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Abstract Oocyte aging is a key constraint on oocyte quality, leading to fertilization failure and abnormal embryonic development. In addition, it is likely to generate unfavorable assisted reproductive technology (ART) outcomes. SCM-198, a synthetic form of leonurine, was found to rescue the rate of oocyte fragmentation caused by postovulatory aging. Therefore, the aim of this study was to conduct a more in-depth investigation of SCM-198 by exploring its relationship with aged oocytes after ovulation or maternal aging and clarifying whether it affects cell quality. The results indicate that, compared to the postovulatory aged group, the 50 µM SCM-198 group significantly improved sperm-egg binding and increased fertilization of aged oocytes, restoring the spindle apparatus/chromosome structure, cortical granule distribution, and ovastacin and Juno protein distribution. The 50 µM SCM-198 group showed significantly normal mitochondrial distribution, low levels of reactive oxygen species (ROS), and a small quantity of early oocyte apoptosis compared to the postovulatory aged group. Above all, in vivo supplementation with SCM-198 effectively eliminated excess ROS and reduced the spindle/chromosome structural defects in aged mouse oocytes. In summary, these findings indicate that SCM-198 inhibits excessive oxidative stress in oocytes and alters oocyte quality both in vitro and in vivo. Graphical Abstract

Abstract Background It was reported that either shorter programmed intermittent epidural bolus (PIEB) intervals or high-speed bolus can produce more extensive epidural spread. We hypothesized that a combination of shortened time interval and increased speed of epidural bolus might further improve analgesic effect and therefore reduce the hourly volume for epidural labour analgesia. Methods This double-blind dose-finding study used a biased coin up-and-down sequential allocation method to determine the 90% effective bolus volume of ropivacaine combined with sufentanil while using the push pump at a rate of 400 mL/hr and interval of 30 min to provide effective analgesia without breakthrough pain. We used 0.1% ropivacaine with 0.4 µg/mL sufentanil, with bolus volumes ranging from 3 to 6 mL. The first patient was assigned a volume of 3 mL, and the remaining volumes were assigned according to the biased coin-up-and-down method. Results The estimated 90% effective volume (EV90) of ropivacaine combined with sufentanil for epidural labour analgesia at a time interval of 30 min was 4.88 mL (95% confidence interval 4.83–5.38). Conclusions The optimum bolus volume of ropivacaine with sufentanil while using push pump at a time interval of 30 min is approximately 5 mL. It could probably further reduce the hourly bolus volume for epidural labour analgesia.

Abstract Background The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear. Results Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomics. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P

This is an article in the field of ceramics and composites. Alkali-activated Slag-fly Ash-based Geopolymer (ASFG) has excellent properties such as high early strength, acid and alkali resistance, but its large brittleness and poor toughness affect its popularization and application. In order to improve the properties of ASFG and broaden the types of mineral admixtures that can be used for ASFG modification, six kinds of mineral admixtures, including metakaolin, zeolite powder, bentonite, wollastonite powder, light calcium carbonate and silica fume, are used as modified materials, and their modification effects on ASFG are studied. The optimum modified material is silica fume. In order to further explore the improvement effect of silica fume on the mechanical properties of ASFG, the effect of the content of silica fume on the mechanical properties of ASFG is studied, and the optimal content of silica fume is determined. Finally, Alkali-activated Slag-fly Ash-silica Fume-based Geopolymer Concrete (ASFSGC) is prepared, and its workability, quasi-static mechanical properties and impermeability are studied. The results show that bentonite, wollastonite powder, light calcium carbonate and silica fume can significantly improve the flexural strength of ASFG. Wollastonite powder and silica fume can significantly improve the compressive strength of ASFG. For ASFG, silica fume is a premium mineral admixture. With the increase of silica fume content, the mechanical properties of ASFG first increase and then decrease, and the optimal content of silica fume is 4%. ASFSGC has good workability and excellent impermeability, and the ductility of ASFSGC is 14.1% larger than that of ordinary Portland cement concrete.

This paper is devoted to dealing with a kind of new Kirchhoff-type problem in $ \mathbb{R}^N $ that involves a general double-phase variable exponent elliptic operator $ \mathit{\boldsymbol{\phi}} $. Specifically, the operator $ \mathit{\boldsymbol{\phi}} $ has behaviors like $ |\tau|^{q(x)-2}\tau $ if $ |\tau| $ is small and like $ |\tau|^{p(x)-2}\tau $ if $ |\tau| $ is large, where $ 1 < p(x) < q(x) < N $. By applying some new analytical tricks, we first establish existence results of solutions for this kind of Kirchhoff-double-phase problem based on variational methods and critical point theory. In particular, we also replace the classical Ambrosetti–Rabinowitz type condition with four different superlinear conditions and weaken some of the assumptions in the previous related works. Our results generalize and improve the ones in [Q. H. Zhang, V. D. Rădulescu, J. Math. Pures Appl., 118 (2018), 159–203.] and other related results in the literature.

Our focus in this study was on examining the convergence problem of a novel method, inspired by the Ulm-Chebyshev-like Cayley transform method, which was designed to solve the inverse eigenvalue problems (IEPs) with multiple eigenvalues. Compared with other existing methods, the proposed method has higher convergence order and/or requires less operations. Under the assumption that the relative generalized Jacobian matrices at a solution are nonsingular, the proposed method was proved to be convergent with cubic convergence. Experimental findings demonstrated the practicality and efficiency of the suggested approaches.

