correlation between hypertension and the triglyceride‐glucose (TyG) index and its associated indices, and to compare their abilities to identify hypertension. Four thousand eight hundred and sixty‐six non‐hypertensive participants were enrolled from the China National Health Survey in 2009. The data on new‐onset hypertension were gathered in both 2011 and 2015. The TyG index and its associated indices were derived from the fasting triglyceride, blood glucose levels, and anthropometric parameters. Multivariate logistic regression analyses and receiver operating characteristic curve analysis were used. The adjusted odds ratio (OR) and 95% confidence interval (CI) for the new‐onset hypertension for the TyG‐waist‐to‐height ratio (TyG‐WHtR), TyG‐waist circumference (TyG‐WC), TyG‐waist‐to‐hip ratio (TyG‐WHR), TyG‐body mass index (TyG‐BMI), and TyG index were 1.379 (1.230–1.546), 1.002 (1.001–1.003), 1.156 (1.069–1.251), 1.007 (1.005–1.009), and 1.187 (1.051–1.341), respectively. In addition, comparing the lowest quartile (Q1) group with the highest quartile (Q4), the adjusted OR and 95% CI for the new‐onset hypertension were found to be 1.86 (1.48–2.35), 1.93 (1.53–2.43), 1.71 (1.36–2.16), 2.00 (1.60–2.50), and 1.49 (1.19–1.88) for TyG‐WHtR, TyG‐WC, TyG‐WHR, TyG‐BMI, and TyG index, respectively, among all participants. The TyG‐WHtR had the largest area under the curve (AUC) for hypertension (AUC, 0.628; 95% CI, 0.614–0.641) in all participants. Stratified analysis also indicated that the TyG‐WHtR exhibited the greatest AUC in both males (AUC, 0.608; 95% CI, 0.587–0.629) and females (AUC, 0.648; 95% CI, 0.629–0.666). In conclusions, the TyG index and its associated indices were positively associated with hypertension. Among these indices, TyG‐WHtR was the most valuable indicator for predicting hypertension.

Abstract Recent studies have reported the role of the M3 muscarinic acetylcholine receptor (M3R), a member of the G‐protein coupled receptor superfamily, encoded by the CHRM3 gene, in cardiac function and the regulation of blood pressure (BP). The aim of this study was to investigate the associations of CHRM3 genetic variants with salt sensitivity, longitudinal BP changes, and the development of hypertension in a Chinese population. We conducted a chronic dietary salt intervention experiment in a previously established Chinese cohort to analyze salt sensitivity of BP. Additionally, a 14‐year follow‐up was conducted on all participants in the cohort to evaluate the associations of CHRM3 polymorphisms with longitudinal BP changes, as well as the incidence of hypertension. The single nucleotide polymorphism (SNP) rs10802811 within the CHRM3 gene displayed significant associations with low salt‐induced changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), while rs373288072, rs114677844, and rs663148 exhibited significant associations with SBP and MAP responses to a high‐salt diet. Furthermore, the SNP rs58359377 was associated with changes in SBP and pulse pressure (PP) over the course of 14 years. Additionally, the 14‐year follow‐up revealed a significant association between the rs619288 polymorphism and an increased risk of hypertension (OR = 1.74, 95% CI: 1.06‐2.87, p = .029). This study provides evidence that CHRM3 may have a role in salt sensitivity, BP progression, and the development of hypertension.

Background and aim: Prostate cancer is a leading malignant tumor in men, associated with a high rate of mortality. Androgen deprivation therapy is commonly used to treat prostate cancer, which contributes to the progression of castration-resistant prostate cancer (CRPC). The current therapy has a low survival rate in patients with CRPC. Our study aims to develop a novel effective approach for CRPC treatment and improve survival benefits. Experimental procedure: CRPC cell line PC-3-Luc expressing luciferase and the CRPC cell line PC-3-IL6-Luc stably overexpressing IL-6 were used to establish the xenograft tumor mouse model. The tumor was monitored weekly using Bioluminescence imaging. Infiltrated macrophages were quantified by fluorescence-activated cell sorting using flow cytometry. IL6 mRNA level was determined using quantitative real-time PCR. The protein levels of total STAT3 and phosphorylated STAT3 were determined using Western blot. Results and conclusion: Zhoushi Qi Ling decoction (ZQD) treatment significantly reduced PC3 the xenograft tumor progression and the number of infiltrated macrophages when compared with saline treatment. IL6 mRNA level was remarkedly suppressed by ZQD treatment. Notably, the protein level of phosphorylated STAT3 was significantly decreased in PC3 the xenograft tumor treated with ZQD compared to saline treatment. Our findings demonstrated that ZQD treatment significantly reduced the progression of prostate cancer, evidenced by the reduced population of infiltrated macrophages and the inhibition of the IL6/STAT3 pathway.

