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Abstract Aim Clinical diagnosis and surgical treatment of chondrosarcoma (CS) are continuously improving. The purpose of our study is to evaluate the effectiveness of microwave ablation (MWA) assisted degradation therapy in the surgical treatment of intramedullary chondrosarcoma of the extremities, to provide a new reference and research basis for the surgical treatment of CS. Methods We recruited 36 patients with intramedullary CS who underwent MWA assisted extended curettage. Preoperative patient demographics and clinical data were recorded. Surgery was independently assisted by a medical team. Patients were followed up strictly and evaluated for oncological prognosis, radiological results, limb joint function, pain, and complications. Results We included 15 men and 21 women (mean age: 43.5 ± 10.1). The average length of the lesion was 8.1 ± 2.5 cm. Based on preoperative radiographic, clinical manifestations, and pathological results of puncture biopsy, 28 patients were preliminarily diagnosed with CS-grade I and eight patients with CS-grade II. No recurrence or metastasis occurred in the postoperative follow-up. The average Musculoskeletal Tumor Society score was 28.8 ± 1.0, significantly better than presurgery. Secondary shoulder periarthritis and abduction dysfunction occurred in early postoperative stage CS of the proximal humerus in some, but returned to normal after rehabilitation exercise. Secondary bursitis occurred at the knee joint in some due to the internal fixation device used in treatment; however, secondary osteoarthritis and avascular necrosis of the femoral head were not observed. Overall, oncological and functional prognoses were satisfactory. Conclusions The application of MWA assisted degradation therapy in intramedullary CS can achieve satisfactory oncology and functional prognosis, providing a new option for the limited treatment of CS.

Abstract Background Changes in economy and dietary guidelines brought a great shock to diet quality and meal behaviors, but if these transformations have extended to minerals intake and their sources was still poorly understood. It is essential to evaluate time trends in minerals intake and their sources to inform policy makers. Objective To investigate trends in minerals intake and their sources among U.S. adults. Methods This analysis used dietary data collected by 24-h recalls from U.S. adults (≥ 20 years) in NHANES (1999-March 2020). Minerals intake, age-adjusted percentage of participants meeting recommendations, and minerals sources were calculated among all participants and by population subgroups in each NHANES survey cycle. Weighted linear or logistic regression models were used to examine the statistical significance of time trends. Results A total of 48223 U.S. adults were included in this analysis. From 1999 to March 2020, intake of calcium (from 0.94 to 1.02 g/day), magnesium (from 308.07 to 321.85 mg/day), phosphorus (from 1.24 to 1.30 g/day), and sodium (from 3.24 to 3.26 mg/day) from food and beverages (FB) and dietary supplements (DSs) significantly increased, and intake of iron (from 19.17 to 16.38 mg/day), zinc (from 16.45 to 14.19 mg/day), copper (from 1.79 to 1.38 mg/day), and potassium (from 2.65 to 2.50 g/day) from FB + DSs decreased (all FDR

Abstract Tyrosine kinase inhibitors have been the standard treatment for patients with Philadelphia chromosome-positive (Ph+) leukemia. However, a series of issues, including drug resistance, relapse and intolerance, are still an unmet medical need. Here, we report the targeted siRNA-based lipid nanoparticles in Ph+ leukemic cell lines for gene therapy of Ph+ leukemia, which specifically targets a recently identified NEDD8 E3 ligase RAPSYN in Ph+ leukemic cells to disrupt the neddylation of oncogenic BCR-ABL. To achieve the specificity for Ph+ leukemia therapy, a single-chain fragment variable region (scFv) of anti-CD79B monoclonal antibody was covalently conjugated on the surface of OA2-siRAPSYN lipid nanoparticles to generate the targeted lipid nanoparticles (scFv-OA2-siRAPSYN). Through effectively silencing RAPSYN gene in leukemic cell lines by the nanoparticles, BCR-ABL was remarkably degraded accompanied by the inhibition of proliferation and the promotion of apoptosis. The specific targeting, therapeutic effects and systemic safety were further evaluated and demonstrated in cell line-derived mouse models. The present study has not only addressed the clinical need of Ph+ leukemia, but also enabled gene therapy against a less druggable target. Graphical Abstract

This article presents a study on the distributed optimization operation method for micro-energy grid clusters within an electric, thermal, and hydrogen integrated energy system. The research focuses on precisely modeling the Power-to-Hydrogen (P2H) conversion process in electrolytic cells by considering their startup characteristics. An optimization operation model is established, with each micro-energy grid as the principal entity, to cater to their individual interests and demands. The Alternating Direction Method of Multipliers (ADMM) algorithm is adopted for distributed solution. Case studies demonstrate that the connection topology between micro-energy grids significantly impacts the total operating cost, and the effectiveness of the ADMM algorithm is validated through a comparison with centralized optimization approaches.

Abstract Targeting receptor‐interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic stratagem for neurodegenerative disorders, particularly Alzheimer's disease (AD). A positron emission tomography (PET) probe enabling brain RIPK1 imaging can provide a powerful tool to unveil the neuropathology associated with RIPK1. Herein, the development of a new PET radioligand, [11C]CNY‐10 is reported, which may enable brain RIPK1 imaging. [11C]CNY‐10 is radiosynthesized with a high radiochemical yield (41.8%) and molar activity (305 GBq/µmol). [11C]CNY‐10 is characterized by PET imaging in rodents and a non‐human primate, demonstrating good brain penetration, binding specificity, and a suitable clearance kinetic profile. It is performed autoradiography of [11C]CNY‐10 in human AD and healthy control postmortem brain tissues, which shows strong radiosignal in AD brains higher than healthy controls. Subsequently, it is conducted further characterization of RIPK1 in AD using [11C]CNY‐10‐based PET studies in combination with immunohistochemistry leveraging the 5xFAD mouse model. It is found that AD mice revealed RIPK1 brain signal significantly higher than WT control mice and that RIPK1 is closely related to amyloid plaques in the brain. The studies enable further translational studies of [11C]CNY‐10 for AD and potentially other RIPK1‐related human studies.

Human papillomaviruses (HPVs) account for more than 30% of cancer cases, with definite identification of the oncogenic role of viral E6 and E7 genes. However, the identification of high-risk HPV genotypes has largely relied on lagged biological exploration and clinical observation, with types unclassified and oncogenicity unknown for many HPVs. In the present study, we retrieved and cleaned HPV sequence records with high quality and analyzed their genomic compositional traits of dinucleotide (DNT) and DNT representation (DCR) to overview the distribution difference among various types of HPVs. Then, a deep learning model was built to predict the oncogenic potential of all HPVs based on E6 and E7 genes. Our results showed that the main three groups of Alpha, Beta, and Gamma HPVs were clearly separated between/among types in the DCR trait for either E6 or E7 coding sequence (CDS) and were clustered within the same group. Moreover, the DCR data of either E6 or E7 were learnable with a convolutional neural network (CNN) model. Either CNN classifier predicted accurately the oncogenicity label of high and low oncogenic HPVs. In summary, the compositional traits of HPV oncogenicity-related genes E6 and E7 were much different between the high and low oncogenic HPVs, and the compositional trait of the DCR-based deep learning classifier predicted the oncogenic phenotype accurately of HPVs. The trained predictor in this study will facilitate the identification of HPV oncogenicity, particularly for those HPVs without clear genotype or phenotype.

BackgroundGlobally, the incidence rates of obesity and its related diseases, such as cardiovascular diseases and type 2 diabetes, are continuously rising, posing a significant public health challenge. Studies have indicated a potential correlation between vitamin D deficiency and obesity. However, a quantitative analysis of the studies related vitamin D and obesity is lacking. This investigation aims to fill this gap by providing a comprehensive bibliometric analysis to uncover the collaborative networks, research hotspots, and evolutionary trends within the field of vitamin D and obesity research.MethodsThis study retrieved literature related to vitamin D and obesity from the Web of Science database spanning from 2000 to 2023. Bibliometric analysis was conducted using tools such as HistCite, VOSviewer, and CiteSpace to excavate multi-dimensional information including countries, institutions, authors, journals, citations, and keywords.ResultsA total of 6,144 records were retrieved, involving 123 countries, 6,726 institutions, and 28,156 authors, published in 1,551 journals. The number of published papers and citations showed a generally increasing trend. The United States led in terms of publication volume and influence, with journals such as Nutrients and Obesity Surgery having the highest publication counts. Nasser M. Al-Daghri was the most prolific and influential author. Keyword clustering revealed that research topics covered metabolic health, nutrition, immunity, and bariatric surgery. Citation burst analysis indicated a shift in research focus from the relationship between dietary calcium and obesity to the preventive effects of vitamin D supplementation on metabolic diseases.ConclusionThe application of bibliometric methods to analyze the research literature in the fields of obesity and vitamin D has provided a comprehensive understanding of the collaborative networks, key research focus, and evolutionary trends in this field, offering insights for guiding future research directions.

