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Malignant pleural mesothelioma (MPM) is a rare, highly aggressive, and lethal tumor with poor prognosis. Its survival period ranges from four months to one year, and the 5-year survival rate is only about 10%. MPM is highly resistant to chemotherapy, and conventional treatments such as cisplatin combined with pemetrexed or raltitrexed only have a certain effect in about 20% of patients. In recent years, with the continuous in-depth understanding of the genetic variation characteristics of MPM, some progress has been made in the molecular mechanism underlying the chemotherapy resistance of MPM. This article will summarize the research progress of the molecular mechanism underlying the chemotherapy resistance of MPM, including BAP1 gene mutation, microRNA, MTA1-mediated DNA damage repair pathway, GITR-GITRL pathway, TGFa pathway, tumor stem cell, EGFR, and PTEN. The aim of this work is to provide a reference for exploring new therapeutic targets and combined treatment options for MPM.

Abstract Background Describing the transmission dynamics of infectious diseases across different regions is crucial for effective disease surveillance. The multivariate time series (MTS) model has been widely adopted for constructing cross-regional infectious disease transmission networks due to its strengths in interpretability and predictive performance. Nevertheless, the assumption of constant parameters frequently disregards the dynamic shifts in disease transmission rates, thereby compromising the accuracy of early warnings. This study investigated the applicability of time-varying MTS models in multi-regional infectious disease monitoring and explored strategies for model selection. Methods This study focused on two prominent time-varying MTS models: the time-varying parameter-stochastic volatility-vector autoregression (TVP-SV-VAR) model and the time-varying VAR model using the generalized additive framework (tvvarGAM), and intended to explore and verify their applicable conditions for the surveillance of infectious diseases. For the first time, this study proposed the time delay coefficient and spatial sparsity indicators for model selection. These indicators quantify the temporal lags and spatial distribution of infectious disease data, respectively. Simulation study adopted from real-world infectious disease surveillance was carried out to compare model performances under various scenarios of spatio-temporal variation as well as random volatility. Meanwhile, we illustrated how the modelling process could help the surveillance of infectious diseases with an application to the influenza-like case in Sichuan Province, China. Results When the spatio-temporal variation was small (time delay coefficient: 0.1–0.2, spatial sparsity:0.1–0.3), the TVP-SV-VAR model was superior with smaller fitting residuals and standard errors of parameter estimation than those of the tvvarGAM model. In contrast, the tvvarGAM model was preferable when the spatio-temporal variation increased (time delay coefficient: 0.2–0.3, spatial sparsity: 0.6–0.9). Conclusion This study emphasized the importance of considering spatio-temporal variations when selecting appropriate models for infectious disease surveillance. By incorporating our novel indicators—the time delay coefficient and spatial sparsity—into the model selection process, the study could enhance the accuracy and effectiveness of infectious disease monitoring efforts. This approach was not only valuable in the context of this study, but also has broader implications for improving time-varying MTS analyses in various applications.

Abstract Background Hereditary spherocytosis (HS, MIM#612641) is one of the most common hereditary hemolytic disorders. This study aimed to confirm a novel variant’s pathogenicity and reveal a patient’s genetic etiology. Methods The clinical data of a patient with HS who underwent genetic sequencing at the Children’s Hospital of Chongqing Medical University were reviewed retrospectively. In silico prediction and in vitro minigene splicing reporter system were then conducted on the detected variant to analyze its intramolecular impact. A summary of the literature related to HS due to SPTB gene variants was also presented. Results A novel variant (c.301–2 A > G) in the SPTB gene (NM_001024858.4) was identified in the proband. Using Sanger sequencing, we conclusively confirmed that the inheritance of the variant could not be traced to the biological parents. The in vitro minigene assay revealed three different transcripts derived from the c.301–2 A > G variant: r.301_474del, r.301_306delCCAAAG, and r.301-1_301-57ins. Through a literature review, patients with HS who had been genotypically validated were summarized and the SPTB gene variant profile was mapped. Conclusion We identified a splicing variant of the SPTB gene, thus confirming its aberrant translation. The novel variant was the probable genetic etiology of the proband with HS. Our findings expanded the variant spectrum of the SPTB gene, thus improving the understanding of the associated hereditary hemolytic disorders from a clinical and molecular perspective and contributing to the foundation of genetic counseling and diagnosis.

Abstract Background Appropriate iron supplementation is essential for neonatal growth and development. However, there are few reports on the effects of iron overload on neonatal growth and immune homeostasis. Thus, the aim of this study was to investigate the effects of iron nutrition on neonatal growth and intestinal immunity by administering different levels of iron to neonatal pigs. Results We found that iron deficiency and iron overload resulted in slow growth in neonatal pigs. Iron deficiency and iron overload led to down-regulation of jejunum intestinal barrier and antioxidant marker genes, and promoted CD8+ T cell differentiation in jejunum and mesenteric lymph nodes (MLN) of pigs, disrupting intestinal health. Moreover, iron levels altered serum iron and tissue iron status leading to disturbances in redox state, affecting host innate and adaptive immunity. Conclusions These findings emphasized the effect of iron nutrition on host health and elucidated the importance of iron in regulating redox state and immunity development. This study provided valuable insights into the regulation of redox state and immune function by iron metabolism in early life, thus contributing to the development of targeted interventions and nutritional strategies to optimize iron nutrition in neonates.

MicroRNAs (miRNAs) have been demonstrated to control chicken skeletal muscle growth, however, the potential function of the miR-181-5p family in chicken myogenesis remains largely unknown. Here, our study identified the two chicken (Gallus gallus; Gga) miR-181-5p family members widely expressed in various tissues, specifically miR-181a-5p and miR-181b-5p. Besides, the breast muscles of fast-growing broilers expressed higher levels of miR-181a-5p and miR-181b-5p than those of slow-growing layers. Functionally, miR-181a-5p and miR-181b-5p both promote the expression level of myogenic factors including myogenin (MyoG), myogenic differentiation 1 (MyoD1), and myosin heavy chain (MyHC), meanwhile accelerating the myotube formation of skeletal muscle satellite cells (SMSCs). Mechanistically, miR-181a-5p and miR-181b-5p directly bind to the 3´ untranslated region (UTR) of the transforming growth factor beta receptor 1 (TGFBR1) mRNA, further reducing the expression of TGFBR1. TGFBR1 is a key Transforming growth factor beta (TGF-β) signaling transduction receptor and had a negative function in muscle cell differentiation. Furthermore, knockdown of TGFBR1 facilitated the expression of chicken myogenic factors, boosted myotube formation, and decreased the SMAD family member 2/3 (SMAD2/3) phosphorylation in chicken SMSCs. SMAD2/3 are downstream of TGF-β signaling, and miR-181a-5p and miR-181b-5p could reduce the expression of TGFBR1 to further diminish the SMAD2/3 phosphorylation. Our findings revealed that the miR-181-5p family targets TGFBR1 to break the TGF-β signaling transduction, which resulted in promoting chicken skeletal muscle development.

