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AIM: To characterize the N6-methyladenosine (m6A) modification patterns in long non-coding RNAs (lncRNAs) in sporadic congenital cataract (CC) and age-related cataract (ARC). METHODS: Anterior capsule of the lens were collected from patients with CC and ARC. Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m6A-tagged lncRNAs and lncRNAs expression. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m6A-lncRNAs. RESULTS: Large amount of m6A peaks within lncRNA were identified for both CC and ARC, while the level was much higher in ARC (49 870 peaks) than that in CC (18 688 peaks), yet those difference between ARC in younger age group (ARC-1) and ARC in elder age group (ARC-2) was quite slight. A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs, as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC. On the other hand, 5893 hypermethylated and 5213 hypomethylated lncRNAs, as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1. Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles, as well as nucleotide excision repair. CONCLUSION: Our results for the first time present an overview of the m6A methylomes of lncRNA in CC and ARC, providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC.

Abstract Single-cell transcriptome sequencing (scRNA-seq) is a powerful tool for describing the transcriptome dynamics of plant development but has not yet been utilized to analyze the tissue ontology of sweetpotato. This study established a stable method for isolating single protoplast cells for scRNA-seq to reveal the cell heterogeneity of sweetpotato root tip meristems at the single-cell level. The study analyzed 12,172 single cells and 27,355 genes in the root tips of the sweetpotato variety Guangshu 87, which were distributed into 15 cell clusters. Pseudo-time analysis showed that there were transitional cells in the apical development trajectory of mature cell types from stem cell niches. Furthermore, we identified novel development regulators of sweetpotato tubers via trajectory analysis. The transcription factor IbGATA4 was highly expressed in the adventitious roots during the development of sweetpotato root tips, where it may regulate the development of sweetpotato root tips. In addition, significant differences were observed in the transcriptional profiles of cell types between sweetpotato, Arabidopsis thaliana, and maize. This study mapped the single-cell transcriptome of sweetpotato root tips, laying a foundation for studying the types, functions, differentiation, and development of sweetpotato root tip cells.

Abstract Pancreatic cancer is one of the leading causes of cancer-associated mortality, with a poor treatment approach. Previous study has shown that inducing pyroptosis in pancreatic ductal adenocarcinoma (PDAC) slows the growth of PDACs, implying that pyroptosis inducers are potentially effective for PDAC therapy. Here, we found that Dronedarone hydrochloride (DH), an antiarrhythmic drug, induces pyroptosis in pancreatic cancer cells and inhibits PDAC development in mice. In PANC-1 cells, DH caused cell death in a dosage- and time-dependent manner, with only pyroptosis inhibitors and GSDMD silencing rescuing the cell death, indicating that DH triggered GSDMD-dependent pyroptosis. Further work revealed that DH increased mitochondrial stresses and caused mitochondrial DNA (mtDNA) leakage, activating the cytosolic STING-cGAS and pyroptosis pathways. Finally, we assessed the anti-cancer effects of DH in a pancreatic cancer mouse model and found that DH treatment suppressed pancreatic tumor development in vivo. Collectively, our investigation demonstrates that DH triggers pyroptosis in PDAC and proposes its potential effects on anti-PDAC growth.

Abstract Androgen receptor (AR) overexpression has been identified in gliomas and its stem cells, suggesting that AR plays an important role in tumor carcinogenesis. The prognostic significance of AR overexpression in gliomas remains unknown. AR mRNA expression in gliomas and relevant clinical data were obtained from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. AR expression levels were compared across gliomas of different histopathologic grades and molecular subtypes. Kaplan–Meier analyses in patients with different AR expression levels were investigated for the potential prognostic values of AR. Compared with normal brain tissue, gliomas show significantly higher AR mRNA expression (p

Abstract Unlocking the intricacies of protein structures and interactions within the dynamic landscape of subcellular organelles presents a significant challenge. To address this, we introduce SPACX, a method for spatially resolved protein complex profiling via biocompatible chemical cross(x)-linking with subcellular isolation, designed to monitor protein conformation, interactions, and translocation in living cells. By rapidly capturing protein complexes in their native physiological state and efficiently enriching cross-linked peptides, SPACX allows comprehensive analysis of the protein interactome within living cells. Leveraging structure refinement with cross-linking restraints, we identify subcellular-specific conformation heterogeneity of PTEN, revealing dynamic differences in its dual specificity domains between the nucleus and cytoplasm. Furthermore, by discerning conformational disparities, we identify 83 cytoplasm-exclusive and 109 nucleus-exclusive PTEN-interacting proteins, each associated with distinct biological functions. Upon induction of ubiquitin-proteasome system stress, we observe dynamic alterations in PTEN assembly and its interacting partners during translocation. These changes, including the identification of components and interaction sites, are characterized using the SPACX approach. Notably, SPACX enables identification of unique interacting proteins specific to PTEN isoforms, including PTEN and PTEN-Long, through the determination of sequence-specific cross-linking interfaces. These findings underscore the potential of SPACX to elucidate the functional diversity of proteins within distinct subcellular sociology.

