Search

Background: Autophagy is an evolutionarily conserved turnover process for intracellular substances in eukaryotes, relying on lysosomal (in animals) or vacuolar (in yeast and plants) mechanisms. In the past two decades, emerging evidence suggests that, under specific conditions, autophagy can target particular macromolecules or organelles for degradation, a process termed selective autophagy. Recently, accumulating studies have demonstrated that the abnormality of selective autophagy is closely associated with the occurrence and progression of many human diseases, including neurodegenerative diseases, cancers, metabolic diseases, and cardiovascular diseases. Aim of Review: This review aims at systematically and comprehensively introducing selective autophagy and its role in various diseases, while unravelling the molecular mechanisms of selective autophagy. By providing a theoretical basis for the development of related small-molecule drugs as well as treating related human diseases, this review seeks to contribute to the understanding of selective autophagy and its therapeutic potential. Key Scientific Concepts of Review: In this review, we systematically introduce and dissect the major categories of selective autophagy that have been discovered. We also focus on recent advances in understanding the molecular mechanisms underlying both classical and non-classical selective autophagy. Moreover, the current situation of small-molecule drugs targeting different types of selective autophagy is further summarized, providing valuable insights into the discovery of more candidate small-molecule drugs targeting selective autophagy in the future. On the other hand, we also reveal clinically relevant implementations that are potentially related to selective autophagy, such as predictive approaches and treatments tailored to individual patients.

Abstract Fire events in South America are becoming more extensive and frequent as climate extremes and human pressures increase, and even repeatedly occurring in some areas within decades. However, the relationship between recurring fires and vegetation dynamics remains unclear. Here, we extracted the number of fire occurrences using burned area satellite product and analysed the relationship between recurring fires and vegetation dynamics with remote sensing land use and vegetation index datasets in South America. We show that approximately 1.39 × 106 km2 of burnt area has experienced recurring fires during 2001–2020. More than half of burnt area of recurring fires occurred in savannahs with remaining burnt area in grasslands, forests and croplands. Although forests tended to be less susceptible to recurring fires among all vegetation types, their coverage loss with recurring fires was the greatest. The greater proportion of forest conversion to croplands concurred with more recurring fires. Conversely, the coverage of croplands and grasslands gained the most with recurring fires. In the areas without vegetation conversion, more frequent recurring fires further suppressed canopy greenness and density, even in fire‐adapted savannahs and grasslands. Our results suggest that recurring fires and land use change are generally coincident, reflecting the intense pressure of human activities on natural vegetation in South America. Thus, coordinated efforts on vegetation conservation and sustainable management of human‐induced burning in the region are urgently needed.

Abstract Background Cerebral venous thrombosis (CVT) is a rare but serious condition that can lead to significant morbidity and mortality. Virchow’s triad elucidates the role of blood hypercoagulability, blood flow dynamics, and endothelial damage in the pathogenesis of CVT. Cerebral venous congestion (CVC) increases the risk of cerebral venous sinus thrombosis and can lead to recurrent episodes and residual symptoms. However, the precise mechanism by which blood congestion leads to thrombosis remains unclear. Our objective was to investigate the cellular and molecular alterations linked to CVC through analysis of the pathological morphology of venous sinus endothelial cells and transcriptomic profiling. Results This study demonstrated a remarkable correlation between CVC and the phenotypic transformation of endothelial cells from an anticoagulant to a procoagulant state. The findings revealed that cerebral venous stasis results in tortuous dilatation of the venous sinuses, with slow blood flow and elevated pressure in the sinuses and damaged endothelial cells of the retroglenoid and internal jugular vein ligation (JVL) rat model. Mechanistically, analysis of transcriptomic results of cerebral venous sinus endothelial cells showed significant activation of platelet activation, complement and coagulation cascades pathway in the JVL rats. Furthermore, the expression of von Willebrand factor (vWF) and coagulation factor VIII (F8) in the complement and coagulation cascades and Fgg and F2 in the platelet activation was increased in the cerebral venous sinuses of JVL rats than in sham rats, suggesting that endothelial cell injury in the venous sinus induced by CVC has a prothrombotic effect. In addition, endothelial cell damage accelerates coagulation and promotes platelet activation. Significantly, the concentrations of vWF, F2 and F8 in venous sinus blood of patients with internal jugular vein stenosis were higher than in their peripheral blood. Conclusion Collectively, our data suggest that CVC can induce endothelial cell damage, which then exhibits a procoagulant phenotype and ultimately increases the risk of CVT. This research contributes to our understanding of the pathophysiology of CVC associated with procoagulant factors and reexamines the components of Virchow’s triad in the context of CVC.

