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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.

In anticipation of potential future pandemics, we examined the challenges and opportunities presented by the COVID-19 outbreak. This analysis highlights how artificial intelligence (AI) and predictive models can support both patients and clinicians in managing subsequent infectious diseases, and how legislators and policymakers could support these efforts, to bring learning healthcare system (LHS) from guidelines to real-world implementation. This report chronicles the trajectory of the COVID-19 pandemic, emphasizing the diverse data sets generated throughout its course. We propose strategies for harnessing this data via AI and predictive modelling to enhance the functioning of LHS. The challenges faced by patients and healthcare systems around the world during this unprecedented crisis could have been mitigated with an informed and timely adoption of the three pillars of the LHS: Knowledge, Data and Practice. By harnessing AI and predictive analytics, we can develop tools that not only detect potential pandemic-prone diseases early on but also assist in patient management, provide decision support, offer treatment recommendations, deliver patient outcome triage, predict post-recovery long-term disease impacts, monitor viral mutations and variant emergence, and assess vaccine and treatment efficacy in real-time. A patient-centric approach remains paramount, ensuring patients are both informed and actively involved in disease mitigation strategies.

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.

Abstract It is unclear how the residual lobe volume changes over time after lobectomy. This study aims to clarify the temporal patterns of volume changes in each remaining lung lobe post-lobectomy. A retrospective review was conducted on patients who underwent lobectomy for lung cancer at Yueyang Central Hospital from January to December 2021. Lung CT images were reconstructed in three dimensions to calculate the volumes of each lung lobe preoperatively and at 1, 6, and 12 months postoperatively. A total of 182 patients were included. Postoperatively, the median total lung volume change rates relative to preoperative values were -20.1%, -9.3%, and -5.9% at 1, 6, and 12 months, respectively. Except for the right middle lobe in patients who underwent right upper lobectomy, the volumes of individual lung lobes exceeded preoperative values. The volume growth of the lung on the side of the resection was significantly more than that of the lung on the opposite side. For left lobectomy patients, the right lower lobe’s volume change rate exceeded that of the right upper and middle lobes. Among right lobectomy patients, the left lower lobe and the relatively inferior lobe of right lung had higher volume change rates than the superior one. Right middle lobe change rate was more in patients with right lower lobectomy than right upper lobectomy. Six months postoperatively, FEV1% and right middle lobectomy were positively correlated with the overall volume change rate. One year postoperatively, only age was negatively correlated with the overall volume change rate. 75 patients had pulmonary function tests. Postoperative FEV1 change linearly correlated with 1-year lung volume change rate, but not with theoretical total lung volume change rate or segmental method calculated FEV1 change. Time-dependent compensatory volume changes occur in remaining lung lobe post-lobectomy, with stronger compensation observed in the relatively inferior lobe compared to the superior one(s). Preoperative lung function and age may affect compensation level.

Abstract Evidence for seed transmission of phytoplasmas has grown in several pathosystems including coconut (Cocos nucifera). Bogia coconut syndrome (BCS) is a disease associated with the lethal yellowing syndrome associated with the presence of ‘Candidatus Phytoplasma noviguineense’ that affects coconut, betel nut (Areca catechu) and bananas (Musa spp.) in Papua New Guinea. Coconut and betel nut drupes were sampled from BCS-infected areas in Papua New Guinea, dissected, the extracted nucleic acid was used in polymerase chain reaction (PCR), and loop mediated isothermal amplification (LAMP) used to check for presence of phytoplasma DNA. In a second study, drupes of both plant species were collected from multiple field sites and grown in insect-proof cages. Leaf samples taken at 6 months were also tested with PCR and LAMP. The studies of dissected coconut drupes detected phytoplasma DNA in several tissues including the embryo. Drupes from betel nut tested negative. Among the seedlings, evidence of possible seed transmission was found in both plant species. The results demonstrate the presence of ‘Ca. P. noviguineense’ in coconut drupes and seedlings, and in seedlings of betel nut; factors that need to be considered in ongoing management and containment efforts.

