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Abstract The identification effector targets and characterization of their functions are crucial for understanding pathogen infection mechanisms and components of plant immunity. Here, we identify the effector UgsL, a ustilaginoidin synthetase with a key role in regulating virulence of the rice false smut fungus Ustilaginoidea virens. Heterologous expression of UgsL in rice (Oryza sativa) enhances plant susceptibility to multiple pathogens, and host-induced gene silencing of UgsL enhances plant resistance to U. virens, indicating that UgsL inhibits rice immunity. UgsL interacts with STRUBBELIG RECEPTOR KINASE 3 (OsSRF3). Genome editing and overexpression of OsSRF3 demonstrate that OsSRF3 plays a pivotal role in the resistance of rice to multiple pathogens. Remarkably, overexpressing OsSRF3 enhances resistance without adversely affecting plant growth or yield. We show that BRASSINOSTEROID RECEPTOR-ASSOCIATED KINASE 1 (OsBAK1) interacts with and phosphorylates OsSRF3 to activate pathogen-triggered immunity, inducing the mitogen-activated protein kinase cascade, a reactive oxygen species burst, callose deposition, and expression of defense-related genes. UgsL interferes with the phosphorylation of OsSRF3 by OsBAK1. Furthermore, UgsL mediates OsSRF3 degradation by facilitating its association with the ubiquitin-26S proteasome. Our results reveal that OsSRF3 positively regulates immunity in rice and that UgsL mediates its degradation, thereby inhibiting the activation of OsBAK1–OsSRF3-mediated immune pathways.

In order to solve the problem of difficult deployment of existing deep learning-based defect detection models in terminal equipment with limited computational capacity, a lightweight steel surface defect testing model LSKA-YOLOv8 was proposed based on the YOLOv8n target detection framework. The model uses KernelWarehouse Conv (KWConv) with lower computational volumes, which significantly reduces the required computational resources. By updating the traditional Feature Pyramid Network (FPN) structure to Bi-directional Feature Pyramid Network (BiFPN), enhance the capture of contextual information and reduce the number of parameters of the model. In addition, the Spatial Pyramid Pooling Fast (SPPF) module was replaced with a more accurate Receptive Field Block (RFB) module, expanding the model’s sensory field and improving characteristic representation. At the same time, the Large Separable Kernel Attention (LSKAttention) module was introduced in the detection head, effectively enhancing the understanding and capture of the target characteristics, thus significantly improving the overall detection performance. Experiments on the NEU-DET dataset showed that the average accuracy of LSKA-YOLO increased by 4.4% on the map@0.5 indicator compared to the benchmark model, while the number of parameters and calculations of the model decreased by 26.7% and 50%, respectively. Provides valuable references and practical applications for deployment of defect detection models on computing-resource-limited terminal devices.

The path planning of Unmanned Aerial Vehicle (UAV) is a critical issue in emergency communication and rescue operations, especially in adversarial urban environments. Due to the continuity of the flying space, complex building obstacles, and the aircraft's high dynamics, traditional algorithms cannot find the optimal collision-free flying path between the UAV station and the destination. Accordingly, in this paper, we study the fast UAV path planning problem in a 3D urban environment from a source point to a target point and propose a Three-Step Experience Buffer Deep Deterministic Policy Gradient (TSEB-DDPG) algorithm. We first build the 3D model of a complex urban environment with buildings and project the 3D building surface into many 2D geometric shapes. After transformation, we propose the Hierarchical Learning Particle Swarm Optimization (HL-PSO) to obtain the empirical path. Then, to ensure the accuracy of the obtained paths, the empirical path, the collision information and fast transition information are stored in the three experience buffers of the TSEB-DDPG algorithm as dynamic guidance information. The sampling ratio of each buffer is dynamically adapted to the training stages. Moreover, we designed a reward mechanism to improve the convergence speed of the DDPG algorithm for UAV path planning. The proposed TSEB-DDPG algorithm has also been compared to three widely used competitors experimentally, and the results show that the TSEB-DDPG algorithm can archive the fastest convergence speed and the highest accuracy. We also conduct experiments in real scenarios and compare the real path planning obtained by the HL-PSO algorithm, DDPG algorithm, and TSEB-DDPG algorithm. The results show that the TSEB-DDPG algorithm can archive almost the best in terms of accuracy, the average time of actual path planning, and the success rate.

Abstract Background The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched. Methods Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells. Results A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy. Conclusions This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.

Artificial Intelligence (AI) has had a significant impact on language education, arousing the related studies from different fields and perspectives. However, the extant review articles only focused on a certain aspect in the field, thus neglecting the multi-disciplinary and multi-perspective features of AI-enhanced language education. The aim of the current study is to bridge this gap by reviewing the 812 articles selected from Web of Science via CiteSpace. The study found that the existing studies were mainly conducted from the perspectives of computer science, linguistics and psychology. Besides, the individualized development of language education supported by technology was not obvious, and the degree of human-computer interaction was weak. Moreover, previous studies focused more on the advantages of AI-enhanced language education than the disadvantages, and the empirical research to analyze specific problems was insufficient. In the future, the research tends to strengthen the cooperation among related disciplines and focus on the individualized development of language education. In addition, empirical research should be strengthened to explore the efficiency of AI-enhanced language education in order to promote the reform of language education.

Summary: Background: Early detection of nasopharyngeal carcinoma (NPC) poses a significant challenge. The absence of highly sensitive and specific diagnostic biomarkers for nasopharyngeal carcinoma contributes to the unfavourable prognosis of NPC patients. Here, we aimed to establish a non-invasive approach for detecting NPC using circulating cell-free DNA (cfDNA). Methods: We investigated the potential of next-generation sequencing (NGS) of peripheral blood cells as a diagnostic tool for NPC. We collected data on genome-wide nucleosome footprint (NF), 5′-end motifs, fragmentation patterns, CNV information, and EBV content from 553 Chinese subjects, including 234 NPC patients and 319 healthy individuals. Through case–control analysis, we developed a diagnostic model for NPC, and validated its detection capability. Findings: Our findings revealed that the frequencies of NF, fragmentation, and motifs were significantly higher in NPC patients compared to healthy controls. We developed an NPC score based on these parameters that accurately distinguished NPC from non-NPC cases according to the American Joint Committee on Cancer staging system from non-NPC (validation set: area under curve (AUC) = 99.9% (95% CI: 99.8%–100%), se: 98.15%, sp: 100%). This model showed superior performance over plasma EBV DNA. Additionally, the NPC score effectively differentiated between NPC patients and healthy controls, even after clinical treatment. Furthermore, the NPC score was found to be independent of potential confounders such as age, sex, or TNM stage. Interpretation: We have developed and verified a non-invasive approach with substantial potential for clinical application in detecting NPC. Funding: A full list of funding bodies that contributed to this study can be found in Funding section.