As a high-value bulk chemical, ethylene glycol plays an important role in many fields such as energy, the chemical industry, and automobile manufacturing. At the same time, methanol, as an economical and efficient raw material, has shown great potential in promoting the innovation of bio-based chemicals and fuels. In view of this, this study focused on the excavation and innovative application of enzymes, and successfully designed an efficient artificial cascade catalytic system. The system cleverly converts methanol into ethylene glycol, and the core is composed of methanol dehydrogenase, glycolaldehyde synthase, and lactoaldehyde–pyruvate oxidoreductase. The three enzyme systems work together, which not only simplifies the metabolic pathway, but also realizes the efficient reuse of coenzymes. Subsequently, after ribosome-binding site (RBS) optimization, isopropyl β-D-Thiogalactoside (IPTG) induction regulation, and methanol concentration adjustment, the concentration of ethylene glycol reached 14.73 mM after 48 h of reaction, and the conversion rate was 58.92%. Furthermore, a new breakthrough in ethylene glycol production was achieved within 48 h by using a two-stage biotransformation strategy and fed-batch feeding in a 5 L fermentor, reaching 49.29 mM, which is the highest yield of ethylene glycol reported so far. This achievement not only opens up a new way for the biotransformation of ethylene glycol, but also lays a foundation for the industrial application in this field in the future.

The rapid geographic spread of the highly pathogenic avian influenza (HPAI) A(H5N1) virus in poultry, wild birds, and other mammalian hosts, including humans, raises significant health concerns globally. The recent emergence of HPAI A(H5N1) in agricultural animals such as cattle and goats indicates the ability of the virus to breach unconventional host interfaces, further expanding the host range. Among the four influenza types—A, B, C, and D, cattle are most susceptible to influenza D infection and serve as a reservoir for this seven-segmented influenza virus. It is generally thought that bovines are not hosts for other types of influenza viruses, including type A. However, this long-standing viewpoint has been challenged by the recent outbreaks of HPAI A(H5N1) in dairy cows in the United States. To date, HPAI A(H5N1) has spread into fourteen states, affecting 299 dairy herds and causing clinical symptoms such as reduced appetite, fever, and a sudden drop in milk production. Infected cows can also transmit the disease through raw milk. This review article describes the current epidemiological landscape of HPAI A(H5N1) in US dairy cows and its interspecies transmission events in other mammalian hosts reported across the globe. The review also discusses the viral determinants of tropism, host range, adaptative mutations of HPAI A(H5N1) in various mammalian hosts with natural and experimental infections, and vaccination strategies. Finally, it summarizes some immediate questions that need to be addressed for a better understanding of the infection biology, transmission, and immune response of HPAI A(H5N1) in bovines.

In the in-situ leaching method of ionic rare earth, ion exchange reaction between rare earth ions and leaching agent ions is carried out, which allows the rare earth ions to be leached from the ore body as the leaching solution flows through the pores. This indicates that the leaching process of rare earth ions is closely related to the seepage field, ion exchange field, and ion migration process of the leaching solution. In this study, an ionic rare earth mine located in Longnan of Jiangxi Province was taken as the research object. By conducting nuclear magnetic resonance scanning on the ore samples of this mine and vectorizing the nuclear magnetic resonance images, a two-dimensional geometric model of pores was obtained. Then, COMSOL Multiphysics software was used to establish a coupled numerical model of seepage–exchange–migration of the ionic rare earth mine during the leaching process at the pore scale to study the seepage situation of leaching solution with different injection strengths and concentrations, as well as the exchange and migration process. The results show that increasing the concentration of magnesium ions can increase the difference of ion diffusion concentration, accelerate the forward exchange rate of ions, promote the forward exchange reaction, and improve the concentration gradient of rare earth ions in the leaching solution. The more significant the diffusion effect, the higher the ion migration rate, while at the same time inhibiting the reverse adsorption of rare earth ions, and accelerating the leaching efficiency of rare earth ions. In addition, increasing the strength of the injection solution allows rare earth ions to leach out of the ore body earlier, shortens the leaching cycle, and thus reduces the peak concentration of leached rare earth ions. By analyzing the effects of the strength of the injection solution and leaching concentration on ionic rare earth leaching, the influence of those two factors on engineering economy can be briefly evaluated, which can be provided as a reference for the optimization of ionic rare earth mining technology.