Abstract Background Breast cancer is one of the most lethal cancers in women. Despite significant advances in the diagnosis and treatment of breast cancer, many patients still succumb to this disease, and thus, novel effective treatments are urgently needed. Natural product coumarin has been broadly investigated since it reveals various biological properties in the medicinal field. Accumulating evidence indicates that histone deacetylase inhibitors (HDACIs) are promising novel anti-breast cancer agents. However, most current HDACIs exhibit only moderate effects against solid tumors and are associated with severe side effects. Thus, to develop more effective HDACIs for breast cancer therapy, hydroxamate of HDACIs was linked to coumarin core, and coumarin-hydroxamate hybrids were designed and synthesized. Methods A substituted coumarin moiety was incorporated into the classic hydroxamate HDACIs by the pharmacophore fusion strategy. ZN444B was identified by using the HDACI screening kit and cell viability assay. Molecular docking was performed to explore the binding mode of ZN444B with HDAC1. Western blot, immunofluorescent staining, cell viability, colony formation and cell migration and flow cytometry assays were used to analyze the anti-breast cancer effects of ZN444B in vitro. Orthotopic studies in mouse models were applied for preclinical evaluation of efficacy and toxicity in vivo. Proteomic analysis, dual-luciferase reporter assay, chromatin immunoprecipitation, co-immunoprecipitation, immunofluorescent staining assays along with immunohistochemical (IHC) analysis were used to elucidate the molecular basis of the actions of ZN444B. Results We synthesized and identified a novel coumarin-hydroxamate conjugate, ZN444B which possesses promising anti-breast cancer activity both in vitro and in vivo. A molecular docking model showed that ZN444B binds to HDAC1 with high affinity. Further mechanistic studies revealed that ZN444B specifically decreases FOS-like antigen 2 (FOSL2) mRNA levels by inhibiting the deacetylase activity of HDAC1 on Sp1 at K703 and abrogates the binding ability of Sp1 to the FOSL2 promoter. Furthermore, FOSL2 expression positively correlates with breast cancer progression and metastasis. Silencing FOSL2 expression decreases the sensitivity of breast cancer cells to ZN444B treatment. In addition, ZN444B shows no systemic toxicity in mice. Conclusions Our findings highlight the potential of FOSL2 as a new biomarker and therapeutic target for breast cancer and that targeting the HDAC1-Sp1-FOSL2 signaling axis with ZN444B may be a promising therapeutic strategy for breast cancer.

Abstract Background Myopia is a major health issue around the world. Myopia in children has increased significantly during the COVID-19 pandemic in China, but reports are scarce on the prevalence of myopia following the pandemic. This study collected vision screening data of school children in China for five consecutive years to observe the changes in myopia after the pandemic and compare the observed prevalence of myopia before and after the pandemic. Methods A school-based vision screening study used stratified samplings to collect the vision screening data in school children aged 6–13 from 45 primary schools in Hangzhou. Vision screening data including uncorrected visual acuity(UCVA) and spherical equivalent refraction(SER). Calculating the mean of SER and the prevalence of myopia and hyperopia from 2019 to 2023. Results A total of 79,068 screening results (158,136 eyes) were included in the analysis. A substantial myopic shift (approximately -0.30 diopters [D] on average) was found in 2020 and 2021 compared with 2019 in all age groups and a substantial myopic shift (approximately 0.4 D on average) was found in 2022 compared with 2021. A slight myopic shift (approximately -0.14 D on average) was found in 2023 compared with 2022. The prevalence of myopia in all age groups was the highest for five years in 2020 or 2021, which was 31.3% for 6-year-olds, 43.0% for 7-year-olds, and 53.7% for 8-year-olds. A positive change in the prevalence rate of myopia was found at 6 years old (0.59%, 0.12%, 0.36%, 0.25%, p

Abstract This research examines the association between blood pressure variability (BPV) and renal damage in a cohort of 129 primary aldosteronism (PA) patients, employing ambulatory blood pressure monitoring (ABPM) for comparative analysis with individuals diagnosed with essential hypertension (EH). The study reveals that PA patients exhibited significantly elevated levels of cystatin C and urine microalbumin/creatinine ratio (UACR). Additionally, a higher prevalence of non‐dipping blood pressure patterns in PA patients suggests an increased risk of circadian blood pressure regulation disturbances. Notably, while most BPV indices were comparable between the two groups, the standard deviation of 24‐h weighted diastolic blood pressure was markedly lower in the PA cohort, distinguishing it as a unique variable. Through multiple linear regression analysis, the duration of hypertension, angiotensin II concentrations, and daytime systolic blood pressure standard deviation emerged as significant determinants of estimated glomerular filtration rate (eGFR) in PA patients. Furthermore, UACR was significantly influenced by variables including the 24‐h weighted standard deviation (wSD) of systolic BP, glycosylated hemoglobin levels, nocturnal systolic BP peaks, aldosterone‐renin ratio (ARR), and total cholesterol, with the most pronounced association observed with the 24‐h wSD of systolic BP (β = 0.383).The study also found significant correlations between the 24‐h wSD of systolic BP, ARR, HbA1c, serum potassium levels, and 24‐h urinary microalbumin, underscoring the critical role of the 24‐h wSD of systolic BP (β = 0.267). These findings underscore the imperative of an integrated management strategy for PA, addressing the intricate interconnections among metabolic abnormalities, blood pressure variability, and renal health outcomes.

Abstract When a high‐speed train approaches the insulated phase‐splitting section embedded between neighbouring power supply arms, the vacuum circuit breaker (VCB) installed on trains must be disconnected to maintain the traction power supply system as a no‐load condition for completing phase‐switching action, as the train passes through the phase‐splitting section depending on its inertia. However, when operating VCBs, the arc is easily triggered between the mobile contacts inside, accompanied by an overvoltage impulse. Herein, to explore the generating mechanism of inrush current and operational overvoltage, a model describing the ‘substation‐catenary‐train’ traction power supply system is launched based on an equivalent circuit modelling technique. Through the analysis of the transient VCB operational process, the phase of catenary voltage is directly related to the characteristics of the VCB switching‐on overvoltage, as the traction current's phase angle is relevant to the amplitude‐frequency characteristics of the VCB switching‐off overvoltage. Inrush current as a noteworthy element is related to the traction transformer's remanence. The automatic phase‐switching technique is utilised to suppress both operational overvoltage and inrush current, as the optimal combination of VCB switching‐on and switching‐off phases considering the balance between overvoltage and inrush current is achieved based on the particle swarm algorithm.

Abstract As the mean age of first-time mothers increases in the industrialized world, inquiries into causes of human reproductive senescence have followed. Rates of ovulatory dysfunction and oocyte aneuploidy parallel chronological age, but poor reproductive outcomes in women older than 35 years are also attributed to endometrial senescence. The current studies, using primary human endometrial stromal cell (ESC) cultures as an in vitro model for endometrial aging, characterize the proinflammatory cytokine, IL-1β-mediated and passage number-dependent effects on ESC phenotype. ESC senescence was accelerated by incubation with IL-1β, which was monitored by RNA sequencing, ELISA, immunocytochemistry and Western blotting. Senescence associated secreted phenotype (SASP) proteins, IL-1β, IL-6, IL-8, TNF-α, MMP3, CCL2, CCL5, and other senescence-associated biomarkers of DNA damage (p16, p21, HMGB1, phospho-γ-histone 2 A.X) were noted to increase directly in response to 0.1 nM IL-1β stimulation. Production of the corresponding SASP proteins increased further following extended cell passage. Using enzyme inhibitors and siRNA interference, these effects of IL-1β were found to be mediated via the c-Jun N-terminal kinase (JNK) signaling pathway. Hormone-induced ESC decidualization, classical morphological and biochemical endocrine responses to estradiol, progesterone and cAMP stimulation (prolactin, IGFBP-1, IL-11 and VEGF), were attenuated pari passu with prolonged ESC passaging. The kinetics of differentiation responses varied in a biomarker-specific manner, with IGFBP-1 and VEGF secretion showing the largest and smallest reductions, with respect to cell passage number. ESC hormone responsiveness was most robust when limited to the first six cell passages. Hence, investigation of ESC cultures as a decidualization model should respect this limitation of cell aging. The results support the hypotheses that “inflammaging” contributes to endometrial senescence, disruption of decidualization and impairment of fecundity. IL-1β and the JNK signaling pathway are pathogenetic targets amenable to pharmacological correction or mitigation with the potential to reduce endometrial stromal senescence and enhance uterine receptivity.