Neurofibromatosis type 1 (NF-1) is commonly associated with a variety of rare tumors. However, no case of multiple gastric gastrointestinal stromal tumors (GISTs) or duodenal ampulla neuroendocrine tumors (NETs) with multiple liver metastases in a patient with NF-1 has yet been reported. Here, we describe a case of a 55-year-old female patient with NF-1 whose serum Pro-Gastrin-Releasing Peptide (pro-GRP) levels were elevated. Gastrointestinal endoscopy and biopsy showed duodenal papilla space-occupying mass, and the pathological diagnosis turned out to be neuroendocrine tumors (NETs). During surgical exploration, multiple tumors were found on the serosal surface of the stomach and numerous miliary metastases in the liver. Following histopathological examination, it was determined that the liver metastases were NF-1 and the tumors in the gastric wall were GISTs. The patient benefited from targeted therapy and had an uneventful hospital stay. In this case, we emphasize treating patients with neurofibromatosis type 1 who exhibit abdominal symptoms with a high degree of clinical suspicion and performing thorough evaluations to rule out multiple tumors.

Abstract Layered composite oxide materials with O3/P2 biphasic crystallographic structure typically demonstrate a combination of high capacities of the O3 phase and high operation voltages of the P2 phase. However, their practical applications are seriously obstructed by difficulties in thermodynamic phase regulation, complicated electrochemical phase transition, and unsatisfactory cycling life. Herein, we propose an efficient structural evolution strategy from biphase to monophase of Na0.766+xLixNi0.33−xMn0.5Fe0.1Ti0.07O2 through Li+ substitution. The role of Li+ substitution not only simplifies the unfavorable phase transition by altering the local coordination of transition metal (TM) cations but also stabilizes the cathode–electrolyte interphase to prevent the degradation of TM cations during battery cycling. As a result, the thermodynamically robust O3‐Na0.826Li0.06Ni0.27Mn0.5Fe0.1Ti0.07O2 cathode delivers a high capacity of 139.4 mAh g−1 at 0.1 C and shows prolonged cycling life at high rates, with capacity retention of 81.6% at 5 C over 500 cycles. This work establishes a solid relationship between the thermodynamic structure evolution and electrochemistry of layered cathode materials, contributing to the development of long‐life sodium‐ion batteries.

Abstract Collagen possesses high biocompatibility with all tissue and cell types in the body, enabling the creation of multifunctional composite materials for medical applications. In biomedical engineering, naturally-sourced collagen is often combined with diverse organic and inorganic bioactive components to eliminate defects and disorders in fields including orthopedics, dermatology, and more. At the same time, medical-related infection issues and the precise treatment needs of patients require collagen composite biomaterials to have antibacterial properties and customized structures. This paper reviews the antibacterial functionalization of collagen composite biomaterials in recent years, including the combination with inorganic or organic antibacterial agents, which is beneficial for preventing and controlling biological contamination in medical applications. Then, the existing problems and future development directions for the architecturalization of collagen composite materials with 3D printing were discussed, providing guidance for personalized customization of multifunctional materials to meet the specific needs of patients in the future. Graphical Abstract

Abstract La-related proteins (LARPs) regulate gene expression by binding to RNAs and exhibit critical effects on disease progression, including tumors. However, the role of LARP4B and its underlying mechanisms in the progression of hepatocellular carcinoma (HCC) remain largely unclear. In this study, we found that LARP4B expression is upregulated and correlates with poor prognosis in patients with HCC. Gain- and loss-of-function assays showed that LARP4B promotes stemness, proliferation, metastasis, and angiogenesis in vitro and in vivo. Furthermore, LARP4B inhibition enhances the antitumor effects of sorafenib and blocks the metastasis-enhancing effects of low sorafenib concentrations in HCC. Mechanistically, LARP4B expression is upregulated by METTL3-mediated N6-methyladenosine (m6A)-IGF2BP3-dependent modification in HCC. RNA- and RNA immunoprecipitation (RIP)- sequencing uncovered that LARP4B upregulates SPINK1 by binding to SPINK1 mRNA via the La motif and maintaining mRNA stability. LARP4B activates the SPINK1-mediated EGFR signaling pathway, which supports stemness, progression and sorafenib resistance in HCC. Additionally, a positive feedback loop with the LARP4B/SPINK1/p-AKT/C/EBP-β axis is responsible for the sorafenib-therapeutic benefit of LARP4B depletion. Overall, this study demonstrated that LARP4B facilitates HCC progression, and LARP4B inhibition provides benefits to sorafenib treatment in HCC, suggesting that LARP4B might be a potential therapeutic target for HCC.

ObjectiveClostridium sp. isolation， identification and analysis and toxin gene detection were carried out on 57 pieces of commercially available infant formula milk powder and 50 pieces of commercially available infant rice noodles sold in Beijing. The data of Clostridium sp. contamination level was obtained， and the identification methods were evaluated.MethodsThe isolates were comprehensively identified by their growth characteristics， Gram staining， morphological characteristics under ordinary microscopy， combined with the results of mass spectrometry identification， 16S rRNA gene sequencing and whole-genome sequencing （WGS）. The botulinum toxin genes of isolated Clostridium sp. were detected by PCR. Then， sequencing and comparative analysis of PCR positive fragments were carried out.ResultsThirty-eight Clostridium sp. in 26 samples of the 57 commercially available infant formula milk powder samples were detected. More than two types of isolates were detected in 9 samples. Five Clostridium sp. were detected in 5 samples of 50 commercially available infant rice flour. PCR amplification of the Clostridium botulinum type E toxin gene of a Clostridium sphenoides was positive， the amplified fragment sequencing comparison results showed that this sequence was not an E-type Clostridium botulinum toxin gene， and the WGS results also confirmed it. There were no toxin genes of Clostridium botulinum in all the 43 isolates.ConclusionIdentification of Clostridium sp. requires comprehensive analysis by multiple methods. The contamination of Clostridium sp. exists in commercial infant formula milk powder and infant formula rice flour. It is necessary to strengthen the monitoring of important Clostridium sp. in infant formula food to provide data support for risk assessment.

We aimed to evaluate the effect of freeze-drying and vacuum-drying on moisture, water activities (aw), total soluble solid (TSS), hydroxymethylfurfural (HMF), diastase activity, total phenolic content (TPCs), and antioxidant activities (ABTS, DPPH, FRAP, ORAC) of longan (Dimocarpus longan Lour.) blossom honey and Siam weed (Chromolaena odorata Lour.) honey. The fresh longan blossom honey and Siam weed honey were collected from a local apiarist in Northern Thailand. Freeze-drying at 0.013 kPa, −54℃ for 72 h or vacuum-drying at 2.5 kPa at 60 ℃ for 12 h was applied to dehydrate fresh honey. The moisture of freeze-dried samples was 10.10% for longan blossom honey and 11.50% for Siam weed honey, and the aw of both freeze-dried honeys was 0.43. Freeze- and vacuum-dried produced more TSS than fresh honey did (p ≤ 0.05). However, the amounts of TSS derived freeze-dry and vacuum-dry were not significantly different. Freeze-dried honey contained the highest HMF and the lowest diastase activity regardless of honey origins (p ≤ 0.05). Drying processes significantly increased the TPCs levels of honey (approximately 2 folds by freeze-drying method). The antioxidant activity of dried honey was significantly higher than that of fresh honey. It was observed that the freeze-drying method tended to better preserve the antioxidant activity of honey compared to vacuum-drying methods in both types of honey. The results indicated that drying processes significantly affect the quality of dried honey, including TSS, HMF, diastase activity, TPCs, and antioxidant activity. In this study, freeze-drying emerged as the relatively low temperature drying method that can preserve the quality of honey, especially in terms of TPCs and antioxidant activity.

