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Abstract Background Osteoporosis is characterized by low systemic bone mineral content and destruction of bone microarchitecture. Promoting bone regeneration and reversing its loss by infusion of exogenous bone marrow mesenchymal stem cells (BMSCs) is a potentially effective treatment for osteoporosis. However, their limited migration to target organs reduces the therapeutic effect of the cells. Stromal cell-derived factor 1 (SDF1) is a chemokine that induces targeted cell migration through the SDF1/CXCR4 (C-X-C chemokine receptor 4) axis and can induce migration of exogenous mesenchymal stem cells to sites of high SDF1 concentration. There are no studies on BMSCs overexpressing SDF1 (SDF1-BMSCs) in osteoporotic mice in vivo. We aimed to investigate if the increased SDF1 concentration facilitated cell migration to the bone. Methods We used lentivirus to construct BMSCs overexpressing SDF1 or knocking down CXCR4. We verified the proliferation ability of the cells in vitro using Cell Counting Kit-8 (CCK8) and 5-Bromodeoxyuridinc (BrdU), the migration ability of the cells using Transwell, and the osteogenic and lipogenic ability of the cells using osteogenic and lipogenic induction solutions. In in vivo experiments, we induced osteoporosis in 72 female mice by ovariectomy and injected different groups of cells via the tail vein. Femoral tissue samples were collected for a fixed time, and the osteogenic and homing abilities of the cells were verified by MicroCT and tissue section staining. Results We successfully demonstrated that high expression of SDF1 promoted cell proliferation and migration in vitro, without affecting their cell differentiation ability. In an ovariectomized mouse model, SDF1-BMSCs were more likely to be home to the femur than the BMSCs, had a better pro-osteogenic ability, and had higher expression of Wnt-1. Blocking the SDF1/CXCR4 axis reduced the homing of exogenous mesenchymal stem cells (MSCs) to the femur and their osteogenic capacity. Conclusions SDF1-BMSCs can further promote bone formation by increasing the number of cells homing to the femur in osteoporotic mice. Our study shows that stem cells can promote their proliferation and home to the femur via the SDF1/CXCR4 axis and further help bone formation via Wnt-1 signaling.

Metabolizing ellagic acid (EA) to urolithin A with numerous bioactivities significantly improve the nutritional value of food rich in EA. In the present study, Streptococcus thermophilus FUA329 was applied to prepare pomegranate juice yogurt. The best process formula was investigated through single-factor experiments and response surface methodology. With S. thermophilus CGMCC1.8748 as control, the viability of strain, rheological properties and antioxidant activity of pomegranate juice yogurt fermented with strain FUA329 were evaluated. The content of urolithin A in pomegranate juice yogurt fermented with strain FUA329 were analyzed by high-performance liquid chromatography. The results showed that the optimal fermentation conditions for preparing pomegranate juice yogurt by S. thermophilus FUA329 were 15.79% pomegranate juice content, 7.08% sucrose content and 3.04% starter inoculum size, fermentation at 37 ℃ for 7 h and comprehensive sensory score was 79.4 points. Under the optimal conditions, the results of basic indicators showed that yogurt acidity was (82.5±1.3)°T, whey precipitation was 9.6%±0.97%, color difference was 68.17±2.75, bacterial activity was 2.01±0.31 (OD600). In terms of antioxidant activity, DPPH radical, ABTS+ radical and superoxide anion radical scavenging rates of fermented pomegranate juice yogurt by strain FUA329 were 82.87%±1.48%, 88.20%±2.10% and 76.92%±1.02%, respectively, which was significantly better than plain yogurt fermented by strain FUA329 and pomegranate juice yogurt fermented by S. thermophilus CGMCC1.8748. In addition, urolithin A content was 3.31 μmol/L in fermented pomegranate juice yogurt by strain FUA329 after 7 h. The results of this study would provide a theoretical basis for fermenting a functional pomegranate juice yogurt, and lay a foundation for the development and utilization of S. thermophilus FUA329.

In order to evaluate the effect of Streptococcus thermophilus fermentation on green tea extract and its storage characteristics, this study used Streptococcus thermophilus FUA329 and S. thermophilus ST1.8748 (control group) to conduct experiments on green tea extracts. After fermentation and storage at 4 ℃ for 0, 30, 60, 120 and 180 d, pH, viable bacterial count, tea polyphenol content, ellagic acid content, and urolithin A content were used as the main evaluation indicators, combined with anti-oxidation activity to evaluate the storage quality of fermented green tea extract. The results showed that compared with the S. thermophilus ST1.8748 control group, the pH of S. thermophilus FUA329 fermented green tea extract during the storage period was between 5.39 and 5.71. The highest number of viable bacteria at 48 h was 9.97×108 CFU/mL. The content of tea polyphenols gradually decreased and the ellagic acid content tended to be stable. Urolithin A was produced at 48 h, and its concentration was 0.664 μmol/L. The antioxidant activity was always maintained at a high level. In summary, S. thermophilus FUA329 fermented green tea extract can significantly delay the quality decline and nutrient loss of green tea extract during storage.

Abstract Background Autism spectrum disorder (ASD) poses a significant challenge due to its diverse impact on individuals, emphasizing the need for personalized treatment plans. The financial burden of ASD-related healthcare is substantial, necessitating a comprehensive understanding of its prevalence and evolving trends. Methods This study aims to analyze the prevalence and trends of ASD, treatment patterns, gender differences, and racial-ethnic disparities in the United States from 2017 to 2020, utilizing nationally representative data from the National Survey of Children's Health (NSCH). The NSCH, a leading annual national survey, provided rich data on child health. A total of 108,142 participants aged 3–17 years were included, with ASD prevalence assessed based on self-reported diagnoses. Results Between 2017 and 2020, ASD prevalence in children aged 3–17 was 2.94% (95% confidence interval: 2.68–3.18). Significant disparities were observed: older age and male gender correlated with higher prevalence, while family income-to-poverty ratio and insurance coverage influenced prevalence. Racial/ethnic disparities existed, with Hispanics showing the highest prevalence. Treatment trends showed stability overall, but age influenced behavioral and medication interventions. The prevalence remained stable from 2017 to 2020, with variations in age groups and a significant increase among non-Hispanic Whites. Conclusions This study highlights a higher but stable overall ASD prevalence, with nuanced disparities among different demographic groups. Gender differences persist, emphasizing the need for tailored interventions. Racial-ethnic disparities call for targeted healthcare strategies. The stability in treatment trends underscores the persistent challenge of addressing core ASD symptoms.

