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AIM: To investigate the efficacy and mechanisms of indirect intense pulsed light (IPL) irradiation on meibomian gland dysfunction (MGD). METHODS: A total of 60 MGD patients was included in this prospective randomized controlled trial. Patients were randomly assigned 1:1 into two groups (3-mm group and 10-mm group) in which IPL was applied at distances from the lower eyelid margin of 3 and 10 mm, respectively. Both groups received three times treatment with 3-week interval. Meibomian gland yield secretion score (MGYSS), standard patient evaluation of eye dryness (SPEED) questionnaire, tear break-up time (TBUT), corneal fluorescein staining (CFS), and in vivo confocal microscopy were performed at baseline and after every treatment. RESULTS: After three IPL treatments, both groups had significant improvement in MGYSS (both P

Abstract Objective The purpose of the study is to develop a prognosis nomogram for esophageal squamous cell carcinoma (ESCC) patients with radical resection and to identify patients who may benefit from postoperative adjuvant radiotherapy/chemoradiotherapy through survival risk stratification. Methods We retrospectively enrolled patients who underwent esophagectomy in the First Affiliated Hospital of Nanjing Medical University from July 2015 to June 2017. Patients with stage I-III esophageal squamous cell carcinoma who received radical R0 resection with or without postoperative adjuvant radiotherapy/chemoradiotherapy were included. Further, patients were randomly allocated into two groups (training and validation cohorts) with a distribution ratio of 7:3. The prognosis nomogram was constructed based on independent factors determined by univariate and multivariate Cox analyses. The area under the receiver operating characteristic curve (AUC) and calibration curve were adopted to evaluate the discriminative ability and reliability of the nomogram. The accuracy and clinical practicability were respectively assessed by C-index values and decision curve analysis (DCA), and further contrasted the nomogram model and the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system. In addition, survival risk stratification was further performed according to the nomogram, and the effect of postoperative adjuvant therapy on each risk group was appraised by the Kaplan-Meier survival analysis. Results A total of 399 patients with esophageal squamous cell carcinoma were recruited in this study, including the training cohort (n = 280) and the validation cohort (n = 119). The nomogram-related AUC values ​​for 1, 3, and 5-year OS were 0.900, 0.795, and 0.802, respectively, and 0.800, 0.865, 0.829 in the validation cohort, respectively. The slope of the calibration curve for both cohorts was close to 1, indicating good consistency. The C-index value of the nomogram was 0.769, which was higher than that of the AJCC 8th TNM staging system by 0.061 (p

Abstract Human action understanding (HAU) is a broad topic that involves specific tasks, such as action localisation, recognition, and assessment. However, most popular HAU datasets are bound to one task based on particular actions. Combining different but relevant HAU tasks to establish a unified action understanding system is challenging due to the disparate actions across datasets. A large‐scale and comprehensive benchmark, namely SkatingVerse is constructed for action recognition, segmentation, proposal, and assessment. SkatingVerse focus on fine‐grained sport action, hence figure skating is chosen as the task object, which eliminates the biases of the object, scene, and space that exist in most previous datasets. In addition, skating actions have inherent complexity and similarity, which is an enormous challenge for current algorithms. A total of 1687 official figure skating competition videos was collected with a total of 184.4 h, exceeding four times over other datasets with a similar topic. SkatingVerse enables to formulate a unified task to output fine‐grained human action classification and assessment results from a raw figure skating competition video. In addition, SkatingVerse can facilitate the study of HAU foundation model due to its large scale and abundant categories. Moreover, image modality is incorporated for human pose estimation task into SkatingVerse. Extensive experimental results show that (1) SkatingVerse significantly helps the training and evaluation of HAU methods, (2) the performance of existing HAU methods has much room to improve, and SkatingVerse helps to reduce such gaps, and (3) unifying relevant tasks in HAU through a uniform dataset can facilitate more practical applications. SkatingVerse will be publicly available to facilitate further studies on relevant problems.

Abstract The application of carbon fibers reinforced carbon matrix (C/C) composite can solve the local wear of metallic finger seals effectively. However, the performance of C/C composite finger seal is complex and variable, which further decreases the sealing performance and life. Therefore, a method of multi-scale modeling and mechanical performance analysis for plain woven C/C composite finger seals was conducted. The circumferential finger beams of C/C composite were modeled by multi-scale structural analysis and weaving simulation. The radial static and dynamic stiffness characteristics of finger beams were investigated. The results showed that the radial static stiffness of the finger beam with three layers was about 3 times that with single layer. The radial stiffness of circumferential finger beams presented a periodic distribution pattern with a period of 90°. The radial dynamic stiffness of C/C composite finger beams increased with the excitation displacement amplitude and rotor speed. But the magnitude and fluctuation degree of dynamic stiffness were greater than those of static stiffness. A large difference in radial stiffness will lead to local wear and hysteretic leakage. This study lays a foundation for the analysis and optimization of the hysteresis and wear characteristics of C/C composite finger seals.

Abstract Youth soccer specialty schools are the primary project to strengthen the foundation of soccer talents, improve the level of soccer development, and achieve the dream of Chinese soccer. Taking 32,775 soccer specialty schools in China as the research sample, ArcGIS spatial analysis technology is used to explore the spatial distribution characteristics of soccer specialty schools and their influencing factors. The analysis shows that the overall distribution of the country forms five quantity concentration area and eight high-density core areas, with a high degree of spatial concentration and significant differences between the East and West. The factors influencing soccer specialty schools include nine factors in four dimensions: historical development, geographical environment, socio-economic, and educational resources. It was found that geographic environment and socio-economy provide the foundation and background for developing educational resources. However, the direct role of educational resources is more significant in a specific educational program, such as soccer specialty schools, followed by socio-economy and geographic environment. This study comprehensively analyzes and interprets soccer specialty schools’ spatial distribution characteristics and influencing factors. These results enrich the research on the spatial layout of sports, providing necessary theoretical support and practical references for the layout and high-quality development of related industries in China and other countries or regions.

Abstract Background In recent years, there has been a significant decrease in the desire to have children among Chinese women of childbearing age, particularly for the first child. This trend has sparked a growing interest in understanding the underlying factors. Although perceived stress has been speculated as an important factor in decreasing fertility intention, the precise mechanism is unclear. The current study, therefore, aims to investigate the psychological mechanisms linking perceived stress to fertility intentions among women of childbearing age without children, a topic of significant relevance and importance. Methods Data were sourced from Chinese residents' psychology and behavior investigation (PBICR-2022). A multistage random sampling method was applied to recruit eligible participants. The Mplus8.3 software constructed a chain path model among the variables. Results The median fertility intention was 30(3–60) on a scale of 0 to 100. The mediation analysis revealed a significant negative influence of perceived stress on fertility intention (β = − 0.076, P

Abstract Background Untreated acute ankle sprains often result in chronic ankle instability (CAI) and can ultimately lead to the development of post-traumatic osteoarthritis (PTOA). At present, a typical animal model of ankle instability in mice is established by transecting the ligaments around the ankle joint. This study aimed to establish a grade I acute ankle sprain animal model by rapid stretching of peri-ankle joint ligaments. Furthermore, we tried to explore the pathophysiological mechanism of ankle osteoarthritis. Methods In all, 18 male C57BL/6 J mice (7 weeks) were randomly divided into three groups: calcaneofibular ligament (CFL) laxity group, deltoid ligament (DL) laxity group, and SHAM group. One week after the surgical procedure, all mice were trained to run in the mouse rotation fatigue machine daily. The mice were tested on the balance beam before surgery and three days, 4 weeks, 8 weeks, and 12 weeks after surgery. Footprint analyses were performed on each mouse before surgery and 12 weeks after surgery. Micro-CT scanning was then performed to evaluate the degeneration of ankle joints and histological staining was performed to analyze and evaluate PTOA caused by ankle joint instability. Results After surgery, the mice in the CFL and DL laxity groups took longer to cross the balance beam and slipped more often than those in the SHAM group (p