In this paper, based on the Ulm-Chebyshev iterative procedure, we present a multi-step Ulm-Chebyshev-like method to solve systems of nonlinear equations $ F(x) = 0 $,$ \begin{equation*} \left\{\begin{array}{l} \quad {\bf{y}}_{n} = {\bf{x}}_{n}-B_{n}F( {\bf{x}}_{n}),\\ \quad {\bf z}_{n} = {\bf{y}}_{n}-B_{n}F( {\bf{y}}_{n}),\\ {\bf{x}}_{n+1} = {\bf z}_{n}-B_{n}F( {\bf z}_{n}),\\ \quad \bar{B}_{n} = 2B_{n}-B_{n}A_{n+1}B_{n},\\ B_{n+1} = \bar{B}_{n}+\bar{B}_{n}(2I-A_{n+1}\bar{B}_{n})(I-A_{n+1}\bar{B}_{n}),\quad n = 0,1,2,\ldots, \end{array}\right. \end{equation*} $where $ A_{n+1} $ is an approximation of the derivative $ F'({\bf{x}}_{n+1}) $. This method does not contain inverse operators in its expression, and does not require computing Jacobian matrices for solving Jacobian equations. We have proved that the multi-step Ulm-Chebyshev-like method converges locally to the solution with $ R $-convergence rate 4 under appropriate conditions. Some applications are given, compared with other existing methods, where the most important features of the method are shown.

Abstract Background This study aimed to quantitatively evaluate the left ventricular global and regional myocardial work of patients in Fabry disease (FD) by echocardiographic pressure–strain loop (PSL) analysis. Results The study included 48 patients with FD and 48 healthy controls matched for age and sex. According to the presence/absence of left ventricular hypertrophy (LVH), the patients with FD were divided into an LVH + group and an LVH– group. Left ventricular blood pressure was estimated noninvasively according to echocardiographic valvular events and systolic pressure in the brachial artery. Left ventricular myocardial work parameters were acquired by echocardiographic pressure–strain loop analysis. The FD groups had a significantly lower global longitudinal strain (GLS), global work index, global work efficiency (GWE), global constructive work and higher global waste work than the control group (P

Abstract Background Adolescence is commonly perceived as a distinct and typically healthy stage of life. However, in regions with a high prevalence of HIV, like Ethiopia, numerous adolescents are contracting the virus. Upon testing and diagnosis, they encounter care-related issues, particularly barriers and facilitators of the healthcare transition from adolescent to adult clinics. Hence, the study aimed to investigate the barriers and facilitators influencing the transition of adolescents living with HIV (ALWHs) in the resource-limited settings of Southern Ethiopia. Methods The research employed a phenomenological study design with a qualitative methodology. Purposive sampling was used to gather data through in-depth interviews (IDIs) and focus group discussions (FDGs) involving ALWHs and their parents. The data analysis followed Van Manen’s principles. Results Following Van Manen’s guidelines, the data analysis revealed a conceptual framework with two major themes: “Barriers” and “Facilitators”. The theme barrier was derived from three sub-themes including behavioral barriers, social barriers, and system barriers in the transition. The theme facilitator was derived from four sub-themes including self-acceptance as an adult, a desire to experience new things, a supportive family, and friendly healthcare services. The study identified three levels of factors influencing the transition into adult clinics: individual, family/peer, and healthcare-related factors. The barriers to transition included lack of knowledge, being in a romantic relationship, psychosocial struggles, perceiving us as immature, stigma, negative peer pressure, lack of timely disclosure, absence of transition guidelines, disrespectful treatment, and absence of separate clinics. On the other hand, facilitators such as self-acceptance as an adult, desire for new experiences, family support, informed support and promising outcomes, flexible appointment scheduling, and psycho-social support groups were found to improve the transition process and enhance the overall well-being of adolescents living with HIV. Conclusion The study highlights the complex transition process for ALWHs into adult healthcare. Barriers such as lack of knowledge, stigma, and disrespectful treatment pose challenges during this critical period. Conversely, facilitators like self-acceptance, family support, and youth-friendly healthcare services can enhance the transition experience and well-being of ALWHs. Collaborative efforts among ALWHs, families, and healthcare providers are crucial for successful transitions and improved health outcomes. Separated clinics catering to the unique needs of ALWHs are recommended to address privacy concerns.