201 Stainless steel and 5052 aluminium alloy were laser lap welded, both with and without a Ni foil interlayer. The Ni addition enhanced the metallurgical reaction between molten stainless steel/aluminium, resulting in the formation of the Al0.9Ni1.1 intermetallic compound. First-principles calculations estimated the equilibrium lattice and properties of IMCs (intermetallic compounds). A structural model of the interface revealed that the bonding strengths of Al/IMC and Fe/IMC interfaces surpassed those of IMC/IMC interfaces, making cracks prone to initiate and expand at the latter. Joints without Ni reached a max tensile shear strength of 74.5 N/mm, while those with Ni increased significantly to 101.8 N/mm, marking a substantial 36.6% enhancement.

Abstract Background Amidst growing evidence of the intricate link between physical and mental health, this study aims to dissect the relationship between the waist-to-weight index (WWI) and suicidal ideation within a representative sample of the US population, proposing WWI as a novel metric for suicide risk assessment. Methods The study engaged a sample of 9500 participants in a cross-sectional design. It employed multivariate logistic and linear regression analyses to probe the association between WWI and suicidal ideation. It further examined potential nonlinear dynamics using a weighted generalized additive model alongside stratified analyses to test the relationship's consistency across diverse demographic and health variables. Results Our analysis revealed a significant positive correlation between increased WWI and heightened suicidal ideation, characterized by a nonlinear relationship that persisted in the adjusted model. Subgroup analysis sustained the association's uniformity across varied population segments. Conclusions The study elucidates WWI's effectiveness as a predictive tool for suicidal ideation, underscoring its relevance in mental health evaluations. By highlighting the predictive value of WWI, our findings advocate for the integration of body composition considerations into mental health risk assessments, thereby broadening the scope of suicide prevention strategies.

Abstract This study aimed to unveil the central mechanism of moxibustion treating chronic inflammatory visceral pain (CIVP) from the angle of circRNA-miRNA-mRNA networks in the spinal cord. The rat CIVP model was established using a mixture of 5% (w/v) 2,4,6-trinitrobenzene sulfonic acid and 50% ethanol at a volume ratio of 2:1 via enema. Rats in the moxibustion group received herb-partitioned moxibustion at Tianshu (ST25, bilateral) and Qihai (CV6) points. The abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were adopted for pain behavior observation and pain sensitivity assessment. The circRNA, miRNA, and mRNA expression profiles were detected using the high-throughput sequencing technique. Relevant databases and bioinformatics analysis methods were used to screen for differentially expressed (DE) RNAs and build a circRNA-miRNA-mRNA (competing endogenous RNA) ceRNA regulatory network. The real-time quantitative PCR was employed to verify the sequencing result. CIVP rat models had a significantly higher AWR and lower TWL and MWT than normal rats. Between normal and model rats, there were 103 DE-circRNAs, 16 DE-miRNAs, and 397 DE-mRNAs in the spinal cord. Compared with the model group, the moxibustion group had a lower AWR and higher TWL and MWT; between these two groups, there were 118 DE-circRNAs, 15 DE-miRNAs, and 804 DE-mRNAs in the spinal cord. Two ceRNA networks were chosen to be verified. As a result, moxibustion’s analgesic effect on visceral pain in CIVP rats may be associated with regulating the circRNA_02767/rno-miR-483-3p/Gfap network in the spinal cord and improving central sensitization.

Abstract Acute myocardial infarction (AMI) commonly precedes ventricular remodeling, heart failure. Few dynamic molecular signatures have gained widespread acceptance in mainstream clinical testing despite the discovery of many potential candidates. These unmet needs with respect to biomarker and drug discovery of AMI necessitate a prioritization. We enrolled patients with AMI aged between 30 and 70. RNA-seq analysis was performed on the peripheral blood mononuclear cells collected from the patients at three time points: 1 day, 7 days, and 3 months after AMI. PLC/LC–MS analysis was conducted on the peripheral blood plasma collected from these patients at the same three time points. Differential genes and metabolites between groups were screened by bio-informatics methods to understand the dynamic changes of AMI in different periods. We obtained 15 transcriptional and 95 metabolite expression profiles at three time points after AMI through high-throughput sequencing. AMI-1d: enrichment analysis revealed the biological features of 1 day after AMI primarily included acute inflammatory response, elevated glycerophospholipid metabolism, and decreased protein synthesis capacity. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) might stand promising biomarkers to differentiate post-AMI stage. Anti-inflammatory therapy during the acute phase is an important direction for preventing related pathology. AMI-7d: the biological features of this stage primarily involved the initiation of cardiac fibrosis response and activation of platelet adhesion pathways. Accompanied by upregulated TGF-beta signaling pathway and ECM receptor interaction, GP5 help assess platelet activation, a potential therapeutic target to improve haemostasis. AMI-3m: the biological features of 3 months after AMI primarily showed a vascular regeneration response with VEGF signaling pathway, NOS3 and SHC2 widely activated, which holds promise for providing new therapeutic approaches for AMI. Our analysis highlights transcriptional and metabolomics signatures at different time points after MI, which deepens our understanding of the dynamic biological responses and associated molecular mechanisms that occur during cardiac repair.

