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BackgroundWork-life balance is associated with health behaviors. In the face of digitalization, understanding this link requires a theory-based investigation of problematic internet use and perceived stress, which are so far unknown. ObjectiveOn the basis of the compensatory carry-over action model, this study aimed to determine whether problematic internet use and perceived stress mediate the relationship between health behaviors and work-life balance in two groups of internet users from different environments (residents in Germany and China). We also investigated whether the place of residence was a moderator. MethodsAn online questionnaire (N=877) was administered to residents from Germany (n=374) and China (n=503) in 3 languages (German, English, and Chinese). Moderated mediation analyses were run with health behaviors as the independent variable, work-life balance as the dependent variable, problematic internet use and perceived stress as the mediator variables, and place of residence as a potential moderator. ResultsOn a mean level, individuals in Germany reported less problematic internet use and more health behaviors than individuals in China; however, they also had lower work-life balance and higher perceived stress. Results showed that health behaviors seem to be directly related to work-life balance in both groups. Among the residents of Germany, a partial mediation was revealed (β=.13; P=.01), whereas among the residents of China, a full mediation was found (β=.02; P=.61). The mediator role of perceived stress was compared with problematic internet use in all the serial models and the parallel model. Residence moderated the relationship between health behaviors and work-life balance: The interrelation between health behaviors and work-life balance was stronger in Germany (β=.19; P

Abstract Background Sorafenib is a standard therapeutic agent for advanced hepatocellular carcinoma (HCC). However, its efficacy is moderate, as the survival of patients is prolonged for only a few months, and the response rate is low. The mechanism of low efficacy remains unclear. In this study, we investigated the effect of Toll-like receptor 3 (TLR3) on the effects of sorafenib on HCC. Methods Polyinosinic-polycytidylic acid [poly(I: C)] was used as a double-stranded RNA analog and TLR3 agonist in subsequent experiments. After orthotopic implantation of HCC tumors in BALBc nu/nu or C57BL/6 mice, survival time, tumor growth, and metastasis in the abdomen and lungs were analyzed. Flow cytometry and cytotoxicity assays were used to analyze NK cells isolated from the spleen or peripheral blood. ELISA was used to detect the expression of plasma interferon (IFN)-γ and monocyte chemoattractant protein (MCP)-1. In addition, the expression of phosphorylated-extracellular regulated kinase 1/2 (pERK1/2), phosphorylated-protein kinase B (pAKT), ERK1/2 and AKT was analyzed by Western blotting. Results Sorafenib reduced the number and activity of NK cells in tumor-bearing mice and simultaneously decreased the levels of MCP-1 and IFN-γ in the plasma. The combination of sorafenib and poly(I: C) synergistically inhibited tumor growth and metastasis in tumor xenograft mice and prolonged survival. Poly(I: C) not only exerts a direct inhibitory effect on tumor growth and metastasis by targeting the TLR3 receptor on tumor cells but also facilitates the proliferation and activation of NK cells, indirectly impeding tumor progression. Mechanistically, poly(I: C) decreased the sorafenib-induced inhibition of ERK phosphorylation and increased the phosphorylation of IκB in NK cells, thereby enhancing NK cell function. Conclusion Activation of TLR3 can enhance the antitumor effect of sorafenib on HCC. The combination of a TLR3 activator and sorafenib may be a new strategy for the treatment of HCC.

High-performance BaTiO3(BTO)-based dielectric ceramics have great potential for high-power energy storage devices. However, its poor temperature reliability and stability due to its low Curie temperature impedes the development of most electronic applications. Herein, a series of BTO-based ceramics are designed and prepared on the basis of entropy engineering. Owing to the incorporation of Bi(Mg0.5Ti0.5)O3, relaxation behavior and low dielectric loss at high temperatures have been achieved. Moreover, the high-entropy strategy also promotes lattice distortion, grain refinement and excellent resistance, which together increase the breakdown field strength. These simultaneous effects result in outstanding energy storage performance, ultimately achieving stable energy density (Ue) of 5.76 J·cm−3 and efficiency (η) of 89%. Most importantly, the outstanding temperature stability makes high-entropy BTO-based ceramics realize a significant energy storage density of 4.90±0.14 J·cm−3 with the efficiency above 89%, spanning a wide temperature range of 25–250 °C, as well as cycling reliability with negligible performance deterioration after 3×105 cycles at 300 kV∙cm−1 and 200 °C. This research presents an effective method for designing temperature-stable and reliable dielectrics with comprehensive energy storage performance.