Constipation symptoms of Parkinson's disease (PD) seriously reduce the quality of life of patients and aggravate the development of the disease, but current treatment options still cannot alleviate the progress of constipation. Electroacupuncture (EA) is a new method for the treatment of constipation, which can effectively treat the symptoms of constipation in PD patients. However, the specific regulatory mechanisms of EA in the treatment of constipation symptoms in PD remain unclear. The aim of this study is to investigate the therapeutic effect of EA on PD constipation rats and its regulatory mechanism. A rotenone (ROT)-induced gastrointestinal motility disorder model was used to simulate the pathological process of constipation in PD. The results showed that EA could effectively promote gastrointestinal peristalsis, reduce α-synuclein accumulation in substantia nigra and colon and colonic injury in rats after ROT administration. Mechanistically, EA activation of the central-cholinergic pathway increases acetylcholine release in the colon. At the same time, EA up-regulated the co-expression of enteric glial cells (EGCs) and α7 nicotinic acetylcholine receptor (α7nAChR). EA increased the expression of choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and tyrosine hydroxylase (TH) in the colon of PD rats. Further mechanistic studies showed that EA increased the expression of glial cell-derived neurotrophic factor (GDNF), GFRa1 and p-AKT in colon tissues. The present study confirmed that EA upregulates α7nAChR through a central-cholinergic mechanism to promote GDNF release from EGCs, thereby protecting intestinal neurons and thereby improving gastrointestinal motility.

Objective: This study aimed to assess the relationship between implantation and soluble HLA-G (sHLA-G) expression in cleavage embryo culture medium (ECM) in conjunction with early developmental kinetics determined by time-lapse imaging (TLI).Methods: A retrospective, single-center study was conducted involving 238 embryos from 165 patients who underwent Frozen-thawed embryo transfer (FET) using autologous oocytes, with either single or double embryo transfer. TLI morphokinetic parameters (t2, t3, t4, t5, t6, t7, t8, cc2, s2, cc3, s3) of embryos were analyzed, and sHLA-G levels in D3 ECM were measured using an enzyme-linked immunosorbent assay (ELISA). A hierarchical classification model was developed to categorize embryos into five groups (A, B, C, D, E). The correlation between sHLA-G levels, TLI classification of embryos, and embryo implantation was investigated to establish a non-invasive method for evaluating implantation potential. Multivariate logistic regression analysis was performed to identify potential influencing factors, and receiver operating characteristic (ROC) curves were used to evaluate the predictive value for implantation.Results: Multivariate unconditional logistic regression analysis indicated that TLI parameters t5 and s3 and sHLA-G level in ECM were independent risk factors affecting embryo implantation. The implantation rate decreased from TLI classification A to E. The proposed classification model effectively assessed the implantation potential of embryos. The implantation rate was higher in the sHLA-G positive group compared to the sHLA-G negative group (p < 0.001). The expression of sHLA-G in D3 ECM, combined with the TLI classification model, accurately evaluated the implantation potential of embryos with an AUC of 0.876.Conclusion: The integration of cleavage kinetics and embryonic sHLA-G expression could reliably identify embryos with a high likelihood of successful implantation.

Abstract Due to multidimensional complexity of solid tumor, development of rational T‐cell combinations and corresponding formulations is still challenging. Herein, a triple combination of T cells are developed with Indoleamine 2,3‐dioxygenase inhibitors (IDOi) and Cyclin‐dependent kinase 4/6 inhibitors (CDK4/6i). To maximize synergism, a spatiotemporally controlled T‐cell engineering technology to formulate triple drugs into one cell therapeutic, is established. Specifically, a sequentially responsive core‐shell nanoparticle (SRN) encapsulating IDOi and CDK4/6i is anchored onto T cells. The yielded SRN‐T cells migrated into solid tumor, and achieved a 1st release of IDOi in acidic tumor microenvironment (TME). Released IDOi restored tryptophan supply in TME, which activated effector T cells and inhibited Tregs. Meanwhile, 1st released core is internalized by tumor cells and degraded by glutathione (GSH), to realize a 2nd release of CDK4/6i, which induced up‐regulated expression of C‐X‐C motif chemokine ligand 10 (CXCL10) and C‐C motif chemokine ligand 5 (CCL5), and thus significantly increased tumor infiltration of T cells. Together, with an enhanced recruitment and activation, T cells significantly suppressed tumor growth, and prolonged survival of tumor‐bearing mice. This study demonstrated rationality and superiority of a tri‐drug combination mediated by spatiotemporally controlled cell‐engineering technology, which provides a new treatment regimen for solid tumor.

[Introduction] The purpose of this paper is to research and analyze the influence of water resources on the development of the green hydrogen industry in China, reveal the contradiction between water resources and the development of green hydrogen industry, analyze the future development trend of the green hydrogen industry and to provide useful reference for the development layout of renewable energy hydrogen production projects in China. [Method] In order to prove that water resources could limit the development of the green hydrogen industry in "Northeast China, North China, Northwest China" and other areas, the analysis and the demonstration were made based on the field investigations and the documentary materials, considering water resources policies, water usage in traditional chemical industries, and hydrogen production technologies. [Result] The analysis results show that under the restriction of China's water resources-related policies, the layout of green hydrogen industry should consider the constraints of water resources, and the large-scale production of green hydrogen and its substitution for fossil energy hydrogen production cannot effectively save water. Instead, it may lead to an increase in water consumption by the chemical industry. Under the constraint of water resources, the development of China's green hydrogen industry must consider the layout from a holistic perspective, fully integrate the development trend of the existing chemical industry, and consider the abundant resources available such as seawater. [Conclusion] The development of the green hydrogen industry in China should not ignore the problems of existing policy framework, technology level, industrial layout and characteristics of existing resources. When arranging the layout of the green hydrogen projects, the current situation and future trends should be fully considered, and the problems posed by water resources on the green hydrogen industry should be solved from the perspective of the overall planning, the coordinated industrial development and the effective utilization of resources.

Abstract Background Neurodevelopmental disorders (NDDs), such as Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Tourette Syndrome (TS), have been extensively studied for their multifaceted impacts on social and emotional well-being. Recently, there has been growing interest in their potential relationship with fracture risks in adulthood. This study aims to explore the associations between these disorders and fracture rates, in order to facilitate better prevention and treatment. Methods Employing a novel approach, this study utilized Mendelian randomization (MR) analysis to investigate the complex interplay between ADHD, ASD, TS, and fractures. The MR framework, leveraging extensive genomic datasets, facilitated a systematic examination of potential causal relationships and genetic predispositions. Results The findings unveil intriguing bidirectional causal links between ADHD, ASD, and specific types of fractures. Notably, ADHD is identified as a risk factor for fractures, with pronounced associations in various anatomical regions, including the skull, trunk, and lower limbs. Conversely, individuals with specific fractures, notably those affecting the femur and lumbar spine, exhibit an increased genetic predisposition to ADHD and ASD. In this research, no correlation was found between TS and fractures, or osteoporosis.These results provide a genetic perspective on the complex relationships between NDDs and fractures, emphasizing the importance of early diagnosis, intervention, and a holistic approach to healthcare. Conclusion This research sheds new light on the intricate connections between NDDs and fractures, offering valuable insights into potential risk factors and causal links. The bidirectional causal relationships between ADHD, ASD, and specific fractures highlight the need for comprehensive clinical approaches that consider both NDDs and physical well-being.