Abstract Background COVID-19 has been shown to increase the risk of extracorporeal coagulation during hemodialysis in patients, but the underlying mechanism remains unclear. This study aimed to investigate the effect and mechanism of COVID-19 on the risk of extracorporeal coagulation in patients with chronic kidney disease undergoing hemodialysis. Methods A retrospective analysis of the extracorporeal coagulation status of 339 hemodialysis patients at our center before and after COVID-19 infection was performed, including subgroup analyses. Post-infection blood composition was analyzed by protein spectrometry and ELISA. Results Compared to the pre-COVID-19 infection period, COVID-19-induced extracorporeal coagulation predominantly occurred in patients with severe/critical symptoms. Further proteomic analysis demonstrated that in patients with severe/critical symptoms, the coagulation cascade reaction, platelet activation, inflammation, and oxidative stress-related pathways were significantly amplified compared to those in patients with no/mild symptoms. Notably, the vWF/FBLN5 pathway, which is associated with inflammation, vascular injury, and coagulation, was significantly upregulated. Conclusions Patients with severe/critical COVID-19 symptoms are at a higher risk of extracorporeal coagulation during hemodialysis, which is associated with the upregulation of the vWF/FBLN5 signaling pathway. These findings highlight the importance of early anticoagulant therapy initiation in COVID-19 patients with severe/critical symptoms, particularly those undergoing hemodialysis. Additionally, vWF/FBLN5 upregulation may be a novel mechanism for virus-associated thrombosis/coagulation.

Abstract Background Cetaceans, having experienced prolonged adaptation to aquatic environments, have undergone evolutionary changes in their respiratory systems. This process of evolution has resulted in the emergence of distinctive phenotypic traits, notably the abundance of elastic fibers and thickened alveolar walls in their lungs, which may facilitate alveolar collapse during diving. This structure helps selective exchange of oxygen and carbon dioxide, while minimizing nitrogen exchange, thereby reducing the risk of DCS. Nevertheless, the scientific inquiry into the mechanisms through which these unique phenotypic characteristics govern the diving behavior of marine mammals, including cetaceans, remains unresolved. Results This study entails an evolutionary analysis of 42 genes associated with pulmonary fibrosis across 45 mammalian species. Twenty-one genes in cetaceans exhibited accelerated evolution, featuring specific amino acid substitutions in 14 of them. Primarily linked to the development of the respiratory system and lung morphological construction, these genes play a crucial role. Moreover, among marine mammals, we identified eight genes undergoing positive selection, and the evolutionary rates of three genes significantly correlated with diving depth. Specifically, the SFTPC gene exhibited convergent amino acid substitutions. Through in vitro cellular experiments, we illustrated that convergent amino acid site mutations in SFTPC contribute positively to pulmonary fibrosis in marine mammals, and the presence of this phenotype can induce deep alveolar collapse during diving, thereby reducing the risk of DCS during diving. Conclusions The study unveils pivotal genetic signals in cetaceans and other marine mammals, arising through evolution. These genetic signals may influence lung characteristics in marine mammals and have been linked to a reduced risk of developing DCS. Moreover, the research serves as a valuable reference for delving deeper into human diving physiology.