Abstract Osteotomy can correct kyphosis, restore the spinal sequence, and restore the healthy appearance of a patient. However, the aorta is stretched during pedicle subtraction osteotomy (PSO), and some surgeons are concerned about aortic injury. We used finite element analysis to construct an aortic model to simulate hemodynamic changes during osteotomy. 16 patients with ankylosing spondylitis kyphosis who had undergone a two-level osteotomy at the L1 and L3 levels was included in this study. Aortic computed tomography angiography (CTA) was performed, and a 3D image model was constructed. The length, transverse diameter, and curvature of the aorta were used to evaluate morphological changes. Finite element analysis was used to analyze the changes in aortic fluid dynamics. Blood pressure, wall shear stress, and blood flow velocity were compared pre- and postoperatively. The overall length of the aorta before surgery was 424.3 ± 42.9 mm, and the overall length of the aorta after surgery was 436.2 ± 54.8 mm. The aortic curvature decreased from 0.27 ± 0.13 to 0.17 ± 0.09. The mean transverse diameter of the aorta did not change (19.3 ± 6.6 vs. 19.2 ± 7.4 mm, P > 0.05). The blood flow velocity (2.8 ± 1.1 vs. 1.5 ± 0.8 m/s, P

Abstract Denticleless E3 ubiquitin protein ligase homolog (DTL), the substrate receptor of the CRL4A complex, plays a central role in genome stability. Even though the oncogenic function of DTL has been investigated in several cancers, its specific role in hepatocellular carcinoma (HCC) still needs further elucidation. Data from a clinical cohort (n = 209), RNA-sequencing, and public database (TCGA and GEO) were analyzed, indicating that DTL is closely related to patient prognosis and could serve as a promising prognostic indicator in HCC. Functionally, DTL promoted the proliferation, metastasis, and sorafenib resistance of HCC in vitro. In the orthotopic tumor transplantation and tail vein injection model, DTL promoted the growth and metastasis of HCC in vivo. Mechanically, we revealed for the first time that DTL was transcriptionally activated by hypoxia-inducible factor 1α (HIF-1α) under hypoxia and functioned as a downstream effector molecule of HIF-1α. DTL promotes the ubiquitination of SAFB-like transcription modulator (SLTM) and subsequently relieves the transcriptional repression of Notch1. These results suggested that DTL may be a potential biomarker and therapeutic target for HCC.

In response to global carbon neutrality targets, there is an urgent need for large-scale, clean hydrogen production technologies to supplant fossil fuels and underpin the establishment of a ‘hydrogen economy’. The prospect of large-scale on-site green hydrolysis of Mg-based materials for hydrogen production has attracted wide attention. Aiming at the problems of easy formation of inert oxide layer on its surface and the production of Mg(OH)2 to hinder the hydrolysis process, it is urgent to explore efficient, low-cost and green modification strategies. In this work, the green modification strategy for hydrolyzing hydrogen production of Mg-based materials was summarized, and the fast initial kinetics and high hydrogen production rate could be achieved by adjusting hydrolysis medium conditions and modifying Mg-based material. The significance of hydrolytic hydrogen production technology and device development for the realization of Mg-based hydrolytic hydrogen production was evaluated. Meanwhile, this work looks forward to the future direction of hydrogen production modification by hydrolysis of Mg-based alloy, and gradually optimizes the hydrolysis performance of industrial multi-component waste Mg alloy under the premise of green hydrogen production, and proposes the goal of efficient modification of waste Mg alloy, high-quality utilization of seawater, and low-cost and controllable hydrogen production process.

Abstract Some patients with polycystic ovarian syndrome (PCOS) suffered from metabolic syndrome (MetS) including dyslipidemia, hyperinsulinism, but the underlying mechanism is unclear. Although C-terminal Binding Protein 1 (CTBP1) is a transcriptional co-repressor frequently involved in hormone secretion disorders and MetS-associated diseases, the role of CTBP1 in PCOS is rarely reported. In the present study, we found that CTBP1 expression was significantly elevated in primary granulosa cells (pGCs) derived from the PCOS with MetS patients and was positively associated with serum triglyceride, but negatively correlated with serum estradiol (E2) or high-density lipoprotein. Mechanistic study suggested that CTBP1 physically bound to the promoter II of cytochrome P450 family 19 subfamily A member 1 (CYP19A1) to inhibit the aromatase gene transcription and expression, resulting in the reduced E2 synthesis. Moreover, CTBP1 interacted with the phosphorylated SREBP1a at S396 in nuclei, leading to the FBXW7-dependent protein degradation, resulting in the reduced lipid droplets formation in pGCs. Therefore, we conclude that CTBP1 in GCs dysregulates the synthesis of steroid hormones and lipids through suppression of aromatase expression and promotion of SREBP1a protein degradation in PCOS patients, which may offer some fresh insights into the potential pathological mechanism for this tough disease.

Abstract The Hippo-Yes-associated protein (Hippo-YAP) signaling pathway, a conserved pathway that regulates organ size, participates in tumor progression. However, there are few comprehensive analyses of tumor prognosis and immunity. In the present study, TCGA, GTEx, GEO, TIMER2, STRING, GSCA, ImmuCellAI, and other bioinformatics tools were used to reveal the involvement of the Hippo-YAP signaling pathway in the prognosis and immunity of pan-cancers. The obtained results showed that mRNA expression differences of Hippo-YAP pathway genes between normal samples and tumor samples in pan-cancers and some genes (such as TEAD4, MAP4K4, and STK3) might affect the prognosis of patients with skin cutaneous melanoma (SKCM) and pancreatic adenocarcinoma (PAAD). Furthermore, mutation and methylation of the Hippo-YAP signaling pathway genes in normal and primary tumor tissues differ in various cancers (KIRP, BRCA). Additionally, the relationship between the tumor microenvironment, molecular pathways, and the Hippo-YAP pathway indicated that it might lead to a suppressive immune microenvironment that affects the efficacy of immunotherapy. This is a pan-cancer overview of the Hippo-YAP signaling pathway genes, which explores the aberrant expression or mutation of this pathway that regulates the tumor microenvironment and immunotherapy.

Abstract The direct laser writing (DLW) of photoluminescent metal clusters is inspiring intensive research in functional glasses. However, understanding the influence of the host structure on cluster formation and visualizing DLW-induced clusters at the atomic scale remains challenging. In this work, we develop a highly photosensitive fluorophosphate glass through fluorine incorporation. The addition of fluorine establishes a conducive environment for Ag+ ions before DLW and enhances the availability of reducing agents and diffusion pathways during DLW. These advantages facilitate the formation of Ag clusters under low-energy single-pulsed DLW. Increasing laser energy results in a combination of Ag clusters and glasses defect, forming a dot + ring photoluminescent pattern. Atom probe tomography (APT), a technique capable of mapping the elemental spatial distribution and identifying clustering, is employed to gain more information on laser-induced clusters. Comparison of APT results between samples without and with DLW reveals the formation of Ag clusters after laser writing. The design concept and characterization enrich the understanding of Ag cluster behavior in glasses. This knowledge opens the possibility of rational design of clusters confined in glasses and inspires their synthesis for various applications.

Abstract Accurately predicting ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties early in drug development is essential for selecting compounds with optimal pharmacokinetics and minimal toxicity. Existing ADMET-related benchmark sets are limited in utility due to their small dataset sizes and the lack of representation of compounds used in drug discovery projects. These shortcomings hinder their application in model building for drug discovery. To address this issue, we propose a multi-agent data mining system based on Large Language Models that effectively identifies experimental conditions within 14,401 bioassays. This approach facilitates merging entries from different sources, culminating in the creation of PharmaBench. Additionally, we have developed a data processing workflow to integrate data from various sources, resulting in 156,618 raw entries. Through this workflow, we constructed PharmaBench, a comprehensive benchmark set for ADMET properties, which comprises eleven ADMET datasets and 52,482 entries. This benchmark set is designed to serve as an open-source dataset for the development of AI models relevant to drug discovery projects.