As a result of the rapid advancement in information and communication technologies, learning cyberspace has become a channel for teachers to share learning resources. This study explored the influencing factors of learning resource sharing in teacher learning cyberspace. The study sample consisted of 363 high-quality teacher learning cyberspaces that had received platform awards from 2015 to 2019, among which 41% of cyberspace owners were male (N = 149) and 59% were female (N = 214). The number of space-associated friends, space follows, space followers, space messages, resources spread, space visits, community contributions, external rewards, the proportion of original resources and uploaded resources, which were collected by the web crawler technology were taken as measurement dimensions. The results of structural equation model indicated that trust positively correlated with learning resource sharing, while self-efficacy and reciprocity were not significantly related to learning resource sharing. In addition, it was shown that trust affected self-efficacy and reciprocity dramatically. Based on this, the trust level of teachers in learning cyberspace can be improved by adding the function of friend circle, setting up effective incentives, and copyright protection mechanisms to facilitate teachers' learning resource sharing.

With the boom of the communication systems on some independent platforms (such as satellites, space stations, airplanes, and vessels), co-site interference is becoming prominent. The adaptive interference cancellation method has been adopted to solve the co-site interference problem. But the broadband interference cancellation performance of traditional Adaptive Co-site Interference Cancellation System (ACICS) with large delay mismatching and antenna sway is relatively poor. This study put forward an Adaptive Co-site Broadband Interference Cancellation System With Two Auxiliary Channels (ACBICS-2A). The system model was established, and the steady state weights and Interference Cancellation Ratio (ICR) were deduced by solving a time-varying differential equation. The relationship of ICR, system gain, modulation factor, interference signal bandwidth and delay mismatching degree was acquired through an in-depth analysis. Compared with traditional adaptive interference cancellation system, the proposed ACBICS-2A can improve broadband interference cancellation ability remarkably with large delay mismatching and antenna sway for the effect of auxiliary channel. The maximum improved ICR is more than 25 ​dB. Finally, the theoretical and simulation results were verified by experiments.

In order to solve the problem of poor mirror polishing effect of steel used in plastic die， the polishing efficiency of die steel is improved by optimizing smelting process. The results showed that the mirror effect was closely related to the purity of steel. From the electric arc furnace burden structure， deoxidization system， LF refining furnace argon blowing control， high vacuum degree cycle of VD vacuum furnace and mold casting process optimization， more comprehensive improvement measures were taken， that is， increasing the use of DRI， using silicon predeoxygenation， optimizing the argon blowing control of steel ladle bottom and improving the high vacuum cycle of VD.The effective size of inclusions decreased from 27.93 μm to 23.65 μm before optimization. The number density of inclusions decreased from 256 / cm2 to 176 / cm2， and the number density of inclusions decreased by 31.2%. The total amount of B and DS and TiN inclusions was controlled， and the customer satisfaction of polishing performance was recognized.

Fermented fruit and vegetable products are an important part of traditional fermented food in China. During production, fresh vegetables and fruits are used as raw materials. The fermentation is conducted by the interactions between microorganisms including lactic acid bacteria and fungi which are naturally carried by raw materials. After fermentation, the composition and quantity of microorganisms in fruits and vegetables tend to become out of control, which often leads to post-acidification, softening, spoilage and other problems. Therefore, the development of sterilization technology suitable for fermented fruit and vegetable products has important industrial value. Compared with the destructive effect of traditional heat sterilization, the non-thermal sterilization technology without heating can not only kill the spoilage and pathogenic microorganisms, but also reduce the impact on probiotics, and greatly alleviate the deterioration of fermented fruit and vegetable products. Therefore, non-thermal sterilization technologies have gradually become one of the research hotspots in the field of fermented fruit and vegetable products sterilization. In this paper, the application progress of common non-thermal sterilization technologies in fermented fruit and vegetable products is reviewed. The sterile effect and influencing factors of non-thermal sterilization technologies in fermented fruit and vegetable products are summarized. Its influence on quality and safety attributes of products is discussed. The aim of this study is to provide a theoretical basis for the large-scale application of non-thermal sterilization technologies in the industrial production of fermented fruit and vegetable products.

Abstract Prenatal exposure to Benzo[a]pyrene (BaP) has been suggested to increase the risk of adverse pregnancy outcomes. However, the role of placental apoptosis on BaP reproductive toxicity is poorly understood. We conducted a maternal animal model of C57BL/6 wild-type (WT) and transformation-related protein 53 (Trp53) heterozygous knockout (p53KO) mice, as well as a nested case–control study involving 83 women with PB and 82 term birth from a birth cohort on prenatal exposure to BaP and preterm birth (PB). Pregnant WT and p53KO mice were randomly allocated to BaP treatment and control groups, intraperitoneally injected of low (7.8 mg/kg), medium (35 mg/kg), and high (78 mg/kg) doses of 3,4-BaP per day and equal volume of vegetable oil, from gestational day 10.5 until delivery. Results show that high-dose BaP treatment increased the incidence of preterm birth in WT mice. The number of fetal deaths and resorptions increased with increasing doses of BaP exposure in mice. Notably, significant reductions in maternal and birth weights, increases in placental weights, and decrease in the number of livebirths were observed in higher-dose BaP groups in dose-dependent manner. We additionally observed elevated p53-mediated placental apoptosis in higher BaP exposure groups, with altered expression levels of p53 and Bax/Bcl-2. In case–control study, the expression level of MMP2 was increased among women with high BaP exposure and associated with the increased risk of all PB and moderate PB. Our study provides the first evidence of BaP-induced reproductive toxicity and its adverse effects on maternal–fetal outcomes in both animal and population studies.