To reduce CO2 emissions from coal-fired power plants, the development of low-carbon or carbon-free fuel combustion technologies has become urgent. As a new zero-carbon fuel, ammonia (NH3) can be used to address the storage and transportation issues of hydrogen energy. Since it is not feasible to completely replace coal with ammonia in the short term, the development of ammonia–coal co-combustion technology at the current stage is a fast and feasible approach to reduce CO2 emissions from coal-fired power plants. This study focuses on modifying the boiler and installing two layers of eight pure-ammonia burners in a 300-MW coal-fired power plant to achieve ammonia–coal co-combustion at proportions ranging from 20% to 10% (by heat ratio) at loads of 180- to 300-MW, respectively. The results show that, during ammonia–coal co-combustion in a 300-MW coal-fired power plant, there was a more significant change in NOx emissions at the furnace outlet compared with that under pure-coal combustion as the boiler oxygen levels varied. Moreover, ammonia burners located in the middle part of the main combustion zone exhibited a better high-temperature reduction performance than those located in the upper part of the main combustion zone. Under all ammonia co-combustion conditions, the NH3 concentration at the furnace outlet remained below 1 parts per million (ppm). Compared with that under pure-coal conditions, the thermal efficiency of the boiler slightly decreased (by 0.12%–0.38%) under different loads when ammonia co-combustion reached 15 t·h−1. Ammonia co-combustion in coal-fired power plants is a potentially feasible technology route for carbon reduction.

Abstract Background Addressing the shortage of high-quality protein resources, this study was conducted to investigate the effects of replacing soybean meal (SBM) with different levels of enzymolysis-fermentation compound protein feed (EFCP) in the diets of growing-finishing pigs, focusing on growth performance, nutrients digestibility, carcass traits, and meat quality. Methods Sixty DLY (Duroc × Landrace × Yorkshire) pigs with an initial body weight of 42.76 ± 2.05 kg were assigned to 5 dietary treatments in a 2 × 2 + 1 factorial design. These dietary treatments included a corn-soybean meal diet (CON), untreated compound protein feed (UCP) substitution 50% (U50) and 100% SBM (U100) diets, and EFCP substitution 50% (EF50) and 100% SBM (EF100) diets. Each treatment had 6 pens (replicates) with 2 pigs per pen, and the experiment lasted 58 d, divided into phase I (1–28 d) and phase II (29–58 d). Following phase I, only the CON, U50, and EF50 groups were continued for phase II, each with 5 replicate pens. On d 59, a total of 15 pigs (1 pig/pen, 5 pens/treatment) were euthanized. Results During phase I, the EF50 group had a higher average daily gain (ADG) in pigs (P

Abstract Background Colorectal cancer is the third most common cancer and the second leading cause of cancer death. There are limited therapeutic options for the treatment of locally advanced or metastatic colorectal cancers which fail first-line chemotherapy. Phase I/II studies showed that the combined application of the raltitrexed and irinotecan has significant synergistic effect and acceptable toxicity. However, most of these previous studies have relatively small sample size. Methods This is a prospective open-label, single-arm, multi-center, Phase II trial. Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of 5-FU and oxaliplatin therapy. Enrolled patients received raltitrexed (3 mg/m2, d1) and irinotecan (180 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, and the secondary endpoints were disease control rate, objective response rate, overall survival and safety. Results A total of 108 patients were enrolled between September 2016 and May 2020. The median age was 61 years, ECOG 1 score accounts for 67.6%, the rest were ECOG 0. A total of 502 cycles were completed, with an average of 4.6 cycles and a median of 4 cycles. 108 patients were evaluated, with an objective response rate of 17.6%, and disease control rate of 76.9%. The median follow-up time was 27 months (range:3.1–61.0 m) at data cut-off on March 2023. Median progression-free survival was 4.9 months (95% CI 4.1–5.7) and median overall survival was 13.1 months (95% CI 12.2–15.5). The most common adverse events that were elevated are alanine aminotransferase increased, aspartate aminotransferase increased, fatigue, diarrhoea, neutrocytopenia, thrombocytopenia, hypohemoglobin, and leukocytopenia. Most of the adverse events were Grade I/II, which were relieved after symptomatic treatment, and there were no treatment-related cardiotoxicities and deaths. Conclusions The combination of raltitrexed and irinotecan as second-line treatment for mCRC could be a reliable option after failure of standard 5-Fu-first-line chemotherapy in locally advanced or metastatic colorectal cancers, especially for patients with 5-FU intolerance (cardiac events or DPD deficiency patients). Trial registration ClinicalTrials.gov identifier: NCT03053167, registration date was 14/2/2017.

Abstract Taking a rear‐wheel drive pure electric vehicle as the research object, considering the safety during braking and improving energy recovery rate, a study was conducted on the distribution strategy of front and rear axle braking force. During the braking process, the feedback braking force of the motor and the hydraulic braking force with an electronic stability controller (ESC) were coordinated and controlled, to ensure that the total required braking force was met. A fuzzy logic controller has been designed, with three variables of battery state of charge, vehicle speed, and braking intensity as inputs, and a modified motor braking ratio as output variable to prevent wheel lockup. Using Cruise software, a co‐simulation model was established with Amesim and Simulink, and simulation validation was conducted on the braking process and cycling conditions. The simulation results showed that the brake recovery strategy based on fuzzy control can effectively improve the vehicle's control performance and energy recovery rate compared to the Economic Commission of Europe regulation. The NEDC (New European Driving Cycle) working condition improved by 10.41% and the CLTC‐P (China Light‐duty Vehicle Test Cycle‐passenger) working condition improved by 10.57%. Effectively improving power consumption per 100 km, NEDC decreased by 1.81% and CLTC‐P decreased by 2.62%.

Abstract Arboviruses can be paternally transmitted by male insects to offspring for long-term persistence, but the mechanism remains largely unknown. Here, we use a model system of a destructive rice reovirus and its leafhopper vector to find that insect ribosome-rescuer Pelo-Hbs1 complex expressed on the sperm surface mediates paternal arbovirus transmission. This occurs through targeting virus-containing tubules constituted by viral nonstructural protein Pns11 to sperm surface via Pns11-Pelo interaction. Tubule assembly is dependent on Hsp70 activity, while Pelo-Hbs1 complex inhibits tubule assembly via suppressing Hsp70 activity. However, virus-activated ubiquitin ligase E3 mediates Pelo ubiquitinated degradation, synergistically causing Hbs1 degradation. Importantly, Pns11 effectively competes with Pelo for binding to E3, thus antagonizing E3-mediated Pelo-Hbs1 degradation. These processes cause a slight reduction of Pelo-Hbs1 complex in infected testes, promoting effective tubule assembly. Our findings provide insight into how insect sperm-specific Pelo-Hbs1 complex is modulated to promote paternal virus transmission without disrupting sperm function.