Abstract Background The region-specific importance of carcinogenic HPV genotypes is required for optimizing HPV-based screening and promoting appropriate multivalent HPV prophylactic vaccines. This information is lacking for Ningbo, one of the first cities of China’s Healthy City Innovation Pilot Program for Cervical Cancer Elimination. Here, we investigated high-risk HPV (HR-HPV) genotype-specific distribution and attribution to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) before mass vaccination in Ningbo, China. Methods A total of 1393 eligible CIN2+ archived blocks (including 161 CIN2, 1107 CIN3, and 125 invasive cervical cancers [ICC]) were collected from 2017 to 2020 in Ningbo. HR-HPV DNA was genotyped using the SPF10-DEIA-LiPA25 version 1 detection system and the SureX HPV 25X Genotyping Kit. Genotype-specific attribution to CIN2+ was estimated using a fractional contribution approach. Results Ranking by the attributable proportions, HPV16 remained the most important genotype in both cervical precancers and cancers, accounting for 36.8% of CIN2, 53.2% of CIN3, and 73.3% of ICC cases. Among cervical precancers, HPV52 (17.3% in CIN2, 12.7% in CIN3) and HPV58 (13.9%, 14.9%) ranked second and third, while HPV33 (8.3%, 7.9%) and HPV31 (6.5%, 4.1%) ranked fourth and fifth, respectively. However, among ICCs, HPV18 (5.7%) accounted for the second highest proportion, followed by HPV33 (5.4%), HPV58 (4.0%), and HPV45 (3.2%). HPV18/45 together accounted for 46.8% of adenocarcinomas, which was slightly lower than that of HPV16 (47.7%). The remaining HR-HPV genotypes (HPV35/39/51/56/59/66/68) combined accounted for only 6.7% of CIN2, 2.9% of CIN3, and 4.2% of ICC. Conclusions With Ningbo’s strong medical resources, it will be important to continue HPV16/18 control efforts, and could broaden to HPV31/33/45/52/58 for maximum health benefits. However, different strategies should be proposed for other HR-HPV genotypes based on their lower carcinogenic risks.

Abstract Ischemic stroke is a common cause of mortality and severe disability in human and currently lacks effective treatment. Neuronal activation and neuroinflammation are the major two causes of neuronal damage. However, little is known about the connection of these two phenomena. This study uses middle cerebral artery occlusion mouse model and chemogenetic techniques to study the underlying mechanisms of neuronal excitotoxicity and severe neuroinflammation after ischemic stroke. Chemogenetic inhibition of neuronal activity in ipsilesional M1 alleviates infarct area and neuroinflammation, and improves motor recovery in ischemia mice. This study identifies that ischemic challenge triggers neuron to produce unique small extracellular vesicles (EVs) to aberrantly activate adjacent neurons which enlarge the neuron damage range. Importantly, these EVs also drive microglia activation to exacerbate neuroinflammation. Mechanistically, EVs from ischemia-evoked neuronal activity induce neuronal apoptosis and innate immune responses by transferring higher miR-100-5p to adjacent neuron and microglia. MiR-100-5p can bind to and activate TLR7 through U18U19G20-motif, thereby activating NF-κB pathway. Furthermore, knock-down of miR-100-5p expression improves poststroke outcomes in mice. Taken together, this study suggests that the combination of inhibiting aberrant neuronal activity and the secretion of specific EVs-miRNAs may serve as novel methods for stroke treatment. Graphical Abstract