Abstract Electrocatalytic alkynes semi-hydrogenation to produce alkenes with high yield and Faradaic efficiency remains technically challenging because of kinetically favorable hydrogen evolution reaction and over-hydrogenation. Here, we propose a hierarchically nanoporous Cu50Au50 alloy to improve electrocatalytic performance toward semi-hydrogenation of alkynes. Using Operando X-ray absorption spectroscopy and density functional theory calculations, we find that Au modulate the electronic structure of Cu, which could intrinsically inhibit the combination of H* to form H2 and weaken alkene adsorption, thus promoting alkyne semi-hydrogenation and hampering alkene over-hydrogenation. Finite element method simulations and experimental results unveil that hierarchically nanoporous catalysts induce a local microenvironment with abundant K+ cations by enhancing the electric field within the nanopore, accelerating water electrolysis to form more H*, thereby promoting the conversion of alkynes. As a result, the nanoporous Cu50Au50 electrocatalyst achieves highly efficient electrocatalytic semi-hydrogenation of alkynes with 94% conversion, 100% selectivity, and a 92% Faradaic efficiency over wide potential window. This work provides a general guidance of the rational design for high-performance electrocatalytic transfer semi-hydrogenation catalysts.

The unique flavor properties and rich nutrients of traditional fermented food are closely related to its complex and variable microbial structure, which also makes it difficult to control the quality of final fermented product. In order to explore the changes of microbial structure and sensory property and nutritional property in the process of food fermentation and the internal relationship between them, the data analysis process is a key step. Therefore, it is necessary to establish a fast and accurate data analysis method for quality control of fermented food. Machine learning has the advantages of high-dimensional simplification rate, large data throughput and high prediction accuracy, showing great application potential in the field of quality control of fermented food. Hence, machine learning has become one of the research hotspots. This paper reviews the application of machine learning in the quality control of fermented food. On the basis of an overview of common models of machine learning, this paper systematically summarizes the application of machine learning in the prediction of microbial structure evolution, flavor compound composition analysis and customization of personalized consumption in the process of food fermentation. The problems and developmental trends in the application of machine learning to quality control of traditional fermented food are summarized and prospected. Although the application of machine learning in fermented food is still confined by the problems such as insufficient general applicability of the model, limited quality indicators, and limited personalized consumption scenario, etc., with the iterative update of the technical model, the adaptation for multi-factors and whole process, and the application expansion in the background of personalized consumption, machine learning will show a greater value for practical application in the field of fermented food. The purpose of this study is to provide guidance for the further application of machine learning in the standardized and controllable production of traditional fermented food.

Abstract Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5’-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Objective This study aimed to evaluate the development of atherosclerosis in ApoE-deficient dogs fed with a high-fat diet (HFD) using vascular duplex ultrasonography (VDU). Methods Thirty beagle dogs were enrolled, including 10 wild-type, 16 heterozygous (ApoE-/+), and four homozygous (ApoE-/-) mutant dogs. The dogs were categorized into either the normal diet (ND) or HFD group. Plasma lipids levles were tested at baseline and then after feeding the dog a different diet for 6 months. The carotid arteries, abdominal aorta (AO) and iliac arteries were examined using VDU. Artery sections of the ApoE-/- dogs were analyzed. Results After HFD, lipids especially triglycerides, total cholesterol and low-density lipoprotein (LDL) in the wild type and ApoE-/+ dogs were significantly increased. Both the intima-media thickness (IMT) of the common carotid artery (CCA) and AO in the wild type and ApoE-/+ dogs significantly increased. In the ApoE-/+ dogs, the mean percentages increases in CCA-IMT and AO-IMT after HFD were higher than those in the ND dogs. The mean values of CCA-IMT and AO-IMT in the ApoE-/-dogs increased to 2-2.5 folds after HFD. Histological analysis confirmed that the carotid and iliac arteries had advanced atherosclerotic lesions in the ApoE-/- dogs. Conclusions HFD may accelerate the development of atherosclerosis in ApoE-deficient dogs, which is an optimal large-animal model of atherosclerosis.

Abstract Recent studies have highlighted ChatGPT’s remarkable capabilities in machine translation. However, little attention has been paid to its application in literary translation, particularly within the realm of Chinese classical poetry. To explore the potential of ChatGPT’s abilities in poetry translation, we conducted a comparative analysis of poetry translation quality, contrasting ChatGPT (with two different prompts) with Google Translate and DeepL Translator regarding fidelity, fluency, language style, and machine translation style. The results revealed that ChatGPT outperformed Google Translate and DeepL Translator in all evaluation criteria, suggesting its exceptional ability in poetry translation. Furthermore, when employing a prompt that instructs ChatGPT to preserve the rhythm and rhyme of poems, ChatGPT demonstrated a remarkable ability to retain the beauty of the original poetic language, setting itself apart from conventional machine translation systems. Our analysis further elucidated ChatGPT’s proficiency in comprehending and translating some common symbols, imagery, and underlined semantic components which contributes to coherent and fluent translations. Our research opens up ChatGPT’s new possibilities in translating ancient literary texts into foreign languages.

The bromodomain and extraterminal domain (BET) family proteins serve as primary readers of acetylated lysine residues and play crucial roles in cell proliferation and differentiation. Dysregulation of BET proteins has been implicated in tumorigenesis, making them important therapeutic targets. BET-bromodomain (BD) inhibitors and BET-targeting degraders have been developed to inhibit BET proteins. In this study, we found that the BET inhibitor MS645 exhibited superior antiproliferative activity than BET degraders including ARV771, AT1, MZ1 and dBET1 in triple-negative breast cancer (TNBC) cells. Treatment with MS645 led to the dissociation of BETs, MED1 and RNA polymerase II from the E2F1–3 promoter, resulting in the suppression of E2F1–3 transcription and subsequent inhibition of cell growth in TNBC. In contrast, while ARV771 displaced BET proteins from chromatin, it did not significantly alter E2F1–3 expression. Mechanistically, ARV771 induced BRD4 depletion at protein level, which markedly increased EGR1 expression. This elevation of EGR1 subsequently recruited septin 2 and septin 9 to E2F1–3 promoters, enhancing E2F1–3 transcription and promoting cell proliferation rate in vitro and in vivo. Our findings provide valuable insights into differential mechanisms of BET inhibition and highlight potential of developing BET-targeting molecules as therapeutic strategies for TNBC.