Abstract Background DEAD-box RNA helicase 19 A (DDX19A) is overexpressed in cervical squamous cell carcinoma. However, its role in gastric cancer remains unclear. The present study aimed to explore the role and underlying mechanism of DDX19A in the development of gastric cancer. Methods The expression of DDX19A in gastric cancer and paracancerous tissues was evaluated through quantitative polymerase chain reaction, western blotting, and immunohistochemical staining. The biological functions of DDX19A in gastric cancer were determined using CCK8, plate colony-forming, and Transwell migration assays. The specific mechanism of DDX19A in gastric cancer cells was studied using western blotting, RNA-binding protein immunoprecipitation, mRNA half-life detection, and nuclear and cytoplasmic RNA isolation. Results DDX19A was highly expressed in gastric cancer and positively associated with malignant clinicopathological features and poor prognosis. Additionally, DDX19A promoted gastric cancer cell proliferation, migration, and epithelial–mesenchymal transition phenotypes. Mechanistically, DDX19A activated the PI3K/AKT pathway by upregulating phosphatidylinositol-3-kinase (PIK3CA) expression. Furthermore, DDX19A interacted with PIK3CA mRNA, stabilized it, and facilitated its export from the nucleus. Conclusions Our study reveals a novel mechanism whereby DDX19A promotes the proliferation and migration of gastric cancer cells by enhancing the stability and nuclear export of PIK3CA mRNA, thereby activating the PI3K/AKT pathway.

Osteochondral regeneration involves the highly challenging and complex reconstruction of cartilage and subchondral bone. Silicon (Si) ions play a crucial role in bone development. Current research on Si ions mainly focuses on bone repair, by using silicate bioceramics with complex ion compositions. However, it is unclear whether the Si ions have important effect on cartilage regeneration. Developing a scaffold that solely releases Si ions to simultaneously promote subchondral bone repair and stimulate cartilage regeneration is critically important. Diatomite (DE) is a natural diatomaceous sediment that can stably release Si ions, known for its abundant availability, low cost, and environmental friendliness. Herein, a hierarchical osteochondral repair scaffold is uniquely designed by incorporating gradient DE into GelMA hydrogel. The adding DE microparticles provides a specific Si source for controlled Si ions release, which not only promotes osteogenic differentiation of rBMSCs (rabbit bone marrow mesenchymal stem cells) but also enhances proliferation and maturation of chondrocytes. Moreover, DE-incorporated hierarchical scaffolds significantly promoted the regeneration of cartilage and subchondral bone. The study suggests the significant role of Si ions in promoting cartilage regeneration and solidifies their foundational role in enhancing bone repair. Furthermore, it offers an economic and eco-friendly strategy for developing high value-added osteochondral regenerative bioscaffolds from low-value ocean natural materials.

Abstract The purpose of present study was to examine the current prevalence and recent trends of overactive bladder (OAB) among US adult men and examine the correlations between OAB and several potential risk factors. The study used the nationally representative data between 2005 and 2020 from the National Health and Nutrition Examination Survey in the US. A total of 18,386 participants aged ≥ 20 years were included in the study. We divided the data into three groups: 2005–2008, 2009–2014 and 2015–2020 to investigate the trends in OAB prevalence. The weighted prevalence and corresponding 95% confidence intervals (CI) of OAB were calculated. The differences (95% CI) in prevalence between the surveys were calculated and multivariate-adjusted weighted logistic regression analysis was performed to determine the correlates of OAB. Among all US adult men, the overall prevalence of OAB increased slightly from 11.3% in 2005–2008 to 11.7% in 2009–2014 and significantly increased to 14.5% in 2015–2020 (difference, 3.2% [95% CI (1.9–4.4%)]; P

Abstract Background As an innovative lipid parameter, NHHR (the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol) can serve as a valuable tool for assessing cardiovascular disease risk. Nevertheless, the relationship between NHHR and the risk of kidney stones remains unexplored. Methods A cross-sectional survey utilized data from the National Health and Population Survey (NHANES) database in the United States spanning from 2007 to 2018. Distinct statistical analyses were applied, including weighted logistic regression, stratified and interaction analysis and restricted cubic spline curve (RCS) models, to examine the correlation between NHHR and the incidence of kidney stones. Results This analysis encompassed 24,664 participants, with 9.63% reporting incidents of kidney stones. Following multivariate logistic regression and comprehensive adjustments, participants in NHHR quartile 4 (OR 1.34; 95% CI 1.12, 1.60, P

Compared with the wheat steamed bread, this article was to explore the quality (color difference, structure, texture, sensory evaluation, etc.) and physiological activity (antioxidant properties, in vitro digestive characteristics and glucose production index) of the steamed breads with different ratios of black rice spent grains (BRSG). The results showed that BRSG had significant effects on the specific volume, color difference, structure and texture of steamed bread (P

This article reviews the existing literature and outlines recent advances in quantitative Magnetic Resonance Imaging (MRI) techniques for the assessment of lower extremity muscle microtrauma following a marathon. Single-modality quantitative MRI techniques include T2 mapping to assess the dynamics of muscle inflammatory edema and variability at the site of injury, Diffusion Tensor Imaging (DTI) to detect subclinical changes in muscle injury, Intravoxel Incoherent Motion (IVIM) imaging to provide simultaneous information on perfusion and diffusion in muscle tissue without the need for intravenous contrast, and Magnetic Resonance Spectroscopy (MRS) to noninvasively detect intramyocellular lipid (IMCL) content in muscle before and after marathon exercise to explain the use of fatty acids as an energy source in skeletal muscle during long-distance running. As well as Chemical Exchange Saturation Transfer (CEST) is particularly suitable for detecting changes in free creatine, pH values and lactate concentrations in muscles before and after exercise, providing a more detailed picture of muscle physiology and chemistry. These metabolic MRI methods enhance the understanding of biochemical alterations occurring in muscles pre- and post-exercise. Multimodal techniques combine different modalities to provide a comprehensive evaluation of muscle structural and functional changes. These advanced techniques aim to better assess microtrauma and guide clinical treatment, though further validation with larger studies is needed to establish their potential over traditional qualitative methods.

Abstract The magnetic phase transition is explored in CrSBr flakes through non‐magnetic ion irradiation, revealing a novel method for magnetic control in two‐dimensional (2D) materials. The rise and fall of the ferromagnetic phase is observed in antiferromagnetic CrSBr with increasing the irradiation fluence. The irradiated CrSBr shows ferromagnetic critical temperature ranging from 110 to 84 K, well above liquid N2 temperature. Raman spectroscopy reveals phonon softening, suggesting the formation of defects. These findings not only highlight CrSBr's potential in spintronics, but also present ion irradiation as an effective tool for tuning magnetic properties in 2D materials, opening new avenues for the development of spintronic devices based on air‐stable van der Waals semiconductors.

This paper presents a technique for predicting noise generated by airfoil structures that combines deep learning techniques with traditional numerical methods. In traditional numerical methods, accurately predicting the noise of airfoil structures requires significant computational resources, making it challenging to perform low-noise optimization design for these structures. To expedite the prediction process, this study introduces Conditional Generative Adversarial Networks (CGAN). By replacing the generator and discriminator of CGAN with traditional regression neural network models, the suitability of CGAN for regression prediction is ensured. In this study, the data computation was accelerated by expanding the kernel function in the traditional boundary element method using a Taylor series. Based on the resulting data, an alternative predictive model for wing structure noise was developed by integrating Conditional Generative Adversarial Networks (CGAN). Finally, the effectiveness and feasibility of the proposed method are demonstrated through three case studies.