Abstract Background Human immunodeficiency virus (HIV), a viral infection impacting CD4 cells, requires an understanding of factors influencing CD4 cell counts to reduce acquired immunodeficiency syndrome(AIDS)-related morbidity and mortality. Despite its importance, no studies have examined predictors of CD4 cell count progression post-transition to adult-oriented HIV care in Ethiopia. This study aimed to identify predictors affecting CD4 cell count trends among adolescents and young adults transitioning to adult-oriented HIV care. Therefore, this study aimed to identify the predictors that affect the trends of CD4 cell count over time among adolescents and young adults who transitioned to adult-oriented HIV care. Methods A retrospective cohort study was conducted among 206 adolescents and young adults who transitioned to adult-oriented HIV care and had at least two CD4 cell counts in eight selected health facilities in Southern Ethiopia. These facilities were chosen due to their high volume of people living with HIV. A multivariable linear mixed effect model was fitted to identify the predictors of CD4 cell count progression through time. Multi-collinearity between variables was checked using the variance inflation factor. Model comparisons were done using Akaike and Bayesian information criteria. Regression coefficients with 95% confidence intervals (CI) and P-value ≤ 0.05 were used to measure the strength of association and significance level. Results The average CD4 cell count was raised by 6.7 cells/mm3 every six months among the study participants. Transitioning at the age of 18 or older (β = 204.71; 95% CI = 81.86347, 327.5574; P

Abstract Needle selection plays a pivotal role in determining the success of fine needle aspiration (FNA) procedures. Two commonly utilized puncture needles for thyroid FNA are the conventional syringe needle and the stylet needle. Syringe needles are known for their cost-effectiveness in comparison to stylet needles. This study aimed to determine if FNA with syringe needles is non-inferior to FNA with stylet needles in terms of specimen adequacy while also comparing the direct costs associated with both needle types. A total of 220 thyroid nodules from 185 patients were prospectively included in this study. The same operator performed a total of four punctures on the same nodule twice using a syringe and a stylet needle. The results of this study show that the utilization of syringe needles for thyroid FNA was non-inferior to the use of stylet needles in terms of specimen adequacy. Cost analysis revealed that syringe needle FNA was not only less expensive (CNY 500.9 versus CNY 780) but also more effective (adequacy 85.91% versus 84.55%). In summary, given the global prevalence of FNA procedures, the economic considerations are paramount, and our findings support the routine use of syringe needles in thyroid FNA.

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 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 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.

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

Antimony (Sb) is a metalloid, widely presents in the environment and associates with human health. In this study, we aimed to decipher whether Sb exposure is harmful to female reproduction and explore the underlying mechanisms. The ICR mice were exposed to 0, 5, 10, and 20 mg/kg acetate potassium Sb tartrate trihydrate by intraperitoneal injection for 10 days, then mouse oocytes were collected for further analysis. We first found a significant decrease in the proportion of MII-stage oocytes obtained from supernumerary ovulation in the fallopian tubes and early embryo development under Sb treatment. Then a series of tests showed Sb affects oocyte maturation by damaging the cytoskeleton of microtubule and actin. Moreover, the abnormal distribution of cortical granules and their component Ovastacin in oocytes, combined with reduced expression levels of Juno, affected sperm-oocyte binding and led to fertilization failure. Based on the sequencing results and experimental validation, it was demonstrated that Sb exposure impairs mitochondrial distribution and membrane potential, elevated levels of mitochondrial superoxide, finally caused energy supply deficits. Mitochondrial damage in oocytes after Sb exposure results in the excessive oxidative stress and early apoptosis. Taken together, these data suggest that Sb exposure decreases oocyte quality and female fertilization ability by impairing mitochondrial function and redox perturbation.

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 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.

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.