Hydrogen sulfide (H2S) is a gaseous signaling molecule that influences digestive and nervous system functions. Enteric glial cells (EGCs) are integral to the enteric nervous system and play a role in regulating gastrointestinal motility. This study explored the dual effects of exogenous H2S on EGCs and the influence of apoptosis-related pathways and ion channels in EGCs. We also administered honokiol for further interventional studies. The results revealed that low-concentration H2S increased the mitochondrial membrane potential (MMP) of EGCs, decreased the whole-cell membrane potential, downregulated BAX and caspase-3, upregulated Bcl2 expression, reduced apoptosis, and promoted cell proliferation. The Ca2+ concentration, Cx43 mRNA, and protein expression were also increased. A high concentration of H2S had the opposite effect. In addition, GFAP mRNA expression was upregulated in the test-low group, downregulated in the test-high group, and upregulated in the test-high + Hon group. Honokiol treatment increased MMP, reduced whole-cell membrane potential, inhibited BAX and caspase-3 expression, increased Bcl2 expression, decreased cell apoptosis, and increased cell proliferation. The Ca2+ concentration, Cx43 mRNA, and protein expression were also upregulated. In conclusion, our study showed that exogenous H2S can bidirectionally regulate EGC proliferation and apoptosis by affecting MMP and cell membrane potential via the Bcl2/BAX/caspase-3 pathway and modulate Cx43-mediated Ca2+ responses in EGCs to regulate colonic motility bidirectionally. Honokiol can ameliorate the damage to EGCs induced by high H2S concentrations through the Bcl2/BAX/caspase-3 pathway and improve colon motility by increasing Cx43 expression and Ca2+ concentration.

Abstract In this study, a newly developed composite of biochar-poly(m-phenylenediamine) (BC-PmPD) exhibiting a distinct skeletal structure was synthesized for the purpose of extracting Cr(VI) from aqueous solutions. BC was employed as a supportive carrier onto which PmPD nanoparticles were uniformly affixed through in-situ polymerization and oxidation synthesis, both within and outside the layered configuration of BC. The structural stability and morphologies of BC-PmPD were assessed utilizing Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy, thermogravimetric analysis, analysis of specific surface area and pore size, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction. In comparison to other modified BCs reported, BC-PmPD exhibited the highest Cr(VI) removal rate. Specifically, at 303 K, BC-PmPD achieved a maximum Cr(VI) removal capacity of 775 mg g−1, surpassing the capabilities of unmodified BC and PmPD by 10.4 and 2.13 times, respectively. Analyses involving XPS, FTIR, and density functional theory calculation confirmed that proton transfer happened between protonated amine (−NH2) functional group within the structure of BC-PmPD and HCrO4 − before the formation of hydrogen bond. Subsequently, environmentally persistent free radicals facilitated the reduction of the adsorbed Cr(VI). Quantification of the functional groups indicated that the amino group was responsible for 93.0% of the Cr(VI) adsorption in BC-PmPD. BC-PmPD displayed potent adsorption and reduction capabilities, alongside notable stability, repeatability, and promising potential for application in the remediation for high concentrations of Cr(VI) in electroplating wastewater scenarios. Graphical Abstract

Abstract Objective Asprosin, a newly identified adipokine, is pathologically increased in type 2 diabetes. The aim of this study is to see whether serum asprosin concentrations are linked to diabetes mellitus-induced erectile dysfunction (DMED). Methods 90 male patients with type 2 diabetes were included. According to the International Index of Erectile Function (IIEF-5) score, they were classified into two groups: 45 type 2 diabetes patients without erectile dysfunction (DM group) (IIEF-5 > 21),45 patients with diabetes induced erectile dysfunction (DMED group) (IIEF-5 ≤ 21)0.45 healthy male volunteers with normal blood glucose, IIEF-5 score > 21 points, and age matched with the DMED group were included as the control group. Anthropometric and biochemical variables were determined in all participants. Results When compared to the controls, T2DM ( Type 2 Diabetes Mellitus)patients had higher serum asprosin levels. The DMED group had significantly higher serum asprosin than the T2DM groups(p

Abstract Understanding the physiological and biochemical responses of tree seedlings under extreme drought stress, along with recovery during rewatering, and potential intra-species differences, will allow us to more accurately predict forest responses under future climate change. Here, we selected seedlings from four provenances (AH (Anhui), JX (Jiangxi), HN (Hunan) and GX (Guangxi)) of Schima superba and carried out a simulated drought-rewatering experiment in a field-based rain-out shelter. Seedlings were progressively dried until they reached 50% and 88% loss of xylem hydraulic conductivity (PLC) (i.e. P 50 and P 88), respectively, before they were rehydrated and maintained at field capacity for 30 days. Leaf photosynthesis (A sat), water status, activity of superoxide dismutase (SOD), and proline (Pro) concentration were monitored and their associations were determined. Increasing drought significantly reduced A sat, relative water content (RWC) and SOD activity in all provenances, and Pro concentration was increased to improve water retention; all four provenances exhibited similar response patterns, associated with similar leaf ultrastructure at pre-drought. Upon rewatering, physiological and biochemical traits were restored to well-watered control values in P 50-stressed seedlings. In P 88-stressed seedlings, Pro was restored to control values, while SOD was not fully recovered. The recovery pattern differed partially among provenances. There was a progression of recovery following watering, with RWC firstly recovered, followed by SOD and Pro, and then A sat, but with significant associations among these traits. Collectively, the intra-specific differences of S. superba seedlings in recovery of physiology and biochemistry following rewatering highlight the need to consider variations within a given tree species coping with future more frequent drought stress.