ABSTRACT The potential of CRISPR/Cas systems for nucleic acid detection in novel biosensing applications is remarkable. The current clinical diagnostic detection of Streptococcus pyogenes (S. pyogenes) is based on serological identification, culture, and PCR. We report a rapid, simple, and sensitive method for detecting and screening for S. pyogenes. This novel method is a promising supplemental test. After 10 min of the sample processing and 10 min of recombinase polymerase amplification, followed by 10 min of Cas12 reaction and 3 min of lateral flow biosensor (LFB) readout, a visible outcome can be observed without the need for magnification within 33 min. This platform is robust, inexpensive, and appropriate for on-site testing. A new technique for detection was created using CRISPR-Cas12a technology, which includes two measurements: a fluorescent-CRISPR-S. pyogenes test and a LFB-CRISPR-S. pyogenes test. An approach utilizing CRISPR Cas12a was developed, and the accuracy and precision of this technique were assessed. The LoD for the fluorescence-CRISPR- S. pyogenes assay was 1 copy/μL, and the technique effectively differentiated S. pyogenes from other microorganisms. Moreover, the detection outcomes were presented in a user-friendly manner using lateral flow biosensor strips. Conclusion: A rapid and sensitive Cas12a/crRNA assay using recombinase RPA and LFB was developed to detect S. pyogenes. The Cas12a/crRNA-based assay exhibited high specificity among different bacteria strains and extremely high sensitivity. The accuracy and rapidity of this method make it a promising tool for S. pyogenes detection and screening.IMPORTANCEPatients may experience a range of symptoms due to Streptococcus pyogenes infections, including superficial skin infections, pharyngitis, and invasive diseases in subcutaneous tissues like streptococcal toxic shock syndrome. At present, the clinical diagnostic detection of S. pyogenes is based on serological identification, culture, and PCR. These detection methods are time-consuming and require sophisticated equipment, making these methods challenging for routine laboratories. Thus, there is a need for a detection platform that is capable of quickly and accurately identifying S. pyogenes. In this study, a rapid and sensitive Cas12a/crRNA assay using recombinase RPA and LFB was developed to detect S. pyogenes. The Cas12a/crRNA-based assay exhibited high specificity among different bacteria strains and extremely high sensitivity. This method probably plays an important role for S. pyogenes detection and screening.

Introduction: This cross-sectional study was conducted to investigate the impact of type 2 diabetes mellitus(DM) and its duration on indicators such as lid wiper epitheliopathy(LWE), and to assess the significance of LWE for early diagnosis of dry eye disease(DED) in DM patients. Methods: A total of 137 subjects with ocular surface disease index(OSDI) score ≥13 were divided into the non-DM group, the short-term DM group (duration

Endothelial cells (ECs) rely on glycolysis for energy production to maintain vascular homeostasis and the normalization of hyperglycolysis in tumor vessels has recently gained attention as a therapeutic target. We analyzed the TCGA database and found reduced Foxp1 expression in lung carcinoma. Immunostaining demonstrated reduced expression more restricted at tumor vascular ECs. Therefore, we investigated the function and mechanisms of Foxp1 in EC metabolism for tumor angiogenesis required for tumor growth. EC-Foxp1 deletion mice exhibited a significant increase of tumor and retinal developmental angiogenesis and Hif1α was identified as Foxp1 target gene, and Hk2 as Hif1α target gene. The Foxp1-Hif1α-Hk2 pathway in ECs is important in the regulation of glycolytic metabolism to govern tumor angiogenesis. Finally, we used genetic deletion of EC-Hif1α and RGD-peptide nanoparticles EC target delivery of Hif1α/Hk2-siRNAs to knockdown gene expression which reduced the tumor EC hyperglycolysis state and restricted angiogenesis for tumor growth. This study advances our understanding of EC metabolism for tumor angiogenesis, and meanwhile provides evidence for future therapeutic intervention of hyperglycolysis in tumor ECs for suppression of tumor growth.

Solid-state electrolytes (SSEs) are regarded as crucial materials, thus determining the comprehensive properties of solid-state lithium batteries (SSLBs). However, the existing issues of ion transport and interface limit their further development and application. As the inorganic solid-state electrolytes (ISEs) and polymer solid-state electrolytes (PSEs) both present obvious advantages and defects, the strategy of preparing composite solid-state electrolytes (CSEs) by incorporating inorganic components in polymer matrix is considered an effective way to overcome the above-mentioned problems. Nanowires with high aspect ratios are widely used in CSEs. Moreover, nanowires can not only effectively enhance the mechanical properties and ion transport efficiency of SSEs, but also boost the contact between electrolyte and electrode interface, thereby improving the cycle stability and safety of SSLBs. This review systematically categorized nanowires according to their morphology, function, and Li+ conductivity, and discussed their structural properties and synthesis strategies in detail. Moreover, application examples and mechanisms of nanowires in different polymer matrices are also introduced. In the summary and prospect section, we anticipate the existing challenges and future objectives of nanowires in the future research of CSEs.

Abstract In the United States (US), chlamydia is the most frequently reported sexually transmitted infection that is nationally notifiable. We examined trends in chlamydia prevalence in the US in 2011–2016 compared with 2005–2010. Cross-sectional, nationally representative surveys, National Health and Nutrition Examination Surveys (NHANES), were used to compare national chlamydia prevalence estimates from 2011 to 2016 with those from 2005 to 2010, and changes in prevalence since 1999–2004 were also reviewed. Persons aged 18–39 years were included in these analyses. Prevalence of chlamydia was based on results from urine specimens. Results were weighted to represent the U.S. civilian, noninstitutionalized population. The baseline characteristics of the study population were similar in gender, age and race/ethnicity between the two groups (P > 0.05). The overall chlamydia prevalence was 1.88% (95% confidence interval [CI] 1.55–2.22%) in 2011–2016 and 1.57% (95% CI 1.27–1.87%) in 2005–2010, a relative increase of 19.7% (95% CI 0.2–39.2%; P high school educational level, never married, age at first sex 5 sexual partners. The chlamydia prevalence had an increasing trend from 2005–2010 to 2011–2016. Those with high chlamydia prevalence such as sexually active young adults and Non-Hispanic Black should be screened annually so that infected persons can be diagnosed and they and their sex partners can be treated promptly.

Abstract Topologically associating domains (TADs), megabase-scale features of chromatin spatial architecture, are organized in a domain-within-domain TAD hierarchy. Within TADs, the inner and smaller subTADs not only manifest cell-to-cell variability, but also precisely regulate transcription and differentiation. Although over 20 TAD callers are able to detect TAD, their usability in biomedicine is confined by a disagreement of outputs and a limit in understanding TAD hierarchy. We compare 13 computational tools across various conditions and develop a metric to evaluate the similarity of TAD hierarchy. Although outputs of TAD hierarchy at each level vary among callers, data resolutions, sequencing depths, and matrices normalization, they are more consistent when they have a higher similarity of larger TADs. We present comprehensive benchmarking of TAD hierarchy callers and operational guidance to researchers of life science researchers. Moreover, by simulating the mixing of different types of cells, we confirm that TAD hierarchy is generated not simply from stacking Hi-C heatmaps of heterogeneous cells. Finally, we propose an air conditioner model to decipher the role of TAD hierarchy in transcription.