Abstract Background The introduction of highly active antiretroviral therapy has significantly improved the life expectancies of children and adolescents living with HIV, leading to an increased number transitioning to adult care. However, there has been a lack of studies in Ethiopia focusing on factors influencing the success of this transition. Therefore, this study aimed to determine predictors of a successful transition from pediatric to adult HIV clinics among adolescents and young adults living with HIV in health facilities in southern Ethiopia. Methods A retrospective cohort study included 337 adolescents and young adults who transitioned to adult-oriented HIV care. Successful transition was defined as having a viral load of less than 1000 copies/ml and maintaining care during the first year post-transition. Patients’ antiretroviral therapy (ART) cards and monitoring charts were reviewed. Secondary data analysis was conducted using a multivariable binary logistic regression model to identify predictors of a successful transition. Using the variance inflation factor, we checked for multi-collinearity between variables and assessed model fitness with the Hosmer and Lemeshow goodness-of-fit test. Adjusted Odds Ratio (AOR) with 95% confidence intervals (CI) and P-value ≤ 0.05 measured the strength of association and statistical significance. Results Of 337 participants, 230 (68.25%) successfully transitioned (95% CI = 63.25, 73.25). Transitioning at age 18 or older (AOR = 4.25; 95% CI = 2.29, 7.87), residing in an urban area (AOR = 1.78; 95% CI = 1.04, 3.02), and being on antiretroviral therapy for more than two years (AOR = 4.25; 95% CI = 1.17, 4.94; P

Genetic algorithm with storage mechanism and adaptive cross mutation is proposed to solve the problem of difficulty in optimizing the prestress of string supported lattice shell structures. Firstly, storage mechanism strategy is introduced into genetic algorithm(GA) to sort the individuals in the population in real-time, fully utilizing the direction information and search state of the current population. Then, heuristic adaptive crossover strategy and non-uniform adaptive mutation strategy are introduced to achieve adaptive adjustment of crossover mutation probability factor, effectively avoiding the population from falling into local optimal solutions in the later stage of iteration. Test function simulation experiments and engineering case applications show that compared with IGA, GDOIGA and IMPGA, AMCGA has fewer iterations, stronger global search ability, and higher quality of optimal solutions. When it is applied in prestress optimization of chord supported lattice shell structures, it has higher optimization efficiency and better optimization effect.

Highlights Transient response plays a crucial role as a performance indicator for organic electrochemical transistors (OECTs), particularly in their application in high-speed logic circuits and neuromorphic computing systems. This review presents a systematic overview on the fundamental principles underlying OECT transient responses, emphasizing the essential roles of transient electron and ion dynamics, as well as structural evolution, in both volatile and non-volatile behaviors. We also discuss the materials, morphology, device structure strategies on optimizing transient responses.

Abstract Osteoporosis is a metabolic bone disease that involves gradual loss of bone density and mass, thus resulting in increased fragility and risk of fracture. Inflammatory cytokines, such as tumour necrosis factor α (TNF‐α), inhibit osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and several microRNAs are implicated in osteoporosis development. This study aimed to explore the correlation between TNF‐α treatment and miR‐27a‐3p expression in BMSC osteogenesis and further understand their roles in osteoporosis. An osteoporosis animal model was established using ovariectomized (OVX) mice. Compared with Sham mice, the OVX mice had a significantly elevated level of serum TNF‐α and decreased level of bone miR‐27a‐3p, and in vitro TNF‐α treatment inhibited miR‐27a‐3p expression in BMSCs. In addition, miR‐27a‐3p promoted osteogenic differentiation of mouse BMSCs in vitro, as evidenced by alkaline phosphatase staining and Alizarin Red‐S staining, as well as enhanced expression of the osteogenic markers Runx2 and Osterix. Subsequent bioinformatics analysis combined with experimental validation identified secreted frizzled‐related protein 1 (Sfrp1) as a downstream target of miR‐27a‐3p. Sfrp1 overexpression significantly inhibited the osteogenic differentiation of BMSCs in vitro and additional TNF‐α treatment augmented this inhibition. Moreover, Sfrp1 overexpression abrogated the promotive effect of miR‐27a‐3p on the osteogenic differentiation of BMSCs. Furthermore, the miR‐27a‐3p–Sfrp1 axis was found to exert its regulatory function in BMSC osteogenic differentiation via regulating Wnt3a–β‐catenin signalling. In summary, this study revealed that TNF‐α regulated a novel miR‐27a‐3p–Sfrp1 axis in osteogenic differentiation of BMSCs. The data provide new insights into the development of novel therapeutic strategies for osteoporosis.

The field of cancer genomics and transcriptomics has evolved from targeted profiling to swift sequencing of individual tumor genome and transcriptome. The steady growth in genome, epigenome, and transcriptome datasets on a genome-wide scale has significantly increased our capability in capturing signatures that represent both the intrinsic and extrinsic biological features of tumors. These biological differences can help in precise molecular subtyping of cancer, predicting tumor progression, metastatic potential, and resistance to therapeutic agents. In this review, we summarized the current development of genomic, methylomic, transcriptomic, proteomic and metabolic signatures in the field of cancer research and highlighted their potentials in clinical applications to improve diagnosis, prognosis, and treatment decision in cancer patients.

Abstract Reservoir dispatching regulations are a crucial basis for reservoir operation, and using information extraction technology to extract entities and relationships from heterogeneous texts to form triples can provide structured knowledge support for professionals in making dispatch decisions and intelligent recommendations. Current information extraction technologies require manual data labeling, consuming a significant amount of time. As the number of dispatch rules increases, this method cannot meet the need for timely generation of dispatch plans during emergency flood control periods. Furthermore, utilizing natural language prompts to guide large language models in completing reservoir dispatch extraction tasks also presents challenges of cognitive load and instability in model output. Therefore, this paper proposes an entity and relationship extraction method for reservoir dispatch based on structured prompt language. Initially, a variety of labels are refined according to the extraction tasks, then organized and defined using the Backus–Naur Form (BNF) to create a structured format, thus better guiding large language models in the extraction work. Moreover, an AI agent based on this method has been developed to facilitate operation by dispatch professionals, allowing for the quick acquisition of structured data. Experimental verification has shown that, in the task of extracting entities and relationships for reservoir dispatch, this AI agent not only effectively reduces cognitive burden and the impact of instability in model output but also demonstrates high extraction performance (with F1 scores for extracting entities and relationships both above 80%), offering a new solution approach for knowledge extraction tasks in other water resource fields.