ObjectiveTo compare the effectiveness of radiomic features based on 18F-FDG PET/CT images within (intranodular) and around (perinodular) lung nodules/masses in distinguishing between lung adenocarcinoma and pulmonary granulomas.MethodsFor this retrospective study, 18F-FDG PET/CT images were collected for 228 patients. Patients diagnosed with lung adenocarcinoma (n = 156) or granulomas (n = 72) were randomly assigned to a training (n = 159) and validation (n = 69) groups. The volume of interest (VOI) of intranodular, perinodular (1–5 voxels, termed Lesion_margin1 to Lesion_margin5) and total area (intra- plus perinodular region, termed Lesion_total1 to Lesion_total5) on PET/CT images were delineated using PETtumor and Marge tool of segmentation editor. A total of 1,037 radiomic features were extracted separately from PET and CT images, and the optimal features were selected to develop radiomic models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC).ResultsGood and acceptable performance was, respectively, observed in the training (AUC = 0.868, p < 0.001) and validation (AUC = 0.715, p = 0.004) sets for the intranodular radiomic model. Among the perinodular models, the Lesion_margin2 model demonstrated the highest AUC in both sets (0.883 and 0.616, p < 0.001 and p = 0.122). Similarly, in terms of total models, Lesion_total2 model was found to outperform others in the training (AUC = 0.879, p < 0.001) and validation (AUC = 0.742, p = 0.001) sets, slightly surpassing the intranodular model.ConclusionWhen intra- and perinodular radiomic features extracted from the immediate vicinity of the nodule/mass up to 2 voxels distance on 18F-FDG PET/CT imaging are combined, improved differential diagnostic performance in distinguishing between lung adenocarcinomas and granulomas is achieved compared to the intra- and perinodular radiomic features alone.

Abstract As a signaling molecule, nitric oxide (NO) regulates the development and stress response in different organisms. The major biological activity of NO is protein S‐nitrosylation, whose function in fungi remains largely unclear. Here, it is found in the rice blast fungus Magnaporthe oryzae, de‐nitrosylation process is essential for functional appressorium formation during infection. Nitrosative stress caused by excessive accumulation of NO is harmful for fungal infection. While the S‐nitrosoglutathione reductase GSNOR‐mediated de‐nitrosylation removes excess NO toxicity during appressorium formation to promote infection. Through an indoTMT switch labeling proteomics technique, 741 S‐nitrosylation sites in 483 proteins are identified. Key appressorial proteins, such as Mgb1, MagB, Sps1, Cdc42, and septins, are activated by GSNOR through de‐nitrosylation. Removing S‐nitrosylation sites of above proteins is essential for proper protein structure and appressorial function. Therefore, GSNOR‐mediated de‐nitrosylation is an essential regulator for appressorium formation. It is also shown that breaking NO homeostasis by NO donors, NO scavengers, as well as chemical inhibitor of GSNOR, shall be effective methods for fungal disease control.

Introduction: Tripterygium species have been traditionally used in Chinese medicine for treating various conditions. The aim of the study was to construct a drug-modified renal infarction targeting liposome (rTor-LIP) containing Tripterygium in order to improve the therapeutic effect on renal injury.Methods: rTor-LIP was prepared using the extruder method containing Tripterygium solution. The preparation was characterized by transmission electron microscopy, Marvin laser particle size analyzer, and Western blotting. In vitro experiments were conducted to verify the biocompatibility of rTor-LIP, and in vivo experiments were conducted to verify the therapeutic effect of rTor- LIP on renal injury.Results and discussion: The surface of rTor-LIP was regular and oval. In vitro results showed that after co-incubation with rTor-LIP, endothelial cells did not show significant apoptosis, and there were no significant abnormalities in the mitochondrial metabolism. The in vivo results showed that the morphology of endothelial cells in the rTor-LIP group was uniform and the cytoplasmic striations were clear, but the local striations had disappeared. Thus, rTor-LIP nano-targeted liposomes can effectively target hypoxic kidney tissue, providing a new idea for the treatment of renal infarction.

The incidence of postoperative pancreatic fistula is influenced by the effectiveness of the pancreaticojejunostomy, and the most suitable pancreaticojejunostomy for pancreaticoduodenectomy remains uncertain. Since grade A postoperative pancreatic fistula is no longer considered a true fistula, the purpose of this meta-analysis was to compare the effectiveness of duct-to-mucosa anastomosis and invagination anastomosis in reducing the incidence of grade B/C postoperative pancreatic fistula. The meta-analysis was conducted using software Review Manager 5.3, and the fixed-effect model was employed for pooled statistic calculations. The Cochrane Collaboration Risk of Bias Tool was utilized for quality assessment. Ten randomized controlled trials from Embase, Web of Science, MEDLINE, and the Cochrane Library (1990.01–2022.10) including 1471 patients, met the inclusion criteria. This meta-analysis has been registered on PROSPERO with the registration number CRD42023491673. The incidence of grade B/C fistula was significantly lower in the invagination group (7.7 %) compared to the duct-to-mucosa group (12.8 %, mostly Cattell manner)(RR = 1.65, 95%CI: 1.14–2.39, P = 0.008; heterogeneity: P = 0.008, I2 = 68 %),heterogeneity among the results was addressed through sensitivity analysis. In patients with a soft pancreas, the incidence of grade B/C fistula was significantly lower in those who underwent invagination anastomosis (10 %) compared to those who underwent duct-to-mucosa anastomosis (41.9 %)(RR = 4.19, 95%CI: 1.33–13.25, P = 0.01).No significant differences were observed in terms of the occurrence of grade B/C fistula in firm pancreas, postoperative mortality, other major postoperative complications, anastomosis time, and postoperative bile leak. Therefore, we concluded that invagination anastomosis is significantly superior to duct-to-mucosa anastomosis in reducing the incidence of grade B/C fistula, especially in patients with a soft pancreas.