Abstract Introduction In recent years, insulin eye drops have attracted increasing attention from researchers and ophthalmologists. The aim of this study was to investigate the efficacy and possible mechanism of action of insulin eye drops in diabetic mice with corneal wounds. Methods A type 1 diabetes model was induced, and a corneal epithelial injury model of 2.5 mm was established. We used corneal fluorescein staining, hematoxylin-eosin (H-E) staining and the Cochet-Bonnet esthesiometer to examine the process of wound healing. Subsequently, the expression levels of Ki-67, IL-1β, β3-tubulin and neuropeptides, including substance P (SP) and calcitonin gene-related peptide (CGRP), were examined at 72 h after corneal injury. Results Fluorescein staining demonstrated an acceleration of the recovery of corneal epithelial injury in diabetic mice compared with the saline treatment, which was further evidenced by the overexpression of Ki-67. Moreover, 72 h of insulin application attenuated the expression of inflammatory cytokines and neutrophil infiltration. Remarkably, the results demonstrated that topical insulin treatment enhanced the density of corneal epithelial nerves, as well as neuropeptide SP and CGRP release, in the healing cornea via immunofluorescence staining. Conclusions Our results indicated that insulin eye drops may accelerate corneal wound healing and decrease inflammatory responses in diabetic mice by promoting nerve regeneration and increasing levels of neuropeptides SP and CGRP.

Abstract Background GBM, also known as glioblastoma multiforme, is the most prevalent and lethal type of brain cancer. The cell proliferation, invasion, angiogenesis, and treatment of gliomas are significantly influenced by oxidative stress. Nevertheless, the connection between ORGs and GBM remains poorly comprehended. The objective of this research is to investigate the predictive significance of ORGs in GBM and their potential as targets for therapy. Methods We identified differentially expressed genes in glioma and ORGs from public databases. A risk model was established using LASSO regression and Cox analysis, and its performance was evaluated with ROC curves. We then performed consistent cluster analysis on the model, examining its correlation with immunity and drug response. Additionally, PCR, WB and IHC were employed to validate key genes within the prognostic model. Results 9 ORGs (H6PD, BMP2, SPP1, HADHA, SLC25A20, TXNIP, ACTA1, CCND1, EEF1A1) were selected via differential expression analysis, LASSO and Cox analysis, and incorporated into the risk model with high predictive accuracy. Enrichment analyses using GSVA and GSEA focused predominantly on malignancy-associated pathways. Subtype C of GBM had the best prognosis with the lowest risk score. Furthermore, the model exhibited a strong correlation with the infiltration of immune cells and had the capability to pinpoint potential targeted therapeutic medications for GBM. Ultimately, we selected HADHA for in vitro validation. The findings indicated that GBM exhibits a significant upregulation of HADHA. Knockdown of HADHA inhibited glioma cell proliferation and diminished their migration and invasion capacities and influenced the tumor growth in vivo. Conclusion The risk model, built upon 9 ORGs and the identification of GBM subtypes, suggests that ORGs have a broad application prospect in the clinical immunotherapy and targeted drug treatment of GBM. HADHA significantly influences the development of gliomas, both in vivo and in vitro.

Abstract Background The link between low grip strength, diminished physical performance, and adverse health outcomes in older adults has been well-established. However, the impact of older adults who cannot complete these tests on disability and mortality rates remains unexplored without longitudinal study. Methods We collected data from the China Health and Retirement Longitudinal Study (CHARLS). Participants aged 60–101 were enrolled at baseline. We analyzed the prevalence of populations unable to complete handgrip strength (HGS), gait speed (GS), and five times chair stand test (FTCST). Completing risk models were used to estimate the risk of mortality and disability over seven years. Results A total of 3,768 participants were included in the analysis. The percentage of older adults unable to complete the GS and FTCST tests increased notably with age, from 2.68 to 8.90% and 2.60–20.42%, respectively. The proportion of older people unable to perform the HGS was relatively stable, ranging from 1.40 to 3.66%. Compared to older adults who can complete these tests, those who cannot perform FTCST face a significantly higher risk of mortality, with 49.1% higher risk [hazard ratio (HR) = 1.491, 95% CI = 1.156, 1.922; subdistribution hazard ratio (SHR) = 1.491, 95%CI = 1.135,1.958)]. Participants who were unable to complete the GS test had a higher risk of developing ADL disability, regardless of whether they were compared to the lowest-performing group (HR = 1.411, 95%CI = 1.037,1.920; SHR = 1.356, 95%CI = 1.030,1.785) or those who can complete the GS (HR = 1.727, 95%CI = 1.302,2.292; SHR = 1.541, 95%CI = 1.196,1.986). No statistically significant difference in the risk of developing ADL disability among older adults who were unable to complete the HGS test compared with either the poorest performing group (HR = 0.982, 95% CI = 0.578, 1.666; SHR = 1.025, 95% CI = 0.639, 1.642) or those who were able to complete the HGS test (HR = 1.008, 95% CI = 0.601, 1.688; SHR = 0.981, 95% CI = 0.619, 1.553). The risk of all-cause mortality was not significantly different for older adults who were unable to complete the HGS test compared to those with the worst performance (HR = 1.196, 95%CI = 0.709–2.020; SHR = 1.196, 95%CI = 0.674, 2.124) or those who were able to complete the test (HR = 1.462, 95%CI = 0.872–2.450; SHR = 1.462, 95%CI = 0.821,2.605). Conclusion The risks of adverse events faced by older adults unable to complete the tests vary, indicating the necessity for future research to conduct separate analyses on this high-risk population.

Regional inequality significantly influences sustainable development and human well-being. In China, there exists pronounced regional disparities in economic and digital advancements; however, scant research delves into the interplay between them. By analyzing the economic development and digitalization gaps at regional and city levels in China, extending the original Cobb-Douglas production function, this study aims to evaluate the impact of digitalization on China’s regional inequality using seemingly unrelated regression. The results indicate a greater emphasis on digital inequality compared to economic disparity, with variable coefficients of 0.59 for GDP per capita and 0.92 for the digitalization index over the past four years. However, GDP per capita demonstrates higher spatial concentration than digitalization. Notably, both disparities have shown a gradual reduction in recent years. The southeastern region of the Hu Huanyong Line exhibits superior levels and rates of economic and digital advancement in contrast to the northwestern region. While digitalization propels economic growth, it yields a nuanced impact on achieving balanced regional development, encompassing both positive and negative facets. Our study highlights that the marginal utility of advancing digitalization is more pronounced in less developed regions, but only if the government invests in the digital infrastructure and education in these areas. This study’s methodology can be utilized for subsequent research, and our findings hold the potential to the government’s regional investment and policy-making.

Currently approved human epidermal growth factor receptor 2 (HER2)-targeted antibody therapies are largely derived from trastuzumab, including trastuzumab-chemotherapy combinations, fixed-dose trastuzumab-pertuzumab combinations, and trastuzumab antibody-drug conjugates. To expand the options, bispecific antibodies, which may better utilize the benefits of combination therapy, are being developed. Among them, biparatopic antibodies (bpAbs) have shown improved efficacy compared to monoclonal antibody (mAb) combinations in HER2-positive patients. BpAbs bind two independent epitopes on the same antigen, which allows fine-tuning of mechanisms of action, including enhancement of on-target specificity and induction of strong antigen clustering due to the unique binding mode. To fully utilize the potential of bpAbs for anti-HER2 drug development, it is crucial to consider formats that offer stability and high-yield production, along with a functional balance between the two epitopes. In this study, we rationally designed a bpAb, KJ015, that shares a common light chain with two Fab arms and exhibits functionally balanced high affinity for two HER2 non-overlapping epitopes. KJ015 demonstrated high-expression titers over 7 g/L and stable physicochemical properties at elevated concentrations, facilitating subcutaneous administration with hyaluronidase. Moreover, KJ015 maintained comparable antibody-dependent cytotoxicity, phagocytosis, and complement-dependent cytotoxicity with trastuzumab plus pertuzumab. It exhibited enhanced synergy when administered subcutaneously with hyaluronidase and anti-PD-1 mAb in a mouse tumor model, suggesting promising clinical prospects for this combination.