IntroductionIn the Southern Ocean, the large-scale distribution of zooplankton, including their abundance and community composition from the epipelagic to the upper bathypelagic layers, remains poorly understood. This gap in knowledge limits our comprehension of their ecological and biogeochemical roles.MethodsTo better understand their community structure, depth-stratified zooplankton samples were collected from 0 to 1500 m during four summers in the East-Pacific and Indian sectors of the Southern Ocean. In addition, analysis of environmental drivers including temperature, salinity, dissolved oxygen, and chlorophyll a concentration, as well as water masses was conducted.ResultsOur study indicates that zooplankton diversity may be similar between the two sectors, while zooplankton abundance was higher in the East-Pacific sector during different sampling months and years. Moreover, zooplankton abundance decreased with depth in both sectors. Based on cluster analysis, zooplankton communities were generally divided by either the epipelagic or the deeper layers’ communities. In both sectors, the epipelagic layer was dominated by cyclopoid copepods, such as Oithona similis and Oncaea curvata, as well as calanoid copepods including Calanoides acutus, Rhincalanus gigas, and Ctenocalanus citer, while copepods and other taxa including Chaetognatha, Amphipoda, and Ostracoda, were important contributors to the deep layer communities.DiscussionOur analysis revealed that water masses, combined with their physical characteristics such as specific temperature and salinity ranges and depth, along with biological factors such as chlorophyll a concentration, might be the most important drivers for structuring zooplankton communities from epipelagic to upper bathypelagic layer.

The microstructure and grain refinement of Al-4.5Er-1Zr-1.5Ti master alloy were analyzed by the refinement experiment, OM, SEM and XRD. The results show that the grain size of pure aluminum is reduced from 14,000μm to 202μm by Al-4.5Er-1Zr-1.5Ti master alloy, which is mainly due to the nucleation promoted by Ti2Al20Er, Al3Er and Al3Ti. Plastic deformation further improves the refining effect of the material by improving the primary phase size, and the Al-4.5Er-1Zr-1.5Ti −2ARB can refine the pure aluminum from 202 mμm to 150μm, and the refinement was increased by 25.7 %. The master alloy showed a better refinement effect in Al-5Cu alloy than pure aluminum, with a grain size of 92μm and a refinement improvement of 97.8 %.

To avoid sintering and carbon deposition of conventionally loaded catalysts, a spatial confinement strategy was employed to design a high-performance catalyst for the dry reforming of methane (DRM) reaction. With tri-metallic Ni-Co-Mg metal-organic framework (MOF-74) as a precursor, a novel nanostructured NiCoMg@C catalyst was synthesized, where the active metals Ni and Co were confined within the carbon framework derived from MOF pyrolysis. Characterization results indicate that the catalyst synthesized with MOF as template has a high specific surface area, well-dispersed metals, and strong metal-support interactions. The introduction of a high content of Mg promoted the dispersion of active metal Ni and Co and increased the number and strength of surface basic sites. Among the catalysts, NiCoMg20@C exhibited optimal catalytic activity, with initial CH4 and CO2 conversion rates reaching 75.13 % and 85.29 %, respectively. More importantly, the catalyst showed high stability during 100 h DRM reaction at 700 °C without significant carbon deposition. This research provides a new perspective for the development of DRM catalysts.

Ubiquitination is a crucial post-translational modification of proteins that mediates the degradation or functional regulation of specific proteins. This process participates in various biological processes such as cell growth, development, and signal transduction. E3 ubiquitin ligases play both positive and negative regulatory roles in osteogenesis and differentiation by ubiquitination-mediated degradation or stabilization of transcription factors, signaling molecules, and cytoskeletal proteins. These activities affect the proliferation, differentiation, survival, and bone formation of osteoblasts (OBs). In recent years, advances in genomics, transcriptomics, and proteomics have led to a deeper understanding of the classification, function, and mechanisms of action of E3 ubiquitin ligases. This understanding provides new insights and approaches for revealing the molecular regulatory mechanisms of bone formation and identifying therapeutic targets for bone metabolic diseases. This review discusses the research progress and significance of the positive and negative regulatory roles and mechanisms of E3 ubiquitin ligases in the process of osteogenic differentiation. Additionally, the review highlights the role of E3 ubiquitin ligases in bone-related diseases. A thorough understanding of the role and mechanisms of E3 ubiquitin ligases in osteogenic differentiation could provide promising therapeutic targets for bone tissue engineering based on stem cells.