Abstract Background The liver is anatomically divided into eight segments based on the distribution of Glisson's triad. However, the molecular mechanisms underlying each segment and its association with hepatocellular carcinoma (HCC) heterogeneity are not well understood. In this study, our objective is to conduct a comprehensive multiomics profiling of the segmentation atlas in order to investigate potential subtypes and therapeutic approaches for HCC. Methods A high throughput liquid chromatography‐tandem mass spectrometer strategy was employed to comprehensively analyse proteome, lipidome and metabolome data, with a focus on segment‐resolved multiomics profiling. To classify HCC subtypes, the obtained data with normal reference profiling were integrated. Additionally, potential therapeutic targets for HCC were identified using immunohistochemistry assays. The effectiveness of these targets were further validated through patient‐derived organoid (PDO) assays. Results A multiomics profiling of 8536 high‐confidence proteins, 1029 polar metabolites and 3381 nonredundant lipids was performed to analyse the segmentation atlas of HCC. The analysis of the data revealed that in normal adjacent tissues, the left lobe was primarily involved in energy metabolism, while the right lobe was associated with small molecule metabolism. Based on the normal reference atlas, HCC patients with segment‐resolved classification were divided into three subtypes. The C1 subtype showed enrichment in ribosome biogenesis, the C2 subtype exhibited an intermediate phenotype, while the C3 subtype was closely associated with neutrophil degranulation. Furthermore, using the PDO assay, exportin 1 (XPO1) and 5‐lipoxygenase (ALOX5) were identified as potential targets for the C1 and C3 subtypes, respectively. Conclusion Our extensive analysis of the segmentation atlas in multiomics profiling defines molecular subtypes of HCC and uncovers potential therapeutic strategies that have the potential to enhance the prognosis of HCC.

The early stage of life is a critical period for the colonization and formation of the gut microbiota. Research has shown that the colonization and formation of the gut microbiota in the early stage of life is associated with the development of obesity in childhood. The colonization of the infant gut microbiota is highly influenced by early life factors such as mode of delivery, premature birth, exposure to antibiotics, and feeding methods. Understanding the early life influencing factors, changes in the infant gut microbiota, and the trajectory of childhood obesity development can help reveal the potential mechanisms underlying the association between early life factors and childhood obesity. It can also provide reference and guidance for finding intervention targets for childhood obesity and achieving early prevention and control of obesity. Therefore, this article provided a systematic overview of research on the association between gut microbiota-mediated early life influencing factors and childhood obesity.

Soft hydrogels are excellent candidate materials for repairing various tissue defects, yet the mechanical strength, anti-swelling properties, and biocompatibility of many soft hydrogels need to be improved. Herein, inspired by the nanostructure of collagen fibrils, we developed a strategy toward achieving a soft but tough, anti-swelling nanofibrillar hydrogel by combining the self-assembly and chemical crosslinking of nanoparticles. Specifically, the collagen fibril-like injectable hydrogel was subtly designed and fabricated by self-assembling methylacrylyl hydroxypropyl chitosan (HM) with laponite (LAP) to form nanoparticles, followed by the inter-nanoparticle bonding through photo-crosslinking. The assembly mechanism of nanoparticles was elucidated by both experimental and simulation techniques. Due to the unique structure of the crosslinked nanoparticles, the nanocomposite hydrogels exhibited low stiffness (G’< 2 kPa), high compressive strength (709 kPa), and anti-swelling (swelling ratio of 1.07 in PBS) properties. Additionally, by harnessing the photo-crosslinking ability of the nanoparticles, the nanocomposite hydrogels were processed as microgels, which can be three-dimensionally (3D) printed into complex shapes. Furthermore, we demonstrated that these nanocomposite hydrogels are highly biocompatible, biodegradability, and can effectively promote fibroblast migration and accelerate blood vessel formation during wound healing. This work presents a promising approach to develop biomimetic, nanofibrillar soft hydrogels for regenerative medicine applications.

Abstract Background Antepartum depression has been reported to be associated with the intensity of maternal prenatal noise exposure; however, the association between noise exposure duration and the development of antepartum depression has not been established. This study aimed to determine the total and trimester-specific association of prenatal noise exposure duration with the development of antepartum depression. Methods From May 2018 to June 2021, we recruited 2,166 pregnant women from Shengjing Hospital, northeast China. We used a standardized questionnaire to assess women’s prenatal noise exposure and used the Edinburgh Postnatal Depression Scale to assess pregnant women’s antepartum depression during the 1st -, 2nd -, and 3rd - trimesters. We calculated a cumulative noise exposure score ranging from 0 to 3, with a higher score reflecting higher frequency and longer duration of noise exposure during pregnancy. Results Women who were exposed to noise for ≥ 15 min per day had an increased risk of antepartum depression compared with women who were not exposed to noise during pregnancy [odds ratio (OR) = 1.83, 95%CI:1.18, 2.83]. Noise exposure in a specific trimester was associated with higher risk of depression in the same trimester and subsequent trimesters. We observed increases in antepartum depression risk with increasing cumulative noise exposure scores (P for trend

BackgroundMaternal atmospheric pollution during pregnancy may alter fetal intrauterine development programming, thereby increasing the risk of childhood obesity in the future.ObjectiveTo investigate the effects of atmospheric pollution exposure during pregnancy on the incidence of childhood obesity in offspring.MethodsEnglish databases (PubMed, Web of Science, and Medline) and Chinese databases (Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure, and VIP Information Chinese Journal Service Platform) were searched for literature reporting exposure to atmospheric pollution during pregnancy and childhood obesity published from 1 January 2000 to 31 August 2023. The quality of the included literature was evaluated using the quality assessment tools for observational cohort and cross-sectional studies recommended by the US National Institutes of Health.ResultsTwenty-four studies meeting the inclusion criteria were identified and the associated atmospheric pollutants included particulate matter, ozone, nitrogen oxide, carbon oxide, and sulfur oxide. In comparison to the non-exposed group, prenatal exposure to various common atmospheric pollutants were significantly associated with an elevated risk of childhood obesity in offspring.ConclusionMaternal exposure to atmospheric pollution during pregnancy is associated with an elevated risk of childhood obesity in subsequent years. Future studies should pay more attention to the effects of atmospheric pollution on the distribution of children's body fat and metabolic development, and further identify potential mechanisms of atmospheric pollutant exposure leading to childhood obesity.

Abstract Twisted bilayer (TB) transition metal dichalcogenides (TMDCs) beyond TB-graphene are considered an ideal platform for investigating condensed matter physics, due to the moiré superlattices-related peculiar band structures and distinct electronic properties. The growth of large-area and high-quality TB-TMDCs with wide twist angles would be significant for exploring twist angle-dependent physics and applications, but remains challenging to implement. Here, we propose a reconfiguring nucleation chemical vapor deposition (CVD) strategy for directly synthesizing TB-MoS2 with twist angles from 0° to 120°. The twist angles-dependent Moiré periodicity can be clearly observed, and the interlayer coupling shows a strong relationship to the twist angles. Moreover, the yield of TB-MoS2 in bilayer MoS2 and density of TB-MoS2 are significantly improved to 17.2% and 28.9 pieces/mm2 by tailoring gas flow rate and molar ratio of NaCl to MoO3. The proposed reconfiguring nucleation approach opens an avenue for the precise growth of TB-TMDCs for both fundamental research and practical applications.