Abstract The long-term trends in maternal and child health (MCH) in China and the national-level factors that may be associated with these changes have been poorly explored. This study aimed to assess trends in MCH indicators nationally and separately in urban and rural areas and the impact of public policies over a 30‒year period. An ecological study was conducted using data on neonatal mortality rate (NMR), infant mortality rate (IMR), under-five mortality rate (U5MR), and maternal mortality ratio (MMR) nationally and separately in urban and rural areas in China from 1991 to 2020. Joinpoint regression models were used to estimate the annual percentage changes (APC), average annual percentage changes (AAPC) with 95% confidence intervals (CIs), and mortality differences between urban and rural areas. From 1991 to 2020, maternal and child mortalities in China gradually declined (national AAPC [95% CI]: NMRs − 7.7% [− 8.6%, − 6.8%], IMRs − 7.5% [− 8.4%, − 6.6%], U5MRs − 7.5% [− 8.5%, − 6.5%], MMRs − 5.0% [− 5.7%, − 4.4%]). However, the rate of decline nationally in child mortality slowed after 2005, and in maternal mortality after 2013. For all indicators, the decline in mortality was greater in rural areas than in urban areas. The AAPCs in rate differences between rural and urban areas were − 8.5% for NMRs, − 8.6% for IMRs, − 7.7% for U5MRs, and − 9.6% for MMRs. The AAPCs in rate ratios (rural vs. urban) were − 1.2 for NMRs, − 2.1 for IMRs, − 1.7 for U5MRs, and − 1.9 for MMRs. After 2010, urban‒rural disparity in MMR did not diminish and in NMR, IMR, and U5MR, it gradually narrowed but persisted. MCH indicators have declined at the national level as well as separately in urban and rural areas but may have reached a plateau. Urban‒rural disparities in MCH indicators have narrowed but still exist. Regular analyses of temporal trends in MCH are necessary to assess the effectiveness of measures for timely adjustments.

Abstract Intrinsically stretchable organic photovoltaics have emerged as a prominent candidate for the next-generation wearable power generators regarding their structural design flexibility, omnidirectional stretchability, and in-plane deformability. However, formulating strategies to fabricate intrinsically stretchable organic photovoltaics that exhibit mechanical robustness under both repetitive strain cycles and high tensile strains remains challenging. Herein, we demonstrate high-performance intrinsically stretchable organic photovoltaics with an initial power conversion efficiency of 14.2%, exceptional stretchability (80% of the initial power conversion efficiency maintained at 52% tensile strain), and cyclic mechanical durability (95% of the initial power conversion efficiency retained after 100 strain cycles at 10%). The stretchability is primarily realised by delocalising and redistributing the strain in the active layer to a highly stretchable PEDOT:PSS electrode developed with a straightforward incorporation of ION E, which simultaneously enhances the stretchability of PEDOT:PSS itself and meanwhile reinforces the interfacial adhesion with the polyurethane substrate. Both enhancements are pivotal factors ensuring the excellent mechanical durability of the PEDOT:PSS electrode, which further effectively delays the crack initiation and propagation in the top active layer, and enables the limited performance degradation under high tensile strains and repetitive strain cycles.

Abstract Background Associations between perceived and actual risk of HIV infection and HIV prevention services uptake are inconclusive. This study aimed to evaluate the discrepancy between the perceived and actual HIV risk, and quantify the associations between perceived and actual risk of HIV infection and three HIV prevention services utilization among men who have sex with men (MSM) in Shandong province, China. Methods A cross-sectional study was conducted in Shandong province in June 2021. Participants were eligible if they were born biologically male, aged 18 years or older, had negative or unknown HIV status, and had sex with men in the past year. Participants were recruited online. The discrepancy between their perceived and actual risk of HIV infection was evaluated by calculating the Kappa value. Bayesian model averaging was used to assess the associations between perceived and actual risk of HIV infection and HIV prevention services uptake. Results A total of 1136 MSM were recruited, most of them were 30 years old or younger (59.9%), single (79.5%), with at least college education level (74.7%). Most participants (97.4%) perceived that they had low risk of HIV infection, and 14.1% were assessed with high actual risk. The discrepancy between their perceived and actual risk of HIV infection was evaluated with a Kappa value of 0.076 (P

Objective To explore the relationship between the intraoperative plasma transfusion volume, the changes of blood coagulation test values and the clinical prognosis of surgical patients, so as to provide a theoretical basis for guiding the rational use of blood during the operation. Methods The clinical data of 556 surgical patients who received plasma infusion from January 2017 to December 2020 in Sun Yat-sen Memorial Hospital were collected. Patients were divided into low plasma dose group (

Abstract Studies have suggested that endoplasmic reticulum stress (ERS) is involved in neurological dysfunction and that electroacupuncture (EA) attenuates neuropathic pain (NP) via undefined pathways. However, the role of ERS in the anterior cingulate cortex (ACC) in NP and the effect of EA on ERS in the ACC have not yet been investigated. In this study, an NP model was established by chronic constriction injury (CCI) of the left sciatic nerve in rats, and mechanical and cold tests were used to evaluate behavioral hyperalgesia. The protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that glucose-regulated protein 78 (BIP) and inositol-requiring enzyme 1α (IRE-1α) were co-localized in neurons in the ACC. After CCI, BIP, IRE-1α, and phosphorylation of IRE-1α were upregulated in the ACC. Intra-ACC administration of 4-PBA and Kira-6 attenuated pain hypersensitivity and downregulated phosphorylation of IRE-1α, while intraperitoneal injection of 4-PBA attenuated hyperalgesia and inhibited the activation of P38 and JNK in ACC. In contrast, ERS activation by intraperitoneal injection of tunicamycin induced behavioral hyperalgesia in naive rats. Furthermore, EA attenuated pain hypersensitivity and inhibited the CCI-induced overexpression of BIP and pIRE-1α. Taken together, these results demonstrate that EA attenuates NP by suppressing BIP- and IRE-1α-mediated ERS in the ACC. Our study presents novel evidence that ERS in the ACC is implicated in the development of NP and provides insights into the molecular mechanisms involved in the analgesic effect of EA.