The use of next-generation probiotics (NGP) in pigs for combating diseases has been subject to limited research. Here we explored the potential of a well-known NGP candidate Akkermansia muciniphila targeting pig gut health. In the first screening experiment, we found that the abundance of A. muciniphila peaked at 14 d old but decreased at weaning (21 d old; P

Benzyl and phenylpropanoid acids are widely used in organic synthesis of fine chemicals, such as pharmaceuticals and condiments. However, biocatalysis of these acids has received less attention than chemical synthesis. One of the main challenges for biological production is the limited availability of alcohol dehydrogenases and aldehyde dehydrogenases. Environmental microorganisms are potential sources of these enzymes. In this study, 129 alcohol dehydrogenases and 42 aldehyde dehydrogenases from Corynebacterium glutamicum, Pseudomonas aeruginosa, and Bacillus subtilis were identified and explored with various benzyl and phenylpropanoid alcohol and aldehyde substrates, among which four alcohol dehydrogenases and four aldehyde dehydrogenases with broad substrate specificity and high catalytic activity were obtained. Moreover, a cascade whole-cell catalytic system including ADH-90, ALDH-40, and the NAD(P)H oxidase LreNox was established, which showed high efficiency in converting cinnamyl alcohol and p-methylbenzyl alcohol into the respective carboxylic acids. Remarkably, this biocatalytic system can be easily scaled up to gram-level production, facilitating preparation purposes.

Enhancing the capabilities of unmanned space exploration, such as satellite monitoring and space science missions, requires efficient and reliable nuclear power systems. A viable solution is found in the 1–10 kWe power level of space nuclear reactor power systems, offering advantages such as a manageable research and development process, and relatively low investment requirements. This paper introduces a conceptual design for a 5 kWe space nuclear reactor power system, outlining its components and characteristics. The study includes a thorough analysis of potential challenges, encompassing heat pipe failure accidents, re-entry scenarios, and weight estimation considerations. The results demonstrate that the proposed space nuclear reactor power system effectively meets the safety requirements. The total mass of the power system is estimated at approximately 1.5 tons, with a specific mass of around 300 kg/kWe. This research contributes valuable insights for the design of space nuclear reactor power systems operating within a similar power range.

In this study, the keyhole dynamic behavior and molten pool flow were investigated to elucidate the effects of oscillating laser on porosity in narrow-gap oscillating laser-MIG hybrid welding of aluminum alloys. A weld with a porosity of 0.08% was produced at the laser oscillating frequency of 600 Hz and diameter of 1 mm, while 2.27% without oscillating laser. Compared to non-oscillating laser, keyhole opening size increased by about 2.3 times and keyhole depth fluctuation was suppressed. The forces acted on the interface between keyhole wall and molten pool became more balanced. The increased vapor recoil pressure overcame the combined closure effect of gravity and molten pool pressure. While applying oscillating laser, the vortex in molten pool was eliminated and the liquid metal flow was more stable. The combined impact force caused by droplets transfer and liquid metal convection due to constraining effect of narrow gap was buffered, which had less effect on molten pool and keyhole stability. The liquid metal tended to flow from the molten pool inside to surface, which favored the escape of bubbles from the molten pool.

To explain the moisture adsorption properties and improve the package material of polydextrose product, the adsorption and desorption isotherms of five domestic samples with initial moisture content (IMC) of 1.01%~4.89% were determined in this study in the range of 20~35 ℃ and ERH10%~90% using a dynamic water sorption analyzer. The adsorption and desorption isotherms were sigmoidal-shaped curves, and there was a hysteresis between desorption isotherm and the adsorption isotherm when ERH was less than 80%. Because polydextrose is an amorphous phase powder, we assumed that the water adsorption process of polydextrose was an equilibrium that existed among the vapor phase, the liquid phase (polylayer adsorption) and the solid solution (monolayer adsorption), and the adsorptive and desorptive sigmoidal-shaped isotherms can be de-convolved into a monolayer (Mh) and a polylayer component (Md) in accordance with Hailwood- Horrobin (HH) model. The polylayer water content of adsorption and desorption showed a sigmoidal increase with increasing ERH. The monolayer water content of desorption remained constant with increasing ERH, while that of the adsorption increased slowly for samples a1 to a4 with IMC 4.87% to 2.35% and decreased almost linearly for sample a5 with IMC 1.01%. As the IMCs of the samples decreased, the molecular weight of the polymer at the sorption site was maximum for sample a1 and minimum for sample a5. Although the FTIR showed the smallest intensity of hydroxyl group (3 416 cm–1) and amorphous structural functional group (1 027 cm–1) for a5 sample, a5 sample had the largest moisture absorption rate. These results suggested that, for the lower moisture content of polydextrose samples processed by different processes, their adsorptive monolayer water content seemed to decrease almost linearly with an increase of ERH. However their adsorptive polylayer water content sigmoidally increased with an increase of ERH, and their moisture absorption rate and hygroscopic capacity increased.

Abstract Multi‐label image recognition (MLR) is a significant branch of image classification that aims to assign multiple categorical labels to each input. Previous research has focused on enhancing the learning of category‐related regional features. However, the potential impact of multi‐scale distributions in intra‐ and inter‐category targets on MLR tends to be neglected. Besides, semantic consistency for categories is restricted to be considered on single‐scale features, resulting in suboptimal feature extraction. To address the limitations of above, a Multi‐stage Feature Aggregation (MSFA) network is proposed. In MSFA, a novel local feature extraction method is suggested to progressively extract category‐related high‐resolution local features in both spatial and channel dimensions. Subsequently, local and global features are fused without additional up‐ and down‐sampling to enrich the scale diversity of the features while incorporating refined class‐specific information. Furthermore, a hierarchical prediction scheme for MLR is proposed, which generates classification confidence corresponding to different scales under hierarchical loss supervision. Consequently, the final output of the network comes from the joint prediction by the classifiers on multi‐scale features, ensuring a stronger feature extraction capability. The extensive experiments have been carried on VOC and MS‐COCO datasets, and the superiority of MSFA over existing mainstream methods has been verified.

Abstract The Australian culturally and linguistically diverse (CALD) communities may be at higher risk of salt intake than recommended given the use of a combination of discretionary sources and exposure to processed foods within a western country. This survey aimed to understand the knowledge, attitudes, and behaviors toward dietary salt and the acceptability of salt substitutes in the CALD communities. An online cross‐sectional survey was conducted among adults who self‐reported being a part of a CALD community, which was defined as non‐Indigenous cultural groups in Australia having cultural or linguistic connections with their overseas place of birth, ancestry or ethnic origin, religion, preferred language or language spoken at home. A total of 218 respondents opened the survey link. A total of 196 completed the entire survey. The majority of respondents (162, 83%) were aware that high salt intake causes serious health problems. Altogether 134 (69%) respondents were aware that there is a recommended amount for daily salt consumption although only 59 (44%) knew precise recommendations as

Abstract Background Emerging evidence indicates carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the development of atherosclerosis (AS). However, the roles and functions of CEACAM1 in AS remain unknown. Therefore, this study aims to investigate the roles and molecular functions of CEACAM1 in AS. Methods We constructed a diabetes mellitus (DM) + high-fat diet (HFD) mouse model based on the streptozotocin (STZ)-induced apolipoprotein E-knockdown (ApopE−/−) mouse to investigate the roles and regulatory mechanism of miR-449a/CEACAM1 axis. The mRNA expression and protein levels in this study were examined using quantity PCR, western blot, immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC), respectively. And the lipid deposition and collagen content were detected using Oil Red O and Sirius Red staining. Cell apoptosis, migration, invasion, and tuber formation were detected by Annexin-V FITC/PI, wound healing, transwell, and tuber formation assays, respectively. The relationship between miR-449a and CEACAM1 was determined by a dual-luciferase reporter gene assay. Results miR-449a and MMP-9 were upregulated, and CEACAM1 was downregulated in the DM + HFD MOUSE model. Upregulation of CEACAM1 promoted atherosclerotic plaque stability and inhibited inflammation in the DM + HFD mouse model. And miR-449a directly targeted CEACAM1. Besides, miR-449a interacted with CEACAM1 to regulate atherosclerotic plaque stability and inflammation in DM-associated AS mice. In vitro, the rescue experiments showed miR-449a interacted with CEACAM1 to affect apoptosis, migration, invasion, and tuber formation ability in high glucose (HG)-induced HUVECs. Conclusion These results demonstrated that miR-449a promoted plaque instability and inflammation in DM and HFD-induced mice by targeting CEACAM1.