The presence of interstitial electrons in electrides endows them with interesting attributes, such as low work function, high carrier concentration, and unique magnetic properties. Thorough knowledge and understanding of electrides are thus of both scientific and technological significance. Here, we employ first-principles calculations to investigate Mott-insulating Ae5X3 (Ae = Ca, Sr, and Ba; X = As and Sb) electrides with Mn5Si3-type structure, in which half-filled interstitial electrons serve as ions and are spin-polarized. The Mott-insulating property is induced by strong electron correlation between the nearest interstitial electrons, resulting in spin splitting and a separation between occupied and unoccupied states. The half-filled antiferromagnetic configuration and localization of the interstitial electrons are critical for the Mott-insulating properties of these materials. Compared with that in intermetallic electrides, the orbital hybridization between the half-filled interstitial electrons and the surrounding atoms is weak, leading to highly localized magnetic centers and pronounced correlation effects. Therefore, the Mott-insulating electrides Ae5X3 have very large indirect bandgaps (∼0.30 eV). In addition, high pressure is found to strengthen the strong correlation effects and enlarge the bandgap. The present results provide a deeper understanding of the formation mechanism of Mott-insulating electrides and provide guidance for the search for new strongly correlated electrides.

Abstract The live transport of farmed fish is an important practice in Chinese aquaculture due to consumer preferences in its domestic market. However, live transport can be stressful for fish and may cause many welfare issues. This study aimed to examine the effects of transport density on the welfare of largemouth bass (Micropterus salmoides). Adult fish were allocated to four experimental treatments in a two‐factor design (N = 5 groups per treatment). Factor one was stocking density of either 39 (low density) or 78 (high density) g L−1. Factor two was transport, with half of the fish groups exposed to simulated transport stress for 3 h using a motion platform, and the other half kept in static tanks for the same length of time. Baseline behavior and physiology were determined from a subset of fish after acclimation but before selection into groups and application of transport. To determine the effects of transport, stocking density, and their interaction on the experimental groups, physiological sampling and behavioral recording were carried out immediately after simulated transport, and water quality was measured both before and after transport. Changes in water quality were observed between two timepoints, with decreased dissolved oxygen levels and increased water temperature. Total ammonia nitrogen levels significantly increased in all treatments over time, particularly in the high‐density groups. Fish ventilation rates were significantly elevated in the groups kept at a high stocking density regardless of whether they also experienced transport stress. Fish transported at a high stocking density also showed more fear‐related behaviors such as freezing and thigmotaxis than non‐transported groups. Serum cortisol, catalase, and aspartate transaminase levels were significantly higher in the transported treatment groups compared to the baseline fish, but no difference was found for serum glucose, lactate, and glutathione peroxidase. We concluded that 3 h of simulated transport was stressful to largemouth bass kept at 78 g L−1, as evidenced by altered fish physiological and behavioral indicators of stress, as well as deteriorated water quality. Additionally, we identified a positive correlation between serum and skin mucus samples for cortisol, glucose, and lactate in transported fish, providing important information for developing less invasive methods for the welfare assessment of largemouth bass.

Backgroundsystemic inflammation disorders were observed in chronic kidney disease (CKD). Whether the systemic inflammatory indicators could be optimal predictors for the survival of CKD remains less studied.MethodsIn this study, participants were selected from the datasets of the National Health and Nutrition Examination Survey (NHANES) between 1999 to 2018 years. Four systemic inflammatory indicators were evaluated by the peripheral blood tests including systemic immune-inflammation index (SII, platelet*neutrophil/lymphocyte), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR). Kaplan-Meier curves, restricted cubic spline (RCS), and Cox regression analysis were used to evaluate the association between the inflammatory index with the all-cause mortality of CKD. Receiver operating characteristic (ROC) and concordance index (C-index) were used to determine the predictive accuracy of varied systemic inflammatory indicators. Sensitive analyses were conducted to validate the robustness of the main findings.ResultsA total of 6,880 participants were included in this study. The mean age was 67.03 years old. Among the study population, the mean levels of systemic inflammatory indicators were 588.35 in SII, 2.45 in NLR, 133.85 in PLR, and 3.76 in LMR, respectively. The systemic inflammatory indicators of SII, NLR, and PLR were all significantly positively associated with the all-cause mortality of CKD patients, whereas the high value of LMR played a protectable role in CKD patients. NLR and LMR were the leading predictors in the survival of CKD patients [Hazard ratio (HR) =1.21, 95% confidence interval (CI): 1.07-1.36, p = 0.003 (3rd quartile), HR = 1.52, 95%CI: 1.35-1.72, p

Abstract Background Laparoscopic access to liver segment 7 (S7) is difficult for deep surgical situations and bleeding control. Herein, our proposed laparoscopic technique for S7 lesions using a self-designed tube method is introduced. Methods Clinical data of patients who underwent laparoscopic anatomical liver resection of S7 (LALR-S7) with the help of our self-designed tube to improve the exposure of S7 and bleeding control in the Second Affiliated Hospital, Third Military Medical University (Army Medical University) from April 2019 to December 2021 were retrospectively analyzed to evaluate feasibility and safety. Results Nineteen patients were retrospectively reviewed. The mean age was 51.3 ± 10.3 years; mean operation time, 194.5 ± 22.7 min; median blood loss, 160.0 ml (150.0–205.0 ml); and median length of hospital stay, 8.0 days (7.0–9.0 days). There was no case conversion to open surgery. Postoperative pathology revealed all cases of hepatocellular carcinoma (HCC). Free surgical margins were achieved in all patients. No major postoperative complications were observed. Patients with postoperative complications recovered after conservative treatment. During outpatient follow-up examination, no other abnormality was presented. All patients survived without tumor recurrence. Conclusions The preliminary clinical effect of our method was safe, reproducible and effective for LALR-S7. Further research is needed due to some limitations of this study.

Corn, as one of the three major grain crops in China, plays a crucial role in ensuring national food security through its yield and quality. With the advancement of agricultural intelligence, agricultural robot technology has gained significant attention. High-precision navigation is the basis for realizing various operations of agricultural robots in corn fields and is closely related to the quality of operations. Corn leaf and stalk recognition and ranging are the prerequisites for achieving high-precision navigation and have attracted much attention. This paper proposes a corn leaf and stalk recognition and ranging algorithm based on multi-sensor fusion. First, YOLOv8 is used to identify corn leaves and stalks. Considering the large differences in leaf morphology and the large changes in field illumination that lead to discontinuous identification, an equidistant expansion polygon algorithm is proposed to post-process the leaves, thereby increasing the average recognition completeness of the leaves to 86.4%. Secondly, after eliminating redundant point clouds, the IMU data are used to calculate the confidence of the LiDAR and depth camera ranging point clouds, and point cloud fusion is performed based on this to achieve high-precision ranging of corn leaves. The average ranging error is 2.9 cm, which is lower than the measurement error of a single sensor. Finally, the stalk point cloud is processed and clustered using the FILL-DBSCAN algorithm to identify and measure the distance of the same corn stalk. The algorithm combines recognition accuracy and ranging accuracy to meet the needs of robot navigation or phenotypic measurement in corn fields, ensuring the stable and efficient operation of the robot in the corn field.