Abstract Background Managing infertility patients with poor ovarian response (POR) to ovarian stimulation remains unmet clinically. Besides economic burdens, patients with POR have a poor prognosis during in vitro fertilization and embryo transfer (IVF-ET). In this study, we assessed the efficacy and safety of Shen Que (RN8) moxibustion on reproductive outcomes in POSEIDON patients (Group 2a). Methods Women eligible for IVF were invited to participate in this randomized, open-label, superiority trial at an academic fertility center from January 2022 to December 2023. One hundred patients ≤ 44 years old equally divided between Shen Que moxibustion (SQM) and control groups were randomized. These patients must meet the POSEIDON criteria, Group 2a, which requires antral follicle count (AFC) ≥ 5 or anti-müllerian hormone (AMH) ≥ 1.2ng/ml, and a previous unexpected POR (

Abstract Background Social support is widely recognized as a protective factor against psychological distress, especially for the elderly with chronic diseases. Therefore, effective tools for measuring social support are of great significance for both research and clinical practice. This study aims to cross-culturally adapt the German Social Support Scale (F-SozU) into Chinese and assess its psychometric properties among older adults with chronic diseases. Methods A cross-sectional study was conducted in a Chinese tertiary hospital. Four hundred ninety-six older adults that were approached via a convenience sampling method completed the Chinese version of the F-SozU. Content validity was evaluated using the two-round Delphi method. Psychometric properties, including item analysis, content validity, structure validity, convergent and discriminant validity and reliability were examined. Result The final version of C-F-SozU is a three-factor structure consisting of 23 items. All indicators of item analysis are acceptable. Adequate content validity was ensured by the expert panel (I-CVI = 0.80–1.00, S-CVI = 0.965) and participants. The confirmatory factor analysis model revealed that the factor structure of the C-F-SozU fitted the original scale (χ 2 /df = 2.088, CFI = 0.998, GFI = 0.943, TLI = 0.997, IFI = 0.998, RMSEA = 0.064 and SRMR = 0.043). The total Cronbach’s α was 0.956, and the test–retest reliability coefficient was 0.887. The convergent validity (average variance extracted = 0.517–0.995) and discriminant validity were found to be satisfactory. No floor/ceiling effect was found. Conclusion The 23-item C-F-SozU demonstrates robust reliability and validity, rendering it a valuable instrument for evaluating social support among older adults with chronic diseases in China. The three-factor structure of the scale allows for a more detailed assessment of the social support, with the scores of each dimension and the total score being of significant reference value. More comprehensive studies may be required to confirm its effectiveness and applicability.

This paper expounds the basic principles and structures of the whole petroleum system to reveal the pattern of conventional oil/gas – tight oil/gas – shale oil/gas sequential accumulation and the hydrocarbon accumulation models and mechanisms of the whole petroleum system. It delineates the geological model, flow model, and production mechanism of shale and tight reservoirs, and proposes future research orientations. The main structure of the whole petroleum system includes three fluid dynamic fields, three types of oil and gas reservoirs/resources, and two types of reservoir-forming processes. Conventional oil/gas, tight oil/gas, and shale oil/gas are orderly in generation time and spatial distribution, and sequentially rational in genetic mechanism, showing the pattern of sequential accumulation. The whole petroleum system involves two categories of hydrocarbon accumulation models: hydrocarbon accumulation in the detrital basin and hydrocarbon accumulation in the carbonate basin/formation. The accumulation of unconventional oil/gas is self-containment, which is microscopically driven by the intermolecular force (van der Waals force). The unconventional oil/gas production has proved that the geological model, flow model, and production mechanism of shale and tight reservoirs represent a new and complex field that needs further study. Shale oil/gas must be the most important resource replacement for oil and gas resources of China. Future research efforts include: (1) the characteristics of the whole petroleum system in carbonate basins and the source-reservoir coupling patterns in the evolution of composite basins; (2) flow mechanisms in migration, accumulation, and production of shale oil/gas and tight oil/gas; (3) geological characteristics and enrichment of deep and ultra-deep shale oil/gas, tight oil/gas and coalbed methane; (4) resource evaluation and new generation of basin simulation technology of the whole petroleum system; (5) research on earth system – earth organic rock and fossil fuel system – whole petroleum system.