Achieving superior ductility, microstructure, and strength simultaneously in tailor-welded blanks remains challenging. To address this, pre-aging blanks before friction stir welding was proposed. Systematic studies were conducted on the microstructure, ductility, and post-aging strength of pre-aged 2219 aluminium alloy after friction stir welding. Uniaxial tensile tests evaluated the ductility of tailor-welded blanks at room and cryogenic temperatures, along with their mechanical properties after artificial aging. Microstructural characterization and Vickers hardness measurements elucidated the strengthening mechanisms between the welded region and base material. No abnormal grain growth was observed in the welded region post pre-aging welding; instead, a finer grain structure prevailed. Ductility of the tailor-welded blanks initially increased and then decreased with increasing rotational speed. Excellent elongations, 27.8% at room temperature and 32.4% at cryogenic temperatures, were obtained at a rotational speed of 1300 rpm, reaching 91.5% of the base material. This attributed to the finer grain boundary strengthening in the welded regions. After artificial aging, a joint efficiency of 93.5% was achieved, owing to effective compensation of the reduction in precipitation strengthening caused by the welded heat input through finer grain strengthening. This approach represents a novel method for preparing ultrawide blanks for forming integral large-sized aluminum alloy components.

As a persistent organic pollutant, perfluorooctane sulfonate (PFOS) has a serious detrimental impact on human health. It has been suggested that PFOS is associated with liver inflammation. However, the underlying mechanisms are still unclear. Here, PFOS was found to elevate the oligomerization tendency of voltage-dependent anion channel 1 (VDAC1) in the mice liver and human normal liver cells L-02. Inhibition of VDAC1 oligomerization alleviated PFOS-induced nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome activation. Cytoplasmic membrane VDAC1 translocated to mitochondria was also observed in response to PFOS. Therefore, the oligomerization of VDAC1 occurred mainly in the mitochondria. VDAC1 was found to interact with the ATP synthase beta subunit (ATP5B) under PFOS treatment. Knockdown of ATP5B or immobilization of ATP5B to the cytoplasmic membrane alleviated the increased VDAC1 oligomerization and NLRP3 inflammasome activation. Therefore, our results suggested that PFOS induced NLRP3 inflammasome activation through VDAC1 oligomerization, a process dependent on ATP5B to transfer VDAC1 from the plasma membrane to the mitochondria. The findings offer novel perspectives on the activation of the NLRP3 inflammasome, the regulatory mode on VDAC1 oligomerization, and the mechanism of PFOS toxicity.

Abstract Background Human immunodeficiency virus (HIV) infection is an important risk factor for Coronavirus Disease 2019 (COVID‐19), but data on the prevalence of COVID‐19 among people living with HIV (PLWH) is limited in low‐income countries. Our aim was to assess the seroprevalence of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) specific antibodies and associated factors among PLWH in Sierra Leone. Methods We conducted a cross‐sectional survey of PLWH aged 18 years or older in Sierra Leone between August 2022 and January 2023. Participants were tested for SARS‐CoV‐2 antibodies using a rapid SARS‐CoV‐2 antibody (immunoglobulin M/immunoglobulin G [IgG]) kits. Stepwise logistic regression was used to explore factors associated with SARS‐CoV‐2 antibody seroprevalence with a significance level of p

Background: Aging is characterized by a decline in the adaptability and resistance of the body. In this study, Bushen Kangshuai Granules (BKG), as a kind of Chinese herbal formula, was developed and shown to alleviate aging-related symptoms.Methods: Self-controlled study combined with RNA-seq and metabonomics were used to expound the efficacy and safety of BKG and revealed the regulation mechanism of BKG treating aging. In vitro experiments were used to confirm the analytical results. The aging cell model of AC16 cells were treated with D-galactose. The RT-qPCR was used to detect the impact of BKG on telomere length. The DCFH-DA staining was used for detecting intracellular ROS. The targeted signaling pathway was selected and verified using Western blot.Results: After 8 weeks of treatment, BKG significantly reduced SOD level (p = 0.046), TCM aging symptoms (p < 0.001) and TNF-α level (p = 0.044) in the elderly participants. High-throughput sequencing showed that BKG reversed the expression of 70 and 79 age-related genes and metabolites, respectively. Further enrichment analysis indicated that BKG downregulated the PI3K-AKT signaling pathway, extracellular matrix (ECM)-receptor interaction, and Rap1 signaling pathway, while up-regulating sphingolipid metabolism. The results of in vitro experiments show that, after D-gal treatment, the viability and telomere length of AC16 cells significantly decreased (p < 0.05), while the expression of ROS increased (p < 0.05), BKG significantly increased the telomere length of AC16 cells and reduced the level of ROS expression (p < 0.05). In addition, BKG decreased the expression of THBS1, PDGFRA, and EPS8L1(p < 0.05), consistent with the RNA-seq results. Our results also showed that BKG affects PI3K-AKT signaling pathway.Conclusion: BKG can significantly improve aging-related symptoms and increase SOD levels, which may be associated with the reversal of the expression of various aging-related genes. The PI3K-AKT signaling pathway and sphingolipid metabolism may be potential mechanisms underlying BKG anti-aging effects.