Abstract Diabetes mellitus (DM) is a well-documented risk factor of intervertebral disc degeneration (IVDD). The current study was aimed to clarify the effects and mechanisms of NADH: ubiquinone oxidoreductase subunit A3 (NDUFA3) in human nucleus pulposus cells (HNPCs) exposed to high glucose. NDUFA3 was overexpressed in HNPCs via lenti-virus transduction, which were co-treated with high glucose and rotenone (a mitochondrial complex I inhibitor) for 48 h. Cell activities were assessed for cell viability, cell apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) ratio, oxygen consumption rate (OCR) and mitochondrial complexes I activities. High glucose decreased cell viability, increased apoptotic cells, increased ROS production, decreased MMP levels and OCR values in HNPCs in a dose-dependent manner. Rotenone co-treatment augmented the high glucose-induced injuries on cell viability, apoptosis, ROS production and mitochondrial function. NDUFA3 overexpression counteracted the high glucose-induced injuries in HNPCs. HDAC/H3K27ac mechanism was involved in regulating NDUFA3 transcription. NDUFA3 knockdown decreased cell viability and increased apoptotic cells, which were reversed by ROS scavenger N-acetylcysteine. HDAC/H3K27ac-mediated transcription of NDUFA3 protects HNPCs against high glucose-induced injuries through suppressing cell apoptosis, eliminating ROS, improving mitochondrial function and oxidative phosphorylation. This study sheds light on candidate therapeutic targets and deepens the understanding of molecular mechanisms behind DM-induced IVDD.

To determine the promoting effects of enzyme hydrolysis products of Larimichthys polyactis on the proliferation of Streptococcus thermophilus FUA329. The in vitro antioxidant activity of the enzymatic hydrolysis with different molecular weights were determined. Papain was selected for the enzymatic hydrolysis of its by-products on the basis of selecting different enzymes to hydrolyze the processing by-products of Larimichthys polyactis. Taking the proliferative effect of enzymatic degradation products on Streptococcus thermophilus as an indicator of evaluation. The enzymatic hydrolysis conditions were optimized through single factor and response surface methodology. The in vitro antioxidant activity of the hydrolysis products of the by-products of Larimichthys polyactis (HPBL) were determined. The results showed that the best enzymatic hydrolysis conditions included the hydrolysis time, material-liquid ratio and enzyme loading were 5 h, 1:5.1 (w/v) and 2.8% (w/v), respectively. The HPBL prepared under the optimized conditions was separated by ultrafiltration into four fragments, according to the molecular weight: >10000 Da, 5000~10000 Da, 3000~5000 Da,

Cancer stem cells (CSCs) play a pivotal role in tumor initiation, proliferation, metastasis, drug resistance, and recurrence. Consequently, targeting CSCs has emerged as a promising avenue for cancer therapy. Recently, 3-phosphoglycerate dehydrogenase (PHGDH) has been identified as being intricately associated with the regulation of numerous cancer stem cells. Yet, reports detailing the functional regulators of PHGDH that can mitigate the stemness across cancer types are limited. In this study, the novel “molecular glue” LXH-3-71 was identified, and it robustly induced degradation of PHGDH, thereby modulating the stemness of colorectal cancer cells (CRCs) both in vitro and in vivo. Remarkably, LXH-3-71 was observed to form a dynamic chimera, between PHGDH and the DDB1-CRL E3 ligase. These insights not only elucidate the anti-CSCs mechanism of the lead compound but also suggest that degradation of PHGDH may be a more viable therapeutic strategy than the development of PHGDH inhibitors. Additionally, compound LXH-3-71 was leveraged as a novel ligand for the DDB1-CRL E3 ligase, facilitating the development of new PROTAC molecules targeting EGFR and CDK4 degradation.

Abstract MicroRNAs (miRNAs) are a key class of endogenous non-coding RNAs that play a pivotal role in regulating diseases. Accurately predicting the intricate relationships between miRNAs and diseases carries profound implications for disease diagnosis, treatment, and prevention. However, these prediction tasks are highly challenging due to the complexity of the underlying relationships. While numerous effective prediction models exist for validating these associations, they often encounter information distortion due to limitations in efficiently retaining information during the encoding-decoding process. Inspired by Multi-layer Heterogeneous Graph Transformer and Machine Learning XGboost classifier algorithm, this study introduces a novel computational approach based on multi-layer heterogeneous encoder—machine learning decoder structure for miRNA-disease association prediction (MHXGMDA). First, we employ the multi-view similarity matrices as the input coding for MHXGMDA. Subsequently, we utilize the multi-layer heterogeneous encoder to capture the embeddings of miRNAs and diseases, aiming to capture the maximum amount of relevant features. Finally, the information from all layers is concatenated to serve as input to the machine learning classifier, ensuring maximal preservation of encoding details. We conducted a comprehensive comparison of seven different classifier models and ultimately selected the XGBoost algorithm as the decoder. This algorithm leverages miRNA embedding features and disease embedding features to decode and predict the association scores between miRNAs and diseases. We applied MHXGMDA to predict human miRNA-disease associations on two benchmark datasets. Experimental findings demonstrate that our approach surpasses several leading methods in terms of both the area under the receiver operating characteristic curve and the area under the precision-recall curve.

Abstract Background Circulating tumor cells (CTCs) are pivotal in tumor metastasis across cancers, yet their specific role in renal cancer remains unclear. Methods This study investigated C–C motif chemokine ligand 5 (CCL5)'s tumorigenic impact on renal cancer cells and CTCs using bioinformatics, in vivo, and in vitro experiments. It also assessed renal cancer patients' CTCs prognostic value through Lasso regression and Kaplan–Meier survival curves. Results Bioinformatics analysis revealed differential genes focusing on cellular adhesion and migration between CTCs and tumor cells. CCL5 exhibited high expression in various CTCs, correlating with poor prognosis in renal cancer. In 786-O-CTCs, CCL5 enhanced malignancy, while in renal cell carcinoma cell line CAKI-2 and 786-O, it promoted epithelial-mesenchymal transition (EMT) via smad2/3, influencing cellular characteristics. The nude mouse model suggested CCL5 increased CTCs and intensified EMT, enhancing lung metastasis. Clinical results shown varying prognostic values for different EMT-typed CTCs, with mesenchymal CTCs having the highest value. Conclusions In summary, CCL5 promoted EMT in renal cancer cells and CTCs through smad2/3, enhancing the malignant phenotype and facilitating lung metastasis. Mesenchymal-type CTC-related factors can construct a risk model for renal cancer patients, allowing personalized treatment based on metastatic risk prediction.

From the 1950s to the 1970s, China exported 16 foreign aid stadiums, which occupied a considerable proportion of China’s foreign aid construction and stood out due to their unique qualities. This study aims to explore the historical development of these stadiums in the initial period to clarify the development trends of early China’s stadium aid and the main factors influencing it. According to an exploration based on a series of historical studies, qualitative comparative analyses, interviews and case studies, this study reveals that China’s foreign stadium aid transitioned from labour support to design support under the influence of governmental, architectural and additional factors. This study fills a gap in the academic literature, provides new perspectives for current research into China’s foreign aid construction, and provides indispensable supplements for Chinese sports architecture and modern architecture.