Objective Surgical procedures for patients with posttraumatic syringomyelia (PTS) remain controversial. Until now, there have been no effective quantitative evaluation methods to assist in selecting appropriate surgical plans before surgery. Methods We consecutively enrolled PTS patients (arachnoid lysis group, n = 42; shunting group, n = 14) from 2003 to 2023. Additionally, 19 intrathecal anesthesia patients were included in the control group. All patients with PTS underwent physical and neurological examinations and spinal magnetic resonance imaging preoperatively, 3–12 months postoperatively and during the last follow-up. Preoperative lumbar puncture was performed and blood-spinal cord barrier disruption was detected by quotient of albumin (Qalb, cerebrospinal fluid/serum). Results The ages (p = 0.324) and sex (p = 0.065) of the PTS and control groups did not differ significantly. There were also no significant differences in age (p = 0.216), routine blood data and prognosis (p = 0.399) between the arachnoid lysis and shunting groups. But the QAlb level of PTS patients was significantly higher than that of the control group (p < 0.001), and the shunting group had a significantly higher QAlb (p < 0.001) than the arachnoid lysis group. A high preoperative QAlb (odds ratio, 1.091; 95% confidence interval, 1.004–1.187; p = 0.041) was identified as the predictive factor for the shunting procedure, with the receiver operating characteristic curve showing 100% specificity and 80.95% sensitivity for patients with a QAlb > 12.67. Conclusion Preoperative QAlb is a significant predictive factor for the types of surgery. For PTS patients with a QAlb > 12.67, shunting represents the final recourse, necessitating the exploration and development of novel treatments for these patients.

Abstract Iron-based nanotubes are promising candidates for high performance electromagnetic wave absorbing fillers due to their high aspect ratio, light weight, high axial permeability and high saturation magnetization. Furthermore, the introduction of carbon can improve dielectric loss and block the agglomeration of iron nanotubes. Here, Fe@C composite nanotubes were prepared by introducing carbon onto the surface of precursor α-FeOOH’ fibers followed by hydrogen-thermal annealing. We find that Fe@C composite nanotubes retain the one-dimensional nanostructure of the precursor throughout the annealing. The well-developed lattice and nanostructure of Fe@C nanotubes endow high saturation magnetization, high anisotropy, suppressed eddy current effect and cross-particle exchange coupling as well, and thus contribute to an enhanced permeability. Coatings with Fe@C as fillers achieve a reflection loss of up to −69.34 dB at 3.37 GHz at the matching thickness of 3.97 mm. The Fe@C composite nanotubes developed here are a promising candidate for high performance electromagnetic wave absorbing fillers.

Abstract Background CRISPR/Cas-derived base editor enables precise editing of target sites and has been widely used for basic research and crop genetic improvement. However, the editing efficiency of base editors at different targets varies greatly. Results Here, we develop a set of highly efficient base editors in cotton plants. GhABE8e, which is fused to conventional nCas9, exhibits 99.9% editing efficiency, compared to GhABE7.10 with 64.9%, and no off-target editing is detected. We further replace nCas9 with dCpf1, which recognizes TTTV PAM sequences, to broaden the range of the target site. To explore the functional divergence of TERMINAL FLOWER 1 (TFL1), we edit the non-coding and coding regions of GhTFL1 with 26 targets to generate a comprehensive allelic population including 300 independent lines in cotton. This allows hidden pleiotropic roles for GhTFL1 to be revealed and allows us to rapidly achieve directed domestication of cotton and create ideotype germplasm with moderate height, shortened fruiting branches, compact plant, and early-flowering. Further, by exploring the molecular mechanism of the GhTFL1 L86P and GhTFL1 K53G+S78G mutations, we find that the GhTFL1 L86P mutation weakens the binding strength of the GhTFL1 to other proteins but does not lead to a complete loss of GhTFL1 function. Conclusions This strategy provides an important technical platform and genetic information for the study and creation of ideal plant architecture.

Abstract It has recently become well-established that there is a connection between Alzheimer’s disease pathology and gut microbiome dysbiosis. We have previously demonstrated that antibiotic-mediated gut microbiota perturbations lead to attenuation of Aβ deposition, phosphorylated tau accumulation, and disease-associated glial cell phenotypes in a sex-dependent manner. In this regard, we were intrigued by the finding that a marine-derived oligosaccharide, GV-971, was reported to alter gut microbiota and reduce Aβ amyloidosis in the 5XFAD mouse model that were treated at a point when Aβ burden was near plateau levels. Utilizing comparable methodologies, but with distinct technical and temporal features, we now report on the impact of GV-971 on gut microbiota, Aβ amyloidosis and microglial phenotypes in the APPPS1-21 model, studies performed at the University of Chicago, and independently in the 5X FAD model, studies performed at Washington University, St. Louis. Methods To comprehensively characterize the effects of GV-971 on the microbiota-microglia-amyloid axis, we conducted two separate investigations at independent institutions. There was no coordination of the experimental design or execution between the two laboratories. Indeed, the two laboratories were not aware of each other’s experiments until the studies were completed. Male and female APPPS1-21 mice were treated daily with 40, 80, or 160 mg/kg of GV-971 from 8, when Aβ burden was detectable upto 12 weeks of age when Aβ burden was near maximal levels. In parallel, and to corroborate existing published studies and further investigate sex-related differences, male and female 5XFAD mice were treated daily with 100 mg/kg of GV-971 from 7 to 9 months of age when Aβ burden was near peak levels. Subsequently, the two laboratories independently assessed amyloid-β deposition, metagenomic, and neuroinflammatory profiles. Finally, studies were initiated at the University of Chicago to evaluate the metabolites in cecal tissue from vehicle and GV-971-treated 5XFAD mice. Results These studies showed that independent of the procedural differences (dosage, timing and duration of treatment) between the two laboratories, cerebral amyloidosis was reduced primarily in male mice, independent of strain. We also observed sex-specific microbiota differences following GV-971 treatment. Interestingly, GV-971 significantly altered multiple overlapping bacterial species at both institutions. Moreover, we discovered that GV-971 significantly impacted microbiome metabolism, particularly by elevating amino acid production and influencing the tryptophan pathway. The metagenomics and metabolomics changes correspond with notable reductions in peripheral pro-inflammatory cytokine and chemokine profiles. Furthermore, GV-971 treatment dampened astrocyte and microglia activation, significantly decreasing plaque-associated reactive microglia while concurrently increasing homeostatic microglia only in male mice. Bulk RNAseq analysis unveiled sex-specific changes in cerebral cortex transcriptome profiles, but most importantly, the transcriptome changes in the GV-971-treated male group revealed the involvement of microglia and inflammatory responses. Conclusions In conclusion, these studies demonstrate the connection between the gut microbiome, neuroinflammation, and Alzheimer’s disease pathology while highlighting the potential therapeutic effect of GV-971. GV-971 targets the microbiota-microglia-amyloid axis, leading to the lowering of plaque pathology and neuroinflammatory signatures in a sex-dependent manner when given at the onset of Aβ deposition or when given after Aβ deposition is already at higher levels.

The Adam algorithm is a common choice for optimizing neural network models. However, its application often brings challenges, such as susceptibility to local optima, overfitting and convergence problems caused by unstable learning rate behavior. In this article, we introduce an enhanced Adam optimization algorithm that integrates Warmup and cosine annealing techniques to alleviate these challenges. By integrating preheating technology into traditional Adam algorithms, we systematically improved the learning rate during the initial training phase, effectively avoiding instability issues. In addition, we adopt a dynamic cosine annealing strategy to adaptively adjust the learning rate, improve local optimization problems and enhance the model's generalization ability. To validate the effectiveness of our proposed method, extensive experiments were conducted on various standard datasets and compared with traditional Adam and other optimization methods. Multiple comparative experiments were conducted using multiple optimization algorithms and the improved algorithm proposed in this paper on multiple datasets. On the MNIST, CIFAR10 and CIFAR100 datasets, the improved algorithm proposed in this paper achieved accuracies of 98.87%, 87.67% and 58.88%, respectively, with significant improvements compared to other algorithms. The experimental results clearly indicate that our joint enhancement of the Adam algorithm has resulted in significant improvements in model convergence speed and generalization performance. These promising results emphasize the potential of our enhanced Adam algorithm in a wide range of deep learning tasks.