Pareto dominance-based algorithms face a significant challenge in handling many-objective optimization problems. As the number of objectives increases, the sharp rise in non-dominated individuals makes it challenging for the algorithm to differentiate their quality, resulting in a loss of selection pressure. The application of the penalty-based boundary intersection (PBI) method can balance convergence and diversity in algorithms. The PBI method guides the evolution of individuals by integrating the parallel and perpendicular distances between individuals and reference vectors, where the penalty factor is crucial for balancing these two distances and significantly affects algorithm performance. Therefore, a comprehensive adaptive penalty scheme was proposed and applied to NSGA-III, named caps-NSGA-III, to achieve balance and symmetry between convergence and diversity. Initially, each reference vector’s penalty factor is computed based on its own characteristic. Then, during the iteration process, the penalty factor is adaptively adjusted according to the evolutionary state of the individuals associated with the corresponding reference vector. Finally, a monitoring strategy is designed to oversee the penalty factor, ensuring that adaptive adjustments align with the algorithm’s needs at different stages. Through a comparison involving benchmark experiments and two real-world problems, the competitiveness of caps-NSGA-III was demonstrated.

This study focuses on the sintering phenomenon that easily occurs during the direct combustion of molded fuel made from fungus bran (FB). To investigate the key factors influencing sintering, experiments are designed and conducted using a muffle furnace and a high-temperature drop furnace. The experimental results show that the combustion temperature is the primary factor triggering the sintering phenomenon. To effectively mitigate this issue, this study proposes two improvement strategies: water washing pretreatment and the use of additives. The analysis shows that water washing pretreatment effectively removes K and Mg elements, with the removal rates increasing as the washing temperature and time increase. Specifically, the removal rate of K ranges from 37.68% to 55.91%, and that of Mg ranges from 33.16% to 58.52%. Water washing pretreatment also reduces the degree of sintering; at 1400 °C, the TSF (tendency to slag formation) of the fuel increases by 25–40% after pretreatment, with a greater increases observed at higher washing temperatures and longer durations. Kaolin, used as an additive, significantly raises the ash melting point of FB and alleviates sintering, while P2O5 exacerbates it. Increasing the proportion of kaolin does not significantly enhance the TSF of high-temperature ash, but raising the P2O5 content from 5% to 10% lowers the TSF by 10–20% at the corresponding temperature.

The remarkable efficacy of COVID-19 vaccines has established mRNA as a highly promising biomedical technology. However, the adequate application of mRNA therapeutics necessitates additional measures to mitigate the inherent immunogenicity, which is predominantly caused by dsRNA. As a byproduct of the in vitro transcription of mRNA, dsRNA was reported to be originated through several distinct mechanisms, including the extension of 3′ loop-back hairpins, the extension of hybridized abortive transcripts, and promoter-independent transcription. The intricate mechanisms involved pose a dilemma as the reduction in dsRNA results in a concomitant decrease in other critical quality attributes of mRNA. Here, we demonstrate that the promoter binding motifs of T7 RNA polymerase directly impact the production of promoter-independent transcription-based dsRNA. Specifically, the G753A mutation significantly reduces the formation of dsRNA byproducts, which can further combine with modified nucleotides to enhance the effectiveness of dsRNA mitigation and with previously reported high-integrity mutation K389A to minimize side effects. Accordingly, the present study reports a cost-effective approach to synthesize high-purity, less immunostimulatory mRNA by using an engineered T7 RNA polymerase mutant.