Due to the existence of cotton weeds in a complex cotton field environment with many different species, dense distribution, partial occlusion, and small target phenomena, the use of the YOLO algorithm is prone to problems such as low detection accuracy, serious misdetection, etc. In this study, we propose a YOLOv8-DMAS model for the detection of cotton weeds in complex environments based on the YOLOv8 detection algorithm. To enhance the ability of the model to capture multi-scale features of different weeds, all the BottleNeck are replaced by the Dilation-wise Residual Module (DWR) in the C2f network, and the Multi-Scale module (MSBlock) is added in the last layer of the backbone. Additionally, a small-target detection layer is added to the head structure to avoid the omission of small-target weed detection, and the Adaptively Spatial Feature Fusion mechanism (ASFF) is used to improve the detection head to solve the spatial inconsistency problem of feature fusion. Finally, the original Non-maximum suppression (NMS) method is replaced with SoftNMS to improve the accuracy under dense weed detection. In comparison to YOLO v8s, the experimental results show that the improved YOLOv8-DMAS improves accuracy, recall, mAP0.5, and mAP0.5:0.95 by 1.7%, 3.8%, 2.1%, and 3.7%, respectively. Furthermore, compared to the mature target detection algorithms YOLOv5s, YOLOv7, and SSD, it improves 4.8%, 4.5%, and 5.9% on mAP0.5:0.95, respectively. The results show that the improved model could accurately detect cotton weeds in complex field environments in real time and provide technical support for intelligent weeding research.

OBJECTIVES/GOALS: Healthcare sectors are rushing to develop AI models. Yet, a dearth of coordinated practices leaves many teams struggling to implement models into practice. The Enterprise AI Translation Advisory Board uses across-disciplinary team to facilitate AI translation. METHODS/STUDY POPULATION: The Mayo Clinic Enterprise AI Translation Advisory Board was established to assess AI solutions lever aging cross-disciplinary team science to accelerate AI innovation and translation. The 23-member board reflects expertise in data science, qualitative research, user experience, IT, human factors, informatics, regulatory compliance,ethics, and clinical care, with members spanning thought leadership, decision-making, and clinical practice. Taking an approach of respectful communication, transparency, scientific debate, and open discussion, the Board has consulted onover two dozen projects at various stages of the AI life cycle. RESULTS/ANTICIPATED RESULTS: Common issues identified for projects earlier in the AI life cycle, sometimes fatal but often address able once identified, include a lack of buy-in from potential product users, a lack of planningabout integration into clinical workflow, inadequately labeled data, and attempting to use machine learning when what is desired is really a causal model for intervening. Recommendations for projects later in the AI life cycle include details of a testing plan (silent evaluation, pragmatic clinical trials), advice about clinical integration, both post-hoc and on going auditing for performance disparities, and planning for regulatory clearance. DISCUSSION/SIGNIFICANCE: Advising is more valuable for projects at the ideation phase, when multi disciplinary interrogation can identify weaknesses. But at all phases, projects have gaps related to a lack of specific disciplinary expertise. A multi disciplinary cluster like the AI Translation Advisory Board seeks to address these gaps.

Abstract Background Traditional human epidermal growth factor receptor 2 (HER2)‐negative breast cancer (BC) is recommended to be divided into HER2‐low and HER2‐zero subtypes due to different prognosis. However, few studies investigated their differences in clinical characteristics and prognosis among Chinese HER2‐negative BC and their stratified differences by hormone receptor (HR), while fewer studies investigated their differences in epidemiological factors and genetic susceptibility. Methods A total of 11,911 HER2‐negative BC were included to compare the clinical characteristics and prognosis between HER2‐zero and HER2‐low BC, and 4227 of the 11,911 HER2‐negative BC were further compared to 5653 controls to investigate subtype‐specific epidemiological factors and single nucleotide polymorphisms(SNPs). Results Overall, 64.2% of HER2‐negative BC were HER2‐low BC, and the stratified proportions of HER2‐low BC were 61.9% and 75.2% for HR‐positive and HR‐negative BC, respectively. Compared to HER2‐zero BC, HER2‐low BC among HR‐positive BC showed younger age at diagnosis, later stage, poorer differentiation, and higher Ki‐67, while elder age at diagnosis and lower mortality were observed for HER2‐low BC among HR‐negative BC (all p values

Abstract Background Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. Methods We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. Results We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1β, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. Conclusion These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.

In this article, we introduce a notion of capillary Schwarz symmetrization in the half-space. It can be viewed as the counterpart of the classical Schwarz symmetrization in the framework of capillary problem in the half-space. A key ingredient is a special anisotropic gauge, which enables us to transform the capillary symmetrization to the convex symmetrization introduced in Alvino et al. https:/doi.org/10.1016/S0294-1449(97)80147-3.

BackgroundThis study evaluates the efficacy of alpha-fetoprotein (AFP) response as a surrogate marker for determining recurrence-free survival (RFS) in patients with unresectable hepatocellular carcinoma (uHCC) who undergo salvage hepatectomy following conversion therapy with tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody-based regimen.MethodsThis multicenter retrospective study included 74 patients with uHCC and positive AFP (>20 ng/mL) at diagnosis, who underwent salvage hepatectomy after treatment with TKIs and anti-PD-1 antibody-based regimens. The association between AFP response—defined as a ≥ 80% decrease in final AFP levels before salvage hepatectomy from diagnosis—and RFS post-hepatectomy was investigated.ResultsAFP responders demonstrated significantly better postoperative RFS compared to non-responders (P

Real-time thermal sensing through flexible temperature sensors in extreme environments is critically essential for precisely monitoring chemical reactions, propellant combustions, and metallurgy processes. However, despite their low response speed, most existing thermal sensors and related sensing materials will degrade or even lose their sensing performances at either high or low temperatures. Achieving a microsecond response time over an ultrawide temperature range remains challenging. Here, we design a flexible temperature sensor that employs ultrathin and consecutive Mo1−xWxS2 alloy films constructed via inkjet printing and a thermal annealing strategy. The sensing elements exhibit a broad work range (20 to 823 K on polyimide and 1,073 K on flexible mica) and a record-low response time (about 30 μs). These properties enable the sensors to detect instantaneous temperature variations induced by contact with liquid nitrogen, water droplets, and flames. Furthermore, a thermal sensing array offers the spatial mapping of arbitrary shapes, heat conduction, and cold traces even under bending deformation. This approach paves the way for designing unique sensitive materials and flexible sensors for transient sensing under harsh conditions.