Abstract With the rapid growth of social media, fake news (rumors) are rampant online, seriously endangering the health of mainstream social consciousness. Fake news detection (FEND), as a machine learning solution for automatically identifying fake news on Internet, is increasingly gaining the attentions of academic community and researchers. Recently, the mainstream FEND approaches relying on deep learning primarily involves fully supervised fine-tuning paradigms based on pre-trained language models (PLMs), relying on large annotated datasets. In many real scenarios, obtaining high-quality annotated corpora are time-consuming, expertise-required, labor-intensive, and expensive, which presents challenges in obtaining a competitive automatic rumor detection system. Therefore, developing and enhancing FEND towards data-scarce scenarios is becoming increasingly essential. In this work, inspired by the superiority of semi-/self- supervised learning, we propose a novel few-shot rumor detection framework based on semi-supervised adversarial learning and self-supervised contrastive learning, named Detection Yet See Few (DetectYSF). DetectYSF synergizes contrastive self-supervised learning and adversarial semi-supervised learning to achieve accurate and efficient FEND capabilities with limited supervised data. DetectYSF uses Transformer-based PLMs (e.g., BERT, RoBERTa) as its backbone and employs a Masked LM-based pseudo prompt learning paradigm for model tuning (prompt-tuning). Specifically, during DetectYSF training, the enhancement measures for DetectYSF are as follows: (1) We design a simple but efficient self-supervised contrastive learning strategy to optimize sentence-level semantic embedding representations obtained from PLMs; (2) We construct a Generation Adversarial Network (GAN), utilizing random noises and negative fake news samples as inputs, and employing Multi-Layer Perceptrons (MLPs) and an extra independent PLM encoder to generate abundant adversarial embeddings. Then, incorporated with the adversarial embeddings, we utilize semi-supervised adversarial learning to further optimize the output embeddings of DetectYSF during its prompt-tuning procedure. From the news veracity dissemination perspective, we found that the authenticity of the news shared by these collectives tends to remain consistent, either mostly genuine or predominantly fake, a theory we refer to as “news veracity dissemination consistency”. By employing an adjacent sub-graph feature aggregation algorithm, we infuse the authenticity characteristics from neighboring news nodes of the constructed veracity dissemination network during DetectYSF inference. It integrates the external supervisory signals from “news veracity dissemination consistency” to further refine the news authenticity detection results of PLM prompt-tuning, thereby enhancing the accuracy of fake news detection. Furthermore, extensive baseline comparisons and ablated experiments on three widely-used benchmarks demonstrate the effectiveness and superiority of DetectYSF for few-shot fake new detection under low-resource scenarios.

This is an article in the field of mineral processing engineering. In order to accurately grasp the influence of various types of ores on field production, the process mineralogy of various types of ores was systematically and deeply studied by means of chemical analysis and automatic mineral analysis system (AMICS). Based on the process mineralogy, the ore blending scheme was drawn up, and the whole process test was carried out according to the optimal ore blending ratio. The results show that all kinds of ores are lean iron ores with high silicon, low iron and low sulfur and phosphorus. The embedding characteristics of various types of ores are complex, which has a certain influence on the grindability of ores and monomer dissociation. According to the washability test results of various types of ores in the mining area, the comprehensive ore blending ratio is determined as follows: (magnetic ore∶ sub-iron ore∶ eastern red ore∶mixed ore∶ chlorite ore∶ iron carbonate ore) =(25∶25∶25∶10∶10∶5). Through the closed-circuit process of weak magnetic field-strong magnetic field-mixed magnetic fine anion reverse flotation, the comprehensive ore blending obtained good indexes of comprehensive concentrate grade of 66.06%, yield of 34.60%, comprehensive tailings grade of 15.20% and yield of 65.40%.

Abstract Objective Employing whole‐exome sequencing (WES) technology to investigate the etiology of infantile epileptic spasm syndrome (IESS), and determining whether different etiologies exhibit phenotypic variations, while elucidating the potential associated factors, might improve short‐term responses to first‐line treatment. Methods We retrospectively evaluated patients with IESS admitted for treatment between January 2018 and June 2023. Clinical phenotypic differences among etiological classifications and clinical manifestations were analyzed. Variable selection using the best subset method was performed, followed by logistic regression analysis to identify the factors influencing treatment response. Results A total of 577 patients were included; 412 completed trio‐WES. Magnetic resonance imaging abnormalities were detected in 387 patients (67.1%). Patients with etiology as structural abnormalities were likelier to have non‐spasms at the initial seizure onset. A total of 532 patients completed the first‐line treatment; 273 patients received it for the first time at our hospital (initial response rates: 30.1% and 42.1%, respectively). The response group had a lower proportion of early‐onset seizures (≤3 months) than the no‐response group (11.3% vs. 23.7%, p

Abstract Background This study investigates the effectiveness of a self-developed intelligent monitoring system for home-based knee rehabilitation following total knee arthroplasty (TKA). Methods In this randomized controlled trial, 120 patients undergoing TKA were divided using random digit allocation. Preoperative and one-month postoperative assessments of knee function, quality of life, and isometric knee extension strength were conducted with the Intelligent Monitoring System. Patients received group-specific rehabilitation instructions pre-discharge and performed exercises for one month. Results Changes in isometric knee extensor strength on the affected side within one month post-surgery for the brace-monitored rehabilitation group showed a significant decrease three days after surgery compared to one day before surgery. Subsequent measurements taken at postoperative days 5, 7, 14, and 21 indicated a gradual increase in strength, although these increases did not reach statistical significance when compared with previous measurements. One month post-surgery, all groups demonstrated significant improvements in knee joint function and mobility compared to pre-surgery levels. Notably, the brace-monitored group showed statistically significant improvements in 36-Item Short-Form Health Survey (SF-36) scores over the conventional rehabilitation group. Conclusions The Intelligent Monitoring System provides effective real-time monitoring and guidance for home-based knee rehabilitation post-TKA. It significantly enhances knee joint function, isometric knee extension strength, and quality of life shortly after surgery compared to traditional rehabilitation methods. This system offers a promising approach for improving postoperative recovery in TKA patients. Trial registration This study was approved by the Medical Ethics Committee of Xiangya Hospital, Central South University (Ethics Approval Number 202209008-2). It was registered with the China Clinical Trial Registry, a primary registry of the World Health Organization’s International Clinical Trials Registry Platform (Registration Number ChiCTR2300068852).

Abstract As cross‐shelf gradients of most properties are typically much steeper than those in the alongshore direction, transport across isobaths tends to be inhibited, particularly at oceanic fronts where cross‐shelf gradients are markedly pronounced. Consequently, variations in cross‐shelf gradients may exert a significant influence on offshore transport; however, this influence is not yet well understood. This study employs reconstructed daily suspended sediment concentration (SSC) data from the Yellow Sea's offshore region to investigate the dynamics of offshore transport. Our analysis on an interannual scale shows that offshore SSC correlates more with temperature gradients at the oceanic front than with winter storms, despite the latter's vital role in causing frontal instability. The observed increase in offshore transport over the past two decades is likely connected to Kuroshio Current warming, which has strengthened the horizontal density gradient at the oceanic front, driving the strengthened offshore transport of coastal sediments during instability episodes.

Abstract Background Mitochondria play crucial roles in the growth, development, and adaptation of plants. Blackcurrant (Ribes nigrum L.) stands out as a significant berry species due to its rich nutritional profile, medicinal properties, and health benefits. Despite its importance, the mitochondrial genome of blackcurrant remains unassembled. Results This study presents the first assembly of the mitochondrial genome of R. nigrum in the Grossulariaceae family. The genome spans 450,227 base pairs (bp) and encompasses 39 protein-coding genes (PCGs), 19 transfer RNAs (tRNAs), and three ribosomal RNAs (rRNAs). Protein-coding regions constitute 8.88% of the entire genome. Additionally, we identified 180 simple sequence repeats, 12 tandem repeats, and 432 pairs of dispersed repeats. Notably, the dispersed sequence R1 (cotig3, 1,129 bp) mediated genome recombination, resulting in the formation of two major conformations, namely master and double circles. Furthermore, we identified 731 C-to-U RNA editing sites within the PCGs. Among these, cox1-2, nad1-2, and nad4L-2 were associated with the creation of start codons, whereas atp6-718 and rps10-391 were linked to termination codons. We also detected fourteen plastome fragments within the mitogenome, constituting 1.11% of the total length. Phylogenetic analysis suggests that R. nigrum might have undergone multiple genomic reorganization and/or gene transfer events, resulting in the loss of two PCGs (rps2 and rps11) during its evolutionary history. Conclusions This investigation unveils the molecular characteristics of the R. nigrum mitogenome, shedding light on its evolutionary trajectory and phylogenetic implications. Furthermore, it serves as a valuable reference for evolutionary research and germplasm identification within the genus.