Abstract Background Good preoperative conditions help patients to counteract surgical injury. Prehabilitation is a multimodal preoperative management strategy, including physical, nutritional, psychological, and other interventions, which can improve the functional reserve of patients and enhance postoperative recovery. The purpose of this study is to show the evolution trend and future directions of research related to the prehabilitation of surgical patients. Methods The global literature regarding prehabilitation was identified from The Web of Science Core Collection database. Bibliometric methods of the Bibliometrix package of R (version 4.2.1) and VOSviewer were used to analyze publication trends, cooperative networks, study themes, and co-citation relationships in the field. Results A total of 638 publications were included and the number of publications increased rapidly since 2016, with an average annual growth rate of 41.0%. “Annals of Surgery”, “British Journal of Surgery” and “British Journal of Anesthesia” were the most cited journals. Experts from the USA, Canada, the UK, and the Netherlands contributed the most in this field, and an initial cooperative network among different countries and clinical teams was formed. Malnutrition, older patients, frailty, and high-risk patients were the hotspots of recent studies. However, among the top 10 cited articles, the clinical effects of prehabilitation were conflicting. Conclusion This bibliometric review summarized the most influential publications as well as the publication trends and clarified the progress and future directions of prehabilitation, which could serve as a guide for developing evidence-based practices.

Abstract Background Stable carbon isotope composition (δ13Cp) can be used to estimate the changes in intrinsic water use efficiency (iWUE) in plants, which helps us to better understand plants’ response strategies to climate change. This study focused on the variations in δ13Cp and iWUE for the different life-form plants (i.e., herbs, shrubs, and trees) along an altitudinal gradient (3300, 3600, 3900, 4100, 4300, and 4500 m) on the eastern slope of Yulong Snow Mountain, southeastern margin of the Qinghai-Tibet Plateau. The response mechanisms of δ13Cp and iWUE for different life-form plants to altitude were thoroughly analyzed in this mountain ecosystem. Results The δ13Cp values of plants on the eastern slopes of Yulong Snow Mountain ranged from − 30.4‰ to − 26.55‰, with a mean of − 28.02‰, indicating a dominance of C3 plants. The δ13Cp and iWUE values varied among different life-form plants in the order of herbs > shrubs > trees, particularly in 3600, 3900, and 4300 m. The δ13Cp and iWUE values for herbs and shrubs increased with altitude and were mainly controlled by air temperature. The two parameters for trees exhibited a trend of initial decrease followed by an increase with altitude. Below 3900 m, the δ13Cp and iWUE values decreased with altitude, influenced by soil moisture. However, above 3900 m, the two parameters increased with altitude, mainly regulated by air temperature. In addition, iWUE was positively correlated with leaf P content but negatively correlated with leaf N:P ratio, especially for herbs and trees, suggesting that P plays a key role in modulating iWUE in this region. Conclusions The differentiated responses of water availability for different life-form plants to a higher altitudinal gradient are regulated by air temperature, soil moisture, and leaf P content in the Yulong Snow Mountain. These results provide valuable insights into understanding the water–carbon relationships in high-altitude ecosystems.

Abstract Objective To identify the risk factors of cervical high-grade squamous intraepithelial lesion(HSIL) complicated with occult cervical cancer and standardize the management of initial treatment for HSIL. Method The clinical data of patients who underwent total hysterectomy directly due to HSIL in the obstetrics and gynecology department of two tertiary hospitals and three secondary hospitals from 2018 to 2023 were collected. Their general characteristics, pathological parameters and survival status were analyzed. Logistic regression model was used to analyze the correlation between clinical parameters and postoperative pathological upgrading. Result 1. Among the 314 patients with HSIL who underwent total hysterectomy directly, 73.2% were from primary hospitals. 2. 25 patients (7.9%) were pathologically upgraded to cervical cancer, all of which were early invasive cancer. 3. Up to now, there was no recurrence or death in the 25 patients with early-stage invasive cancer, and the median follow-up period was 21 months(range 2–59 months). 4. Glandular involvement(OR 3.968; 95%CI 1.244–12.662) and lesion range ≥ 3 quadrants (OR 6.527; 95% CI 1.78–23.931), HPV 16/18 infection (OR 5.382; 95%CI 1.947–14.872), TCT ≥ ASC-H (OR 4.719; 95%CI 1.892–11.766) were independent risk factors that affected the upgrading of postoperative pathology. 5. The area under the curve (AUC) calculated by the Logistic regression model was 0.840, indicating that the predictive value was good. Conclusion There is a risk of occult cervical cancer in patients with HSIL. Glandular involvement, Lesion range ≥ 3 quadrants, HPV 16/18 infection and TCT ≥ ASC-H are independent risk factors for HSIL combined with occult cervical cancer. The prognosis of biopsy-proved HSIL patients who underwent extrafascial hysterectomy and unexpected early invasive cancer was later identified on specimen may be good.