Abstract Background The objective of this investigation is to analyze the levels and clinical relevance of serum PYCARD (Pyrin and CARD domain-containing protein, commonly known as ASC—apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), interleukin-38 (IL-38), and interleukin-6 (IL-6) in individuals afflicted with rheumatoid arthritis (RA). Methods Our study comprised 88 individuals diagnosed with RA who sought medical attention at the Affiliated Hospital of Chengde Medical University during the period spanning November 2021 to June 2023, constituting the test group. Additionally, a control group of 88 individuals who underwent health assessments at the same hospital during the aforementioned timeframe was included for comparative purposes. The study involved the assessment of IL-38, IL-6, PYCARD, anti-cyclic citrullinated peptide antibody (anti-CCP), and erythrocyte sedimentation rate (ESR) levels in both groups. The research aimed to explore the correlations and diagnostic efficacy of these markers, employing pertinent statistical analyses for comprehensive evaluation. Results The test group had higher expression levels of PYCARD, IL-6, and IL-38 than the control group (P

Abstract Background Autism spectrum disorder (ASD) is heritable neurodevelopmental disorders (NDDs), but environmental risk factors have also been suggested to a play a role in its development. Prenatal, perinatal and parental factors have been associated with an increased risk of ASD in children. The aim of the present study was to explore the prenatal, perinatal, and parenting risk factors in children with autism spectrum disorder (ASD) from Beijing, China by comparing them with typically developing (TD) children. Methods A sample of 151 ASD children’s parents who from rehabilitation institutions in Beijing were enrolled in this study, and an additional 151 children from kindergartens in Beijing were recruited as a control group (child age: mean = 4.4 years). TD children were matched according to age, sex and maternal education. We explored the maternal AQ (Autism Spectrum Quotient) scores (mean:19.40-19.71, no significant difference between two groups) to referring the genetic baseline. This study evaluated 17 factors with unadjusted and adjusted analyses. Results Birth asphyxia was associated with a more than a thirteen-fold higher risk of ASD (adjusted odds ratio (AOR) = 13.42). Breastfeeding difficulties were associated with a higher risk of ASD(AOR = 3.46). Parenting influenced the risk of ASD, with low responding (LR) and harsh or neglectful parenting associated with a higher risk of ASD in offspring (AOR = 2.37 for LR, AOR = 3.42 for harsh parenting and AOR = 3.01 for neglectful parenting). Maternal fever during pregnancy was associated with a higher risk of ASD in offspring (AOR = 3.81). Conclusions Many factors were associated with ASD in offspring. Further assessment is needed to elucidate the role of modifiable environmental factors to inform prevention strategies.

Abstract Funduscopic diseases, including diabetic retinopathy (DR) and age‐related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision and irreversible blindness. Delivering drugs to the posterior segment of the eye remains a challenge due to the presence of multiple physiological and anatomical barriers. Conventional drug delivery methods often prove ineffective and may cause side effects. Nanomaterials, characterized by their small size, large surface area, tunable properties, and biocompatibility, enhance the permeability, stability, and targeting of drugs. Ocular nanomaterials encompass a wide range, including lipid nanomaterials, polymer nanomaterials, metal nanomaterials, carbon nanomaterials, quantum dot nanomaterials, and so on. These innovative materials, often combined with hydrogels and exosomes, are engineered to address multiple mechanisms, including macrophage polarization, reactive oxygen species (ROS) scavenging, and anti‐vascular endothelial growth factor (VEGF). Compared to conventional modalities, nanomedicines achieve regulated and sustained delivery, reduced administration frequency, prolonged drug action, and minimized side effects. This study delves into the obstacles encountered in drug delivery to the posterior segment and highlights the progress facilitated by nanomedicine. Prospectively, these findings pave the way for next‐generation ocular drug delivery systems and deeper clinical research, aiming to refine treatments, alleviate the burden on patients, and ultimately improve visual health globally.

In field hydraulic fracturing operation of shale gas development, the high pressure and large displacement liquid-particle two-phase fracturing fluid can be forced to change direction many times through high-pressure double-elbow, and be transported from the outlet pipeline of the fracturing pump to the main pipeline. The high-pressure double-elbow is prone to be affected by erosion wear and Fluid-Structure Interaction (FSI), resulting in perforation and fracture, posing a potential safety threat to field operation. In this study, we conducted the erosion wear experiments on 35CrMo steel used for high-pressure double-elbow in shale-gas fracturing. The erosion rates under different impact angles and flow velocities were obtained, and proposed a novel model of erosion prediction for high-pressure double-elbow. Then the numerical investigation was employed to conduct a comprehensive analysis of erosion wear, structural stress and deformation by the coupling of Computational Fluid Dynamics (CFD) and Finite Element Analysis (FEA). The effects of structural parameters such as connection straight pipe length, pipe inner diameter and fluid turning direction were discussed. The results indicate that with the increase of connection straight pipe length, the flow erosion decreases first then varies little, and the deformation gradually increases. Slight erosion wear but large structural stress and deformation in major inner diameter pipe. And the minimum degree of erosion and flow-induced deformation present with the fluid turning direction of double-elbow as 0°. The study can provide references for the design, installation and detection of high-pressure double-elbow and ensure safety in the process of shale gas fracturing.