Abstract In the last decade, laboratory-scale single-junction perovskite solar cells have achieved a remarkable power conversion efficiency exceeding 26.1%. However, the transition to industrial-scale production has unveiled a significant efficiency gap. The central challenge lies in the difficulty of achieving uniform, high-quality perovskite films on a large scale. To tackle this issue, various innovative strategies for manipulating crystallization have emerged in recent years. Based on an in-depth fundamental understanding of the nucleation and growth mechanisms in large-area perovskite films prepared through blade/slot-die coating methods, this review offers a critical examination of crystallization manipulation strategies for large-area perovskite solar modules. Lastly, we explore future avenues aimed at enhancing the efficiency and stability of large-area PSMs, thereby steering the field toward commercially viable applications.

Abstract The function of proteins depends on their correct structure and proper dynamics. Understanding the dynamics of target proteins facilitates drug design and development. However, dynamic information is often hidden in the spatial structure of proteins. It is important but difficult to identify the specific residues that play a decisive role in protein dynamics. Here, we report that a critical glycine residue (Gly463) dominates the motion of threonyl-tRNA synthetase (ThrRS) and the sensitivity of the enzyme to antibiotics. Obafluorin (OB), a natural antibiotic, is a novel covalent inhibitor of ThrRS. The binding of OB induces a large conformational change in ThrRS. Through five crystal structures, biochemical and biophysical analyses, and computational simulations, we found that Gly463 plays an important role in the dynamics of ThrRS. Mutating this flexible residue into more rigid residues did not damage the enzyme’s three-dimensional structure but significantly improved the thermal stability of the enzyme and suppressed its ability to change conformation. These mutations cause resistance of ThrRS to antibiotics that are conformationally selective, such as OB and borrelidin. This work not only elucidates the molecular mechanism of the self-resistance of OB-producing Pseudomonas fluorescens but also emphasizes the importance of backbone kinetics for aminoacyl-tRNA synthetase-targeting drug development.

Abstract Bioengineering and regenerative medicine strategies are promising for the treatment of vascular diseases. However, current limitations inhibit the ability of these approaches to be translated to clinical practice. Here we summarize some of the big bottlenecks that inhibit vascular regeneration in the disease applications of aortic aneurysms, stroke, and peripheral artery disease. We also describe the bottlenecks preventing three-dimensional bioprinting of vascular networks for tissue engineering applications. Finally, we describe emerging technologies and opportunities to overcome these challenges to advance vascular regeneration.

Abstract Mucus injury associated with goblet cell (GC) depletion constitutes an early event in inflammatory bowel disease (IBD). Using single-cell sequencing to detect critical events in mucus dysfunction, we discover that the Kazal-type serine protease inhibitor SPINK4 is dynamically regulated in colitic intestine in parallel with disease activities. Under chemically induced colitic conditions, the grim status in Spink4-conditional knockout mice is successfully rescued by recombinant murine SPINK4. Notably, its therapeutic potential is synergistic with existing TNF-α inhibitor infliximab in colitis treatment. Mechanistically, SPINK4 promotes GC differentiation using a Kazal-like motif to modulate EGFR-Wnt/β-catenin and -Hippo pathways. Microbiota-derived diacylated lipoprotein Pam2CSK4 triggers SPINK4 production. We also show that monitoring SPINK4 in circulation is a reliable noninvasive technique to distinguish IBD patients from healthy controls and assess disease activity. Thus, SPINK4 serves as a serologic biomarker of IBD and has therapeutic potential for colitis via intrinsic EGFR activation in intestinal homeostasis.

Abstract Objective Through a randomized controlled trial on older adults with sarcopenia, this study compared the training effects of an AI-based remote training group using deep learning-based 3D human pose estimation technology with those of a face-to-face traditional training group and a general remote training group. Methods Seventy five older adults with sarcopenia aged 60–75 from community organizations in Changchun city were randomly divided into a face-to-face traditional training group (TRHG), a general remote training group (GTHG), and an AI-based remote training group (AITHG). All groups underwent a 3-month program consisting of 24-form Taichi exercises, with a frequency of 3 sessions per week and each session lasting 40 min. The participants underwent Appendicular Skeletal Muscle Mass Index (ASMI), grip strength, 6-meter walking pace, Timed Up and Go test (TUGT), and quality of life score (QoL) tests before the experiment, during the mid-term, and after the experiment. This study used SPSS26.0 software to perform one-way ANOVA and repeated measures ANOVA tests to compare the differences among the three groups. A significance level of p 0.05). The same was in post-term tests (p > 0.05). Conclusion Compared to the pre-experiment, there was no significant difference at the post- experiment in the recovery effects on the muscle quality, physical activity ability, and life quality of patients with sarcopenia between the AI-based remote training group and the face-to-face traditional training group. 3D pose estimation is equally as effective as traditional rehabilitation methods in enhancing muscle quality, functionality and life quality in older adults with sarcopenia. Trial registration The trial was registered in ClinicalTrials.gov (NCT05767710).

Fertilizer application plays a crucial role in the decomposition of white poplar leaf litter and cycling of nutrients within forest ecosystems. The impact of various fertilizer additions on white poplar leaf litter and nutrient cycling is poorly understood. In this study, seven treatments were conducted at the following levels: Control (CK), no adding mineral fertilizers, N fertilization (+N), N and P fertilization (+NP), N, P, K fertilization (+NPK), P, K (+PK), manure fertilizer (+MF), and bird fertilizers (+BF) in a white poplar plantation in Qadis district, and used the litterbag techniques to measure litter mass remaining. The main objectives of our study were: (1) to explore the response of white poplar leaf litter decomposition to various fertilizers and accelerate the decomposition process; (2) to examine the relationship between C, N, and P concentration and their stoichiometric characteristic in leaf litter and soil. In this investigation, our results showed that white poplar leaf litter was significantly affected by fertilizers, and the decomposition process was greatly accelerated with + MF, +NPK, and + BF. The decay rate constant k (year −1) shows the decomposition rate of white poplar leaf litter as follows: +MF > +NPK > +BF > +PK > +NP > +N > CK (0.56, 0.53, 0.52, 0.51,0.51,0.5, and 0.46). Soil nutrients N, P and K increased significantly during the decomposition time with + MF, +NPK, and + BF, respectively, while C:N, C:P, and N:P ratios were highest in the white poplar leaf litter, and lowest in soil, we observed significant association between nutrients concentrations in soil and white poplar leaf and their stoichiometric. This current study concluded that adding + MF, +NPK and + BF fertilizers might be the preferred management option as they provided potentially beneficial changes in leaf litter decomposition and increased nutrient concentration. The data obtained will be a valuable reference for fertilization management strategies in forest ecosystems.