Abstract It is well-established that women are disproportionately affected by Alzheimer’s disease. The mechanisms underlying this sex-specific disparity are not fully understood, but several factors that are often associated-including interactions of sex hormones, genetic factors, and the gut microbiome-likely contribute to the disease's etiology. Here, we have examined the role of sex hormones and the gut microbiome in mediating Aβ amyloidosis and neuroinflammation in APPPS1-21 mice. We report that postnatal gut microbiome perturbation in female APPPS1-21 mice leads to an elevation in levels of circulating estradiol. Early stage ovariectomy (OVX) leads to a reduction of plasma estradiol that is correlated with a significant alteration of gut microbiome composition and reduction in Aβ pathology. On the other hand, supplementation of OVX-treated animals with estradiol restores Aβ burden and influences gut microbiome composition. The reduction of Aβ pathology with OVX is paralleled by diminished levels of plaque-associated microglia that acquire a neurodegenerative phenotype (MGnD-type) while estradiol supplementation of OVX-treated animals leads to a restoration of activated microglia around plaques. In summary, our investigation elucidates the complex interplay between sex-specific hormonal modulations, gut microbiome dynamics, metabolic perturbations, and microglial functionality in the pathogenesis of Alzheimer's disease.

Manganese (Mn) is necessary for various biological processes, yet its function in innate immunity has been less studied, especially in fish. Stimulator of interferon (IFN) genes (STING) is an essential factor for IFN induction in virus infection. Our study demonstrated that Mn2+ increases the ability of zebrafish to resist spring viraemia of carp virus (SVCV) infection by enhancing the expression of STING. Further mechanistic studies indicated that Mn2+ promotes the expression of STING by increasing its ubiquitination. Furthermore, Mn2+treatment promoted STING-mediated activation of IFN and reversed the decrease in STING protein induced by SVCV. Collectively, our findings showed the vital involvement and necessity of Mn2+ in protecting fish against SVCV infection.

ObjectiveThis paper summarizes the research progress into stimulation methods used in rehabilitation equipment for pediatric cerebral palsy (CP) for the past 20 years from 2003 to 2023. We also provide ideas for innovative research and development of artificial intelligence-based rehabilitation equipment.MethodsThrough a certain search strategy, Keywords are searched in the China National Knowledge Network Database (CNKI), the Wanfang Database knowledge service platform, the Chongqing VIP information service, PubMed, Web of Science, Cochrane, ScienceDirect, Medline, Embase, and IEEE database. A total of 3,049 relevant articles were retrieved, and 49 articles were included that mentioned research and development of rehabilitation equipment. We excluded articles that were not specific to children with CP, were duplicated or irrelevant literature, were missing data, the full article was not available, the article did not describe the method of stimulation used with the rehabilitation equipment on children with CP, were not Chinese and English, and were the types of reviews and commentaries.ResultsPhysical stimulation is the main stimulation method of rehabilitation equipment for children with CP. Force stimulation is the main mode of physical stimulation, and there are 17 articles that have verified the clinical efficacy of force stimulation-based equipment.ConclusionResearch on the stimulation mode of pediatric cerebral palsy rehabilitation equipment is likely to focus on simulating the force of the Chinese medicine called “tuina manipulation.” When this method is combined with artificial intelligence and personalized direction we believe this will lay the foundation for future development of a novel therapy for children with CP.

Summary: Sepsis trains stressed granulocytes to boost nonspecific response and trigger a new wave of inflammation when facing secondary infection. Here, we present a protocol for a murine model of sepsis with secondary infection. We describe steps for cecal ligation and puncture operation and rechallenging with lipopolysaccharide or Pseudomonas aeruginosa during the recovery phase. We also detail steps to characterize the stressed granulocytes by assessing their functional phenotypes and effect on the mortality of rechallenged mice.For complete details on the use and execution of this protocol, please refer to Wang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Plant growth-promoting rhizobacteria (PGPR) are known to have the effect of promoting plant growth. In this paper, three PGPR strains were selected from the previous work, which had plant growth-promoting activities such as phosphate solubilization, nitrogen fixation, phosphorus mobilization, etc. These strains named FJS-3(Burkholderia pyromania), FJS-7(Pseudomonas rhodesiae), and FJS-16(Pseudomonas baetica), respectively, were prepared into solid biological agents. Three widely planted commercial crops (tea plant, tobacco, and chili pepper) were selected for PGPR growth promotion verification. The results showed that the new shoots of tea seedlings under PGPR treatment were much more than the control. We also used tobacco, another important crop in Guizhou, to test the growth-promoting effect of individual bacteria, and the results showed that each of them could promote the growth of tobacco plants, and FJS-3(Burkholderia pyrrocinia) had the best effect. In addition, we carried out experiments on tobacco and pepper using multi-strain PGPR, the tobacco plants' height, fresh, and root weight increased by 30.15 %, 37.36 %, and 54.5 %, respectively, and the pepper plants' increased by 30.10 %, 56.38 % and 43.18 %, respectively, which both showed significantly better effects than that of a single strain. To further test the field performance, field trials were carried out in a mature Longjing43 tea plantation in Guizhou. There were four treatments: no fertilization (T1), combined application of PGPR biological agent and compound fertilizer (T2), only application of PGPR (T3), and only application of compound fertilizer (T4). In terms of yield, grouped with or without PGPR, there was a 15.38 % (T2:T4) and 92.31 % (T3:T1) increase between them, respectively. The tea's yield and tea flavor substances such as tea polyphenols, caffeine, and theanine were detected, and the T2 showed the most significant positive effect on both sides. Especially, an important indicator of Matcha green tea is the color, chlorophyll content was then tested, and PGPR application increased it and improved the appearance. All these results demonstrated that the PGPR we screened could significantly promote plant growth and quality improvement, and had good application potential in crop planting, which could contribute to environmental protection and economic growth.

ABSTRACT: Understanding the characteristics of bacteriophages is crucial for the optimization of phage therapy. In this study, the biological and genomic characteristics of coliphage LHE83 were determined and its synergistic effects with different types of antibiotics against E. coli E82 were investigated. Phage LHE83 displayed a contractile tail morphology and had a titer of 3.02 × 109 pfu/mL at an optimal MOI of 0.01. Meanwhile, phage LHE83 exhibited good physical and chemical factors tolerance. The 1-step growth analysis revealed a latent period of approx. 10 min with a burst size of 87 pfu/infected cell. Phage LHE83 belongs to the genus Dhakavirus. Its genome consists of 170,464 bp with a 40% GC content, and a total of 268 Open Reading Frames (ORF) were predicted with no detected virulent or resistant genes. ORF 213 was predicted to encode the receptor binding protein (RBP) and confirmed by the antibody-blocking assay. Furthermore, a phage-resistant strain E. coli E82R was generated by co-culturing phage LHE83 with E. coli E82. Genomic analysis revealed that OmpA served as the receptor for phage LHE83, which was further confirmed by phage adsorption assay using E. coli BL21ΔOmpA, E. coli BL21ΔOmpA: OmpA and E. coli BL21:OmpA strains. Additionally, a synergistic effect was observed between phage LHE83 and spectinomycin against the drug-resistant strain E. coli E82. These results provide a theoretical basis for understanding the interactions between phages, antibiotics, and host bacteria, which can assist in the clinical application of phages and antibiotics against drug-resistant bacteria.

Dust accumulation on the surface of solar photovoltaic panels diminishes their power generation efficiency, leading to reduced energy generation. Regular monitoring and cleaning of solar photovoltaic panels is essential. Thus, developing optimal procedures for their upkeep is crucial for improving component efficiency, reducing maintenance costs, and conserving resources. This study introduces an improved Adam optimization algorithm designed specifically for detecting dust on the surface of solar photovoltaic panels. Although the traditional Adam algorithm is the preferred choice for optimizing neural network models, it occasionally encounters problems such as local optima, overfitting, and not convergence due to inconsistent learning rates during the optimization process. To mitigate these issues, the improved algorithm incorporates Warmup technology and cosine annealing strategies with traditional Adam algorithm, that allows for a gradual increase in the learning rate, ensuring stability in the preliminary phases of training. Concurrently, the improved algorithm employs a cosine annealing strategy to dynamically tweak the learning rate. This not only counters the local optimization issues to some degree but also bolsters the generalization ability of the model. When applied on the dust detection on the surface of solar photovoltaic panels, this improved algorithm exhibited superior convergence and training accuracy on the surface dust detection dataset of solar photovoltaic panels in comparison to the standard Adam method. Remarkably, it displayed noteworthy improvements within three distinct neural network frameworks: ResNet-18, VGG-16, and MobileNetV2, thereby attesting to the effectiveness of the novel algorithm. These findings hold significant promise and potential applications in the field of surface dust detection of solar photovoltaic panels. These research results will create economic benefits for enterprises and individuals, and are an important strategic development direction for the country.