Abstract Background Under a changing climate, the joint effects of temperature and relative humidity on tuberculosis (TB) are poorly understood. To address this research gap, we conducted a time-series study to explore the joint effects of temperature and relative humidity on TB incidence in China, considering potential modifiers. Methods Weekly data on TB cases and meteorological factors in 22 cities across mainland China between 2011 and 2020 were collected. The proxy indicator for the combined exposure levels of temperature and relative humidity, Humidex, was calculated. First, a quasi-Poisson regression with the distributed lag non-linear model (DLNM) was constructed to examine the city-specific associations between humidex and TB incidence. Second, a multivariate meta-regression model was used to pool the city-specific effect estimates, and to explore the potential effect modifiers. Results A total of 849,676 TB cases occurred in the 22 cities between 2011 and 2020. Overall, a conspicuous J-shaped relationship between humidex and TB incidence was discerned. Specifically, a decrease in humidex was positively correlated with an increased risk of TB incidence, with a maximum relative risk (RR) of 1.40 (95% CI: 1.11–1.76). The elevated RR of TB incidence associated with low humidex (5th humidex) appeared on week 3 and could persist until week 13, with a peak at approximately week 5 (RR: 1.03, 95% CI: 1.01–1.05). The effects of low humidex on TB incidence vary by Natural Growth Rate (NGR) levels. Conclusion A J-shaped exposure-response association existed between humidex and TB incidence in China. Humidex may act as a better predictor to forecast TB incidence compared to temperature and relative humidity alone, especially in regions with higher NGRs.

Objective To develop a deep learning model for automated age estimation based on 3D CT reconstructed images of Han population in western China, and evaluate its feasibility and reliability. Methods The retrospective pelvic CT imaging data of 1 200 samples （600 males and 600 females） aged 20.0 to 80.0 years in western China were collected and reconstructed into 3D virtual bone models. The images of the ischial tuberosity feature region were extracted to create sex-specific and left/right site-specific sample libraries. Using the ResNet34 model, 500 samples of different sexes were randomly selected as training and verification set, the remaining samples were used as testing set. Initialization and transfer learning were used to train images that distinguish sex and left/right site. Mean absolute error （MAE） and root mean square error （RMSE） were used as primary indicators to evaluate the model. Results Prediction results varied between sexes, with bilateral models outperformed left/right unilateral ones, and transfer learning models showed superior performance over initial models. In the prediction results of bilateral transfer learning models, the male MAE was 7.74 years and RMSE was 9.73 years, the female MAE was 6.27 years and RMSE was 7.82 years, and the mixed sexes MAE was 6.64 years and RMSE was 8.43 years. Conclusion The skeletal age estimation model, utilizing ischial tuberosity images of Han population in western China and employing the ResNet34 combined with transfer learning, can effectively estimate adult ischium age.

Abstract Although asymmetric molecular design has been widely demonstrated effective for organic photovoltaics (OPVs), the correlation between asymmetric molecular geometry and their optoelectronic properties is still unclear. To access this issue, we have designed and synthesized several symmetric-asymmetric non-fullerene acceptors (NFAs) pairs with identical physical and optoelectronic properties. Interestingly, we found that the asymmetric NFAs universally exhibited increased open-circuit voltage compared to their symmetric counterparts, due to the reduced non-radiative charge recombination. From our molecular-dynamic simulations, the asymmetric NFA naturally exhibits more diverse molecular interaction patterns at the donor (D):acceptor (A) interface as compared to the symmetric ones, as well as higher D:A interfacial charge-transfer state energy. Moreover, it is observed that the asymmetric structure can effectively suppress triplet state formation. These advantages enable a best efficiency of 18.80%, which is one of the champion results among binary OPVs. Therefore, this work unambiguously demonstrates the unique advantage of asymmetric molecular geometry, unveils the underlying mechanism, and highlights the manipulation of D:A interface as an important consideration for future molecular design.

Abstract Background Brain function and neuronal activity depend on a constant supply of blood from the cerebral circulation. The cerebral venous system (CVS) contains approximately 70% of the total cerebral blood volume; similar to the cerebral arterial system, the CVS plays a prominent role in the maintenance of central nervous system (CNS) homeostasis. Impaired venous autoregulation, which can appear in forms such as cerebral venous congestion, may lead to metabolic abnormalities in the brain, causing severe cerebral functional defects and even chronic tinnitus. However, the role of cerebral venous congestion in the progression of tinnitus is underrecognized, and its pathophysiology is still incompletely understood. This study elucidated the specific pathogenetic role of cerebral venous congestion in the onset and persistence of tinnitus and the possible neurophysiological mechanisms. Results We found that a rat model of cerebral venous congestion exhibited tinnitus-like behavioral manifestations at 14 days postoperatively; from that point onward, they showed signs of persistent tinnitus without significant hearing impairment. Subsequent neuroimaging and neurochemical findings showed CNS homeostatic plasticity disturbance in rats with cerebral venous congestion, reflected in increased neural metabolic activity, ultrastructural synaptic changes, upregulated synaptic efficacy, reduced inhibitory synaptic transmission (due to GABA deficiency), and elevated expression of neuroplasticity-related proteins in central auditory and extra-auditory pathways. Conclusion Collectively, our data suggest that alternations in CNS homeostatic plasticity may play a vital role in tinnitus pathology caused by cerebral venous congestion. These findings provide a new perspective on tinnitus related to cerebral venous congestion and may facilitate the development of precise interventions to interrupt its pathogenesis.

Abstract Background Hemorrhagic fever with renal syndrome (HFRS) signals a recurring risk in Eurasia in recent years owing to its continued rise in case notifications and the extension of geographical distribution. This study was undertaken to investigate the spatiotemporal drivers and incidence heterogeneity of HFRS transmission in Shandong Province. Methods The epidemiological data for HFRS, meteorological data and socioeconomic data were obtained from China Information System for Disease Control and Prevention, China Meteorological Data Sharing Service System, and Shandong Statistical Yearbook, respectively. The spatial-temporal multicomponent model was employed to analyze the values of spatial-temporal components and the heterogeneity of HFRS transmission across distinct regions. Results The total effect values of the autoregressive, epidemic, and endemic components were 0.451, 0.187, and 0.033, respectively, exhibiting significant heterogeneity across various cities. This suggested a pivotal role of the autoregressive component in propelling HFRS transmission in Shandong Province. The epidemic component of Qingdao, Weifang, Yantai, Weihai, and Jining declined sharply at the onset of 2020. The random effect identified distinct incidence levels associated with Qingdao and Weifang, signifying regional variations in HFRS occurrence. Conclusions The autoregressive component emerged as a significant driver in the transmission of HFRS in Shandong Province. Targeted preventive measures should be strategically implemented across various regions, taking into account the predominant component influencing the epidemic.