Abstract City-scale traffic data, such as traffic flow, speed, and density on every road segment, are the foundation of modern urban research. However, accessing such data on a city scale is challenging due to the limited number of sensors and privacy concerns. Consequently, most of the existing traffic datasets are typically limited to small, specific urban areas with incomplete data types, hindering the research in urban studies, such as transportation, environment, and energy fields. It still lacks a city-scale traffic dataset with comprehensive data types and satisfactory quality that can be publicly available across cities. To address this issue, we propose a unified approach for producing city-scale traffic data using the classic traffic assignment model in transportation studies. Specifically, the inputs of our approach are sourced from open public databases, including road networks, traffic demand, and travel time. Then the approach outputs comprehensive and validated citywide traffic data on the entire road network. In this study, we apply the proposed approach to 20 cities in the United States, achieving an average correlation coefficient of 0.79 in average travel time and an average relative error of 5.16% and 10.47% in average travel speed when compared with the real-world data.

Abstract Objective This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. Methods The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). Results A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p

Abstract Background Glioma is a highly heterogeneous brain tumor categorized into World Health Organization (WHO) grades 1–4 based on its malignancy. The suppressive immune microenvironment of glioma contributes significantly to unfavourable patient outcomes. However, the cellular composition and their complex interplays within the glioma environment remain poorly understood, and reliable prognostic markers remain elusive. Therefore, in-depth exploration of the tumor microenvironment (TME) and identification of predictive markers are crucial for improving the clinical management of glioma patients. Results Our analysis of single-cell RNA-sequencing data from glioma samples unveiled the immunosuppressive role of tumor-associated macrophages (TAMs), mediated through intricate interactions with tumor cells and lymphocytes. We also discovered the heterogeneity within TAMs, among which a group of suppressive TAMs named TAM-SPP1 demonstrated a significant association with Epidermal Growth Factor Receptor (EGFR) amplification, impaired T cell response and unfavourable patient survival outcomes. Furthermore, by leveraging genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) dataset, two distinct molecular subtypes with a different constitution of TAMs, EGFR status and clinical outcomes were identified. Exploiting the molecular differences between these two subtypes, we developed a four-gene-based prognostic model. This model displayed strong associations with an elevated level of suppressive TAMs and could be used to predict anti-tumor immune response and prognosis in glioma patients. Conclusion Our findings illuminated the molecular and cellular mechanisms that shape the immunosuppressive microenvironment in gliomas, providing novel insights into potential therapeutic targets. Furthermore, the developed prognostic model holds promise for predicting immunotherapy response and assisting in more precise risk stratification for glioma patients. Graphical abstract

Chinese cabbage (Brassica rapa ssp. pekinensis) has a long cultivation history and is one of the vegetable crops with the largest cultivation area in China. However, salt stress severely damages photosynthesis and hormone metabolism, nutritional balances, and results in ion toxicity in plants. To better understand the mechanisms of salt-induced growth inhibition in Chinese cabbage, RNA-seq and physiological index determination were conducted to explore the impacts of salt stress on carbon cycle metabolism and photosynthesis in Chinese cabbage. Here, we found that the number of thylakoids and grana lamellae and the content of starch granules and chlorophyll in the leaves of Chinese cabbage under salt stress showed a time-dependent response, first increasing and then decreasing. Chinese cabbage increased the transcript levels of genes related to the photosynthetic apparatus and carbon metabolism under salt stress, probably in an attempt to alleviate damage to the photosynthetic system and enhance CO2 fixation and energy metabolism. The transcription of genes related to starch and sucrose synthesis and degradation were also enhanced; this might have been an attempt to maintain intracellular osmotic pressure by increasing soluble sugar concentrations. Soluble sugars could also be used as potential reactive oxygen species (ROS) scavengers, in concert with peroxidase (POD) enzymes, to eliminate ROS that accumulate during metabolic processes. Our study characterizes the synergistic response network of carbon metabolism and photosynthesis under salt stress.

Abstract Organic solar cells (OSCs) are considered as a crucial energy source for flexible and wearable electronics. Pseudo-planar heterojunction (PPHJ) OSCs simplify the solution preparation and morphology control. However, non-halogenated solvent-printed PPHJ often have an undesirable vertical component distribution and insufficient donor/acceptor interfaces. Additionally, the inherent brittleness of non-fullerene small molecule acceptors (NFSMAs) in PPHJ leads to poor flexibility, and the NFSMAs solution shows inadequate viscosity during the printing of acceptor layer. Herein, we propose a novel approach termed polymer-incorporated pseudo-planar heterojunction (PiPPHJ), wherein a small amount of polymer donor is introduced into the NFSMAs layer. Our findings demonstrate that the incorporation of polymer increases the viscosity of acceptor solution, thereby improving the blade-coating processability and overall film quality. Simultaneously, this strategy effectively modulates the vertical component distribution, resulting in more donor/acceptor interfaces and an improved power conversion efficiency of 17.26%. Furthermore, PiPPHJ-based films exhibit superior tensile properties, with a crack onset strain of 12.0%, surpassing PPHJ-based films (9.6%). Consequently, large-area (1 cm2) flexible devices achieve a considerable efficiency of 13.30% and maintain excellent mechanical flexibility with 82% of the initial efficiency after 1000 bending cycles. These findings underscore the significant potential of PiPPHJ-based OSCs in flexible and wearable electronics.