MYBL2 (MYB proto-oncogene like 2) is an emerging prognostic marker for malignant tumors, and its potential role in osteosarcoma and its relationship with immune infiltration in pan-cancer is yet to be elucidated. We constructed a transcription factor activity profile of osteosarcoma using the single-cell regulatory network inference algorithm based on single-cell RNA sequencing data obtained from the Gene Expression Omnibus. Subsequently, we calculated the extent of MYBL2 activation in malignant proliferative osteoblasts. We also explored the association between MYBL2 and chemotherapy resistance in osteosarcoma. Furthermore, we systematically correlated MYBL2 with immunological signatures in the tumor microenvironment in pan-cancer, including immune cell infiltration, immune checkpoints, and tumor immunotherapy prognosis. Finally, we developed and validated a risk score (MRGS), derived an osteosarcoma risk score nomogram based on MRGS, and tested its ability to predict prognosis. MYBL2 and gene enrichment analyses in osteosarcoma and pan-cancer revealed that MYBL2 was positively correlated with cell proliferation and tumor immune pathways. MYBL2 expression positively correlated with SLC19A1 in pan-cancer and osteosarcoma cell lines. Pan-cancer immune infiltration analysis revealed that MYBL2 was correlated with myeloid-derived suppressor cells, Th2 cell infiltration, CD276, RELT gene expression, and tumor mutation burden. In summary, MYBL2 regulates proliferation, progression, and immune infiltration in osteosarcoma and pan-cancer. Therefore, we found that MYBL2 could be used as a potential marker for predicting the osteosarcoma prognosis. Patients with osteosarcoma and high MYBL2 expression are theoretically more sensitive to methotrexate. An osteosarcoma prognostic nomogram can provide new ideas in the search for osteosarcoma prognostic markers.

Regulation of host interferon (IFN) production is a crucial strategy for viral immune escape. We propose that the LxIS motif language, a marker for exogenous viral proteins, interacts with host retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) factors. In this study, the viral proteins containing the LxIS motif of grass carp reovirus (GCRV), and cyprinid herpesvirus 3 (CyHV-3), which belong to the fish RNA and DNA viruses, were found to interact with RLRs, and the general functions of these proteins were negative regulation of IFN activation. Terrestrial animal viruses with this motif language, such as SARS-CoV-2 and so on, are also examined. Several viral proteins that were not reported previously were found to be associated with the RLR pathway. Taken together, the LxIS motif language elucidates a straightforward and efficient method for identifying viral proteins that target host RLRs to regulate IFN expression, and is conserved in both lower and higher vertebrates.

BackgroundMotor impairment is the most prevalent consequence following a stroke. Interhemispheric homotopic connectivity, which varies regionally and hierarchically along the axis of the somatomotor-association cortex, plays a critical role in sustaining normal motor functions. However, the impact of strokes occurring in various locations on homotopic connectivity is not fully understood. This study aimed to explore how motor deficits resulting from acute strokes in different locations influence homotopic connectivity.MethodsEighty-four acute ischemic stroke patients with dyskinesia were recruited and divided into four demographically-matched subgroups based on stroke locations: Group 1 (G1; frontoparietal, n = 15), Group 2 (G2; radiation coronal, n = 16), Group 3 (G3; basal ganglia, n = 30), and Group 4 (G4; brain stem, n = 23). An additional 37 demographically-matched healthy controls were also recruited in the study. Multimodal MRI data, motor function assessments, and cognitive tests were gathered for analysis. Interhemispheric homotopic functional and structural connectivity were measured using resting-state functional MRI and diffusion tensor imaging, respectively. These measurements were then correlated with motor function scores to investigate the relationships.ResultsVoxel-mirrored homotopic connectivity (VMHC) analysis showed that strokes in the frontoparietal and basal ganglia regions led to diminished homotopic connectivity in the somatosensory/motor cortex. In contrast, strokes in the radiation coronal and brainstem regions affected subcortical motor circuits. Structural homotopic connectivity analysis using diffusion tensor imaging showed that frontoparietal and basal ganglia strokes predominantly affected association fibers, while radiation coronal and brainstem strokes caused widespread disruption in the integrity of both cortical-cortical and cortical-subcortical white matter fibers. Correlation analyses demonstrated significant associations between the Fugl-Meyer Assessment (FMA), Modified Barthel Index (MBI), and National Institutes of Health Stroke Scale (NIHSS) scores with the VMHC in the inferior temporal gyrus for G1 (G1; r = 0.838, p < 0.001; r = 0.793, p < 0.001; and r = −0.834, p < 0.001, respectively). No statistically significant associations were observed in Groups 2, 3, and 4.ConclusionOur results suggest that motor deficits following strokes in various regions involve distinct pathways from cortical to subcortical areas. Alterations in lesion topography and regional functional homotopy provide new insights into the understanding of neural underpinnings of post-stroke dyskinesia.

Abstract Bacteriophage endolysin is a novel antibacterial agent that has attracted much attention in the prevention and control of drug‐resistant bacteria due to its unique mechanism of hydrolysing peptidoglycans. Although endolysin exhibits excellent bactericidal effects on Gram‐positive bacteria, the presence of the outer membrane of Gram‐negative bacteria makes it difficult to lyse them extracellularly, thus limiting their application field. To enhance the extracellular activity of endolysin and facilitate its crossing through the outer membrane of Gram‐negative bacteria, researchers have adopted physical, chemical, and molecular methods. This review summarizes the characterization of endolysin targeting Gram‐negative bacteria, strategies for endolysin modification, and the challenges and future of engineering endolysin against Gram‐negative bacteria in clinical applications, to promote the application of endolysin in the prevention and control of Gram‐negative bacteria.

Background: Particulate matter (PM) has been found to elevate the risk of pulmonary embolism (PE) onset. Among the contributors to PM, dust PM stands as the second natural source, and its emissions are escalating due to climate change. Despite this, information on the effect of dust PM on PE onset is scarce. Hence, this study aims to investigate the impacts of dust PM10, dust PM2.5–10, and dust PM2.5 on PE onset. Methods: A nationwide time-stratified case-crossover study was conducted between 2015 and 2020, using data from 18,616 PE onset cases across 1,921 hospitals in China. The analysis employed a conditional logistic regression model to quantify the associations between dust PM10, dust PM2.5–10, and dust PM2.5 and PE onset. Furthermore, the study explored the time-distributed lag pattern of the effect of dust PM on PE development. Stratified analyses were performed based on sex, age, region, and season. Results: Dust PM10, dust PM2.5–10, and dust PM2.5 exhibited significant health effects on PE onset, particularly concerning exposure on the same day. The peak estimates were observed at lag 01 day, with the odds ratio being 1.011 [95 % confidence interval (CI): 1.003, 1.019], 1.014 (95 % CI: 1.003, 1.026), and 1.039 (95 % CI: 1.011, 1.068), for a 10 μg/m3 increase in the concentration of dust PM10, dust PM2.5–10, and dust PM2.5, respectively. In addition, the study identified a higher risk of PE onset associated with dust PM exposure during the warm season than that in cool season, particularly for dust PM2.5. Conclusions: The findings from this study suggest that short-term exposure to dust PM, particularly dust PM2.5, may trigger PE onset, posing a significant health threat. Implementing measures to mitigate dust PM emissions and protect patients with PE from dust PM exposure is imperative.