Abstract Background Family-centered empowerment programs have been widely used in the pediatric field. Therefore, the current study investigated the effectiveness of family empowerment programs on caregiving ability and adverse mood among caregivers of children with acute leukemia. Objective To evaluate the effect of a family empowerment program on the caregiving ability and adverse mood of caregivers of children with acute leukemia. Methods Sixty-eight children with acute leukemia and their family caregivers admitted to our hospital were selected for the study. The control group received routine care during hospitalization, and the family empowerment program was implemented in the intervention group to compare the changes in caregiving capacity (FCTI), illness uncertainty (PPUS) and anxiety(SAS)of the caregivers of the two groups. Results After 8 weeks of intervention, the FCTI score of the intervention group was significantly lower than that of the control group (P

Abstract Introduction Chronic non-infectious uveitis affecting the posterior segment (NIU-PS), which can be recurrent and persistent for numerous years, mainly affects people of working age and significantly increases the risk of visual impairment. This study aimed to investigate the cost-effectiveness of fluocinolone acetonide intravitreal (FAI) implant in the treatment of patients with chronic NIU-PS from the Chinese healthcare perspective. Methods A Markov model with a 2-week cycle was constructed from the perspective of the Chinese healthcare system over a lifetime time horizon. The model consists of four health states: on-treatment, treatment failure, blindness, and death. The outcomes for effectiveness were based on the Chinese real-world study (RWS). Utilities and mortality rates were derived from published literature and standard sources. Costs were determined from the MENET website, prices of medical service items at local providers, published literature, and expert surveys. Outcomes were measured in quality-adjusted life years (QALYs). Sensitivity analyses were performed to account for the impact of uncertainty. Results It was estimated that in the base case, the FAI implant provided 0.43 incremental QALYs compared with the limited current practice (LCP) at an additional cost of $7503.72 (¥50,575.05), resulting in an incremental cost-effectiveness ratio (ICER) of $17,373.49 (¥117,097.33) per QALY gained. Parameters related to utility emerged as the primary influencers on the outcomes. In probabilistic sensitivity analysis (PSA), considering the willingness-to-pay (WTP) threshold of $19,072 (¥128,547) and $38,145 (¥257,094), the FAI implant had 67.70% and 99.50% probability of being cost-effective, respectively. As demonstrated in the scenario analysis, if the FAI implant aligns its price reduction with the average rate from the 2023 negotiation of the National Reimbursement Drug List (NRDL), it would result in lower costs and represent an absolute advantage. Conclusions The FAI implant, which can effectively reduce the recurrence rate and maintain the incremental costs within the WTP limit, is likely to be cost-effective in treating chronic NIU-PS in China.

Abstract Background The association between the triglyceride glucose (TyG) index and the risk of early-onset atherosclerotic cardiovascular disease (ASCVD) events or all-cause mortality in young and middle-aged people is not fully elucidated. Methods The present study included 64,489 young and middle-aged people who participated in the 2006 Kailuan Study physical examination. Multivariate Cox proportional hazards models and restricted cubic spline curves were used to assess the association of TyG index with early-onset ASCVD events and all-cause mortality. Results During a median of 11-year follow-up, 1984 (3.08%) participants experienced at least one ASCVD event and 1,392 (2.16%) participants experienced all-cause death. A higher TyG index was significantly associated with a higher risk of early-onset ASCVD events (HR: 1.61, 95% CI 1.38–1.89) and all-cause mortality (HR: 1.39, 95% CI 1.17–1.65), respectively. For each unit increase in TyG index, the risk of early-onset ASCVD events increased by 20%. In addition, there was a non-linear association between the TyG index and early-onset ASCVD events (P for non-linear

Abstract Brasenia schreberi, a plant species traditionally utilized in Chinese medicine and cuisine, represents an early evolutionary stage among flowering plants (angiosperms). While the plastid genome of this species has been published, its mitochondrial genome (mitogenome) has not been extensively explored, with a notable absence of thorough comparative analyses of its organellar genomes. In our study, we had assembled the entire mitogenome of B. schreberi utilizing the sequencing data derived from both Illumina platform and Oxford Nanopore. The B. schreberi mitogenome mostly exists as six circular DNA molecules, with the largest being 628,257 base pairs (bp) and the smallest 110,220 bp, amounting to 1.49 megabases (Mb). Then we annotated the mitogenome of B. schreberi. The mitogenome encompasses a total of 71 genes: 40 of these are coding proteins genes (PCGs), 28 are genes for transfer RNA (tRNA), and the remaining 3 are genes for ribosomal RNA (rRNA). In the analysis of codon usage, we noted a unique codon preference specific to each amino acid. The most commonly used codons exhibited an average RSCU of 1.36, indicating a noticeable bias in codon selection. In the repeat sequence analysis, a total of 553 simple sequence repeats (SSRs) were identified, 1,822 dispersed repeats (comprising 1,015 forward and 807 palindromic repeats), and 608 long terminal repeats (LTRs). Additionally, in the analysis of homologous sequences between organelle genomes, we detected 38 homologous sequences derived from the plastid genome, each exceeding 500 bp, within the B. schreberi mitochondrial genome. Notably, ten tRNA genes (trnC-GCA, trnM-CAU, trnI-CAU, trnQ-UUG, trnN-GUU, trnT-GGU, trnW-CCA, trnA-UGC, trnI-GAU, and trnV-GAC) appear to have been completely transferred from the chloroplast to the mitogenome. Utilizing the Deepred-mt to predict the RNA editing sites in the mitogenome, we have identified 675 high-quality RNA editing sites in the 40 mitochondrial PCGs. In the final stage of our study, we performed an analysis of colinearity and inferred the phylogenetic relationship of B. schreberi with other angiosperms, utilizing the mitochondrial PCGs as a basis. The results showed that the non-coding regions of the B. schreberi mitogenome are characterized by an abundance of repetitive sequences and exogenous sequences, and B. schreberi is more closely related with Euryale ferox.

Abstract Background HIV-tuberculosis (HIV-TB) co-infection is a significant public health concern worldwide. TB delay, consisting of patient delay, diagnostic delay, treatment delay, increases the risk of adverse anti-TB treatment (ATT) outcomes. Except for individual level variables, differences in regional levels have been shown to impact the ATT outcomes. However, few studies appropriately considered possible individual and regional level confounding variables. In this study, we aimed to assess the association of TB delay on treatment outcomes in HIV-TB co-infected patients in Liangshan Yi Autonomous Prefecture (Liangshan Prefecture) of China, using a causal inference framework while taking into account individual and regional level factors. Methods We conducted a study to analyze data from 2068 patients with HIV-TB co-infection in Liangshan Prefecture from 2019 to 2022. To address potential confounding bias, we used a causal directed acyclic graph (DAG) to select appropriate confounding variables. Further, we controlled for these confounders through multilevel propensity score and inverse probability weighting (IPW). Results The successful rate of ATT for patients with HIV-TB co-infection in Liangshan Prefecture was 91.2%. Total delay (OR = 1.411, 95% CI: 1.015, 1.962), diagnostic delay (OR = 1.778, 95% CI: 1.261, 2.508), treatment delay (OR = 1.749, 95% CI: 1.146, 2.668) and health system delay (OR = 1.480 95% CI: (1.035, 2.118) were identified as risk factors for successful ATT outcome. Sensitivity analysis demonstrated the robustness of these findings. Conclusions HIV-TB co-infection prevention and control policy in Liangshan Prefecture should prioritize early treatment for diagnosed HIV-TB co-infected patients. It is urgent to improve the health system in Liangshan Prefecture to reduce delays in diagnosis and treatment.