Decision on travel choices in dynamic multimodal transportation networks is non-trivial. In this paper, we tackle this problem by proposing a new joint travel mode and departure time choice (JTMDTC) model based on deep reinforcement learning (DRL). The objective of the model is to maximize individuals travel utilities across multiple days, which is accomplished by establishing a problem-specific Markov decision process to characterize the multi-day JTMDTC, and developing a customized Deep Q-Network as the resolution scheme. To render the approach applicable to many individuals with travel decision-making requests, a clustering method is integrated with DRL to obtain representative individuals for model training, thus resulting in an elegant and computationally efficient approach. Extensive numerical experiments based on multimodal microscopic traffic simulation are conducted in a real-world network of Suzhou, China to demonstrate the effectiveness of the proposed approach. The results indicate that the proposed approach is able to make (near-)optimal JTMDTC for different individuals in complex traffic environments, that it consistently yields higher travel utilities compared with other alternatives, and that it is robust to different model parameter changes.

Abstract Purpose The aim of this study was to explore whether MAF bZIP transcription factor B (MAFB) might alleviate ulcerative colitis (UC) in dextran sulfate sodium (DSS)‐induced mice and LPS‐induced IEC‐6 cells. Methods UC in vivo and in vitro model was established by using DSS and LPS, respectively. The mice body weight and disease activity index (DAI) score were recorded daily, and colon length was measured. Moreover, the permeability was evaluated utilizing a fluorescein isothiocyanate dextran (FITC‐Dextran) probe. Histopathological changes of DSS‐induced colitis mice was assessed utilizing H&E staining. Next, qRT‐PCR was performed to detect IL‐1β, IL‐6, TNF‐α, and IL‐10 level in in vivo and in vitro. Furthermore, the level of MDA, SOD, CAT, and GSH were evaluated in colon tissues. Besides, the expressions of tight junction proteins and NF‐κB pathway relative proteins were examined in colitis mice and IEC‐6 cells using western blot, immunohistochemistry and immunofluorescence. Results MAFB level was downregulated in DSS‐induced colitis mice. Moreover, the upregulation of MAFB protected mice from DSS‐induced colitis by suppressing DSS‐induced inflammation, oxidative stress, and intestinal barrier impairment. We also demonstrated that the upregulation of MAFB inactivated NF‐κB pathway in DSS‐caused colitis mice. Subsequently, we observed that MAFB upregulation could inhibit LPS‐caused epithelial barrier impairment and inflammation in IEC‐6 cells. Additionally, MAFB overexpression could suppress the activation of NF‐κB pathway in IEC‐6 cells. Conclusion The upregulation of MAFB could protect against UC via the suppression of inflammation and the intestinal barrier impairment through inhibiting the NF‐κB pathway.

Abstract Halogenation of Y‐series small‐molecule acceptors (Y‐SMAs) is identified as an effective strategy to optimize photoelectric properties for achieving improved power‐conversion‐efficiencies (PCEs) in binary organic solar cells (OSCs). However, the effect of different halogenation in the 2D‐structured large π‐fused core of guest Y‐SMAs on ternary OSCs has not yet been systematically studied. Herein, four 2D‐conjugated Y‐SMAs (X‐QTP‐4F, including halogen‐free H‐QTP‐4F, chlorinated Cl‐QTP‐4F, brominated Br‐QTP‐4F, and iodinated I‐QTP‐4F) by attaching different halogens into 2D‐conjugation extended dibenzo[f,h]quinoxaline core are developed. Among these X‐QTP‐4F, Cl‐QTP‐4F has a higher absorption coefficient, optimized molecular crystallinity and packing, suitable cascade energy levels, and complementary absorption with PM6:L8‐BO host. Moreover, among ternary PM6:L8‐BO:X‐QTP‐4F blends, PM6:L8‐BO:Cl‐QTP‐4F obtains a more uniform and size‐suitable fibrillary network morphology, improved molecular crystallinity and packing, as well as optimized vertical phase distribution, thus boosting charge generation, transport, extraction, and suppressing energy loss of OSCs. Consequently, the PM6:L8‐BO:Cl‐QTP‐4F‐based OSCs achieve a 19.0% efficiency, which is among the state‐of‐the‐art OSCs based on 2D‐conjugated Y‐SMAs and superior to these devices based on PM6:L8‐BO host (17.70%) and with guests of H‐QTP‐4F (18.23%), Br‐QTP‐4F (18.39%), and I‐QTP‐4F (17.62%). The work indicates that halogenation in 2D‐structured dibenzo[f,h]quinoxaline core of Y‐SMAs guests is a promising strategy to gain efficient ternary OSCs.

Abstract BackgroundStudies have reported the adverse effects of cold events on influenza. However, the role of critical factors, such as characteristics of cold spells, and regional variations remain unresolved. ObjectiveWe aimed to systematically evaluate the association between cold spells and influenza incidence in mainland China. MethodsThis time series analysis used surveillance data of daily influenza from 325 sites in China in the 2014‐2019 period. A total of 15 definitions of cold spells were adopted based on combinations of temperature thresholds and days of duration. A distributed lag linear model was used to estimate the short-term effects of cold spells on influenza incidence during the cool seasons (November to March), and we further explored the potential impact of cold spell characteristics (ie, intensity, duration, and timing during the season) on the estimated associations. Meta-regressions were used to evaluate the modification effect of city-level socioeconomic indicators. ResultsThe overall effect of cold spells on influenza incidence increased with the temperature threshold used to define cold spells, whereas the added effects were generally small and not statistically significant. The relative risk of influenza-associated with cold spells was 3.35 (95% CI 2.89‐3.88), and the estimated effects were stronger during the middle period of cool seasons. The health effects of cold spells varied geographically and residents in Jiangnan region were vulnerable groups (relative risk 7.36, 95% CI 5.44‐9.95). The overall effects of cold spells were positively correlated with the urban population density, population size, gross domestic product per capita, and urbanization rate, indicating a sterner response to cold spells in metropolises. ConclusionsCold spells create a substantial health burden on seasonal influenza in China. Findings on regional and socioeconomic differences in the health effects of cold spells on seasonal influenza may be useful in formulating region-specific public health policies to address the hazardous effects of cold spells.