The Zhuqing vanadium–titanium magnetite is a large deposit recently discovered in the western margin of the Yangtze Block, where the Zhuqing gabbroic intrusion and associated Fe–Ti–V oxide deposits are fund and dated at 1647 ± 39 Ma (MSWD = 0.79) through U–Pb dating of gabbro zircons. The εHf(t) values of zircons are all positive, with an average of 10.7. The average age of the one-stage model age (TDM) is 1661 Ma, which is very close to the diagenetic and metallogenic age 1647 ± 39 Ma (MSWD = 0.79). These new results indicate that the magma source come directly from the mantle. The contents of Al2O3, CaO, and (Na2O + K2O) increases with the increase of SiO2 contents, while, the contents of MgO, TiO2, and Fe2O3 decreases with the increase of SiO2 contents. Mg# is relatively stable with the increase of SiO2 contents. In the primitive mantle-normalized trace element spider diagrams and chondrite-normalized rare earth element patterns, the characteristics of all samples are similar to that of ocean island basalts (OIBs), showing a right inclination curve. Meanwhile the western margin of the Yangtze Block as an essential part of the supercontinent of Colombia, began to extend at 1.7 Ga, lasted to ca. 1.4 Ga, and finally split. These suggest that the Zhuqing gabbroic intrusion and associated Fe–Ti–V oxide deposits with OIB characteristics formed in the Late Paleoproterozoic, which is a response to the breakup of the Colombian supercontinent in the western margin of the Yangtze Block.

Background: The COVID-19 pandemic has exposed healthcare workers (HCWs) to serious risk of infection. The aims of our study were to investigate the epidemiological characteristics and risk factors of SARS-CoV-2 infection among HCWs, and evaluate the vaccine effectiveness (VE) during the Omicron pandemic in Shanghai, China. Methods: Active surveillance of COVID-19 was performed among HCWs who worked in Shanghai General Hospital from December 2022 to January 2023. A case-control study was conducted by questionnaire survey to analyse the infection-related risk factors. A retrospective cohort study was explored to evaluate VE against primary infection. Results: During the Omicron outbreak, 2,008 of 2,460 (81.6%) HCWs were infected with SARS-CoV-2. The infection rate was higher in women, younger age groups, nurses and medical technicians. Among the 1,742 participants in the questionnaire, 1,463 (84.0%) were tested positive, and 95.1% of them developed symptoms. Most of the infections (53.0%) were acquired outside the hospital. The risk factors associated with higher odds of infection were working in the emergency department (aOR 3.77, 95% CI 1.69–8.38) and medical examination area (aOR 2.47, 95% CI 1.10–5.51). The protective factors associated with lower odds of infection were previous infection with SARS-CoV-2 (aOR 0.01, 95% CI 0–0.07) and receiving four doses of vaccines (aOR 0.40, 95% CI 0.17–0.97). For frontline HCWs, those who had oral-nasal exposure to coworkers were more likely to be infected (aOR 1.74, 95% CI 1.21–2.51). In VE analysis, the risk of primary infection was lower in HCWs who received the emergency heterologous booster (the fourth dose) during the epidemic (aHR 0.25, 95% CI 0.15–0.40), resulting in an adjusted-VE of 75.1%. Conclusions: In response to future pandemic, it is important for public health policies to aim at protecting HCWs through risk-differentiated infection control measures, strengthening personal protection and recommending vaccination to vulnerable individuals before the arrival of Omicron wave.

Sesuvium portulacastrum L. is a flowering succulent halophyte in the ice plant family Aizoaceae. There are various ecotypes distributed in sandy coastlines and salty marshlands in tropical and subtropical regions with the common name of sea purslane. These plants are tolerant to salt, drought, and flooding stresses and have been used for the stabilization of sand dunes and the restoration of coastal areas. With the increased salinization of agricultural soils and the widespread pollution of toxic metals in the environment, as well as excessive nutrients in waterbodies, S. portulacastrum has been explored for the desalination of saline soils and the phytoremediation of metals from contaminated soils and nitrogen and phosphorus from eutrophic water. In addition, sea purslane has nutraceutical and pharmaceutical value. Tissue analysis indicates that many ecotypes are rich in carbohydrates, proteins, vitamins, and mineral nutrients. Native Americans in Florida eat it raw, pickled, or cooked. In the Philippines, it is known as atchara after being pickled. S. portulacastrum contains high levels of ecdysteroids, which possess antidiabetic, anticancer, and anti-inflammatory activities in mammals. In this review article, we present the botanical information, the physiological and molecular mechanisms underlying the tolerance of sea purslane to different stresses, its nutritional and pharmaceutical value, and the methods for its propagation and production in saline soils and waterbodies. Its adaptability to a wide range of stressful environments and its role in the production of valuable bioactive compounds suggest that S. portulacastrum can be produced in saline soils as a leafy vegetable and is a valuable genetic resource that can be used for the bioremediation of soil salinity and eutrophic water.