AIM: To investigate the effects of diquafosol sodium (DQS) for dry eye model induced with povidone-iodine (PI) solution. METHODS: Ten Sprague Dawley rats as the control group. Thirty Sprague Dawley rats were used to establish the dry eye model with stimulation of 10 g/L PI for 14d, then divided rats into three groups: dry eye group with no treatment (DED group, n=10); phosphate buffer saline treated group (PBS group, n=10); diquafosol treated group (DQS group, n=10). Clinical changes were observed by tear production test, fluorescein staining, tear break-up time (TBUT) test, corneal confocal microscope and ocular surface comprehensive analyzer. Eyeballs were collected on day 10 of treatment for hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and alcian blue staining. TUNEL assay, polymorphonuclear (PMN) and mucin 1 (MUC1) immunofluorescence were performed and corneal ultrastructural changes were detected by electron microscopy. RESULTS: Compared with DED and PBS groups, tear production (7.26±0.440 vs 4.07±0.474 mm; 7.26±0.440 vs 3.74±0.280 mm; all P

AbstractFollowing a major earthquake, disaster information services must deliver accurate damage assessment results during the emergency ‘black box’ phase when data is scarce. Seismic intensity maps contain crucial information for determining the damage in the affected area. For earthquakes with Mw between 5.5 and 7, this study proposes using GIS analysis to mine aftershock events in early aftershock sequences that are closely related to the mainshock fault, and then using these events to generate seismic intensity assessment maps. Regression curves were first obtained using a nonparametric method (rLowess) to analyse the geographical coordinates of early aftershocks. Then, a buffer of 1 or 1.5 km radius was made for the curve, and the aftershocks in the buffer were used to calculate the predicted peak ground velocity (PGV) values over a specific km-grid range. Finally, rapid mapping of seismic intensity was assessed based on the intensity scale. This straightforward and repeatable method employs seismic station data obtained shortly after the mainshock. The assessed seismic intensity accurately reflects the location and extent of the hardest hit areas and can be cross-referenced with geophysical results to accurately assess the damage in the affected areas.

Accurate water quality predictions are critical for water resource protection, and dissolved oxygen (DO) reflects overall river water quality and ecosystem health. This study proposes a hybrid model based on the fusion of signal decomposition and deep learning for predicting river water quality. Initially, complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) is employed to split the internal series of DO into numerous internal mode functions (IMFs). Subsequently, we employed multi-scale fuzzy entropy (MFE) to compute the entropy values for each IMF component. Time-varying filtered empirical mode decomposition (TVFEMD) is used to further extract features in high-frequency subsequences after linearly aggregating the high-frequency sequences. Finally, support vector machine (SVM) and long short-term memory (LSTM) neural networks are used to predict low- and high-frequency subsequences. Moreover, by comparing it with single models, models based on ‘single layer decomposition-prediction-ensemble’ and combination models using different methods, the feasibility of the proposed model in predicting water quality data for the Xinlian section of Fuhe River and the Chucha section of Ganjiang River was verified. As a result, the combined prediction approach developed in this work has improved generalizability and prediction accuracy, and it may be used to forecast water quality in complicated waters. HIGHLIGHTS Quadratic modal decomposition of water quality data to extract more informative features.; High-frequency and low-frequency sequences were separately predicted using the appropriate deep-learning models, respectively.; The model proposed in this study has more accurate point prediction and interval prediction results compared to other models.;

Abstract A large number of La-related proteins (LARPs), most of which share a La-motif and one or more adjacent RNA-recognition (RRM) domains, are known to play a function in diverse processes. Among the LAPRs, LARP4 and LARP5 have been mainly reported to act as positive translation factors. In Phytophthora sojae, only one protein with typical LARP protein features was identified, and it was named LARP4_5 due to the presence of an RRM_LARP4_5-like domain. The PsLARP4_5 gene was significantly upregulated in zoospores and during the infection stage. By comparing the biological characteristics of a wild-type strain with three PsLARP4_5 knockout transformants, it was found that PsLARP4_5 was involved in mycelial growth, sporangium and zoospore production, and pathogenicity of P. sojae. Further analysis of the transcriptome indicated that many differentially expressed genes could participate in several essential biological processes in the PsLARP4_5 transformant, including translation, as structural constituents of ribosomes or cytosolic large ribosomal subunits and others. Notably, 76 genes with a role in the ribosome pathway were downregulated in the PsLARP4_5 transformant, suggesting that PsLARP4_5 might affect translation. Overall, these findings indicate that PsLARP4_5 plays an essential role in the development and pathogenicity of P. sojae.

Abstract In the context of the digital economy, understanding the impact of digital participation on farmers’ environmental behavior is crucial for promoting environmental literacy and improving quality of life. This study focuses on the influence of internet use on domestic waste sorting among farm households in rural areas of eastern, central, and western China, based on data from a micro survey conducted in 2126 households. The study utilizes an ordered probability model to examine the impact of internet use on waste sorting behavior and explores any heterogeneity in this relationship. The results reveal that internet use significantly increases the likelihood of farmers participating in domestic waste sorting. This finding remains consistent even after conducting robustness tests. Furthermore, the study demonstrates that internet use reduces the probability of non-participation in waste separation by 14.9%, while increasing the proportion of waste sorting into two, three, and four categories by 3.86, 5.99, and 5.04%, respectively. In other words, farmers who use the internet are more likely to engage in proper waste separation practices. Heterogeneity analysis indicates that the promotion of internet use facilitates information access for traditionally marginalized groups, such as women, older individuals, those with low income, and those with low education levels. Consequently, these groups are more likely to participate in household waste sorting. This study serves as an important reference for developing countries and regions that aim to enhance residential waste participation through internet use.

Abstract Enhancing energy-environmental efficiency (EEE) is crucial for achieving energy conservation and emission reduction goals. Investigating the mechanism through which green technology innovation (GTI) affects EEE and understanding the role of environmental regulation (ER) in this process provides a theoretical basis for efficient utilization of GTI and ER. This study employs a Dynamic Spatial Durbin Model and utilizes panel data from 2003 to 2017 for 30 Chinese provinces to examine the impact of GTI on EEE in the presence of ER. The empirical results reveal: (1) GTI has a U-shaped impact on EEE, primarily driven by SubGI. (2) GTI’s influence on EEE is predominantly reflected in PTE, also stemming from SubGI. (3) The interaction term between ER and GTI is 0.0022, while the GTI coefficient is − 0.0741, and the GTI quadratic term coefficient is 0.0007, all statistically significant. This implies that ER mitigates the negative impact of GTI on EEE while strengthening its positive effect. These findings provide empirical evidence and policy insights for more effectively utilizing GTI and ER to enhance EEE and achieve energy conservation and emissions reduction goals.

China's glacier water resources (GWRs) are not only indispensable suppliers of fresh water for humans living in large domestic areas but also affect the water supply to downstream neighbouring countries. Therefore, it is crucial to systematically evaluate the spatiotemporal (mis-) matches between the supply and demand potentials of China's GWRs and the combined supply and demand effects in the 21st century to enable regional sustainable development. To facilitate such research, in this study, we first regionalized the importance of China's GWRs in terms of the supply potential and downstream human dependence to reveal the spatial (mis-) matches between supply and demand potentials. Then, changes in the service potential of glacier meltwater and in population dynamics, as well as their temporal (mis-) matches and associated opportunities and risks, were further assessed at the river basin scale. The results showed that GWR plays an important role in 4 of 16 macroscale glacier-fed basins (i.e., Tarim, Junggar, Ili, and Zangxi) and 11 of 37 subbasins within the China region due to higher supply potential and demand potential in those basins. The importance of China's GWRs increases dramatically when taking the demand potential of downstream countries into account, especially in the Ganges and Indus river basins. The peaks in meltwater runoff from the most glacierized basins of the eastern Tianshan Mountains, eastern Qilian Mountains, and southeastern Tibetan Plateau of China occur slightly earlier than the projected peak population (around 2030) under the mid-range Shared Socioeconomic Pathway (SSP245), leading to a compound risk in terms of decreasing meltwater supply and increasing human dependence at the end of the 2020s. However, the peak meltwater is expected to occur later than the peak population in the Tarim, Qiangtang Plateau, and Qaidam basins. The opportunities offered by the increase in meltwater can relieve the water resource pressure for those populations under water-stressed conditions. Greater attention should also be paid to water shortage risks in the transboundary river basins, especially in the Indus and Ganges basins, because the peak meltwater within China is generally expected to occur sooner than the projected peak population of downstream countries. This study provides an effective planning and decision-making basis for the full utilization of China's GWRs and adaptation when glacier runoff declines.