Abstract Background This study was designed to assess the associations between emerging cardiometabolic indices—the atherogenic index of plasma (AIP), the stress hyperglycemia ratio (SHR), the triglyceride-glucose (TyG) index, and the homeostasis model assessment of insulin resistance (HOMA-IR)—and the incidence of diabetic kidney disease (DKD) in type 2 diabetes (T2D) patients. Methods We consecutively enrolled 4351 T2D patients. The AIP, SHR, TyG index, and HOMA-IR were calculated from baseline parameters. DKD was defined as a urine albumin/creatinine ratio > 30 mg/g or an eGFR

Abstract Background Centromeres play a crucial and conserved role in cell division, although their composition and evolutionary history in green algae, the evolutionary ancestors of land plants, remains largely unknown. Results We constructed near telomere-to-telomere (T2T) assemblies for two Trebouxiophyceae species, Chlorella sorokiniana NS4-2 and Chlorella pyrenoidosa DBH, with chromosome numbers of 12 and 13, and genome sizes of 58.11 Mb and 53.41 Mb, respectively. We identified and validated their centromere sequences using CENH3 ChIP-seq and found that, similar to humans and higher plants, the centromeric CENH3 signals of green algae display a pattern of hypomethylation. Interestingly, the centromeres of both species largely comprised transposable elements, although they differed significantly in their composition. Species within the Chlorella genus display a more diverse centromere composition, with major constituents including members of the LTR/Copia, LINE/L1, and LINE/RTEX families. This is in contrast to green algae including Chlamydomonas reinhardtii, Coccomyxa subellipsoidea, and Chromochloris zofingiensis, in which centromere composition instead has a pronounced single-element composition. Moreover, we observed significant differences in the composition and structure of centromeres among chromosomes with strong collinearity within the Chlorella genus, suggesting that centromeric sequence evolves more rapidly than sequence in non-centromeric regions. Conclusions This study not only provides high-quality genome data for comparative genomics of green algae but gives insight into the composition and evolutionary history of centromeres in early plants, laying an important foundation for further research on their evolution.

To understand the cause for the increasing water absorption rate of wheat shorts after cold plasma treatment, a dynamic moisture adsorption instrument was used to measure the moisture sorption isotherms of samples treated with 120 W low-pressure strong radio frequency helium or oxygen CP for different times. The result was that the Caurie equation can fit an isotherm, and its coefficient C0 gived the density of water adsorbed by the sample. For adsorbed or desorbed samples, as the helium or oxygen CP treatment time at the same power increased, there was no difference in the density of adsorbed water, and the coefficient M0 gived the adsorbed water content of the monomolecular layer of the sample. For adsorbed or desorbed samples, as the helium CP treatment time at the same power increased, the water content of the monomolecular layer increased significantly. For samples treated with oxygen plasma, the content of the adsorbed monomolecular layer water first decreased and then increased as the treatment time increased, while the desorbed single-molecule water content showed a decreasing trend with the increased time. In order to improve the fitting of the Caurie equation, M0 was corrected to A+Bt (t was the temperature, A and B were constants). Analysis of the coefficients of the modified Caurie equation showed that as the 120 W helium CP treatment time (0~180 s) increased, the monomolecular layer of water, the number of adsorbed water molecule layers, the bound water content, and the water adsorption surface area all showed a continuous increase trend. For oxygen CP, these indicators showed an increasing trend in the first 60 s of processing, and then showed a decreasing trend if the processing time was extended. The results showed that compared with oxygen-cold plasma, high-energy helium-cold plasma improved the hydrophilicity of wheat shorts proteins and polysaccharides. As the treatment time increased, the surface area and number of layers of water adsorbed by these macromolecules and the monomolecular layer, and the bound water content steadily continued to increase.

Abstract This study aims to develop and validate nomogram models utilizing clinical and thoracic aorta imaging factors to assess the risk of hypertension for lung cancer screening cohorts. We included 804 patients and collected baseline clinical data, biochemical indicators, coexisting conditions, and thoracic aorta factors. Patients were randomly divided into a training set (70%) and a validation set (30%). In the training set, variance, t-test/Mann–Whitney U-test and standard least absolute shrinkage and selection operator were used to select thoracic aorta imaging features for constructing the AIScore. Multivariate logistic backward stepwise regression was utilized to analyze the influencing factors of hypertension. Five prediction models (named AIMeasure model, BasicClinical model, TotalClinical model, AIBasicClinical model, AITotalClinical model) were constructed for practical clinical use, tailored to different data scenarios. Additionally, the performance of the models was evaluated using receiver operating characteristic (ROC) curves, calibration curves and decision curve analyses (DCA). The areas under the ROC curve for the five models were 0.73, 0.77, 0.83, 0.78, 0.84 in the training set, and 0.77, 0.78, 0.81, 0.78, 0.82 in the validation set, respectively. Furthermore, the calibration curves and DCAs of both sets performed well on accuracy and clinical practicality. The nomogram models for hypertension risk prediction demonstrate good predictive capability and clinical utility. These models can serve as effective tools for assessing hypertension risk, enabling timely non-pharmacological interventions to preempt or delay the future onset of hypertension.

Abstract In this paper, a composite pressure-sensitive mechanism combining diaphragm bending and volume compression was developed for resonant pressure microsensors to achieve high-pressure measurements with excellent accuracy. The composite mechanism was explained, and the sensor structure was designed based on theoretical analysis and finite element simulation. An all-silicon resonant high-pressure microsensor with multiple miniaturized cavities and dual resonators was developed, where dual resonators positioned in two resonant cavities with suitably different widths are used to perform opposite characteristics in pressure and the same characteristics at different temperatures, which can improve pressure sensitivities and realize temperature self-compensation by differential frequency output. The microsensor was fabricated by microfabrication, and the experimental results showed that the sensor had an accuracy of ±0.015% full scale (FS) in a pressure range of 0.1~100 MPa and a temperature range of −10~50 °C. The pressure sensitivity of the differential frequency was 261.10 Hz/MPa (~2523 ppm/MPa) at a temperature of 20 °C, and the temperature sensitivities of the dual resonators were −1.54 Hz/°C (~−14.5 ppm/°C) and −1.57 Hz/°C (~−15.6 ppm/°C) at a pressure of 2 MPa. The differential output had an outstanding stability within ±0.02 Hz under constant temperature and pressure. Thus, this research provides a convenient solution for high-pressure measurements because of its advantages, namely, large range, excellent accuracy and stability.

Abstract Background Childhood maltreatment stands as a salient risk factor in the etiology of juvenile delinquency, with a profound impact on the behavioral trajectories of young offenders. However, there is limited research on latent profile analysis to explore distinctive patterns of childhood maltreatment in Chinese juvenile offenders. Consequently, there is a lack of understanding regarding the associations between maltreatment profiles and relevant variables in this context. The present study aimed to explore meaningful subgroups of childhood maltreatment in juvenile offenders, and we further examined the associations between subgroups and multiple outcomes especially psychopathy. Methods The data was obtained from a sample of Chinese juvenile offenders (N = 625, M age = 17.22, SD = 1.23). This study employed a latent profile analysis (LPA) based on factor scores of the Childhood Trauma Questionnaire-Short Form to identify the subgroups and examined the differences across subgroups using outcomes variables including psychopathy, callous-unemotional traits, aggression and anxiety. This study includes three self-report measures to evaluate psychopathy, with due regard for the nuanced considerations on the factor structure inherent in the conceptualization of psychopathy. Results Two subgroups were identified, including the non-maltreatment subgroup (80.2%) and the maltreatment subgroup (19.8%). Maltreatment subgroup was characterized by a greater level of all types of maltreatment with particularly higher of emotion neglect. Besides, we found that maltreatment subgroup showed a significantly higher level of psychopathy across multiple self-report measures, and greater callous-unemotional traits, lack of empathy, aggression and anxiety. We found two subgroups of child maltreatment in Chinese juvenile offenders. Conclusions These findings may provide a further understanding of childhood maltreatment and the clinical intervention on psychopathy in the early period.