Background and objectives: The efficacy of rituximab (RTX) in treating steroid-resistant Graves’ orbitopathy (GO) has been limitedly studied in Asians. Moreover, RTX has been considered even less for patients with steroid-resistant dysthyroid optic neuropathy (DON) who failed to undergo orbital decompression surgery for physical or financial reasons, or who responded poorly to the procedure. This study aimed to investigate the efficacy of RTX in treating steroid-resistant active moderate-to-severe and sight-threatening GO in a Chinese population. Methods: Data from 28 patients with steroid-resistant GO prescribed a single dose of 500 mg RTX were retrospectively retrieved. Treatment responses and contributing factors were analyzed. Results: The median follow-up time was 22 (8–34) weeks. 23 (82.1 %) patients had a positive objective outcome recommended by the European Group on Graves’ Orbitopathy (EUGOGO), while 25 (92.6 %) had a decrease in 7-item clinical activity score (CAS) by at least 2. Diplopia, visual dysfunction, and MRI-detected T2 relaxation time of the involved extraocular muscles improved significantly at the last follow-up compared to baseline (81.0 % vs. 47.6 %, 38.9 % vs. 16.7 %, and 87.8 (8.64) vs. 75.8 (10.9) ms, respectively; all p values

Radish (Raphanus sativus L.) undergoes texture changes in their phy-chemical properties during the long-term dry-salting process. In our study, we found that during the 60-day salting period, the hardness and crispness of radish decreased significantly. In further investigation, we observed that the collaborative action of pectin methylesterase (PME) and polygalacturonase (PG) significantly decreased the total pectin, alkali-soluble pectin (ASP), and chelator-soluble pectin (CSP) content, while increasing the water-soluble pectin (WSP) content. Furthermore, the elevated activities of cellulase and hemicellulase directly led to the notable fragmentation of cellulose and hemicellulose. The above reactions jointly induced the depolymerization and degradation of cell wall polysaccharides, resulting in an enlargement of intercellular spaces and shrinkage of the cell wall, which ultimately led to a reduction in the hardness and crispness of the salted radish. This study provided key insights and guidance for better maintaining textural properties during the dry-salting process of radish.

ABSTRACT: Eggshell is one of the most important indicators of egg quality, and due to low shell strength, pimple eggs (PE) are more susceptible to breakage, thus causing huge economic losses to the egg industry. At the current time, the molecular mechanisms that regulate the formation of pimple eggs are poorly understood. In this study, uterine tissues of PE-laying hens (n = 8) and normal egg (NE) -laying hens (n = 8) were analyzed by whole transcriptome sequencing, and a total of 619 differentially expressed mRNAs (DE mRNAs), 122 differentially expressed lncRNAs (DE lncRNAs) and 21 differentially expressed miRNAs (DE miRNAs) were obtained. Based on the targeting relationship among DE mRNAs, DE lncRNAs and DE miRNAs, we constructed a competitive endogenous RNA (ceRNA) network including 12 DE miRNAs, 19 DE lncRNAs, and 128 DE mRNAs. Considering the large amount of information contained in the network, we constructed a smaller ceRNA network to better understand the complex mechanisms of pimple egg formation. The smaller ceRNA network network contains 7 DE lncRNAs (LOC107056551, LOC121109367, LOC121108909, LOC121108862, LOC112530033, LOC121113165, LOC107054145), 5 DE miRNAs (gga-miR-6568-3p, gga-miR-31-5p, gga-miR-18b-3p, gga-miR-1759-3p, gga-miR-12240-3p) and 7 DE mRNAs (CABP1, DNAJC5, HCN3, HPCA, IBSP, KCNT1, OTOP3), and these differentially expressed genes may play key regulatory roles in the formation of pimpled eggs in hens. This study provides the overall expression profiles of mRNAs, lncRNAs and miRNAs in the uterine tissues of hens, which provides a theoretical basis for further research on the molecular mechanisms of pimpled egg formation, and has potential applications in improving eggshell quality.