Objective: This retrospective study aims to analyze laparoscopic surgical management and clinical consequences of patients with heterotopic pregnancy (HP) who underwent in vitro fertilization and embryo transfer (IVF-ET) and laparoscopic surgical management. Material and methods: We conducted a retrospective analysis of clinical characteristics and pregnancy results of patients with HP who underwent IVF-ET at the Affiliated Maternity and Child Health Care Hospital of Nantong University between January 2013 and December 2022. Results: 21 patients were diagnosed with HP, with an average diagnostic period of 49.1 ± 11.1 days. 11 cases (52.4 %) exhibited clinical manifestations such as abdominal pain and vaginal hemorrhage before the surgery, while 10 cases (47.6 %) were asymptomatic prior to diagnosis. All patients underwent laparoscopic surgery, resulting in 8 cases of miscarriage postoperatively (6.15 %), and all 13 neonates showed no anomalies at birth. Conclusion: Laparoscopic surgery is a safe and effective treatment, and most patients can achieve satisfactory pregnancy outcomes after surgery.

Ice cementation and ice-substrate adfreeze force are the primary contributors to the high bearing capacity of pile foundations in cold regions and the stability of frozen walls in areas subjected to artificial freezing. Given the significant temperature sensitivity of ice’s shear rheology, engineering structures in ice or ice-rich soils continue to deform even under constant external loads. A thorough understanding of shear creep and the long-term adfreeze force at the ice-substrate interface is essential for predicting the continuous deformation of these structures. However, research into the shear creep behavior at frozen interfaces has historically been constrained by the precision of temperature control in experimental settings and the complexity of load paths in shear testing devices. In this study, a temperature- and stress-control device for interface shear creep is assembled firstly, and multilevel loading-unloading creep tests on steel pipes embedded in layered frozen ice were conducted. Through the decoupling of deformation progression, the viscoelastic and viscoplastic shear behaviors at the steel-ice interface under various temperatures and shear stresses were characterized, the principle of sustainable interfacial shear creep along with its underlying physical mechanism were proposed. Subsequently, with the aid of a modified nonlinear Burger model, various interfacial shear creep parameters were derived. Results reveal that the interfacial generalized shear modulus continuously improves but with a gradually weakening degree until a point of accelerating creep is reached. Additionally, the long-term adfreeze force is found to be less than half of the short-term strength, which significantly decreases as the temperature approaches the water phase transition zone. Interestingly, the stress exponent associated with the interfacial steady creep rate is considerably smaller than that predicted by Glen’s law. This research provides a theoretical basis instrumental in the engineering design in cold regions and those structures employing artificial freezing techniques.

This research identified four amino acid residues (Leu174, Asn297, Tyr301, and Gln291) that contribute to substrate recognition by the high-affinity glucose transporter Xltr1p from Trichoderma reesei. Potential hotspots affecting substrate specificity were selected through homology modeling, evolutionary conservation analyses, and substrate-docking modeling of Xltr1p. Variants carrying mutations at these hotspots were subsequently obtained via in silico screening. Replacement of Leu174 or Asn297 in Xltr1p with alanine resulted in loss of hexose transport activity, indicating that Leu174 and Asn297 play essential roles in hexose transport. The Y301W variant exhibited accelerated mannose transport, but lost galactose transport capacity, and mutation of Gln291 to alanine greatly accelerated mannose transport. These results suggest that amino acids located in transmembrane α-helix 7 (Asn297, Tyr301, and Gln291) play critical roles in substrate recognition by the hexose transporter Xltr1p. Our results will help expand the potential applications of this transporter and provide insights into the mechanisms underlying its function and specificity.