Objectives: To explore the therapeutic effects of M2 macrophages in diabetic nephropathy (DN) and their mechanism.Methods: We infused M2 macrophages stimulated with IL-4 into 10-week-old db/db mice once a week for 4 weeks through the tail vein as M2 group. Then we investigated the role of M2 macrophages in alleviating the infammation of DN and explored the mechanism.Results: M2 macrophages hindered the progression of DN, reduced the levels of IL-1β (DN group was 34%, M2 group was 13%, p

Background Empirical research has consistently documented the concurrent manifestation of frailty and chronic kidney disease (CKD). However, the existence of a reverse causal association or the influence of confounding variables on these correlations remains ambiguous.Methods Our analysis of 7,078 participants from National Health and Nutrition Examination Survey(NHANES) (1999–2018) applied weighted logistic regression and Mendelian Randomization (MR) to investigate the correlation between the frailty index (FI) and renal function. The multivariate MR analysis was specifically adjusted for type 2 diabetes and hypertension. Further analysis explored 3282 plasma proteins to link FI to CKD. A two-step network MR highlighted immune cells’ mediating roles in the FI-CKD relationshipResult Genetically inferred FI and various renal function markers are significantly correlated, as supported by NHANES analyses. Multivariate MR analysis revealed a direct causal association between the FI and CKD. Additionally, our investigation into plasma proteins identified Tmprss11D and MICB correlated with FI and CKD, respectively. A two-step network MR to reveal 15 immune cell types, notably Central Memory CD4+ T cells and Lymphocytes, as crucial mediators between FI and CKD.Conclusion Our work establishes a causal connection between frailty and CKD, mediated by specific immune cell profiles. These findings highlight the importance of immune mechanisms in the frailty-CKD interplay and suggest that targeting shared risk factors and immune pathways could improve management strategies for these conditions. Our research contributes to a more nuanced understanding of frailty and CKD, offering new avenues for intervention and patient care in an aging population.

ABSTRACTDNA methylation plays a key role in sex determination and differentiation in vertebrates. However, there are few studies on DNA methylation involved in chicken gonad development, and most focused on male hypermethylated regions (MHM). It is unclear whether there are specific differentially methylated regions (DMRs) in chicken embryonic gonads regulating sex determination and differentiation. Here, the DNA methylation maps showed that the difference of DNA methylation level between sexes was much higher at embryonic day 10 (E10) than that at embryonic day 6 (E6), and the significant differentially methylated regions at both stages were mainly distributed on the Z chromosome, including MHM1 and MHM2. The results of bisulphite sequencing PCR (BSP) and qRT-PCR showed hypomethylation of female MHM and upregulation of long non-coding RNAs (lncRNAs) whose promoter in the MHM region was consistent with the sequencing results, and similar results were in brain and muscle. In female sex-reversed gonads, the methylation pattern of MHM remained unchanged, and the expression levels of the three candidate lncRNAs were significantly decreased compared with those in females, but were significantly increased compared to males. The fluorescence in situ hybridization (FISH) results also showed that these lncRNAs were highly expressed in female embryonic gonads. The results of methyltransferase inhibitor and dual-luciferase reporter assay suggest that lncRNA expression may be regulated by DNA methylation within their promoters. Therefore, we speculated that MHM may be involved in cell-autonomous sex identity in chickens, and that lncRNAs regulated by MHM may be involved in female sexual differentiation.

Considering endangered fish, storage of sterlet (Acipenser ruthenus) gamete is crucial, and investigating the most suitable extender for short-term storage of sperm is necessary. Therefore, the present study aimed to optimize suitable extenders for short-term storage of sterlet spermatozoa and determine the effects of storage periods and different extenders on spermatozoa motility parameters. The sperm of five mature males with good spermatozoa motility (∼80 %) were diluted with 20 different extenders having various Na+ and K+ concentrations and osmolality. Spermatozoa motility performances were assessed using a CASA system within 144 h storage at 0–2 °C. Undiluted sperm was used as a control. Seminal plasma Na+, K+, Ca2+ and Cl- concentrations were 17.56±10.12, 2.48±1.14, 0.11±0.06, and 6.20±3.42 mmol/L with osmolality of 35.60±20.70 mOsm/kg. A two-way ANOVA showed significant effects of storage time, extender, and their interaction on spermatozoa motility, curvilinear velocity (VCL), and straight-line velocity (VSL) (p3 mM resulted in lower spermatozoa motility performance. When the effects of storage time were studied, spermatozoa motility, VCL, and VSL in non-diluted sperm and those diluted with E18-E20 were decreased at 24–48 h and 72–96 h post-storage, respectively. This study shows that extenders with higher osmolality (39–62 mOsm/kg) and lower K+ (1 mmol/L) are the most suitable for storing sterlet sperm for a short period.

The residue generated during the production process of alumina, known as red mud, is a type of solid waste. The engineering properties of red mud can be significantly enhanced through the modification and solidification using inorganic materials. This study primarily utilized red mud as the raw material, supplemented with fly ash, lime, and clay, to conduct a solidification experiment of red mud. Orthogonal tests with three factors of two ash ratio (ratio of lime to fly ash), two ash content (total lime and fly ash), and red mud types were designed to study the changes of different ratios and maintenance conditions, etc., on the engineering properties of red mud. In addition, the micro-mechanisms of modified red mud were investigated by means of XRF, XRD, SEM and EDX. The results show that for optimum moisture content, red mud types are the most important influencing factor and for maximum dry density, two ash content is the most important influencing factor. For strength characteristics, the optimum two ash ratio was 1.5:1, the optimum two ash content was 50%, and the optimum red mud types were 70% CRM (red mud made of Chalco Shandong Co., Ltd) mixed with 30% clay. The addition of lime, fly ash, and clay improves the temperature shrinkage coefficient of the red mud. Through the analysis of microscopic composition and structure, it can be seen that goethite (α-FeO(OH)) and magnetite (γ-Fe2O3) in the red mud reacted with the modified materials to generate crystalline aluminosilicate and amorphous hydrated silicate gel, and these products together with the original calcium carbonate (CaCO3), tricalcium aluminate (Ca3Al2O6) and garnet (Ca3TiFeSi3O12) in the red mud which have certain strengths enhance the structural strength of the modified red mud. The optimum ratio obtained from the combined test results was lime: fly ash: CRM = 30:20:50. Therefore, using lime, fly ash and clay as modified materials can greatly enhance the engineering properties of red mud and realise the resourceful use of red mud.

Background: Previous studies showed that MSCs could mitigate damage in the pancreas during acute pancreatitis (AP). However, acute mortality associated with AP was more often a result of persistent failure of remote organs, rather than local damage, especially in severe acute pancreatitis (SAP), and the effect of MSCs may vary depending on their origin. Methods: An SAP model was induced in 8-week C57BL/6 J male mice by retrograde injection of 5 % sodium taurocholate solution through the bile duct. SAP mice were divided into the SAP group, UC-MSCs group, and BMSCs group, which were treated with saline, 1 × 106 UC-MSCs, and 1 × 106 BMSCs respectively, through the tail vein. After treatment, serum markers, inflammation, and morphology were assessed in the pancreas, kidneys, lungs, and hearts. Results: MSCs infusion ameliorated the systemic inflammatory response in SAP mice. In the MSCs-treated SAP mice, local tissue injury and inflammation response in the pancreas were alleviated. But more importantly, the renal and lung injury were all significantly and drastically mitigated, and the levels of pro-inflammatory factors such as IL-6, MCP-1, IL-1β, and TNF-α in the kidney, lung and heart were sharply decreased. In terms of origin, UC-MSCs exhibited superior efficacy compared with BMSCs. Furthermore, compared to the normal control mice, UC-MSCs showed an earlier appearance, higher distribution densities, and longer duration of presence in the injured tissue. Conclusions: This study provides compelling evidence supporting the therapeutic potential of MSCs in SAP treatment and particularly their ability to mitigate multi-organ failure. Our results also suggested that UC-MSCs may offer greater advantages over BMSCs in SAP therapy.