Recombinant adeno-associated virus (rAAV)-based gene therapy is entering clinical and commercial stages at an unprecedented pace. Triple transfection of HEK293 cells is currently the most widely used platform for rAAV manufacturing. Here, we develop low-cis triple transfection that decreases transgene plasmid use by 10- to 100-fold and overcomes several major limitations associated with standard triple transfection. This new method improves packaging of yield-inhibiting transgenes by up to 10-fold, and generates rAAV batches with reduced plasmid backbone contamination that otherwise cannot be eliminated in downstream processing. When tested in mice and compared with rAAV produced by standard triple transfection, low-cis rAAV shows comparable or superior potency and results in diminished plasmid backbone DNA and RNA persistence in tissue. Mechanistically, low-cis triple transfection relies on the extensive replication of transgene cassette (i.e., inverted terminal repeat-flanked vector DNA) in HEK293 cells during production phase. This cost-effective method can be easily implemented and is widely applicable to producing rAAV of high quantity, purity, and potency.

Abstract To investigate the role of Peg13 in modulating the inflammatory response in sepsis, we established Lipopolysaccharide (LPS)-induced 293T cells and mouse models. Peg13 expression was assessed at various time points after infection using RT-qPCR. The levels of high mobility group box 1 (HMGB1) and interleukin-6 (IL-6) were quantified through ELISA. A total of 44 septic patients and 36 healthy participants were recruited to measure Peg13 and HMGB1 levels in the blood. Peg13 demonstrated significant down-regulation in the supernatant of LPS-induced 293T cells and in the blood of LPS-induced mice. Moreover, the levels of proinflammatory cytokines HMGB1 and IL-6 were elevated in both the supernatant of LPS-induced cell models and blood specimens from LPS-induced murine models, and this elevation could be notably reduced by Peg13 suppression. In a clinical context, Peg13 and HMGB1 levels were higher in septic patients compared to healthy subjects. Peg13 exhibited a negative correlation with HMGB1, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) among septic patients. Peg13 mitigates the inflammatory response by reducing the release of proinflammatory cytokines HMGB1 and IL-6 in sepsis, presenting a potential therapeutic target for alleviating inflammation in sepsis treatment.

Dry eye disease (DED) represents a prevalent ocular surface disease. The development of effective nutritional management strategies for DED is crucial due to its association with various factors such as inflammation, oxidative stress, deficiencies in polyunsaturated fatty acids (PUFAs), imbalanced PUFA ratios, and vitamin insufficiencies. Extensive research has explored the impact of oral nutritional supplements, varying in composition and dosage, on the symptoms of DED. The main components of these supplements include fish oils (Omega-3 fatty acids), vitamins, trace elements, and phytochemical extracts. Beyond these well-known nutrients, it is necessary to explore whether novel nutrients might contribute to more effective DED management. This review provides a comprehensive update on the therapeutic potential of nutrients and presents new perspectives for combination supplements in DED treatment.

College students are inevitably online and at risk of becoming addicted. Life history theory provides an explanatory framework for individual differences in Internet addiction, and childhood harshness and unpredictability may be important antecedents. However, it is unclear whether and how childhood harshness and/or unpredictability affect Internet addiction during college. In this study, we recruited 483 Chinese college students and assessed their childhood harshness, unpredictability, self-control, and Internet addiction. The results of path analysis showed that childhood unpredictability was positively associated with Internet addiction among college students and was partially mediated by self-control. The effect of harshness on Internet addiction showed a suppression effect, i.e., the direct effect of harshness on Internet addiction was negative and the indirect effect through self-control was positive. This suggests that the high risk of Internet addiction stems from harshness and unpredictability in childhood, but that the effects of these factors are independent and distinct. Self-control plays an important role in this process, but many internal mechanisms remain to be tested in future research.