Abstract Fusarium wilt (FW) is widespread in global cotton production, but the mechanism underlying FW resistance in superior‐fiber‐quality Sea Island cotton is unclear. This study reveals that FW resistance has been the target of genetic improvement of Sea Island cotton in China since the 2010s. The key nonsynonymous single nucleotide polymorphism (SNP, T/C) of gene Gbar_D03G001670 encoding protein phosphatase 2C 80 (PP2C80) results in an amino acid shift (L/S), which is significantly associated with FW resistance of Sea Island cotton. Silencing GbPP2C80 increases FW resistance in Sea Island cotton, whereas overexpressing GbPP2C80 reduces FW resistance in Arabidopsis. GbPP2C80 and GbWAKL14 exist synergistically in Sea Island cotton accessions with haplotype forms “susceptible–susceptible” (TA) and “resistant–resistant” (CC), and interact with each other. CRISPR/Cas9‐mediated knockout of GbWAKL14 enhances FW and Verticillium wilt (VW) resistance in upland cotton and overexpression of GbWAKL14 and GbPP2C80 weakens FW and VW resistance in Arabidopsis. GbPP2C80 and GbWAKL14 respond to FW and VW by modulating reactive oxygen species (ROS) content via affecting MPK3 expression. In summary, two tandem genes on chromosome D03, GbPP2C80, and GbWAKL14, functions as cooperative negative regulators in cotton wilt disease defense, providing novel genetic resources and molecular markers for the development of resistant cotton cultivars.

The maintenance of nuclear shape is essential for cellular homeostasis and disruptions in this process have been linked to various pathological conditions, including cancer, laminopathies, and aging. Despite the significance of nuclear shape, the precise molecular mechanisms controlling it are not fully understood. In this study, we have identified the YEATS domain-containing protein 4 (GAS41) as a previously unidentified factor involved in regulating nuclear morphology. Genetic ablation of GAS41 in colorectal cancer cells resulted in significant abnormalities in nuclear shape and inhibited cancer cell proliferation both in vitro and in vivo. Restoration experiments revealed that wild-type GAS41, but not a YEATS domain mutant devoid of histone H3 lysine 27 acetylation or crotonylation (H3K27ac/cr) binding, rescued the aberrant nuclear phenotypes in GAS41-deficient cells, highlighting the importance of GAS41’s binding to H3K27ac/cr in nuclear shape regulation. Further experiments showed that GAS41 interacts with H3K27ac/cr to regulate the expression of key nuclear shape regulators, including LMNB1, LMNB2, SYNE4, and LEMD2. Mechanistically, GAS41 recruited BRD2 and the Mediator complex to gene loci of these regulators, promoting their transcriptional activation. Disruption of GAS41-H3K27ac/cr binding caused BRD2, MED14 and MED23 to dissociate from gene loci, leading to nuclear shape abnormalities. Overall, our findings demonstrate that GAS41 collaborates with BRD2 and the Mediator complex to control the expression of crucial nuclear shape regulators.

A 36-year-old unmarried male chef was incidentally diagnosed with hypokalemia during an evaluation for an acute perianal abscess. Despite potassium supplementation, he developed progressive weakness in his lower limbs, culminating in an inability to stand. Investigations confirmed severe hypokalemia, metabolic alkalosis, hypomagnesemia, secondary hyperaldosteronism, and low urinary calcium excretion, with normotension. The patient’s long-standing stunted growth and lean physique since childhood were noted. Biochemical assays further identified type 2 diabetes mellitus and metabolic syndrome. Genetic analysis revealed three heterozygous SLC12A3 mutations (M1: c.421G>A: p.G141R, M2: c.509T>A:p.L170Q, and M3: c.704C>A: p.T235K), compound heterozygo us and derived from both parents, with M1 and M3 reported here for the first time. Treatment with spironolactone and oral potassium chloride stabilized his potassium levels. Following the administration of SGLT2 inhibitors in patients receiving hypoglycemic therapy, we observed a mild decrease in serum sodium levels. This case highlights the criticality of vigilant metabolic surveillance in Gitelman syndrome and advises prudence with SGLT2 inhibitors in those with concurrent type 2 diabetes, given the risk of potentially aggravate sodium loss.