In situ monitoring of bone regeneration enables timely diagnosis and intervention by acquiring vital biological parameters. However, an existing gap exists in the availability of effective methodologies for continuous and dynamic monitoring of the bone tissue regeneration process, encompassing the concurrent visualization of bone formation and implant degradation. Here, we present an integrated scaffold designed to facilitate real-time monitoring of both bone formation and implant degradation during the repair of bone defects. Laponite (Lap), CyP-loaded mesoporous silica (CyP@MSNs) and ultrasmall superparamagnetic iron oxide nanoparticles (USPIO@SiO2) were incorporated into a bioink containing bone marrow mesenchymal stem cells (BMSCs) to fabricate functional scaffolds denoted as C@M/GLU using 3D bioprinting technology. In both in vivo and in vitro experiments, the composite scaffold has demonstrated a significant enhancement of bone regeneration through the controlled release of silicon (Si) and magnesium (Mg) ions. Employing near-infrared fluorescence (NIR-FL) imaging, the composite scaffold facilitates the monitoring of alkaline phosphate (ALP) expression, providing an accurate reflection of the scaffold's initial osteogenic activity. Meanwhile, the degradation of scaffolds was monitored by tracking the changes in the magnetic resonance (MR) signals at various time points. These findings indicate that the designed scaffold holds potential as an in situ bone implant for combined visualization of osteogenesis and implant degradation throughout the bone repair process.

Abstract Cardiac magnetic resonance imaging (CMR) has emerged as a valuable diagnostic tool for cardiac diseases. However, a significant drawback of CMR is its slow imaging speed, resulting in low patient throughput and compromised clinical diagnostic quality. The limited temporal resolution also causes patient discomfort and introduces artifacts in the images, further diminishing their overall quality and diagnostic value. There has been growing interest in deep learning-based CMR imaging algorithms that can reconstruct high-quality images from highly under-sampled k-space data. However, the development of deep learning methods requires large training datasets, which have so far not been made publicly available for CMR. To address this gap, we released a dataset that includes multi-contrast, multi-view, multi-slice and multi-coil CMR imaging data from 300 subjects. Imaging studies include cardiac cine and mapping sequences. The ‘CMRxRecon’ dataset contains raw k-space data and auto-calibration lines. Our aim is to facilitate the advancement of state-of-the-art CMR image reconstruction by introducing standardized evaluation criteria and making the dataset freely accessible to the research community.

Abstract Background The prognostic value of cellular retinoic acid-binding protein 2 (CRABP2), in lung cancer patients remains to be uncertained. Therefore, our research attempted to assess the relationship between CRABP2 and survival analysis in lung cancer patients through meta-analysis. Method Related literature retrieved from Cochrane Library, Ovid, Embase, PubMed, the CNKI, and the Web of Science. The latest update of the search was May 1, 2023. The outcome indicators included as effective measures in the study were hazard ratio (HR), and 95% confidence interval (CI). The Stata 12.0 software was used to analyze the data. Results A total of4 studies were finally enrolled in our meta-analysis. The increased plasma level of CRABP2 predicted poor OS in lung cancer patient with a combined HR of 1.14 (95% CI: 1.00–1.30), and were not associated with poor PFS with combined HR: 1.15% CI: 0.63–2.09) in lung cancer patients. Conclusions Our meta-analysis found the increased plasma level of CRABP2 was associated with poor OS independently in NSCLC patients. The plasma CRABP2 level may be an indicator of biological aggressiveness of the tumor. Our research was promising regarding the feasibility and utility of plasma CRABP2 as a novel prognostic biomarker in NSCLC, and the findings warrant further investigation.

Abstract Aminoacyl-tRNA synthetases (aaRSs) play a central role in the translation of genetic code, serving as attractive drug targets. Within this family, the lysyl-tRNA synthetase (LysRS) constitutes a promising antimalarial target. ASP3026, an anaplastic lymphoma kinase (ALK) inhibitor was recently identified as a novel Plasmodium falciparum LysRS (PfLysRS) inhibitor. Here, based on cocrystal structures and biochemical experiments, we developed a series of ASP3026 analogues to improve the selectivity and potency of LysRS inhibition. The leading compound 36 showed a dissociation constant of 15.9 nM with PfLysRS. The inhibitory efficacy on PfLysRS and parasites has been enhanced. Covalent attachment of l-lysine to compound 36 resulted in compound 36K3, which exhibited further increased inhibitory activity against PfLysRS but significantly decreased activity against ALK. However, its inhibitory activity against parasites did not improve, suggesting potential future optimization directions. This study presents a new example of derivatization of kinase inhibitors repurposed to inhibit aaRS.

Abstract Fundus neovascularization diseases are a series of blinding eye diseases that seriously impair vision worldwide. Currently, the means of treating these diseases in clinical practice are continuously evolving and have rapidly revolutionized treatment opinions. However, key issues such as inadequate treatment effectiveness, high rates of recurrence, and poor patient compliance still need to be urgently addressed. Multifunctional nanomedicine can specifically respond to both endogenous and exogenous microenvironments, effectively deliver drugs to specific targets and participate in activities such as biological imaging and the detection of small molecules. Nano-in-micro (NIM) delivery systems such as metal, metal oxide and up-conversion nanoparticles (NPs), quantum dots, and carbon materials, have shown certain advantages in overcoming the presence of physiological barriers within the eyeball and are widely used in the treatment of ophthalmic diseases. Few studies, however, have evaluated the efficacy of NIM delivery systems in treating fundus neovascular diseases (FNDs). The present study describes the main clinical treatment strategies and the adverse events associated with the treatment of FNDs with NIM delivery systems and summarizes the anatomical obstacles that must be overcome. In this review, we wish to highlight the principle of intraocular microenvironment normalization, aiming to provide a more rational approach for designing new NIM delivery systems to treat specific FNDs. Graphical Abstract

Abstract The PICALM::MLLT10 fusion gene is a rare but recurrent event in acute leukemia (AL) associated with poor prognosis. It is still confused whether PICALM::MLLT10 can solely correspond to acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) or acute leukemias of ambiguous lineage (ALAL). Here, we reported a series of PICALM::MLLT10 positive AL patients with miscellaneous immunophenotype including T‐ALL, ALAL, AML, and B‐ALL, complex karyotype, half of extramedullary disease (EMD), frequently concomitant PHF6 mutation, and poor initial treatment response to standard chemotherapy aiming to different immunophenotype, but showing sensitivity to combining chemotherapy especially integrated with venetoclax, suggesting this fusion gene may indicate a new subgroup of AL. Eighteen PICALM::MLLT10 positive patients of 533 AL patients (18/533, 3.4%) were identified by RNA sequencing in our center. We found PICALM::MLLT10 positive AL showing miscellaneous immunophenotype, higher expression of leukemic stemness genes and lower expression of biomarkers of venetoclax resistance, more extramedullary involvement, and especially poor response to conventional induction chemotherapy, but may benefit from venetoclax as well as low‐dose Ara‐C, granulocyte colony‐stimulating factor (G‐CSF), and anthracyclines combination chemotherapy. Sequential hematopoietic stem cell transplantation (HSCT) after chemotherapy combined with venetoclax may further improve long‐term survival in AL patients with complete remission (CR) even measurable residual disease (MRD) positive.