Abstract Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Abstract Objective This study aimed to understand how people living with drug‐resistant focal epilepsy (DRE) navigate through lines of antiseizure medications (ASM) and experience adverse events (AEs) in the real‐world setting in the United States. Methods A retrospective study was conducted with medical chart data from clinical practices in the United States. Eligible adults had a confirmed diagnosis of DRE and initiated a third‐line ASM therapy between January 2013 and January 2020 (i.e., the index date). Subjects must have medical history data available for ≥1 year prior to (the baseline) and ≥2 years after the index date (the follow‐up). Treatment patterns were captured from first to fourth lines. After the emergence of drug resistance, time to ASM discontinuation, reasons for discontinuation, AE experience and AE management were reported separately during third and fourth lines of treatment and beyond. Results The study included a total of 345 individuals, with an average (standard deviation) age of 23.9 (11.9) years at first diagnosis. All individuals had at least three lines of ASMs with first and second lines during baseline, and third line during follow‐up. The first line for most individuals was monotherapy. As individuals progressed through additional lines of ASM therapy, they were more likely to receive polytherapy. The regimens were more individualized after meeting drug resistance criteria. The top reasons for discontinuing were uncontrolled seizure and/or intolerance/AEs for both third and subsequent lines. More than a third of individuals experienced at least one AE. Among those with at least one AE, many individuals had to manage these AEs with dose adjustment (39.4%), discontinuation of offending ASM (37.9%), de novo pharmacotherapy (25.8%), emergency room visit (13.6%), and hospitalization (12.1%). Significance This study demonstrated that individuals living with DRE experience significant AEs, and many of these AEs lead to treatment disruption and significant healthcare resource utilization. Plain Language Summary This study examined how individuals with focal epilepsy are treated across various clinics in United States and reported the adverse events these individuals experienced during treatment, along with the consequence associated with these adverse events. We found that as individuals progressed through additional treatments, they were more and more likely to receive more than one antiseizure medication, and a significant portion of individuals experienced at least one adverse event, often manifested as headache, somnolence, dizziness, and fatigue.

Abstract Aims Patients with HFrEF and worsening HF events (WHFE) are at particularly high risk and urgently need disease‐modifying therapy. CHART‐HF assessed treatment patterns and reasons for medication decisions among HFrEF patients with and without WHFE. Methods and results CHART‐HF collected retrospective electronic medical records of outpatients with HF and EF

Abstract Background Extrachromosomal circular DNA (eccDNA), a kind of circular DNA that originates from chromosomes, carries complete gene information, particularly the oncogenic genes. This study aimed to examine the contributions of FAM84B induced by eccDNA to prostate cancer (PCa) development and the biomolecules involved. Methods The presence of eccDNA in PCa cells and the FAM84B transcripts that eccDNA carries were verified by outward and inward PCR. The effect of inhibition of eccDNA synthesis on FAM84B expression in PCa cells was analyzed by knocking down Lig3. The impact of FAM84B on the growth and metastases of PCa cells was verified by Cell Counting Kit-8 (CCK8), EdU, transwell assays, and a xenograft mouse model. Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) and dual-luciferase reporter assays were carried out to examine the effect of FAM84B/MYC on WWP1 transcription, and a co-immunoprecipitation (Co-IP) assay was conducted to verify the modification of CDKN1B by WWP1. The function of this molecular axis in PCa was explored by rescue assays. Results The inhibited eccDNA synthesis significantly downregulated FAM84B in PCa cells, thereby attenuating the growth and metastasis of PCa. FAM84B promoted the transcription of WWP1 by MYC by activating the expression of MYC coterminous with the 8q24.21 gene desert in a beta catenin-dependent approach. WWP1 transcription promoted by MYC facilitated the ubiquitination and degradation of CDKN1B protein and inversely attenuated the repressive effect of CDKN1B on MYC expression. Exogenous overexpression of CDKN1B blocked FAM84B-activated MYC/WWP1 expression, thereby inhibiting PCa progression. Conclusions FAM84B promoted by eccDNA mediates degradation of CDKN1B via MYC/WWP1, thereby accelerating PCa progression.