PurposeAlthough the application of heterosis has significantly increased crop yield over the past century, the mechanisms underlying this phenomenon still remain obscure. Here, we applied transcriptome sequencing to unravel the impacts of parental expression differences and transcriptomic reprogramming in cotton heterosis.MethodsA high-quality transcriptomic atlas covering 15 developmental stages and tissues was constructed for XZM2, an elite hybrid of upland cotton (Gossypium hirsutum L.), and its parental lines, CRI12 and J8891. This atlas allowed us to identify gene expression differences between the parents and to characterize the transcriptomic reprogramming that occurs in the hybrid.ResultsOur analysis revealed abundant gene expression differences between the parents, with pronounced tissue specificity; a total of 1,112 genes exhibited single-parent expression in at least one tissue. It also illuminated transcriptomic reprogramming in the hybrid XZM2, which included both additive and non-additive expression patterns. Coexpression networks between parents and hybrid constructed via weighted gene coexpression network analysis identified modules closely associated with fiber development. In particular, key regulatory hub genes involved in fiber development showed high-parent dominant or over dominant patterns in the hybrid, potentially driving the emergence of heterosis. Finally, high-depth resequencing data was generated and allele-specific expression patterns examined in the hybrid, enabling the dissection of cis- and trans-regulation contributions to the observed expression differences.ConclusionParental transcriptional differences and transcriptomic reprogramming in the hybrid, especially the non-additive upregulation of key genes, play an important role in shaping heterosis. Collectively, these findings provide new insights into the molecular basis of heterosis in cotton.

Sawdust, a solid waste generated during stone processing, poses a serious threat to the environment with its untreated accumulation. This paper first analyzes the chemical composition and physical properties of sawdust, and discusses its mechanism of action in cement mortar. By systematically optimizing the blending ratio and modification method of sawdust, the sawdust-modified cement mortar with excellent performance was prepared. This study evaluates the key performance indicators of sawdust-modified cement mortar, such as compressive strength, flexural strength, and durability, through a series of experiments. The experimental results indicate that the incorporation of an appropriate amount of sawdust significantly enhances the mechanical properties of cement mortar, while also improving its durability, particularly in terms of freeze-thaw resistance. Microstructural analysis reveals the mechanism by which sawdust improves the pore structure of cement mortar; the active components in the sawdust react with the hydration products of cement, resulting in the formation of crystalline structures with higher strength.Therefore, the use of sawdust as a modifier in cement mortar can improve its mechanical properties and durability, while simultaneously reducing the accumulation of solid waste and promoting the sustainable development of building materials.

Abstract The Yunnan‐Guizhou Plateau (YGP) is characterized by the distinctive isolated habitat of the limestone Karst Islands and features the Wumeng Mountains, which divide the YGP into the two Plateaus of Yunnan and Guizhou. This study aimed to assess the effects of geographic isolation and past climate fluctuation on the distribution of flora in the YGP. To achieve this, we carried out the phylogeographical pattern and genetic structure based on chloroplast and nuclear ribosomal DNA sequence in relation to past (Last Glacial Maximum) and present distributions based on ecological niche modeling for Morella nana, an important wild plant resource and endemic to the YGP once considered a vulnerable species. The results suggest that the genetic and chlorotype network structures of M. nana are divided into at least two groups: cpDNA chlorotype H2 (or dominant nrDNA haplotypes h1 and h2), distributed primarily to the east of the Wumeng Mountains, and cpDNA chlorotypes H1 and H3–H10 (or dominant nrDNA haplotype h2 and h3), distributed to the west of the Wumeng Mountains. A deep genetic split was noted within the two groups to reach 25 steps, especially for the cpDNA fragment variation. This east–west divergence reveals the existence of a natural geographical isolation boundary in the form of the Wumeng Mountains, and supports the existence of at least two glacial refuges during the Quaternary glacial period, along with two genetic diversity center, and at least two large geographic protection units for the important species of M. nana. This study indicates that the phylogeographical pattern of M. nana can be attributed to geographic/environmental isolation caused by the Wumeng Mountains and climate fluctuation during the last glacial maximum, and proposes an effective strategy to protecting this important plant resource.

BackgroundAtypical antipsychotics (AAPs)-induced sexual dysfunction (SD) is a frequent issue in clinical practice, often underestimated by clinicians and not extensively researched. The current study aimed to quantify the strength of association between the use of different AAPs and SD using real-world data from the FDA Adverse Event Reporting System (FAERS), as well as investigate the receptor mechanisms that are involved.MethodsData from the FAERS database from the first quarter of 2004 to the third quarter of 2023 were queried through OpenVigil 2.1. Disproportionality analysis was estimated using the reporting odds ratio (ROR) and information component (IC) methods, and linear regression was used to investigate the relationship between ROR and receptor occupancy which was estimated using in vitro receptor binding profiles.ResultsOur analysis yielded 4839 reports that co-mentioned AAP and SD events, and the findings revealed statistical associations between 12 AAPs and SD. The highest signal value was identified for iloperidone reporting retrograde ejaculation with iloperidone (ROR = 832.09, ROR025 = 552.77; IC = 9.58, IC025 = 6.36), followed by compulsive sexual behavior with aripiprazole (ROR = 533.02, ROR025 = 435.90; IC = 7.30, IC025 = 5.97), and psychosexual disorder for aripiprazole (ROR = 145.80, ROR025 = 109.57; IC025 = 6.47, IC025 = 4.86). Different characteristics of the SD side effects in each AAPs were discovered after further data mining. Regression analysis revealed potential effects for receptor occupancy of D2, D3, and 5-HT1A receptors on ROR. However, no significant correlation persisted following sensitivity analyses.ConclusionThis is the first study to investigate the AAP-SD associations by using FAERS. In this study, we report for the first time a significant association between aripiprazole and SD based on real-world data. The study suggests that different AAPs have varying levels of association with SD, and the D2, D3, and 5-HT1A receptor occupancy may contribute to potential mechanisms. The findings of this study warrant further validation of more studies and clinical causality assessment.

It is known that two heavy Majorana right-handed neutrinos are sufficient to generate the baryon asymmetry in the present universe. Thus, it is interesting to identify the third right-handed neutrino N with the dark matter. We impose a new discrete symmetry Z2 on this dark matter neutrino to stabilize it. However, the U(1)B−L gauge boson A′ couples to the right-handed neutrino N. If the B−L breaking scale VB−L is sufficiently low, the dark matter neutrino N can be in the thermal bath. We find that the thermal relic N can explain the dark matter abundance for the B−L breaking scale VB−L∼O(10) TeV. After considering all the constraints from the existing experiments, a narrow mass region of the thermal produced right-handed neutrino dark matter N is still surviving.