Studying the impact of agricultural digitalization (ADT) on the carbon emission intensity of planting industry (PCI) can help promote sustainable development and realize the “dual carbon” goal. Based on the panel data of 31 provinces in China from 2010 to 2020, this study uses the entropy weight method and emission coefficient method to measure the development level of ADT and PCI, respectively. By using the regression analysis method, as well as the robustness test, heterogeneity test, and spatial spillover effect and threshold tests, the impact of ADT on PCI was examined. The results are as follow: (1) PCI is high in the north and low in the south, and the north-south divide is becoming prominent. (2) ADT in China can significantly reduce PCI, as verified through the robustness test. (3) Regional differences exist in the impact of ADT on PCI, with the most significant effect observed in the northeast region, followed by the western and central regions. (4) ADT exerts a significant spatial spillover effect on PCI and an inhibitory effect on PCI of adjacent provinces. (5) The proportion of urban population exerts a threshold effect in the impact of ADT on PCI. When the urban population ratio crosses 69 %, the inhibitory effect of agricultural carbon emissions decreases marginally. Therefore, promoting the green and low-carbon development of the planting industry is highly recommended.

Patients older than the expected age of the local population generally have limited life expectancy. The optimal treatment approach for very elderly patients with head and neck cancer remains uncertain. This study retrospectively analyzed patients over 78 years old, the expected age in 2019 for Chinese individuals, who underwent treatment for head and neck cancer at a tertiary cancer center in China. The study compared the overall survival rates among different treatment groups. The findings revealed that among patients eligible for surgery, radical resection yielded better outcomes compared to radiotherapy-based treatments, with a hazard ratio of 0.362 (95% CI 0.160-0.819, P = 0.015). Among patients who received radiotherapy, those who received a total dose exceeding 60 Gy had a significantly longer survival compared to those who received palliative doses, with median survival time of 31 months versus 14 months (P = 0.003). Among 78 patients who underwent conventional fractionated radiotherapy (CFRT), 15 patients (19.23%) experienced unscheduled treatment breaks with a median duration of 12 days. However, these treatment breaks did not appear to impact survival (P > 0.1). The study also suggested that altered fractionated radiotherapy, including hypofractionated radiotherapy (hypo-RT), could be a viable alternative to CFRT, offering similar survival outcomes with reduced treatment duration. In conclusion, eligible patients should be treated with curative intent, even if they are older than the expected age of the local population. When radiotherapy is indicated, altered fractionation, particularly hypo-RT, may be a favorable option to consider.

Although prior research has implied that emotional contagion occurs automatically and unconsciously, convincing evidence suggests that it is significantly influenced by individuals’ perceptions of their relationships with others or with collectives within specific social contexts. This implies a role for self-representation in the process. The present study aimed to offer a novel explanation of the interplay between social contexts and emotional contagion, focusing on the contextualized nature of self-representation and exploring the social factors that shape emotional contagion. It further posits a causal loop among social contexts, self-representation, and emotional contagion. Drawing from the lens of self-representation, this study concludes with a discussion on potential research directions in this field, commencing with an exploration of the antecedents and consequences of emotional contagion and self-representation.

The early Cambrian period is a critical time in Earth’s history, marked by the second oxygenation of the atmosphere (known as the Neoproterozoic Oxidation Event) and the rapid evolution of animals, as well as the worldwide large-scale deposits. Polymetallic Ni-Mo deposits have been previously reported in the black rocks at the base of the Cambrian strata on the Yangtze Block, South China, while their genesis is still controversial, and their global occurrences are uncertain. Therefore, we conduct a comprehensive analysis of trace elements and rare earth elements in the black rocks at the base of the Yurtus Formation in the Sugaitblak section (SGT) in Aksu, Tarim Block, and then make a comprehensive study by combining our and other data from the Tarim and Yangtze Block. The distribution patterns of the trace and rare earth element data from our study and another two sections in the Aksu area have shown that the black rocks in the Tarim were strongly enriched in V, Sr, Mo, Ba, and U, moderately enriched in Zn, Cu, Cr, and Pb, and slightly depleted in Ni, and Co during the early Cambrian. These enriched elements could mainly originate from the waning hydrothermal fluids, and then precipitate and preserve in sediments under anoxic environment. The comparison of trace elements in the black rocks between the Tarim and the Yangtze Block suggests that the types of enriched metal elements in these two regions were different, and metal concentrations in the Yangtze Block were much higher than those in the Tarim by 1–3 orders of magnitude. This result indicates that there are no polymetallic Ni-Mo enrichment layers in the black rocks in the Tarim during the early Cambrian, and the widespread polymetallic Ni-Mo enrichments in South China have been more likely influenced by the local hydrothermal activity. It could be further speculated that the early Cambrian period may have been an active period for seafloor hydrothermal activity, with locally different chemical components in hydrothermal fluids. Abundant metal nutrients brought by these hydrothermal activities may have been a potential factor for the rapid evolution of life during this period.

Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological, cellular, and clinical levels. Rheumatologists have marked them as two entirely distinct arthropathies. Given recent discoveries in disease initiation and progression, potential mechanisms, cellular signaling pathways, and ongoing clinical therapeutics, there are now more opportunities for discovering osteoarthritis drugs. This review summarized the osteoarthritis and psoriasis arthritis signaling pathways, crosstalk between BMP, WNT, TGF-β, VEGF, TLR, and FGF signaling pathways, biomarkers, and anatomical pathologies. Through bench research, we demonstrated that regenerative medicine is a promising alternative for treating osteoarthritis by highlighting significant scientific discoveries on entheses, multiple signaling blockers, and novel molecules such as immunoglobulin new antigen receptors targeted for potential drug evaluation. Furthermore, we offered valuable therapeutic approaches with a multidisciplinary strategy to treat patients with osteoarthritis or psoriasis arthritis in the coming future in the clinic.

Background: Although workplace violence is prevalent in the healthcare system, the relationship between workplace violence, job satisfaction, and burnout among healthcare workers (HCWs) in mobile cabin hospitals in China during the COVID-19 pandemic has not yet been investigated. This study analyzes the mediating effects of perceived stress and work environment in the relationship between workplace violence, job satisfaction, and burnout. Methods: A cross-sectional study was conducted in December 2022 on 1,199 frontline HCWs working in mobile cabin hospitals in Chongqing, China, during the COVID-19 pandemic. Multiple linear regression and mediation analysis were performed. Results: A positive correlation was observed between workplace violence and burnout (r = 0.420, P

Abstract To advance our comprehension of the complex geological history and mantle dynamics in the North Atlantic region, we employ all available broadband seismic data recorded in Greenland to reveal an abnormal mantle transition zone (MTZ) structure. Central and eastern Greenland exhibits depressed 410 and 660 km discontinuities (d410 and d660, respectively) bordering the MTZ, indicative of a substantial thermal anomaly associated with an underlying plume, surpassing the 1,800°C threshold for post‐garnet phase transitions at the d660. Variations in MTZ thickness across Greenland stem from differing temperature anomalies at the d410 and d660, possibly linked to a tilted plume within the MTZ. These findings corroborate geodynamic models, elucidating the interaction between post‐garnet phase transitions and upwelling plumes. The results shed light on the origin of the enigmatic Icelandic hotspot track and its influence on the thermal and lithospheric structures beneath Greenland.

Introduction: Xinjiang Brown cattle constitute the largest breed of cattle in Xinjiang. Therefore, it is crucial to establish a genomic evaluation system, especially for those with low levels of breed improvement.Methods: This study aimed to establish a cross breed joint reference population by analyzing the genetic structure of 485 Xinjiang Brown cattle and 2,633 Chinese Holstein cattle (Illumina GeneSeek GGP bovine 150 K chip). The Bayes method single-step genome-wide best linear unbiased prediction was used to conduct a genomic evaluation of the joint reference population for the milk traits of Xinjiang Brown cattle. The reference population of Chinese Holstein cattle was randomly divided into groups to construct the joint reference population. By comparing the prediction accuracy, estimation bias, and inflation coefficient of the validation population, the optimal number of joint reference populations was determined.Results and Discussion: The results indicated a distinct genetic structure difference between the two breeds of adult cows, and both breeds should be considered when constructing multi-breed joint reference and validation populations. The reliability range of genome prediction of milk traits in the joint reference population was 0.142–0.465. Initially, it was determined that the inclusion of 600 and 900 Chinese Holstein cattle in the joint reference population positively impacted the genomic prediction of Xinjiang Brown cattle to certain extent. It was feasible to incorporate the Chinese Holstein into Xinjiang Brown cattle population to form a joint reference population for multi-breed genomic evaluation. However, for different Xinjiang Brown cattle populations, a fixed number of Chinese Holstein cattle cannot be directly added during multi-breed genomic selection. Pre-evaluation analysis based on the genetic structure, kinship, and other factors of the current population is required to ensure the authenticity and reliability of genomic predictions and improve estimation accuracy.