BackgroundPeritoneal dialysis (PD) is a common treatment method for patients with renal failure. While peritonitis and tube floating migration are commonly observed complications, visceral perforation caused by PD is relatively rare. We present a case report of a patient undergoing PD due to renal failure, who encountered two instances of visceral perforation. In both occurrences, Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) played a pivotal role in providing accurate diagnoses and precise localization of the perforation sites. This report underscores the paramount significance of SPECT/CT in diagnosing visceral perforations in the context of PD.Case presentationA 73-year-old elderly male has been undergoing PD for 1 year due to renal failure. Recently, there has been impaired drainage of the PD catheter. The clinical team suspected the occurrence of peritonitis. The patient underwent a 99mTc Sodium Pertechnetate (99mTc-NaTcO4) SPECT/CT examination, which identified intestinal perforation. After 20 days of conservative treatment, a SPECT/CT follow-up examination revealed the resolution of the intestinal perforation, but a new bladder perforation emerged. The dialysis catheter was methodically and gradually withdrawn in stages while simultaneously performing bladder decompression. Following these interventions, the patient remained free from peritonitis and cystitis.ConclusionThe utilization of SPECT/CT proved to be highly valuable in the accurate diagnosis of visceral perforation, a relatively rare complication observed in PD patients.

BackgroundPersonalized asthma management depends on a clinician’s ability to efficiently review patient’s data and make timely clinical decisions. Unfortunately, efficient and effective review of these data is impeded by the varied format, location, and workflow of data acquisition, storage, and processing in the electronic health record. While machine learning (ML) and clinical decision support tools are well-positioned as potential solutions, the translation of such frameworks requires that barriers to implementation be addressed in the formative research stages. ObjectiveWe aimed to use a structured user-centered design approach (double-diamond design framework) to (1) qualitatively explore clinicians’ experience with the current asthma management system, (2) identify user requirements to improve algorithm explainability and Asthma Guidance and Prediction System prototype, and (3) identify potential barriers to ML-based clinical decision support system use. MethodsAt the “discovery” phase, we first shadowed to understand the practice context. Then, semistructured interviews were conducted digitally with 14 clinicians who encountered pediatric asthma patients at 2 outpatient facilities. Participants were asked about their current difficulties in gathering information for patients with pediatric asthma, their expectations of ideal workflows and tools, and suggestions on user-centered interfaces and features. At the “define” phase, a synthesis analysis was conducted to converge key results from interviewees’ insights into themes, eventually forming critical “how might we” research questions to guide model development and implementation. ResultsWe identified user requirements and potential barriers associated with three overarching themes: (1) usability and workflow aspects of the ML system, (2) user expectations and algorithm explainability, and (3) barriers to implementation in context. Even though the responsibilities and workflows vary among different roles, the core asthma-related information and functions they requested were highly cohesive, which allows for a shared information view of the tool. Clinicians hope to perceive the usability of the model with the ability to note patients’ high risks and take proactive actions to manage asthma efficiently and effectively. For optimal ML algorithm explainability, requirements included documentation to support the validity of algorithm development and output logic, and a request for increased transparency to build trust and validate how the algorithm arrived at the decision. Acceptability, adoption, and sustainability of the asthma management tool are implementation outcomes that are reliant on the proper design and training as suggested by participants. ConclusionsAs part of our comprehensive informatics-based process centered on clinical usability, we approach the problem using a theoretical framework grounded in user experience research leveraging semistructured interviews. Our focus on meeting the needs of the practice with ML technology is emphasized by a user-centered approach to clinician engagement through upstream technology design.

Abstract Stroke is a major public health concern worldwide. The lack of effective therapies heightens the need for new therapeutic agents. Previous study identified sirtuin 5 (SIRT5) as a positive regulator of microglia‐induced excessive neuroinflammation following ischemic stroke. Interventions targeting SIRT5 should therefore alleviate neuroinflammation and protect against ischemic stroke. Here, we synthesized a membrane‐permeable peptide specifically bound to SIRT5 through a chaperone‐mediated autophagy targeting motif (Tat‐SIRT5‐CTM) and examined its therapeutic effect in vitro and in vivo. First, in primary microglia, Tat‐SIRT5‐CTM suppressed the binding of SIRT5 with annexin‐A1 (ANXA1), leading to SIRT5 degradation and thus inhibition of SIRT5‐mediated desuccinylation of ANXA1, followed by increased membrane accumulation and secretion of ANXA1. These changes, in turn, alleviated microglia‐induced neuroinflammation. Moreover, following intravenous injection, Tat‐SIRT5‐CTM could efficiently pass through the blood‒brain barrier. Importantly, systemic administration of Tat‐SIRT5‐CTM reduced the brain infarct area and neuronal loss, mitigated neurological deficit scores, and improved long‐term neurological functions in a mouse model of ischemic stroke. Furthermore, no toxicity was observed when high doses Tat‐SIRT5‐CTM were injected into nonischemic mice. Collectively, our study reveals the promising efficacy of the peptide‐directed lysosomal degradation of SIRT5 and suggests it as an effective therapeutic approach for the treatment of ischemic stroke.

In this work, we demonstrate the surface functionalization of cellulose triacetate membrane with co-deposition of polydopamine (PDA)/polyethyleneimine (PEI) and silver nanoparticles (AgNPs) for antifouling property in municipal wastewater treatment. PDA/PEI was first coated on the membrane surface by single-step co-deposition, while AgNPs were formed in situ through catechol groups of PDA immobilizing silver ions and subsequently reducing. The successful surface modification was verified by different membrane characterization techniques. The modified PDA/PEI-nAg CTA membrane exhibits enhanced hydrophilicity and improved antiadhesion and antimicrobial activity. Furthermore, the functional layer had an indistinctive effect on the membrane transport parameters. In addition, dynamic forward osmosis (FO) fouling experiment with raw municipal wastewater as feed solution indicated that the PDA/PEI-nAg CTA membrane exhibited notably lower water flux decrease compared to the nascent CTA membrane. The results of confocal laser scanning microscopy (CLSM) showed that PDA/PEI-nAg CTA membranes effectively reduced the adsorption of organic foulants (proteins and polysaccharides) and inhibited the formation and development of the fouling layer. The membrane surface modification of the CTA membrane with PDA/PEI and AgNPs efficiently mitigated membrane fouling in municipal wastewater treatment. HIGHLIGHTS AgNPs were in situ immobilized on a CTA FO membrane with PDA/PEI coating layer.; The PDA/PEI coating and Ag in situ generation had no considerable impact on the mass transport coefficients of the CTA FO membrane.; The PDA/PEI-nAg CTA-modified membrane exhibited excellent antifouling performance for raw municipal wastewater treatment.;

Abstract In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging.

Real-time acquisition of location information for agricultural robotic systems is a prerequisite for achieving high-precision intelligent navigation. This paper proposes a data filtering and combined positioning method, and establishes an active screening model. The dynamic and static positioning drift points of the carrier are eliminated or replaced, reducing the complexity of the original Global Navigation Satellite System (GNSS) output data in the positioning system. Compared with the traditional Kalman filter combined positioning method, the proposed active filtering–Kalman filter algorithm can reduce the maximum distance deviation of the carrier along a straight line from 0.145 m to 0.055 m and along a curve from 0.184 m to 0.0640 m. This study focuses on agricultural robot positioning technology, which has an important influence on the development of smart agriculture.