Abstract Image segmentation is a fundamental task in deep learning, which is able to analyse the essence of the images for further development. However, for the supervised learning segmentation method, collecting pixel-level labels is very time-consuming and labour-intensive. In the medical image processing area for optic disc and cup segmentation, we consider there are two challenging problems that remain unsolved. One is how to design an efficient network to capture the global field of the medical image and execute fast in real applications. The other is how to train the deep segmentation network using a few training data due to some medical privacy issues. In this paper, to conquer such issues, we first design a novel attention-aware segmentation model equipped with the multi-scale attention module in the pyramid structure-like encoder-decoder network, which can efficiently learn the global semantics and the long-range dependencies of the input images. Furthermore, we also inject the prior knowledge that the optic cup lies inside the optic disc by a novel loss function. Then, we propose a self-supervised contrastive learning method for optic disc and cup segmentation. The unsupervised feature representation is learned by matching an encoded query to a dictionary of encoded keys using a contrastive technique. Finetuning the pre-trained model using the proposed loss function can help achieve good performance for the task. To validate the effectiveness of the proposed method, extensive systemic evaluations on different public challenging optic disc and cup benchmarks, including DRISHTI-GS and REFUGE datasets demonstrate the superiority of the proposed method, which can achieve new state-of-the-art performance approaching 0.9801 and 0.9087 F1 score respectively while gaining 0.9657 $$DC_{disc}$$ D C disc and 0.8976 $$DC_{cup}$$ D C cup . The code will be made publicly available.

Pidan is an original traditional food in China, which has attracted extensive attention of researchers because of its unique color, fragrance, taste and functions of clearing heat, purging fire, reducing inflammation. Metallic compounds, alkali concentration, and temperature are important in the process of gel formation. Although many studies related to Pidan have been published, there is no systematic summary on the formation mechanism of gel and flavor profile. In this paper, the regulation mechanism of metal compounds in alkaline solutions, and the formation mechanism of gel, color, flavor profile, and Songhua are systematically and comprehensively reviewed to provide theoretical support for the production development and processing of Pidan.

Rotaviruses (RV) are a major cause of severe gastroenteritis, particularly in neonatal piglets. Despite the availability of effective vaccines, the development of antiviral therapies for RV remains an ongoing challenge. Retinoic acid (RA), a metabolite of vitamin A, has been shown to have anti-oxidative and antiviral properties. However, the mechanism by which RA exerts its intestinal-protective and antiviral effects on RV infection is not fully understood. The study investigates the effects of RA supplementation in Duroc × Landrace × Yorkshire (DLY) piglets challenged with RV. Thirty-six DLY piglets were assigned into six treatments, including a control group, RA treatment group with two concentration gradients (5 and 15 mg/d), RV treatment group, and RV treatment group with the addition of different concentration gradients of RA (5 and 15 mg/d). Our study revealed that RV infection led to extensive intestinal architecture damage, which was mitigated by RA treatment at lower concentrations by increasing the villus height and villus height/crypt depth ratio (P

In the study, the effects of gap sizes on interfacial reaction and mechanical property were investigated for laser welding-brazing of titanium alloy and aluminum alloy. The wetting width on the joint rear surface was initially increased and then decreased with the increase of gap size. A layer of Ti(Al, Si)3 with uniform thickness was primarily formed in the 0.7 mm-joint and the nanophases Ti5Si3 and Ti7Al5Si12 were dispersed in the IMC layer. The inhomogeneous sandwich structure with a continuous Ti5Si3 strip layer was detected at the Ti/Al interface of the 0.4 mm-joint. The maximum line load of the joint with 0.7 mm gap size was about 395.4 N/mm, which was 261.9 % larger than that with 0 mm gap size. The cracks preferentially initiated at Ti5Si3/Ti(Al, Si)3 interface due to their higher interplanar spacing misfit rate and then propagated inside Ti5Si3 and Ti(Al, Si)3. When the gap size was 0.7 mm, the chemical potential gradient of Si decreased by the higher peak temperature at the bottom of the joint. The continuous Ti5Si3 strip layer was inhibited because Si atoms were more evenly distributed at the Ti/Al interface. Moreover, the IMC layer of Ti(Al, Si)3 was uniform and continuous. Thus, the mechanical property was significantly enhanced.

The utilization of regional water resources has the potential to impact carbon emissions. Maintaining a decoupled relationship between water resources and carbon emissions facilitates harmonious regional development. Understanding the mechanism of their coordination is conducive to achieving the ''Double Carbon'' goal and control of regional carbon emissions and water resource consumption. This study examines the decoupling relationship between water resource utilization and carbon emissions in Poyang Lake area, China, employing the Tapio decoupling model and the LMDI(logarithmic mean divisia index) decomposition model. The results indicate that carbon emissions in Poyang Lake area exhibited a gradual increase, accompanied by an annual growth rate of 5.99 %. The water supply exhibited a slow expansion. They have exhibited state of affairs strong negative decoupling and expansive negative decoupling over the past 15 years. Moreover, this situation is most acute and worsening in the secondary industry. The water use structure effect and water economic benefit effect are the primary factors affecting carbon emission increases, contributing 57.93 % and 65.66 %, respectively. Carbon emissions intensity is the largest inhibiting factor, which accounts for a maximum contribution of 42.96 %. The order of potency of the driving factors is as follows: water economic benefit > carbon emission intensity > water use structure > water use efficiency. In summary, this research recognised the enhancement of the water economic efficiency index not only facilitates the decoupling phenomenon but also improves the water-carbon relationship, especially in the secondary industry. It serves as a compelling illustration of the significance of elucidating the interrelationship between regional water and carbon dynamics, and charting the course for the formulation of regional policies that would facilitate the advancement of environmentally conscious and carbon-neutral development, as well as water conservation.

Currently, no specific treatment exists to alleviate metabolic dysfunction-associated fatty liver (MAFLD). Previously, Poria cocos (PC) effectively relieved MAFLD, but its bioactive components are still unknown. The bioactive substances in PC that regulate mitochondria function to alleviate MAFLD were thus determined. The L02 hepatocyte model induced by fat emulsion and the MAFLD rat model induced by a high-fat diet (HFD) were developed to explore the efficacy of PC against MAFLD. The activity of PC-derived components in the liver mitochondria of HFD-fed rats was evaluated using the L02 hepatocyte model. Additionally, the PC-derived components from the liver mitochondria were identified by ultra-high performance liquid chromatography/mass spectrometry. Finally, the anti-steatosis ability of PC-derived monomers and monomers groups was evaluated using the adipocyte model. PC maintained the mitochondrial ultrastructure, alleviated mitochondrial oxidative stress, and regulated the energy metabolism and the fatty acid β oxidation to relieve lipid emulsion-induced cellular steatosis and HFD-induced MAFLD. PC-derived components entering the liver mitochondria inhibited oxidative stress injury and improved the energy metabolism to fight cellular steatosis. Additionally, 15 chemicals were identified in the PC-treated rat liver mitochondria. These identified chemical molecules and molecule groups in the mitochondria prevented cellular steatosis by regulating mitochondrial oxidative stress and energy metabolism. PC restores mitochondrial structure and function, alleviating MAFLD, which is related to oxidative stress, energy metabolism, and fatty acid β oxidation. The identified 15 components may be the main effective PC components regulating mitochondria function to alleviate MAFLD. Thus, PC may be a promising mitochondrial regulator to prevent MAFLD.