ObjectiveDespite the fact that China amounts to one-fifth of the world’s population, has a higher proportion of the elderly, and has a higher prevalence of osteoporosis and fracture, limited studies have investigated the association between dietary patterns and bone mineral density (BMD) as well as fracture risk among the elderly Chinese population. We aimed to investigate the association between different dietary patterns and BMD as well as the risk of fractures, and this association may vary between elderly women and men.MethodsBuilding upon the China Osteoporosis Prevalence Study, we included 17,489 subjects aged ≥40 years old randomly sampled across 44 counties/districts of 11 provinces or municipalities in China who completed a food frequency questionnaire. BMD was measured by dual x-ray absorptiometry. Vertebral fracture was defined based on lateral spine radiographs using the semi-quantitative technique of Genant.ResultsA diet rich in “carnivorous”, “vegetarian”, “dairy, fruit, and egg” was significantly associated with higher BMD at total hip (TH), femoral neck (FN), and lumbar spine 1–4 (L1–4). Yet, a diet rich in “beverage and fried food” was associated with a lower BMD at the FN and L1–4. High quartiles of the carnivorous diet were associated with 34%–39% reduced risk of clinical fracture in the past 5 years and vertebral fracture. Stronger associations were observed among women. Sensitivity analysis among postmenopausal women presented even stronger positive associations between carnivorous and vegetarian diets and high BMD, as well as between carnivorous diet and reduced risk of fractures.ConclusionsOur study suggested that a diet rich in meat, vegetables, and dairy, fruit, and eggs might be associated with greater BMD and a lower fracture risk, while beverage and fried foods may be associated with a lower BMD at L1–4, especially among elderly women. These findings are relevant to provide recommendations on dietary nutrition regarding the elderly population at high risk of osteoporosis and fractures, especially postmenopausal women.

Abstract Incomplete biomass burning produces considerable amounts of pyrogenic carbonaceous materials (PCMs), which are widely distributed in environmental matrices. Those PCMs undergo different environmental processes and consequently have non-negligible impacts on the global carbon cycle, ecological functions and environmental security. This review provided a comprehensive review of qualitative and quantitative methods, carbon sequestration capabilities and other ecosystem functions of PCMs. In addition, the generation mechanism and environmental health risks of emerging contaminants, especially persistent free radicals (EPFRs) and polycyclic aromatic hydrocarbons (PAHs) associated with PCMs were discussed. The results showed that the coexisting kerogen and coal may interfere with PCMs quantification, and that estimates of PCMs pools vary significantly due to methodological differences, natural variability and limited spatial coverage. The input of PCMs into soils increased soil carbon sequestration through direct carbon contribution and indirect negative priming effect on native SOC. In addition, PCMs can improve soil structure and properties and immobilize/degrade pollutants, which is conducive to the restoration of soil ecology. However, various contaminants associated with PCMs may threaten ecological safety, and thus their formation mechanisms and toxicological pathway to living organisms need to be further investigated. The development of standards for PCMs identification and quantification, application protocols of PCMs in pilot scale, and assessing the effects of PCMs on soil health deserve extended studies.

Road target detection is essential for enhancing vehicle safety, increasing operational efficiency, and optimizing user experience. It also forms a crucial part of autonomous driving and intelligent monitoring systems. However, current technologies face significant limitations in multi-level feature fusion and the accurate identification of key targets in complex data environments. To address these challenges, this paper proposes an innovative algorithmic model called BiFPN GAM SimC2f-YOLO (BGS-YOLO), aimed at improving detection performance. Initially, this paper employs the Bidirectional Feature Pyramid Network (BiFPN) to effectively integrate multi-level features. This integration overcomes the limitations in feature extraction and recognition found in existing target detection algorithms. Following this, this paper introduces the Global Attention Module (GAM), which markedly improves the efficiency and accuracy of extracting key target information in complex data environments. Additionally, this paper innovatively designs the SimAM-C2f (SimC2f) network, further advancing feature expressiveness and fusion efficiency. Experiments on the public COCO dataset demonstrate that the BGS-YOLO model significantly outperforms the existing YOLOv8n model. Notably, it shows a 7.3% increase in mean average precision (mAP) and a 2.4% improvement in accuracy. These results highlight the model’s high precision and swift response in detecting road targets in complex traffic scenarios. Consequently, the BGS-YOLO model has the potential to significantly enhance road safety and contribute to a considerable reduction in traffic accident rates.

Vital signs are important indicators to evaluate the health status of patients. Channel state information (CSI) can sense the displacement of the chest wall caused by cardiorespiratory activity in a non-contact manner. Due to the influence of clutter, DC components, and respiratory harmonics, it is difficult to detect reliable heartbeat signals. To address this problem, this paper proposes a robust and novel method for simultaneously extracting breath and heartbeat signals using software defined radios (SDR). Specifically, we model and analyze the signal and propose singular value decomposition (SVD)-based clutter suppression method to enhance the vital sign signals. The DC is estimated and compensated by the circle fitting method. Then, the heartbeat signal and respiratory signal are obtained by the modified variational modal decomposition (VMD). The experimental results demonstrate that the proposed method can accurately separate the respiratory signal and the heartbeat signal from the filtered signal. The Bland-Altman analysis shows that the proposed system is in good agreement with the medical sensors. In addition, the proposed system can accurately measure the heart rate variability (HRV) within 0.5m. In summary, our system can be used as a preferred contactless alternative to traditional contact medical sensors, which can provide advanced patient-centered healthcare solutions.

Abstract Mesenchymal stem cells (MSCs) are novel therapeutics for the treatment of Crohn’s disease. However, their mechanism of action is unclear, especially in disease-relevant chronic models of inflammation. Thus, we used SAMP-1/YitFc (SAMP), a chronic and spontaneous murine model of small intestinal inflammation, to study the therapeutic effects and mechanism of action of human bone marrow-derived MSCs (hMSC). hMSC dose-dependently inhibited naïve T lymphocyte proliferation via prostaglandin E2 (PGE2) secretion and reprogrammed macrophages to an anti-inflammatory phenotype. We found that the hMSCs promoted mucosal healing and immunologic response early after administration in SAMP when live hMSCs are present (until day 9) and resulted in a complete response characterized by mucosal, histological, immunologic, and radiological healing by day 28 when no live hMSCs are present. hMSCs mediate their effect via modulation of T cells and macrophages in the mesentery and mesenteric lymph nodes (mLN). Sc-RNAseq confirmed the anti-inflammatory phenotype of macrophages and identified macrophage efferocytosis of apoptotic hMSCs as a mechanism that explains their long-term efficacy. Taken together, our findings show that hMSCs result in healing and tissue regeneration in a chronic model of small intestinal inflammation and despite being short-lived, exert long-term effects via sustained anti-inflammatory programming of macrophages via efferocytosis.