Abstract Background This study investigated the current status of the quality of life (QOL) of drug-resistant tuberculosis (DR-TB) patients in Nanjing, China, and analyzed the influencing factors. Methods The survey was conducted among patients with DR-TB who were hospitalized in the tuberculosis department of the Second Hospital of Nanjing (Nanjing Public Health Medical Center) from July 2022 to May 2023. The Chinese version of the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire was used to investigate the QOL levels of patients with DR-TB, and a multiple linear regression model was used to analyze the QOL influencing factors. Results A total of 135 patients participated in the study; 69.6% were male, the average age was 46.30 ± 17.98 years, 13.33% had an education level of elementary school or below, and 75.56% were married. The QOL scores were 51.35 ± 17.24, 47.04 ± 20.28, 43.89 ± 17.96, and 35.00 ± 11.57 in the physiological, psychological, social, and environmental domains, respectively. The differences between the four domain scores and the Chinese normative results were statistically significant (P

The rotting wood in freshwater is a unique eco-environment favoring various fungi. During our investigation of freshwater fungi on decaying wood, three hyphomycetes were collected from Jiangxi and Guangxi Provinces, China. Based on the morphological observations and phylogenetic analysis of a combined DNA data containing ITS, LSU, SSU and tef1-α sequences, two new Trichobotrys species, T. meilingensis and T. yunjushanensis, as well as a new record of T. effusa, were introduced. Additionally, a comprehensive description of the genus with both morphological and molecular data was first provided.

Abstract Non-small cell lung cancer (NSCLC) presents a global health challenge due to its low five-year survival rates, underscoring the need for novel therapeutic strategies. Our research explored the synergistic mechanisms of syrosingopine and UK-5099 in treating NSCLC. In vitro experiments showed that the combination of syrosingopine and UK-5099 significantly synergized to suppress NSCLC proliferation. Further experiments revealed that this combination induced cell cycle arrest and promoted apoptosis in NSCLC cells. In vivo experiments demonstrated that the combination of syrosingopine and UK-5099 markedly inhibited tumor growth. Mechanistic studies revealed that this drug combination promoted mitochondrial damage by inducing lactate accumulation and oxidative stress. Additionally, the combination triggered an integrated stress response (ISR) through the activation of heme-regulated inhibitor kinase (HRI). Importantly, our findings suggested that the synergistic suppression of NSCLC by syrosingopine and UK-5099 was dependent on ISR activation. In summary, our study proposed a promising therapeutic approach that involved the combination of Syrosingopine and UK-5099 to activate ISR, significantly hindering NSCLC growth and proliferation.

Melanommataceous species exhibit high diversity with a cosmopolitan distribution worldwide and show a prominent saprobic lifestyle. In this study, we explored five saprobic species collected from plant litter substrates from terrestrial habitats in China and Thailand. A combination of morphological characteristics and multi-locus phylogenetic analyses was used to determine their taxonomic classifications. Maximum Likelihood and Bayesian Inference analyses of combined LSU, SSU, ITS and tef1-α sequence data were used to clarify the phylogenetic affinities of the species. Byssosphaeria poaceicola and Herpotrichia zingiberacearum are introduced as new species, while three new host records, Bertiella fici, By. siamensis and Melanomma populicola are also reported from litter of Cinnamomum verum, Citrus trifoliata and Fagus sylvatica, respectively. Yet, despite the rising interest in the melanommataceous species, there is a considerable gap in knowledge on their host associations and geographical distributions. Consequently, we compiled the host-species associations and geographical distributions of all the so far known melanommataceous species.