ABSTRACT Interactions between photosynthetic microalgae and bacteria impact the physiology of both partners, which influence the fitness and ecological trajectories of each partner in an environmental context-dependent manner. Thermal tolerance of Chlamydomonas reinhardtii can be enhanced through a mutualistic interaction with vitamin B12 (cobalamin)-producing Sinorhizobium meliloti. Here, we used label-free quantitative proteomics to reveal the metabolic networks altered by the interaction under normal and high temperatures. We created a scenario where the growth of Sinorhizobium requires carbon provided by Chlamydomonas for growth in co-cultures, and survival of Chlamydomonas under high temperatures relies on cobalamin and possibly other metabolites produced by Sinorhizobium. Differential abundance analysis identified proteins produced by each partner in co-cultures compared to mono-cultures at each temperature. Proteins involved in cobalamin production by Sinorhizobium increased in the presence of Chlamydomonas under elevated temperatures, whereas in Chlamydomonas, there was an increase in cobalamin-dependent methionine synthase and certain proteins associated with methylation reactions. Co-cultivation and heat stress strongly modulated the central metabolism of both partners as well as various transporters that could facilitate nutrient cross-utilization. Co-cultivation modulated expression of various components of two- or one-component signal transduction systems, transcriptional activators/regulators, or sigma factors, suggesting complex regulatory networks modulate the interaction in a temperature-dependent manner. Notably, heat and general stress-response and antioxidant proteins were upregulated in co-cultures, suggesting that the interaction is inherently stressful to each partner despite the benefits of mutualism. Our results shed insight into the metabolic tradeoffs required for mutualism and how metabolic networks are modulated by elevated temperature.IMPORTANCEPhotosynthetic microalgae are key primary producers in aquatic ecosystems, playing an important role in the global carbon cycle. Nearly every alga lives in association with a diverse community of microorganisms that influence each other and their metabolic activities or survival. One chemical produced by bacteria that influence algae is vitamin B12, an enzyme cofactor used for a variety of metabolic functions. The alga Chlamydomonas reinhardtii benefits from vitamin B12 produced by Sinorhizobium meliloti by producing the amino acid methionine under high temperatures which are required for Chlamydomonas thermotolerance. Yet, our understanding of this interaction under normal and stressful temperatures is poor. Here, we used quantitative proteomics to identify differentially expressed proteins to reveal metabolic adjustments made by Chlamydomonas and Sinorhizobium that could facilitate this mutualism. These findings will enhance our understanding of how photosynthetic algae and their associated microbiomes will respond as global temperatures increase.

Fatigue exerts a profound impact on human health. Jiuzhuan Huangjing Pills (JHP), comprising two functional foods, exhibits homology of medicine and food. In this study, we found that JHP improved fatigue in both in vivo and in vitro models by protecting against structural damage and functional disorders of mitochondria through the reduction of oxidative stress, thereby preventing cell death and enhancing energy metabolism. By investigating metabolomes in serum, skeletal muscle (SM), and SM mitochondria, JHP primarily mitigated oxidative stress by modulating the abundances of organic acids and lipids at multiple levels. Furthermore, we identified the anti-fatigue ingredients derived from JHP and conducted experimental verification to confirm that their pharmacodynamic effects were similar to those of JHP. Our findings suggested that JHP can serve as a candidate dietary supplement to improve fatigue by maintaining mitochondrial homeostasis through its antioxidant properties to enhance overall energy production in the body.

Enteric infection is a major cause of enteric disorder in neonatal pigs during the weaning transition. Dihydromyricetin (DMY) is a natural flavanonol compound extracted from Ampelopsis grossedentata with numerous biological activities such as antioxidative and immunomodulatory functions. The objective of this study was to investigate the effects of dietary dihydromyricetin supplementation on growth performance, immunity, and intestinal functions in weaned pigs challenged by enterotoxigenic Escherichia coli (ETEC). In total, 24 weaned DLY (Duroc × Landrace × Yorkshire) pigs were allotted to 3 treatments. Pigs fed with basal diet or basal diet containing 300 mg/kg DMY were orally infused with sterilized culture or ETEC (2.5 × 1011 colony-forming units). Dietary DMY supplementation significantly elevated the final weight and average daily gain (ADG) but reduced diarrhea incidence in the weaned pigs of the EDMY group compared to the pigs of the ECON group (p

It is increasingly recognized that microplastics (MPs) are being transmitted through the food chain system, but little is known about the microorganisms involved in MP degradation, functional biodegradation genes, and metabolic pathways of degradation in the intestinal tract of foodborne animals. In this study, we explored the potential flora mainly involved in MP degradation in the intestinal tracts of Taoyuan, Duroc, and Xiangcun pigs by macrogenomics, screened relevant MP degradation genes, and identified key enzymes and their mechanisms. The pig colon was enriched with abundant MP degradation-related genes, and gut microorganisms were their main hosts. The fiber diet did not significantly affect the abundance of MP degradation-related genes but significantly reduced their diversity. We identified a total of 94 functional genes for MP degradation and classified them into 27 categories by substrate type, with polystyrene (PS), polyethylene terephthalate (PET), and di(2-ethylhexyl) phthalate (DEHP) were the most predominant degradation types. The MP degradation functional genes were widely distributed in a variety of bacteria, mainly in the phylum Firmicutes and Bacteroidetes. Based on the identified functional genes for MP degradation, we proposed a hypothetical degradation mechanism for the three major MP pollutants, namely, PS, PET, and DEHP, which mainly consist of oxidoreductase, hydrolase, transferase, ligase, laccase, and isomerase. The degradation process involves the breakdown of long polymer chains, the oxidation of short-chain oligomers, the conversion of catechols, and the achievement of complete mineralization. Our findings provide insights into the function of MP degradation genes and their host microorganisms in the porcine colon.

Long‐lasting hydrogen evolution and efficient dew harvest is realized via electrospinning a polyvinylidene fluoride (PVDF) membrane on hybrid hydrogels embedded with photocatalytic g‐C3N4/Pt nanosheets. Due to the hindrance of water evaporation by the hydrophobic PVDF membrane, the drying process of the hybrid hydrogels significantly slows down. Hence, the g‐C3N4/Pt nanosheets can continue working on photocatalytic splitting of the water molecules in the hydrogels. When the thickness of the PVDF membrane is 48 μm, the hydrogen evolution rate can reach 2,543 μmol h−1 g−1, which is 38% more than that of the hybrid hydrogel without covering. Therefore, the hybrid hydrogels covered with PVDF membrane are able to work with high efficiency for 12 h, sufficient for hydrogen evolution during the daytime. In addition, the hydrophobic PVDF membrane and hydrophilic hydrogels construct a Janus structure and induce a fast transport of water molecules from the hydrophobic to hydrophilic side. It is beneficial for the rapid collection of dew in the morning. Based on the long‐lasting hydrogen evolution and efficient dew harvest, the present hybrid hydrogels covered with PVDF membrane are very suitable for the environment rich in solar resource and lack of water supply, such as desert or prairie.