Abstract Achieving effective manipulation of perpendicular exchange bias effect remains an intricate endeavor, yet it stands a significance for the evolution of ultra-high capacity and energy-efficient magnetic memory and logic devices. A persistent impediment to its practical applications is the reliance on external magnetic fields during the current-induced switching of exchange bias in perpendicularly magnetized structures. This study elucidates the achievement of a full electrical manipulation of the perpendicular exchange bias in the multilayers with an ultrathin antiferromagnetic layer. Owing to the anisotropic epitaxial strain in the 2-nm-thick IrMn3 layer, the considerable exchange bias effect is clearly achieved at room temperature. Concomitantly, a specific global uncompensated magnetization manifests in the IrMn3 layer, facilitating the switching of the irreversible portion of the uncompensated magnetization. Consequently, the perpendicular exchange bias can be manipulated by only applying pulsed current, notably independent of the presence of any external magnetic fields.

Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport. For their clinical application, nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects. Therefore, responsive drug-release strategies for inflammation treatment have been explored; however, no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation. Herein, we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes (R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate, RC-NL@DMF) that precisely release encapsulated anti-pyroptotic drugs into pyroptotic cells. The activated key pyroptotic protein, the N-terminal domain of gasdermin E, selectively integrates with the cardiolipin of liposomes, thus forming pores for controlled drug release, pyroptosis, and inflammation inhibition. Therefore, RC-NL@DMF exhibited effective therapeutic efficacies to alleviate autoimmune inflammatory damages in zymosan-induced arthritis mice and dextran sulfate sodium-induced inflammatory bowel disease mice. Our novel approach holds great promise for self-adaptive pyroptosis-responsive on-demand drug delivery, suppressing pyroptosis and treating autoimmune inflammatory diseases.

The thermal environment is closely related to emotion. The thermal environment affects emotional experiences and can enhance them by adjusting its parameters. This study examines three common negative emotions—boredom, anxiety, and irritability—in a controlled environment. We experimentally investigated how these emotions affect thermal sensation, thermal comfort, and physiological parameters under varying temperature and humidity conditions. Results indicated that emotions significantly influenced thermal sensation (TSV) and thermal comfort (TCV) under moderate to high humidity conditions, demonstrating how temperature and humidity moderate the relationship between emotion and thermal comfort. Changes in physiological parameters further reveal how the interaction between emotion and environmental conditions affects physiological responses. A regression model was created using the response surface method to analyze thermal comfort in relation to temperature and humidity under different emotions, identifying the optimal indoor conditions as 22.8 °C and 46.7 % humidity. These findings help reduce negative emotions, improve thermal comfort, enhance our understanding of human thermal comfort, and provide scientific guidance for managing negative emotions during public health emergencies.

Backgrounds: Heart failure (HF) is characterized by progressive cardiac hypertrophy and fibrosis, yet the underlying pathological mechanisms remain unclear. Exosomes are pivotal in cellular communication and are key signaling carriers in HFs. This study investigated the roles of exosomes in HF. Methods: Eight-week-old male mice were divided into three groups: a control group, an Ang II group receiving angiotensin II (Ang II) infusion for 4 weeks, and an Ang II + DMA group receiving Ang II and dimethyl amiloride (DMA) infusion. This study examined the associations between cardiac injury, exosomes, and their substrate Shh. Furthermore, we conducted cellular experiments to assess the effects of Ang II-induced injury in primary cardiomyocytes on other cardiomyocytes and fibroblasts, and to test the therapeutic effects of the exosome inhibitor DMA and the Shh signaling inhibitor cyclopamine (CPN). Results: Ang II-induced cardiac hypertrophy and fibrosis, which were accompanied by exosome secretion and Shh upregulation in vivo. DMA relieved these cardiac lesions. Furthermore, cellular experiments revealed that Ang II-induced cardiomyocytes hypertrophy and activated cardiac fibroblasts by promoting the release of exosomes containing Shh/N-Shh/Gli1. Both DMA and CPN nullified fibroblast activation and proliferation. Conclusions: Ang II-induced cardiomyocyte injury leads to cardiac hypertrophy and fibrosis through the release of exosomes carrying Shh signaling. The suppression of exosome secretion or the Shh pathway could offer new strategies for treating HF.

BackgroundThe aging population is rapidly increasing, leading to physical decline and higher risks of chronic diseases, including sarcopenia, which adversely affects muscle quality and strength. Yi Jin Jing (YJJ), a traditional Chinese exercise method, can enhance flexibility and strength, but evidence regarding its effectiveness in older adults is conflicting. This meta-analysis aims to systematically evaluate the effects of YJJ on muscle strength and physical performance in this demographic.MethodsWe searched seven electronic databases: China National Knowledge Infrastructure, Wanfang Data, Sinomed, Web of Science, PubMed, Cochrane Library, and EMBASE to identify randomized controlled trials (RCTs). Following PRISMA guidelines, we quantified the effects of YJJ on muscle strength (grip strength, isokinetic strength) and physical performance (chair sit-to-stand, squatting-to-standing, shoulder flexibility, sit-and-reach tests). Treatment effects were calculated using Hedges’g. The Cochrane tool assessed risk of bias, the PEDro scale evaluated methodological quality, and the GRADE method assessed evidence quality. Data analysis was conducted using Stata 17.0 software, utilizing standardized mean differences (SMD) and 95% confidence intervals (CIs).ResultsThis meta-analysis included 10 RCTs involving 590 participants. The overall risk of bias was assessed to be low. The methodological quality of these studies was generally moderate, and the quality of the main results varied from low to moderate. The findings revealed that YJJ had considerable effects on the chair sit-to-stand test (Hedges’g = 1.06), squatting-to-standing test (Hedges’g = 1.08), and small to moderate effects on handgrip strength (Hedges’g = 0.25), 60°/s extensor peak torque (Hedges’g = 0.47), 60°/s extensor average power (Hedges’g = 0.31), 60°/s extensor total work (Hedges’g = 0.29), 60°/s flexor peak torque (Hedges’g = 0.42), 60°/s flexor average power (Hedges’g = 0.37), and 180°/s extensor peak torque (Hedges’g = 0.29), and left shoulder flexibility (Hedges’g = 0.4). However, there were no significant improvement effects in 180°/s extensor average power (Hedges’g = 0.19), 180°/s extensor total work (Hedges’g = 0.11), 180°/s flexor peak torque (Hedges’g = 0.01), 180°/s flexor average power (Hedges’g = −0.08), right shoulder flexibility (Hedges’g = 0.09), and sit-and-reach test (Hedges’g = 0.15).ConclusionYJJ significantly enhances specific aspects of physical performance, particularly chair sit-to-stand and squatting-to-standing tests, while showing small and moderate improvements in handgrip strength and knee muscle strength. However, it had no significant effects on other metrics, including shoulder flexibility and sit-and-reach tests.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024530487, Registration number: CRD42024530487.