Abstract Breast tumor‐initiating cells (BTICs) of triple‐negative breast cancer (TNBC) tissues actively repair DNA and are resistant to treatments including chemotherapy, radiotherapy, and targeted therapy. Herein, it is found that a previously reported secreted protein, sclerostin domain containing 1 (SOSTDC1), is abundantly expressed in BTICs of TNBC cells and positively correlated with a poor patient prognosis. SOSTDC1 knockdown impairs homologous recombination (HR) repair, BTIC maintenance, and sensitized bulk cells and BTICs to Olaparib. Mechanistically, following Olaparib treatment, SOSTDC1 translocates to the nucleus in an importin‐α dependent manner. Nuclear SOSTDC1 interacts with the N‐terminus of the nucleoprotein, chromatin helicase DNA‐binding factor (CHD1), to promote HR repair and BTIC maintenance. Furthermore, nuclear SOSTDC1 bound to β‐transducin repeat‐containing protein (β‐TrCP) binding motifs of CHD1 is found, thereby blocking the β‐TrCP‐CHD1 interaction and inhibiting β‐TrCP‐mediated CHD1 ubiquitination and degradation. Collectively, these findings identify a novel nuclear SOSTDC1 pathway in regulating HR repair and BTIC maintenance, providing insight into the TNBC therapeutic strategies.

Organic electrochemical transistors (OECT) have shown great potential in diverse applications; however, in many OECTs, their slow transient response has thus far limited their practical use. One reason for the slow response is the complex interplay between lateral and vertical ion transport that has so far been poorly understood. In this work, we study the impact of lateral ion transport on OECT transient response, introduce a robust pre-charging method to manipulate the slow lateral ion transport. This approach leads to quicker ion redistribution and improved switching speeds. We show the general utility of pre-charging method in enhancing the switching speeds across various material systems, characterized by both low and high ion mobilities, and across different device architectures, achieving nearly symmetric speeds for both on-switching and off-switching. Moreover, we showcase the efficacy of the pre-charging method in enabling slow OECTs to capture rapid signals in real-world applications. Our findings present a groundbreaking strategy for enhancing the response times of OECT devices and deepening our understanding of the transient mechanisms in OECT device.

Phyllodes tumors (PTs) has an increased risk of local relapse and distant metastases. Molecular features correlating to histologic grade and aggressive behavior of PTs are poorly characterized. Here, whole exome sequencing (WES) was performed to explore genetic mutations in 61 samples of fibroepithelial breast tumors, including 16 fibroadenomas (FAs), 18 benign PTs, 19 borderline PTs, and 8 malignant PTs. Our work clearly shows that FA, benign PT, borderline PT, and malignant PT are independent entities at the genomic level. They may exist as hidden sub-clones carrying specific genetic alterations. Malignant PT-specific mutations present a multi-gene co-mutational pattern suggesting a synergistic effect of co-mutated genes in processes associated with malignant behavior. Moreover, we made a combined genomic and transcriptomic analysis, which presented a mutated gene-based interaction with expression profiles. We found that EGFR mutations (c.710C > T, c.758A > G, c.1295A > G, and c.2156G > C) serve as a hub of interaction network in borderline PTs, which suggests EGFR tyrosine kinase inhibitors (EGFRi) might be effective for borderline PTs. We found TP53 mutations (c.730G > T, c.844C > T, and c.1019delA) serves as a hub event of molecular changes of malignant PTs. Thus, our study based on the omics platforms of genome and transcriptome provides a better understanding of relapse process and the potential targeted therapy in PTs, which is pivotal in improving molecular-guided patient selection and designing clinically relevant combination strategies.

Silybum marianum (L.) Gaertn, a herbaceous plant with a long history in traditional medicine for the treatment of hepatobiliary diseases, particularly in Europe, which has attracted attention for its remarkable therapeutic effect. This review systematically summarizes the research progress in the botany, phytochemistry, pharmacology, comprehensive utilization and synthetic biology of S. marianum. Up to now, more than 20 types of flavonolignan components have been isolated from S. marianum. In addition, the rearch on fatty acids and triterpenoids is also constantly improving. Among them, silybin is the most active compound in flavonolignans components. Its pharmacological effects in vivo and in vitro include anti-inflammatory, antioxidant, anti-tumour, hypoglycaemic, neuroprotective and immunoregulatory properties. The use of coniferyl alcohol and taxifolin as substrates to produce silybin and isosilybin under the action of enzyme catalysis is the commonly used biosynthetic pathway of silymarin, which provides support for a comprehensive analysis of the synthetic pathway of silymarin. In addition to medicinal use, the extracts of plants also have broad application prospects in the production of food, healthcare products, cosmetics and other aspects. In addition, the chemical composition, pharmacological mechanism and synthetic biology of S. marianum need to be further studied, which is very important for its clinical efficacy and resource development.