Abstract Is childhood adversity associated with biological aging, and if so, does sex modify the association, and do lifestyle and mental health mediate the association? A lifespan analysis is conducted using data on 142 872 participants from the UK Biobank to address these questions. Childhood adversity is assessed through the online mental health questionnaire (2016), including physical neglect, physical abuse, emotional neglect, emotional abuse, sexual abuse, and a cumulative score. Biological aging is indicated by telomere length (TL) measured from leukocyte DNA using qPCR, and the shorter TL indicates accelerated biological aging; a lifestyle score is constructed using body mass index, physical activity, drinking, smoking, and diet; mental disorder is assessed using depression, anxiety, and insomnia at the baseline survey. The results reveal a sex‐specific association such that childhood adversity is associated with shorter TL in women after adjusting for covariates including polygenic risk score for TL, but not in men. Unhealthy lifestyle and mental disorder partially mediate the association in women. The proportions of indirect effects are largest for sexual and physical abuse. These findings highlight the importance of behavioral and psychological interventions in promoting healthy aging among women who experienced childhood adversity, particularly sexual and physical abuse.

Excessive nitrogen and phosphorus (N/P) input is the important reason for lake eutrophication, a widespread environmental problem that harms freshwater ecosystems worldwide. Land use land cover changes (LULCCs) strongly affect the migration and transformation process on land of N/P. Aiming to improve the accuracy of N/P estimation and deeply understand the spatiotemporal impact of LULCCs on N/P distribution, this study proposed an optimized framework, InVEST-UM, by integrating an unmixing algorithm with the conventional InVEST model. A comprehensive and intuitive index LPI (LULCCs purification capacity index) is developed for the impact assessment and spatialization. Validation shows a strong correlation (0.94) between the LPI and eutrophication degree of Dianshan Lake. This suggests the LPI effectively captures the spatiotemporal influence of LULCCs on lake eutrophication. Based on the sub-pixel results of N/P estimation, dramatic changes of LPI with an average rate of 46.182% were explored. There is a strong positive correlation (0.91) between vegetation area and LULCCs purification capacity for N/P. Conversely, negative relationships are found between LULCCs purification capacity with bare lands (−0.86), and artificial surfaces (−0.75). Changes in the water bodies have weak influence (−0.33) on LULCCs purification capacity. The increase in vegetation area can not only enhance the lake purification capacity, but also help maintain low ecological sensitivity. By employing this comprehensive framework, this study provides valuable insights into the long-term dynamics of LULCCs changes and their implications for lake ecosystems, and could support the protection and land use planning for the sustainability and ecological balance of the lake.

Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. Epidemiological studies have reported that exposure of the population to environmental endocrine-disrupting chemicals (EDCs) is associated with NAFLD. However, EDCs are of different types, and there are inconsistencies in the relevant evidence and descriptions, which have not been systematically summarized so far. Therefore, this study aimed to determine the association between population exposure to EDCs and NAFLD. Three databases, including PubMed, Web of science, and Embase were searched, and 27 articles were included in this study. Methodological quality, heterogeneity, and publication bias of the included studies were assessed using the Newcastle–Ottawa scale, I2 statistics, Begg’s test, and Egger’s test. The estimated effect sizes of the included studies were pooled and evaluated using the random-effects model (I2 > 50 %) and the fixed-effects model ( I2 < 50 %). The pooled-estimate effect sizes showed that population exposure to Phthalates (PAEs) (OR = 1.18, 95 % CI:1.03–1.34), cadmium (Cd) (OR = 1.37, 95 % CI:1.09–1.72), and bisphenol A (OR = 1.43, 95 % CI:1.24–1.65) were positively correlated with the risk of NAFLD. Exposure to mercury (OR =1.46, 95 % CI:1.17–1.84) and Cd increased the risk of “elevated alanine aminotransferase”. On the contrary, no significant association was identified between perfluoroalkyl substances (OR =0.99, 95 % CI:0.93–1.06) and NAFLD. However, female exposure to perfluorooctanoic acid (OR =1.82, 95 % CI:1.01–3.26) led to a higher risk of NAFLD than male exposure. In conclusion, this study revealed that EDCs were risk factors for NAFLD. Nonetheless, the sensitivity analysis results of some of the meta-analyses were not stable and demonstrated high heterogeneity. The evidence for these associations is limited, and more large-scale population-based studies are required to confirm these findings.

Natural products (NPs) play an irreplaceable role in the intervention of various diseases and have been considered a critical source of drug development. Many new pharmacodynamic compounds with potential clinical applications have recently been derived from NPs. These compounds range from small molecules to polysaccharides, polypeptides, proteins, self-assembled nanoparticles, and extracellular vesicles. This review summarizes various active substances found in NPs. The investigation of active substances in NPs can potentiate new drug development and promote the in-depth comprehension of the mechanism of action of NPs that can be beneficial in the prevention and treatment of human diseases.

The aim of this study is to investigate the role of estrogen receptor β (ERβ) in nonylphenol (NP) - induced depression - like behavior in rats and its impact on the regulation of the TPH2/5-HT pathway. In the in vitro experiment, rat basophilic leukaemia cells (RBL-2H3) cells were divided into the four groups: blank group, NP group (20 μM), ERβ agonist group (0.01 μM), and NP＋ERβ agonist group (20 μM＋0.01 μM). For the in vivo experiment, 72 adult male Sprague-Dawley rats were randomly divided into following six groups: the Control, NP (40 mg/kg) group, ERβ agonist (2 mg/kg, Diarylpropionitrile (DPN)) group, ERβ inhibitor (0.1 mg/kg, 4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl) phenol (PHTPP)) group, NP+ERβ agonist (40 mg/kg NP ＋ 2 mg/kg DPN) group, and NP+ERβ inhibitor (40 mg/kg NP + 0.1 mg/kg PHTPP) group, with 12 rats in each group. Each rat in drug group were given NP by gavage and/or received a single intraperitoneal injection of DPN 2 mg/kg or PHTPP 0.1 mg/kg. Both in vivo and in vitro, NP group showed a decrease in the expression levels of ERβ, tryptophan hydroxylase (TPH1), and tryptophan hydroxylase-2 (TPH2) genes and proteins, and reduced levels of DA, NE, and 5-hydroxytryptophan (5-HT) neurotransmitters. RBL-2H3 cells showed signs of cell shrinkage, with rounded cells, increased suspension and more loosely arranged cells. The effectiveness of the ERβ agonist stimulation exhibited an increase exceeding 60% in RBL-2H3 cells. The application of ERβ agonist resulted in an alleviation the aforementioned alterations. ERβ agonist activated the TPH2/5-HT signaling pathways. Compared to the control group, the NP content in the brain tissue of the NP group was significantly increased. The latency to eat for the rats was longer and the amount of food consumed was lower, and the rats had prolonged immobility time in the behavioral experiment of rats. The expression levels of ERβ, TPH1, TPH2, 5-HT and 5-HITT proteins were decreased in the NP group, suggesting NP-induced depression-like behaviours as well as disturbances in the secretion of serum hormones and monoamine neurotransmitters. In the NP group, the midline raphe nucleus showed an elongated nucleus with a dark purplish-blue colour, nuclear atrophy, displacement and pale cytoplasm. ERβ might ameliorate NP-induced depression-like behaviors, and secretion disorders of serum hormones and monoamine neurotransmitters via activating TPH2/5-HT signaling pathways.

Planting concrete (PC) is a type of sustainable concrete. It remains challenging to prepare and design a PC by considering complex factors such as voidage and alkalinity. In this paper, preparation and mix design methods of PC are reviewed and compared, with particular emphasis on the influence of various factors on permeability, mechanical properties, durability, and plant compatibility. Alkali reduction measures, vegetation testing, and plant compatibility cannot be ignored in the design of PC. 25∼30% voidage and 8–10 pH can ensure the durability of vegetation concrete, physiological characteristics of plants and fertilizer retention performance. In addition, the paper summarizes the application of PC in water purification, slope protection and green roof establishment. The cost and applicable conditions of different slope protection methods are further compared and analyzed. Finally, several essential areas that require further research efforts are suggested based on the current research results, including research direction and challenges of PC.