Background: There have been no reports about the application of random survival forest (RSF) model to predict disease progression of HIV-associated B-cell lymphoma. Methods: A total of 44 patients with HIV-associated B-cell lymphoma who were referred to Nanjing Second Hospital from 2012 to 2019 were included. The RSF model was used to find predictors of survival, and the results of the RSF model were compared with those of the Cox model. The data were analyzed using R software (version 4.1.1). Results: One-, 2-, and 3-year survival rates were 74.5%, 57.7%, and 48.6%, respectively, and the median survival was 59.0 months. The first 3 most important predictors of survival included lactate dehydrogenase (LDH), absolute monocyte count (AMC), and white blood cells (WBCs) count. The median survival of high-risk patients was only 4.0 months. Areas under the curve (AUCs) of the RSF model remained at more than 0.90 at 1, 2, and 3 years. The RSF model displayed a lower prediction error rate (21.9%) than the Cox model (25.4%). Conclusions: Lactate dehydrogenase, AMC, and WBCs count are the most important prognostic predictors for patients with HIV-associated B-cell lymphoma. Much larger prospective and/or multicentre studies are required to validtae this RSF model.

The combination of well-balanced mechanical performance, high transparency and appealing eco-friendly attributes endows poly(lactic acid) (PLA) with significantly potential for wide-ranging applications in high-value packaging sectors. However, effectively toughening PLA without compromising its transparency and stiffness remains a formidable challenge. In this study, we synthesized a series of graft copolymers by incorporating hydroxyl-functionalized linear low density polyethylene (LLDPEOH) and copolymers of cycloolefin (COCOH) as the main chain and PLA as the side chain, which were subsequently employed as novel toughening agents for commercial PLA. The achievement of high-performance PLA blends with a balanced combination of toughness, strength, and transparency can be realized through meticulous tuning of the structure and mass fraction of the blended graft copolymers. The maximum elongation at break for the PLA blends increased by about 50 times that of neat PLA, reaching up to 300 %. Furthermore, these materials retained their high strength (54 MPa) and excellent transparency (light transmittance up to 90 %). The excellent properties of PLA blends could be ascribed to the well-designed chain structure of the graft copolymer which leaded to and excellent compatibility with the PLA matrix and unique phase morphology. This work is significant in guiding the design and synthesis of graft copolymers as toughening agents for PLA, thereby expanding its application range in areas where high transparency and toughness are required.

ObjectiveThere is suggestive data indicating a correlation among dietary protein intake and the progression of chronic kidney disease (CKD). Nonetheless, the exact associations between dietary protein intake and the incidence of CKD have remained uncertain. We performed the first meta-analysis to explore the correlation among total protein, plant protein, animal protein intake and CKD risk.MethodsThe study conformed the PRISMA statement guidelines. We comprehensively searched PubMed, Web of Science, and Embase until to December 2023. The retrieved studies underwent rigorous evaluation for eligibility, and relevant data were meticulously extracted. The Newcastle-Ottawa Scale (NOS) tool was applied to evaluate the risk of bias. Subsequently, relevant data were extracted and pooled to evaluate the relations among dietary protein intake and CKD incidence.ResultsTotally, 6,191 articles were identified, six studies were eligible. A total of 148,051 participants with 8,746 CKD cases were included. All studies had a low overall risk of bias. Higher total, plant and animal protein intake were all correlated with decreased CKD incidence, pooled risk ratios (RRs) and 95% confidence intervals (CIs) were as follows: (RR = 0.82, 95% CI = 0.71–0.94, p = 0.005; I2 = 38%, p = 0.17); (RR = 0.77, 95% CI = 0.61–0.97, p = 0.03; I2 = 77%, p = 0.001); (RR = 0.86, 95% CI = 0.76–0.97, p = 0.02; I2 = 0%, p = 0.59), respectively. For fish and seafood within animal protein: RR = 0.84, 95% CI = 0.74–0.94. Subgroup analysis showed that geographical region, sample size, follow-up time, not assessing protein by food frequency questionnaire, using %energy as the measurement index, not adjusting for several covariates may be the sources of heterogeneity for plant protein. A significant non-linear relation among plant protein and incident CKD was observed by dose–response analysis.ConclusionThe data showed a lower CKD risk significantly associated higher-level dietary total, plant or animal protein (especially for fish and seafood) intake. Further prospective studies demonstrating the correlations of precise sources, intake and duration of dietary protein and incident CKD are warranted.

Introduction: Allotetraploid upland cotton (Gossypium hirsutum L.) is native to the Mesoamerican and Caribbean regions, had been improved in the southern United States by the mid-eighteenth century, was then dispersed worldwide. However, a Hainan Island Native Cotton (HIC) has long been grown extensively on Hainan Island, China. Objectives: Explore HIC’s evolutionary relationship and genomic diversity with other tetraploid cottons, its origin and whether it was used for YAZHOUBU (Yazhou cloth, World Intangible Cultural Heritage) weaving, and the role of structural variations (SVs) in upland cotton domestication. Methods: We assembled a high-quality genome of one HIC plant. We performed phylogenetic analysis, divergence time estimation, principal component analysis and population differentiation estimation using cotton assemblies and/or resequencing data. SVs were detected by whole-genome comparison. A F2 population was used for linkage analysis and to study effects of SVs. Buoyancy and salt water tolerance tests for seeds were conducted. Results: We found that the HIC belongs to G. purpurascens. G. purpurascens is best classified as a primitive race of G. hirsutum. The potential for long range transoceanic dispersal of G. purpurascens seeds was proved. A set of SVs, selective sweep regions between G. hirsutum races and cultivars, and quantitative trait loci (QTLs) of eleven agronomic traits were obtained. SVs, especially large-scale SVs, were found to have important effects on cotton domestication and improvement. Of them, eight large-scale inversions strongly associated with yield and fiber quality have probably undergone artificial selection in domestication. Conclusion: G. purpurascens including HIC is a primitive race of G. hirsutum, probably disperse to Hainan from Central America by floating on ocean currents, may have been partly domesticated, planted and was likely used for YAZHOUBU weaving in Hainan much earlier than the Pre-Columbian period. SV plays an important role in cotton domestication and improvement.

A compact single-pixel spectral measurement system based on semiconductor diodes is described in this work. There are no optical components in the system configuration, which contribute to reducing the size of the equipment. Incident spectra can be reconstructed by using the photocurrent of semiconductor diode and spectral response functions. After data collection, data analysis, algorithm processing and other steps.The existing equipment can accurately reconstruct the spectra of narrowband monochromatic light at 508–556 nm and broadband light sources in the 478–598 nm wavelength range, achieving high resolution of 6 nm broadband spectra. The peak signal-to-noise ratio (PSNR) of the reconstructed spectra can reach up to 33.44 dB.

Emotion&speech-based human facial animation technique can be considered as a useful application in many artificial intelligent systems. Given a speech signal, the recognizer output a sequence of the phoneme and emotion pairs. Thereby, we calculate the sequence of viseme and expression pairs accordingly, which are subsequently transformed to a consistent and synchronous video describing facial animation. This article introduces a novel facial animation technique that can intelligently generates real human face animation videos by leveraging an emotional speech. More specifically, we first extract acoustic features sufficiently discriminative to the emotion and phoneme pairs. And the corresponding sequence of phoneme and emotion pairs are computed. Next, we propose a low-rank active learning paradigm for discovering multiple key facial frames that can best represent the above phoneme and emotion pairs in the feature subspace. We associate each phoneme and emotion pair with a key facial frame, based on which the well-known morphing technique fits the associated key facial frames to a smooth animated facial video. We focus on generating multiple transitional facial frames between pairwise temporally adjacent key ones. Experiments demonstrated that the synthesized facial videos look real, smooth, and synchronous with different male/female speeches.