Abstract Sand and Dust Storms (SDS) pose considerable health risks worldwide. Previous studies only indicated risk of SDS on overall mortality. This nationwide multicenter time-series study aimed to examine SDS-associated mortality risks extensively. We analyzed 1,495,724 deaths and 2024 SDS events from 1 February to 31 May (2013–2018) in 214 Chinese counties. The excess mortality risks associated with SDS were 7.49% (95% CI: 3.12–12.05%), 5.40% (1.25–9.73%), 4.05% (0.41–7.83%), 3.45% (0.34–6.66%), 3.37% (0.28–6.55%), 3.33% (0.07–6.70%), 8.90% (4.96–12.98%), 12.51% (6.31–19.08%), and 11.55% (5.55–17.89%) for ischemic stroke, intracerebral hemorrhagic stroke, hypertensive heart disease, myocardial infarction, acute myocardial infarction, acute ischemic heart disease, respiratory disease, chronic lower respiratory disease, and chronic obstructive pulmonary disease (COPD), respectively. SDS had significantly added effects on ischemic stroke, chronic lower respiratory disease, and COPD mortality. Our results suggest the need to implement public health policy against SDS.

Abstract Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with pancreatic injury in HTGP and the mechanism remains unclear. Here, we observe lower diversity of gut microbiota and absence of beneficial bacteria in HTGP patients. In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from HTGP patients recruits neutrophils and increases neutrophil extracellular traps (NETs) formation that exacerbates pancreatic injury and systemic inflammation. We find that decreased abundance of Bacteroides uniformis in gut microbiota impairs taurine production and increases IL-17 release in colon that triggers NETs formation. Moreover, Bacteroides uniformis or taurine inhibits the activation of NF-κB and IL-17 signaling pathways in neutrophils which harness NETs and alleviate pancreatic injury. Our findings establish roles of endogenous Bacteroides uniformis-derived metabolic and inflammatory products on suppressing NETs release, which provides potential insights of ameliorating HTGP through gut microbiota modulation.

Probiotics provide health benefits and are used as feed supplements as an alternative prophylactic strategy to antibiotics. However, the effects of Bacillus-based probiotics containing more than two strains when supplemented to pigs are rarely elucidated. SOLVENS (SLV) is a triple-strain Bacillus-based probiotic. In this study, we investigate the effects of SLV on performance, immunity, intestinal morphology, and microbial community in piglets. A total of 480 weaned pigs [initial body weight (BW) of 8.13 ± 0.08 kg and 28 days of age] were assigned to three treatments in a randomized complete block design: P0: basal diet (CON); P200: CON + 200 mg SLV per kg feed (6.5 × 108 CFU/kg feed); and P400: CON + 400 mg SLV per kg feed (1.3 × 109 CFU/kg feed). Each treatment had 20 replicated pens with eight pigs (four male/four female) per pen. During the 31 d feeding period (Phase 1 = wean to d 14, Phase 2 = d 15 to 31 after weaning), all pigs were housed in a temperature-controlled nursery room (23 to 25 °C). Feed and water were available ad libitum. The results showed that the pigs in the P400 group increased (p < 0.05) average daily gain (ADG) in phase 2 and tended (p = 0.10) to increase ADG overall. The pigs in the P200 and P400 groups tended (p = 0.10) to show improved feed conversion ratios overall in comparison with control pigs. The pigs in the P200 and P400 groups increased (p < 0.05) serum immunoglobulin A, immunoglobulin G, and haptoglobin on d 14, and serum C-reactive protein on d 31. The pigs in the P200 group showed an increased (p < 0.01) villus height at the jejunum, decreased (p < 0.05) crypt depth at the ileum compared with other treatments, and tended (p = 0.09) to have an increased villus–crypt ratio at the jejunum compared with control pigs. The pigs in the P200 and P400 groups showed increased (p < 0.05) goblet cells in the small intestine. Moreover, the pigs in the P400 group showed down-regulated (p < 0.05) interleukin-4 and tumor necrosis factor-α gene expressions, whereas the pigs in the P400 group showed up-regulated occludin gene expression in the ileum. These findings suggest that SLV alleviates immunological reactions, improves intestinal microbiota balance, and reduces weaning stress in piglets. Therefore, SOLVENS has the potential to improve health and performance for piglets.

This paper address the performance optimization of the battery heat sink module by analyzing the lattice structure of the battery heat sink module through in-depth modeling and simulation, and combining the laser powder bed fusion (LPBF)-forming technology with mechanical and corrosion resistance experiments for a comprehensive study. It is found that the introduction of the lattice skeleton significantly improves the thermal conductivity of the phase change material (PCM), realizing the efficient distribution and fast transfer of heat in the system. At the same time, the lattice skeleton makes the heat distribution in the heat exchanger more uniform, improves the utilization rate of the PCM, and helps to maintain the stability of the cell temperature. In addition, the melting of PCM in the lattice heat exchanger is more uniform, thus maximizing its latent heat capacity. In summary, by optimizing the lattice structure and introducing the lattice skeleton, this study successfully improves the performance of the battery heat dissipation system, which provides a strong guarantee for the high efficiency and stable operation of the battery, and provides new ideas and references for the development of the battery heat dissipation technology.

This study considers the problem of controlling multi-unmanned aerial vehicles (UAVs) to consistently track a non-cooperative ground target with uncertain motion in a hostile environment with obstacles. An active information acquisition (AIA) problem is formulated to minimize the uncertainty of the target tracking task. The uncertain motion of the target is represented as a Wiener process. First, we optimize the configuration of the UAV swarm considering the collision avoidance, horizontal field of view (HFOV), and communication radius to calculate the reference trajectories of the UAVs. Next, a novel algorithm called Constrained Iterative Linear Quadratic Gaussian (CILQG) is introduced to track the reference trajectory. The target’s state with uncertainty and the UAV state are described as beliefs. The CILQG algorithm utilizes the Unscented Transform to propagate the belief regarding the UAVs’ motions, while also accounting for the impact of navigation errors on the target tracking process. The estimation error of the target position of the proposed method is under 4 m, and the error of tracking the reference trajectories is under 3 m. The estimation error remains unchanged even in the presence of obstacles. Therefore, this approach effectively deals with the uncertainties involved and ensures accurate tracking of the target.

Backgrounds: Sleep disturbances are prevalent among elderly individuals. While polysomnography (PSG) serves as the gold standard for sleep monitoring, its extensive setup and data analysis procedures impose significant costs and time constraints, thereby restricting the long-term application within the general public. Our laboratory introduced an innovative biomarker, utilizing artificial intelligence algorithms applied to PSG data to estimate brain age (BA), a metric validated in cohorts with cognitive impairments. Nevertheless, the potential of exercise, which has been a recognized means of enhancing sleep quality in middle-aged and older adults to reduce BA, remains undetermined. Methods: We conducted an exploratory study to evaluate whether 12 weeks of moderate-intensity exercise can improve cognitive function, sleep quality, and the brain age index (BAI), a biomarker computed from overnight sleep electroencephalogram (EEG), in physically inactive middle-aged and older adults. Home wearable devices were used to monitor heart rate and overnight sleep EEG over this period. The NIH Toolbox Cognition Battery, in-lab overnight polysomnography, cardiopulmonary exercise testing, and a multiplex cytokines assay were employed to compare pre- and post-exercise brain health, exercise capacity, and plasma proteins. Results: In total, 26 participants completed the initial assessment and exercise program, and 24 completed all procedures. Data are presented as mean [lower 95% CI of mean, upper 95% CI of mean]. Participants significantly increased maximal oxygen consumption (Pre: 21.11 [18.98, 23.23], Post 22.39 [20.09, 24.68], mL/kg/min; effect size: −0.33) and decreased resting heart rate (Pre: 66.66 [63.62, 67.38], Post: 65.13 [64.25, 66.93], bpm; effect size: −0.02) and sleeping heart rate (Pre: 64.55 [61.87, 667.23], Post: 62.93 [60.78, 65.09], bpm; effect size: −0.15). Total cognitive performance (Pre: 111.1 [107.6, 114.6], Post: 115.2 [111.9, 118.5]; effect size: 0.49) was significantly improved. No significant differences were seen in BAI or measures of sleep macro- and micro-architecture. Plasma IL-4 (Pre: 0.24 [0.18, 0.3], Post: 0.33 [0.24, 0.42], pg/mL; effect size: 0.49) was elevated, while IL-8 (Pre: 5.5 [4.45, 6.55], Post: 4.3 [3.66, 5], pg/mL; effect size: −0.57) was reduced. Conclusions: Cognitive function was improved by a 12-week moderate-intensity exercise program in physically inactive middle-aged and older adults, as were aerobic fitness (VO2max) and plasma cytokine profiles. However, we found no measurable effects on sleep architecture or BAI. It remains to be seen whether a study with a larger sample size and more intensive or more prolonged exercise exposure can demonstrate a beneficial effect on sleep quality and brain age.