Abstract Background Alternative splicing (AS) is an omnipresent regulatory mechanism of gene expression that enables the generation of diverse splice isoforms from a single gene. Recently, AS events have gained considerable momentum in the pathogenesis of inflammatory bowel disease (IBD). Methods Our review has summarized the complex process of RNA splicing, and firstly highlighted the potential involved molecules that target aberrant splicing events in IBD. The quantitative transcriptome analyses such as microarrays, next‐generation sequencing (NGS) for AS events in IBD have been also discussed. Results Available evidence suggests that some abnormal splicing RNAs can lead to multiple intestinal disorders during the onset of IBD as well as the progression to colitis‐associated cancer (CAC), including gut microbiota perturbations, intestinal barrier dysfunctions, innate/adaptive immune dysregulations, pro‐fibrosis activation and some other risk factors. Moreover, current data show that the advanced technologies, including microarrays and NGS, have been pioneeringly employed to screen the AS candidates and elucidate the potential regulatory mechanisms of IBD. Besides, other biotechnological progresses such as the applications of third‐generation sequencing (TGS), single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics (ST), will be desired with great expectations. Conclusions To our knowledge, the current review is the first one to evaluate the potential regulatory mechanisms of AS events in IBD. The expanding list of aberrantly spliced genes in IBD along with the developed technologies provide us new clues to how IBD develops, and how these important AS events can be explored for future treatment.

BackgroundEndoscopic retrograde cholangiopancreatography (ERCP) is an effective minimally invasive operation for the management of choledocholithiasis, while successful extraction is hampered by large diameter of stones. Emerging studies have revealed the close correlation between biliary microbiota and common bile duct stones (CBDS). In this study, we aimed to investigate the community characteristics and metabolic functions of biliary microbiota in patients with giant CBDS.MethodsEligible patients were prospectively enrolled in this study in First Affiliated Hospital of Soochow University from February 2022 to October 2022. Bile samples were collected through ERCP. The microbiota was analyzed using 16S rRNA sequencing. Metabolic functions were predicted by PICRUSTs 2.0 calculation based on MetaCyc database. Bile acids were tested and identified using ultra performance liquid chromatography-tandem mass spectrometry.ResultsA total of 26 patients were successfully included into final analysis, 8 in giant stone (GS) group and 18 in control group. Distinct biliary microbial composition was identified in patients with giant CBDS, with a significantly higher abundance of Firmicutes at phylum level. The unique composition at genus level mainly consisted of Enterococcus, Citrobacter, Lactobacillus, Pyramidobacter, Bifidobacterium and Shewanella. Pyramidobacter was exclusively found in GS group, along with the absence of Robinsoniella and Coprococcus. The contents of free bile acids were significantly higher in GS group, including cholic acid (98.39μmol/mL vs. 26.15μmol/mL, p=0.035), chenodesoxycholic acid (54.69μmol/mL vs. 5.86μmol/mL, p=0.022) and ursodeoxycholic acid (2.70μmol/mL vs. 0.17μmol/mL, p=0.047). Decreasing tendency of conjugated bile acids were also observed. Metabolic pathways concerning cholelithiasis were abundant in GS group, including geranylgeranyl diphosphate biosynthesis, gluconeogenesis, glycolysis and L-methionine biosynthesis.ConclusionsThis study demonstrated the community structure and metabolic potential of biliary microbiota in patients with giant CBDS. The unique biliary microbial composition holds valuable predictive potential for clinical conditions. These findings provide new insights into the etiology of giant CBDS from the perspective of biliary microbiota.

Background End-stage renal disease is primarily caused by diabetic kidney disease (DKD). The Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, has anti-inflammatory, lipid-lowering and hypoglycemic properties. It also inhibits renal fibrosis. Although its physiological role is not fully understood, it also plays a role in the control of diabetic nephropathy (DN). Methods In the present study, we examined male FXR & leptin receptor double knockout mice, in which weight, blood glucose, body fat, and other indicators were monitored. After 6 months of rearing, blood and urine samples were collected and biochemical parameters were measured. Fibrosis was assessed by Masson’s stain, while the assessment of the resuscitation case’s condition was performed using succinate dehydrogenase (SDHA) stain immunohistochemistry, which measures aerobic respiration. Expression of molecules such as connective tissue growth factor (CTGF), SMAD family members 3 (Smad3) and 7 (Smad7), and small heterodimer partner were detected by RT-PCR and Western blotting as part of the application. Results FXR knockout decreased body weight and body fat in db/db mice, but increased blood glucose, urine output, and renal fibrosis. Primary mesangial cells (P-MCs) from FXR+/ + mice stimulated with transforming growth factor β1 (TGFβ1) showed significantly higher levels of related fibrosis factors, TGFβ1 and Smad3 mRNA and protein, and significantly reduced levels of Smad7. These effects were reversed by the action of FXR agonist chenodeoxycholic acid (CDCA). P-MCs from FXR−/ − mice stimulated with TGFβ1 resulted in an increase in the expression and protein levels of collagen I and TGFβ1, and the addition of CDCA had no significant effect on TGFβ1 stimulation. However, compared with FXR+/ +db/db mice, the rate of oxygen consumption, the rate of carbon dioxide production, and the rate of energy conversion were increased in FXR−/ −db/db mice, whereas the SDHA succinate dehydrogenase, a marker enzyme for aerobic respiration, was significantly decreased. Conclusions These results provide evidence that FXR plays a critical role in the regulation of mesangial cells in DN. The likely mechanism is that aberrant FXR expression activates TGFβ1, which induces extracellular matrix accumulation through the classical Smad signaling pathway, leading to mitochondrial dysfunction.

Modern anthuriums, Anthurium andraeanum (Hort.) are among the most popular flowering plants and widely used for interior decoration. Their popularity is largely attributed to the exotic spathes with different colors. Previous studies have reported color development in red spathe cultivars, but limited information is available on key genes regulating white and green colored spathes. This study analyzed anthocyanin, chlorophyll, and carotenoid contents as well as transcript differences in spathes of eight cultivars that differed in spathe colors ranging from red to white and green. Results showed that increased expression of a transcription factor AaMYB2 was associated with elevated levels of anthocyanin in spathes, but decreased expression of AaMYB2 and increased expression of AaLAR (leucoanthocyanidin reductase) and AaANR (anthocyanidin reductase) were accompanied with the accumulation of colorless proanthocyanidin, thus the white spathe. As to the green colored spathe, chlorophyll content in the green spathe cultivar was substantially higher than the other cultivars. Correspondingly, transcripts of chlorophyll biosynthesis-related genes AaHemB (porphobilinogen synthase) and AaPor (protochlorophyllide oxidoreductase) were highly upregulated but almost undetectable in white and red spathes. The increased expression of AaHemB and AaPor was correlated with the expression of transcription factor AaMYB124. Subsequently, qRT-PCR analysis confirmed their expression levels in nine additional cultivars with red, white, and green spathes. A working model for the formation of white and green spathes was proposed. White colored spathes are likely due to the decreased expression of AaMYB2 which results in increased expression of AaLAR and AaANR, and the green spathes are attributed to AaMYB124 enhanced expression of AaHemB and AaPor. Further research is warranted to test this working model.