During plant growth and development, the YABBY gene plays a crucial role in the morphological structure, hormone signaling, stress resistance, crop breeding, and agricultural production of plant lateral organs, leaves, flowers, and fruits. Astragalus mongholicus is a perennial herbaceous plant in the legume family, widely used worldwide due to its high medicinal and edible value. However, there have been no reports of the YABBY gene family in A. mongholicus. This study used bioinformatics methods, combined with databases and analysis websites, to systematically analyze the AmYABBY gene family in the entire genome of A. mongholicus and verified its expression patterns in different tissues of A. mongholicus through transcriptome data and qRT-PCR experiments. A total of seven AmYABBY genes were identified, which can be divided into five subfamilies and distributed on three chromosomes. Two pairs of AmYABBY genes may be involved in fragment duplication on three chromosomes. All AmYABBY proteins have a zinc finger YABBY domain, and members of the same group have similar motif composition and intron – exon structure. In the promoter region of the genes, light-responsive and MeJa-response cis-elements are dominant. AmYABBY is highly expressed in stems and leaves, especially AmYABBY1, AmYABBY2, and AmYABBY3, which play important roles in the growth and development of stems and leaves. The AmYABBY gene family regulates the growth and development of A. mongholicus. In summary, this study provides a theoretical basis for in-depth research on the function of the AmYABBY gene and new insights into the molecular response mechanism of the growth and development of the traditional Chinese medicine A. mongholicus.

Objective This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats.Methods CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 μg/kg, and CP + Dex 25 μg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting.Results Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1.Conclusion Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.

Chemodynamic therapy, which relies on the generation of cytotoxic radicals, can be amplified by a nanoplatform that produces hydroxyl radicals while also compromising natural radical scavenging mechanisms. For this purpose, a well-defined amphiphilic terpolymer, poly(oligo(ethylene glycol) monomethyl ether methacrylate)-block-poly(N,N-dimethyl aminoethyl methacrylate-statistical-monomer bearing ferrocene graft via azobenzene linker) (POEGMA-b-P(DMAEMA-st-(M-Azo-Fc), denoted as PAzo-Fc) is prepared by a consecutive reversible addition-fragmentation chain transfer (RAFT) polymerization technique, and is further used for doxorubicin (DOX) encapsulation to afford DOX-loaded stabilized nanomicelles, DOX@PAzo-Fc with an average hydrodynamic diameter of 86.0 nm. DOX@PAzo-Fc shows a self-cascade property for amplified CDT. That is, Azo cleavage-induced glutathione (GSH) depletion alleviates reactive oxygen species (ROS) scavenging. Together with the DOX-enhanced hydrogen peroxide generation, the Fc-mediated Fenton reaction is boosted for enhanced CDT. More importantly, the resulting amplified cascade chemo-chemodynamic therapy exerts a synergistic immunogenic cell death (ICD) enhancement effect for effective cancer immunotherapy, which further resulted in a high tumor inhibition rate of 87.8 % in murine tumor models. The uniqueness of this study is the construction of a minimalist nanoplatform based on M-Azo-Fc units for amplified CDT via simultaneously producing hydroxyl radicals and compromising natural radical scavenging mechanisms. Overall, this self-cascade terpolymer platform fabricated herein offers a facile yet robust approach for advanced combinatory cancer therapy with great potential for clinical translations.

ObjectivesThe aim of this study is to explore the expression of inflammatory cytokines (ICs) in Fabry disease (FD), the correlation between ICs and FD phenotypes, and the impact of enzyme replacement therapy (ERT) on IC expression.MethodsWe recruited 67 FD patients and 44 healthy controls (HCs) and detected concentrations of the following ICs: interferon-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, IL-17F, IL-22, tumor necrosis factor (TNF)-α, and TNF-β. We also analyzed the impact of ERT on IC expression in FD patients and the relationship between IC expression and sex, genotype, phenotype, disease burden, and biomarkers.ResultsMost ICs were significantly higher in FD patients than in HCs. A number of ICs were positively correlated with clinical aspects, including disease burden (Mainz Severity Score Index [MSSI]) and cardiac and renal markers. IL-8 was higher in the high MSSI (P-adj=0.026*) than in the low MSSI.ConclusionsICs were upregulated in FD patients, indicating the role of the innate immune process in FD etiology. ERT ameliorated FD-related inflammatory activation, at least to some extent. IC expression was positively correlated with disease burden and clinical markers in FD. Our findings indicated that the inflammatory pathway may be a promising therapeutic target for FD.

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.