This study addresses the challenges of low detection precision and limited generalization across various ripeness levels and varieties for large non-green-ripe citrus fruits in complex scenarios. We present a high-precision and lightweight model, YOLOC-tiny, built upon YOLOv7, which utilizes EfficientNet-B0 as the feature extraction backbone network. To augment sensing capabilities and improve detection accuracy, we embed a spatial and channel composite attention mechanism, the convolutional block attention module (CBAM), into the head’s efficient aggregation network. Additionally, we introduce an adaptive and complete intersection over union regression loss function, designed by integrating the phenotypic features of large non-green-ripe citrus, to mitigate the impact of data noise and efficiently calculate detection loss. Finally, a layer-based adaptive magnitude pruning strategy is employed to further eliminate redundant connections and parameters in the model. Targeting three types of citrus widely planted in Sichuan Province—navel orange, Ehime Jelly orange, and Harumi tangerine—YOLOC-tiny achieves an impressive mean average precision (mAP) of 83.0%, surpassing most other state-of-the-art (SOTA) detectors in the same class. Compared with YOLOv7 and YOLOv8x, its mAP improved by 1.7% and 1.9%, respectively, with a parameter count of only 4.2M. In picking robot deployment applications, YOLOC-tiny attains an accuracy of 92.8% at a rate of 59 frames per second. This study provides a theoretical foundation and technical reference for upgrading and optimizing low-computing-power ground-based robots, such as those used for fruit picking and orchard inspection.

Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Traditional Chinese medicine can mitigate or even treat sepsis in a human system. This review examines progress on the use of TCM extracts for treating sepsis through different pharmacological action and its mechanisms. The potential targets of TCM extracts and active ingredients for the treatment of sepsis and its complications have been elucidated through molecular biology research, network pharmacology prediction, molecular docking analysis, and visualization analysis. Our aim is to provide a theoretical basis and empirical support for utilizing TCM in the treatment of sepsis and its complications while also serving as a reference for future research and development of sepsis drugs.

BackgroundQuality of work-life issues significantly impact the economic, physical, and psychological well-being of health professionals and their families. Enhancing QWL aims to foster a conducive environment and improve work performance. This study evaluated the quality of work life of health professionals in government and private health institutions in the Awi zone, Ethiopia.MethodsA comparative cross-sectional approach was employed, with study participants selected via the lottery method in 2022. Socio-demographic and organizational-related data were collected, coded, cleaned, and entered into Epi-Data version 3.1, then analyzed using SPSS version 27. Candidate variables were selected using bivariable logistic regression (p

Buried pipelines have been widely used to transport petroleum-based products over long distances in permafrost regions. Field observations reveal that they are endangered by rapid permafrost thawing and resulting massive soil movements, despite adopting some measures to protect pipeline foundation permafrost. A new mitigation technique is proposed to slow down the permafrost thawing ulteriorly. With this technique, a seasonal air-cooled embankment (SACE), mainly composed of a crushed rock layer, supports the pipeline and transfers the heat from the pipeline to ambient air in the cold seasons. A scale model test with the controlled air and oil temperatures was carried out to evaluate the proposed measure. The temperature and volumetric unfrozen water content of the permafrost subgrade beneath both the SACE and the direct-buried pipeline, as well as ground surface displacements, were measured during the whole testing process. A comparison of the hydrothermal process of the subgrade permafrost under the SACE and the direct-buried warm pipeline indicates that the proposed measure can substantially mitigate the rapid thawing of permafrost by controlling the geothermal regimes of the pipeline.

Accumulating oxidative damage is a primary driver of ovarian reserve decline along with aging. However, the mechanism behind the imbalance in reactive oxygen species (ROS) is not yet fully understood. Here we investigated changes in iron metabolism and its relationship with ROS disorder in aging ovaries of mice. We found increased iron content in aging ovaries and oocytes, along with abnormal expression of iron metabolic proteins, including heme oxygenase 1 (HO-1), ferritin heavy chain (FTH), ferritin light chain (FTL), mitochondrial ferritin (FTMT), divalent metal transporter 1 (DMT1), ferroportin1(FPN1), iron regulatory proteins (IRP1 and IRP2) and transferrin receptor 1 (TFR1). Notably, aging oocytes exhibited enhanced ferritinophagy and mitophagy, and consistently, there was an increase in cytosolic Fe2+, elevated lipid peroxidation, mitochondrial dysfunction, and augmented lysosome activity. Additionally, the ovarian expression of p53, p21, p16 and microtubule-associated protein tau (Tau) were also found to be upregulated. These alterations could be phenocopied with in vitro Fe2+ administration in oocytes from 2-month-old mice but were alleviated by deferoxamine (DFO). In vivo application of DFO improved ovarian iron metabolism and redox status in 12-month-old mice, and corrected the alterations in cytosolic Fe2+, ferritinophagy and mitophagy, as well as related degenerative changes in oocytes. Thereby in the whole, DFO delayed the decline in ovarian reserve and significantly increased the number of superovulated oocytes with reduced fragmentation and aneuploidy. Together, our findings suggest that aging-related disturbance in ovarian iron homeostasis contributes to excessive ROS production and that iron chelation may improve ovarian redox status, and efficiently delay the decline in ovarian reserve and oocyte quality in aging mice. These data propose a novel intervention strategy for preserving the ovarian reserve function in elderly women.

In deep strata, there is a risk that geotechnical engineering is simultaneously subjected to chemical corrosion and dynamic loading, which seriously affects the safety of engineering. In this study, Split Hopkinson Pressure Bar (SHPB) was utilized to conduct dynamic loading tests on chemically corroded sandstone, which investigated the dynamic metamorphic properties and chemical damage of sandstone in this condition. Based on the effective bearing area and strain equivalence principles, the damage variables were determined by changes in the porosity of sandstone that were indicated by nuclear magnetic resonance (NMR). The microstructure and particle size distribution of sandstone were quantitatively analyzed by Scanning Electron Microscopy (SEM) and Nano Measurer software. Furthermore, the failure mechanisms of sandstone were explained by chemical reactions between rocks and solutions. The results showed that the porosity of sandstone corroded by chemical solutions increases. With the increase of damage variables, the dynamic compressive strength linearly decreases while the dynamic destructive strain gradually increases. The distribution of particle size has good self-similarity at the micro level and the fractal dimension was positively correlated with the damage variable. Microstructural metamorphism and chemical damage mechanisms of sandstones were revealed through microstructure testing and mineralization analysis. Findings are necessary for the safe operation of rock engineering.