Abstract To rescue ischemic myocardium from progressing to myocardial infarction, timely identification of the infarct size and reperfusion is crucial. However, fast and accurate identification, as well as the targeted protection of injured cardiomyocytes following ischemia/reperfusion (I/R) injury, remain significantly challenging. Here, a near infrared heptamethine dye IR‐780 is shown that has the potential to quickly monitor the area at risk following I/R injury by selectively entering the cardiomyocytes of the at‐risk heart tissues. Preconditioning with IR‐780 or timely IR‐780 administration before reperfusion significantly protects the heart from ischemia and oxidative stress‐induced cell death, myocardial remodeling, and heart failure in both rat and pig models. Furthermore, IR‐780 can directly bind to F0F1‐ATP synthase of cardiomyocytes, rapidly decrease the mitochondrial membrane potential, and subsequently slow down the mitochondrial energy metabolism, which induces the mitochondria into a “quiescent state” and results in mitochondrial permeability transition pore inhibition by preventing mitochondrial calcium overload. Collectively, the findings show the feasibility of IR‐780‐based imaging and protection strategy for I/R injury in a preclinical context and indicate that moderate mitochondrial function depression is a mode of action that can be targeted in the development of cardioprotective reagents.

Bacillus spp. are often used as probiotics; however, they can be infected by phages, leading to significant economic losses. Biocidal and thermal treatments are considered rapid and effective methods for controlling microbial contamination. To prevent viral contamination in industrial dairy production, the impact of temperature and biocides on the viability of Bacillus methylotrophic phage BM-P1 was assessed. The results demonstrated that reconstituted skim milk (RSM) as a medium showed the most effective protective effect on phage BM-P1. Treatment at 90°C for 5 min or 72°C for 10 min inactivated it to nondetectable levels from the initial titer of 7.19 ± 0.11 log, regardless of the culture medium. Sodium hypochlorite exhibited the best inactivating effect, which could reduce the phage titer below the detection level in 4 min at 50 ppm. Additionally, treatment with 75% ethanol for 20 min or 50% isopropanol for 30 min could achieve inactivation to nondetectable levels. The inactivating effect of peracetic acid was limited; even when treated at the highest concentration (0.45%) for 60 min, only a 2.47 ± 0.17 log reduction was observed. This study may provide some theoretical basis and data support for establishing measures against Bacillus spp. phages.

IntroductionIn recent years, growing concern has emerged regarding the mental health and well-being of college students who confront numerous challenges and transitions during their higher education journey. This research aims to investigate the influence of positive childhood experiences on the adaptability of college students and the underlying mechanisms.MethodsA cross-sectional survey was conducted with 5,787 college students from Chinese universities. Participants completed an online questionnaire assessing positive childhood experiences, self-esteem, the number of siblings, and China college students’ adjustment.ResultsThe results revealed that positive childhood experiences positively predicted the adjustment of China college students, with self-esteem playing a mediating role in this positive effect. Moreover, siblings played an antagonistic moderating role in the positive effect of positive childhood experiences on China college students’ adjustment.DiscussionIt is recommended to enhance positive childhood experiences, improve self-esteem, and provide additional care and support to students from multi-sibling families to enhance China college students’ adjustment.

Abstract Histone deacetylase 6 (HDAC6) is one of the key histone deacetylases (HDACs) that regulates various cellular functions including clearance of misfolded protein and immunological responses. Considerable evidence suggests that HDAC6 is closely related to amyloid and tau pathology, the two primary hallmarks of Alzheimer's disease (AD). It is still unclear whether HDAC6 expression changes with amyloid deposition in AD during disease progression or HDAC6 may be regulating amyloid phagocytosis or neuroinflammation or other neuropathological changes in AD. In this work, the pathological accumulation of HDAC6 in AD brains over age as well as the relationship of its regulatory activity ‐ with amyloid pathogenesis and pathophysiological alterations is aimed to be enlightened using the newly developed HDAC6 inhibitor (HDAC6i) PB118 in microglia BV2 cell and 3D‐AD human neural culture model. Results suggest that the structure‐based rational design led to biologically compelling HDAC6i PB118 with multiple mechanisms that clear Aβ deposits by upregulating phagocytosis, improve tubulin/microtubule network by enhancing acetyl α‐tubulin levels, regulate different cytokines and chemokines responsible for inflammation, and significantly reduce phospho‐tau (p‐tau) levels associated with AD. These findings indicate that HDAC6 plays key roles in the pathophysiology of AD and potentially serves as a suitable pharmacological target through chemical biology‐based drug discovery in AD.

Limosilactobacillus (L.) fermentum is widely utilized for its beneficial properties, but lysogenic phages can integrate into its genome and can be induced to enter the lysis cycle under certain conditions, thus accomplishing lysis of host cells, resulting in severe economic losses. In this study, a lysogenic phage, LFP03, was induced from L. fermentum IMAU 32510 by UV irradiation for 70 s. The electron microscopy showed that this phage belonged to Caudoviricetes class. Its genome size was 39,556 bp with a GC content of 46.08%, which includes 20 functional proteins. Compared with other L. fermentum phages, the genome of phage LFP03 exhibited deletions, inversions and translocations. Biological analysis showed that its optimal multiplicity of infection was 0.1, with a burst size of 133.5 ± 4.9 PFU/infective cell. Phage LFP03 was sensitive to temperature and pH value, with a survival rate of 48.98% at 50 °C. It could be completely inactivated under pH 2. The adsorption ability of this phage was minimally affected by temperature and pH value, with adsorption rates reaching 80% under all treated conditions. Divalent cations could accelerate phage adsorption, while chloramphenicol expressed little influence. This study might expand the related knowledge of L. fermentum phages, and provide some theoretical basis for improving the stability of related products and establishing phage control measures.

Abstract The infertile electromagnetic (EM) attenuating behavior of carbon material makes the improvement of its performance remain a significant challenge. Herein, a facile and low‐cost strategy radically distinct from the prevalent approaches by constructing polar covalent bonds between sp2‐hybridized and sp3‐hybridized carbon atoms to introduce strong dipolar polarization is proposed. Through customizing and selectively engineering the N moieties conjugated with carbon rings, the microstructure of the as‐synthesized 2D nanosheet is gradually converted with the partial transition from sp3 carbons to sp2 carbons, where the electric dipoles between them are also tuned. Supported by the DFT calculations, a progressively enhanced sp2─sp3 C─C dipolar polarization is caused by this controllable structure evolution, which is demonstrated to contribute dominantly to the total dielectric loss. By virtue of this unduplicated loss behavior, a remarkable effective absorption bandwidth (EAB) beyond ‐10 dB of 8.28 GHz (2.33 mm) and an ultrawide EAB beyond ‐5 dB of 13.72 GHz (4.93 mm) are delivered, which upgrade the EM performance of carbon material to a higher level. This study not only demonstrates the huge perspective of sp2─sp3‐hybridized carbon in EM elimination but also gives pioneering insights into the carbon–carbon polarization mechanism for guiding the development of advanced EM absorption materials.

Abstract Adoptive T‐cell therapy (ACT), which is an important type of live cell therapy, has achieved unprecedented success in treating hematological malignancies. Recent studies have shown that ACT is also a promising treatment for solid tumors. Visualizing the in vivo fates (distribution, homing, infiltration, proliferation, and exhaustion) of the immune cells used for ACT (ACT immune cells) is of great importance to promote basic research and clinical translation of ACT. Optical imaging techniques, including bioluminescence, fluorescence, and photoacoustic imaging, have the advantages of high sensitivity, high spatiotemporal resolution, minimal exposure to harmful radiation, and simple instrumentation. Recently, various types of optical imaging probes, including bioluminescence, fluorescence, and photoacoustic imaging probes, have been used to visualize ACT immune cells in vivo and evaluate the molecular mechanism, efficacy, and side effects of ACT. In this review, the optical imaging probes and labeling methods that have been used for in vivo visualization of ACT immune cells are summarized, and the opportunities and challenges of using optical imaging to visualize ACT immune cells in vivo are discussed.