BackgroundAutism spectrum disorder (ASD) is often linked to gastrointestinal issues and altered serotonin metabolism. Emerging evidence suggests gut microbiota influence both, with fecal microbiota transplantation (FMT) offering a potential therapeutic approach. However, its impact on serotonin metabolism and ASD symptoms is not well understood. In this study, we aimed to evaluate the clinical effects of FMT and examine changes in specific urinary metabolites in children with ASD.MethodsA randomized double-blind controlled trial was performed to evaluate the clinical effects of FMT on GI and ASD-related symptoms. Gastrointestinal symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS), and the ASD-related symptoms were assessed using the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and Social Responsiveness Scale (SRS) scores. Urinary metabolites were analyzed by homogeneous enzyme immunoassay using commercially available kits.ResultsSignificant improvements in GI and core ASD symptoms were observed following FMT intervention. The average GSRS scores decreased from 30.17 (before) to 19 (after; p

Biomarker testing plays a crucial role in the early detection of liver cancer. Herein, we developed a dual-signal amplification approach utilizing magnetic aggregation and a recognition competition strategy for the simultaneous detection of alpha-fetoprotein (AFP) and manganese superoxide dismutase (MnSOD) in serum. 4-MBA@AuNPs@H1 and DTNB@AuNPs@H2 were synthesized by functionalizing Raman signaling molecules and aptamer complementary chains onto the surface of gold nanoparticles (AuNPs). The detection complex Raman signal molecule@AuNPs@H-Fe3O4@cDNA was assembled by conjugating 4-MBA@AuNPs@H1 and DTNB@AuNPs@H2 with two nucleic acid aptamers (cDNA1 and cDNA2) modified with Fe3O4 through partial base complementary pairing. The target protein exhibited specific binding with the aptamer, leading to the competitive displacement of 4-MBA@AuNPs@H1 and DTNB@AuNPs@H2 from the Fe3O4 array surface, consequently resulting in a reduction of the Surface-Enhanced Raman Spectroscopy (SERS) signal. Through this approach, the limit of detection (LOD) for AFP and MnSOD in serum was achieved at remarkably low levels of 5.89 pg/mL and 6.23 pg/mL, respectively, with a reaction incubation period of only 5 min. Finally, the platform was utilized for the quantification of AFP and MnSOD in the serum of a nude mouse hepatocellular carcinoma model. The results obtained through SERS were consistent with those from enzyme-linked immunosorbent assay (ELISA), validating its accuracy. This methodology presents a novel approach for the swift and concurrent detection of proteins, holding significant clinical promise for the early diagnosis of hepatocellular carcinoma.

Deep learning techniques have been widely utilized for image recognition tasks. However, these techniques remain challenging in detecting aquatic plants due to their complex growing environments, long phenological periods, high species similarity, and the fact that they are often obscured by surrounding objects. To overcome these challenges, this study presents a comprehensive dataset of aquatic plant images in complex environments (DS-AP) and proposes a novel method, APNet-YOLOv8s. APNet-YOLOv8s integrates three modules: the Global Receptive Field-Space Pooling Pyramid-Fast (GRF-SPPF), the Shuffle Attention (SA) Mechanism, and the Fast Detection (FD), each designed to tackle specific challenges in aquatic plant detection. The performance of APNet-YOLOv8s was thoroughly evaluated using the DS-AP dataset. The results demonstrate that APNet-YOLOv8s significantly outperforms YOLOv8s, achieving a mean average precision (mAP50) of 75.3 % with a 2.7 % improvement, and a frame per second (FPS) rate of 30.5 with a 50.2 % increase. Moreover, APNet-YOLOv8s accurately and rapidly identifies aquatic plants in Gradient-weighted Class Activation Mapping (Grad-CAM) visualizations and real-world scenarios, highlighting its practical applications in complex environments. Overall, this study advances the application of deep learning in aquatic environments, providing a potential solution for rapid detection in other challenging environments.

Plant somatic embryogenesis (SE) is an efficient regeneration system for propagation. It involves the regulation of a complex molecular regulatory network encompassing endogenous hormone synthesis, metabolism, and signal transduction processes, induced through exogenous plant growth regulators. Previous studies have focused primarily on traditional propagation methods for Tectona grandis, but there is limited knowledge on SE and its hormonal regulatory mechanisms. In our study, different SE stages, including the nonembryogenic callus (NEC), embryogenic callus (EC), and globular and heart-shaped embryo (E-SEs) stages, were induced in teak cotyledons incubated on MS medium supplemented with 0.1 mg/L thidiazuron (TDZ). Morphological and histological observations indicated that EC primarily originates from the development of embryogenic cell clusters. During SE induction, the levels of six classes of endogenous hormones, IAA, CTK, ETH, ABA, SA, and JA, changed significantly. Transcriptome analysis revealed that endogenous hormones participate in SE induction in teak through various biological processes, such as biosynthesis, metabolism, and signal transduction pathways. We found that IAA biosynthesis primarily occurs through the IAM pathway during these three stages. The ETH receptor kinase gene SERF1 exhibited the highest expression levels in E-SEs. The ABA-, SA-, and JA-related signal transduction genes ABI3, NPR1, and JAZ exhibited no differential expression during different stages. Moreover, key encoding genes of SE regulators, including WUS, WOX and SERK, were differentially expressed during SE. In conclusion, this study offers insights into the roles of endogenous hormones and their interactions during SE induction.

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant and accumulated in the liver of mammals. PFOS exposure is closely associated with the development of pyroptosis. Nevertheless, the underlying mechanism is unclear. We found here that PFOS induced pyroptosis in the mice liver and L-02 cells as demonstrated by activation of the NOD-like receptor protein 3 inflammasome, gasdermin D cleavage and increased release of interleukin-1β and interleukin-18. The level of cytoplasmic calcium was accelerated in hepatocytes upon exposure to PFOS. The phosphorylated/activated form of calcium/calmodulin-dependent protein kinase II (CaMKII) was augmented by PFOS in vivo and in vitro. PFOS-induced pyroptosis was relieved by CaMKII inhibitor. Among various CaMKII subtypes, we identified that CaMKIIγ was activated specifically by PFOS. CaMKIIγ interacted with Smad family member 3 (Smad3) under PFOS exposure. PFOS increased the phosphorylation of Smad3, and CaMKII inhibitor or CaMKIIγ siRNA alleviated PFOS-caused phosphorylation of Smad3. Inhibiting Smad3 activity was found to alleviate PFOS-induced hepatocyte pyroptosis. This study puts forward that CaMKIIγ-Smad3 is the linkage between calcium homeostasis disturbance and pyroptosis, providing a mechanistic explanation for PFOS-induced pyroptosis.

Perfluorooctane sulfonate (PFOS) is known as a persistent organic pollutant. A significant correlation between PFOS and liver ferroptosis has been unveiled, but the precise mechanism needs to be elucidated. In prior research, we found that PFOS treatment provoked mitochondrial iron overload. In this study, we observed a gradual increase in lysosomal iron in L-O2 cells after exposure to PFOS for 0.5–24 h. In PFOS-exposed L-O2 cells, suppressing autophagy relieved the lysosomal iron overload. Inhibiting transient receptor potential mucolipin 1 (TRPML1), a calcium efflux channel on the lysosomal membrane, led to a further rise in lysosomal iron levels and decreased mitochondrial iron overload during PFOS treatment. Suppressing VDAC1, a subtype of voltage-dependent anion-selective channels (VDACs) on the outer mitochondrial membrane, had no impact on PFOS-triggered mitochondrial iron overload, whereas restraining VDAC2/3 relieved this condition. Although silencing VDAC2 relieved PFOS-induced mitochondrial iron overload, it had no effect on PFOS-triggered lysosomal iron overload. Silencing VDAC3 alleviated PFOS-mediated mitochondrial iron overload and led to an additional increase in lysosomal iron. Therefore, we regarded VDAC3 as the specific VDACs subtype that mediated the lysosomes-mitochondria iron transfer. Additionally, in the presence of PFOS, an enhanced association between TRPML1 and VDAC3 was found in mice liver tissue and L-O2 cells. Our research unveils a novel regulatory mechanism of autophagy on the iron homeostasis and the effect of TRPML1-VDAC3 interaction on lysosomes-mitochondria iron transfer, giving an explanation of PFOS-induced ferroptosis and shedding some light on the role of classic calcium channels in iron transmission.