Abstract Objectives Most signatures are constructed on the basis of RNA or protein expression levels. The value of vascular invasion-related signatures based on lncRNA pairs, regardless of their specific expression level in hepatocellular carcinoma (HCC), is not yet clear. Methods Vascular invasion-related differentially expressed lncRNA (DElncRNA) pairs were identified with a two-lncRNA combination strategy by using a novel modeling algorithm. Based on the optimal cutoff value of the ROC curve, patients with HCC were classified into high- and low-risk subgroups. We used KM survival analysis to evaluate the overall survival rate of patients in the high- and low-risk subgroups. The independent indicators of survival were identified using univariate and multivariate Cox analyses. Results Five pairs of vascular invasion-related DElncRNAs were selected to develop a predictive model for HCC. High-risk subgroups were closely associated with aggressive clinicopathological characteristics and genes, chemotherapeutic sensitivity, and highly expressed immune checkpoint inhibitors. Conclusions We identified a signature composed of 5 pairs of vascular invasion-related lncRNAs that does not require absolute expression levels of lncRNAs and shows promising clinical predictive value for HCC prognosis. This predictive model provides deep insight into the value of vascular invasion-related lncRNAs in prognosis.

Objectives: Overuse of antibiotics in healthcare remains prevalent and requires urgent attention in China, particularly in primary healthcare (PHC) facilities. This study aimed to describe the patterns of antibiotic prescriptions for acute upper respiratory tract infections (URTIs) in PHC facilities in China and to investigate how PHC physicians’ knowledge influences their antibiotic prescribing behavior. Methods: A cross-sectional survey linking physician questionnaire responses and their prescription data was conducted in Shaanxi Province, China. The proportions of URTI visits that received at least one antibiotic, combined antibiotics, and broad-spectrum antibiotics were the main outcomes reflecting antibiotic prescribing behavior. Multivariate mixed-effects logistic regressions were applied to analyze the relationship between PHC physicians’ knowledge about antibiotics and their antibiotic prescribing behavior. Results: A total of 108 physicians filled out the questionnaires between February 2021 and July 2021, and a sample of 11,217 URTI visits attended by these physicians from 1 January 2020 to 31 December 2020 were included in the analysis. The overall mean score of our respondents on the knowledge questions was 5.2 (total score of 10). Over sixty percent (61.2%; IQR 50.2–72.1) of the URTI visits received antibiotics. The percentages of URTI visits prescribed with combined and broad-spectrum antibiotics were 7.8% (IQR 2.3–10.2) and 48.3% (IQR 36.7–58.7), respectively. Third-generation cephalosporins were the most frequently used antibiotics. Physicians with lower antibiotic knowledge scores were more inclined to prescribe antibiotics (p < 0.001), combined antibiotics (p = 0.001), and broad-spectrum antibiotics (p < 0.001). Conclusions: Physicians’ insufficient knowledge was significantly associated with antibiotic overprescribing. Professional training targeting physicians’ knowledge of antibiotics is urgently needed to improve the rational use of antibiotics in grassroots healthcare facilities in China.

Background: Ulcerative colitis (UC) is an intestinal disorder marked by chronic, recurring inflammation, yet its underlying mechanisms have not been fully elucidated. Methods: The current research dealt with examining the biological impacts of toll-like receptor 2 (TLR2) on dextran sulfate sodium (DSS)-triggered inflammation in the intestines of wild-type (WT) and TLR2-knockout (TLR2-KO) colitis mouse models. To elucidate the protective function of TLR2 in DSS-triggered colitis, RNA-sequencing (RNA-Seq) was carried out to compare the global gene expression data in the gut of WT and TLR2-KO mice. Further, 16S rRNA gene sequencing revealed notable variations in gut microbiota composition between WT and TLR2-KO colitis mice. Results: It was revealed that TLR2-KO mice exhibited increased susceptibility to DSS-triggered colitis. RNA-Seq results demonstrated that cell cycle pathway-related genes were notably downregulated in TLR2-KO colitis mice (enrichment score = 30, p < 0.001). 16S rRNA gene sequencing revealed that in comparison to the WT colitis mice, the relative abundance of Marinifilacea (p = 0.006), Rikenellacea (p = 0.005), Desulfovibrionaceae (p = 0.045), Tannerellaceae (p = 0.038), Ruminococcaceae (p = 0.003), Clostridia (p = 0.027), and Mycoplasmataceae (p = 0.0009) was significantly increased at the family level in the gut of TLR2-KO colitis mice. In addition, microbiome diversity-transcriptome collaboration analysis highlighted that the relative abundance of Marinifilaceae was negatively linked to the expression of cell cycle signaling-related genes (p values were all less than 0.001). Conclusion: Based on these findings, we concluded that TLR2-KO exacerbates DSS-triggered intestinal injury by mitigating cell cycle signaling in a Marinifilaceae-dependent manner.