Summary: Investigating the correlation between aging mechanisms and state of charge (SOC) can optimize cycling conditions and prolong the life cycle of lithium-ion batteries (LIBs). A long-term cycle between a certain SOC range is usually employed to study this correlation. However, this method necessitates a lengthy period, running from months to years, prolonging the research duration significantly. The aging mechanisms obtained through this method are a result of the coupling of various SOC levels; the aging mechanisms at a specific SOC level are not accurately decoupled and analyzable. The proposed Zero-sum pulse method, using symmetrical pulses with small SOC amplitude variations on SOC, can explore aging mechanisms of LIBs at a specific SOC level and reduce the time to less than a week, which significantly expedite the research process. The aging mechanisms at 30%, 50%, 70%, and 90% SOC levels are explored to verify the accuracy and timeliness of this method.

Purpose: Zoledronic acid can inhibit the activity of osteoclasts, and thus, may slow or inhibit bone loss. The purpose of this study was to systematically evaluate the efficacy and safety of zoledronic acid in the treatment of osteoporosis. Methods: Four databases, PubMed, Embase, Cochrane Library, and Web of Science, were systematically searched up to December 26, 2022. The primary outcomes included bone mineral density (BMD), carboxy-terminal cross-linked telopeptide of type 1 collagen (CTX), bone-specific alkaline phosphatase (BSAP), procollagen type 1 N-terminal prope-ptide (P1NP), adverse events, and fracture. Secondary outcomes included serum sclerostin level, Visual Analogue Scale (VAS) score, and Oswestry Disability Index (ODI). Results: A total of 22 randomized controlled trials were included in this meta-analysis. Meta-analysis results showed that zoledronic acid was effective in increasing BMD of the lumbar spine, femoral neck, trochanter and serum sclerostin level; and reduced CTX, BSAP, P1NP, VAS score, and ODI in patients with osteoporosis. Regarding safety, zoledronic acid could reduce the incidence of fractures but had relatively more adverse events. Conclusion: Zoledronic acid can significantly improve BMD of the lumbar spine, femoral neck and trochanter, and effectively reduce incidence of fracture in patients with osteoporosis, thereby significantly improving patients' quality of life. However, the incidence of adverse events was higher than that of patients treated with placebo.

Objective Research on reefs is highly important for determining sedimentary environments and for oil and gas exploration, but relatively few studies have been conducted on Carboniferous reefs in the Southwest Tarim Basin. Methods Early Carboniferous reefs of the Heshirafu Formation in the Artashi section in the Southwest Tarim Basin formed in the Middle-Late Visean section of the Early Carboniferous. Reef-building organisms and accessory organisms were not quite diversified; the former mainly consisted of colonial corals of different kinds and solitary corals of a small number, and the latter were mostly echinoderms. Results Their growth was suspended due to less supply of terrigenous materials largely related to the frequent sea level changes in the Early Carboniferous in the piedmont structures of the Southwest Tarim Basin. These reefs are among the products of the recovery of metazoan skeleton reefs across the globe after the Late Devonian mass extinction; their occurrence was accompanied by mid- to late-stage Visean climate warming and global sea level rise. These reefs are common in the Early Carboniferous Visean reefs worldwide. In addition, according to the overall sedimentary facies of the Heshirafu Formation in the Artashi section and the adjacent Hantiereke Formation in the Kushanhe section, it is speculated that a transgression occurred from southwest to northeast in the Visean period of the Early Carboniferous in the Southwest Tarim Basin when the global sea level was rising and a passive continental margin was simultaneously forming and beginning to sink. As a result, a narrow platform margin facies belt gradually took shape in the piedmont structure of the Southwest Tarim Basin. This belt was conducive to the development of biological reefs. Then, when the Heshirafu Formation formed, a depositional system of "shore facies-lagoon facies-platform margin facies-slope facies-continental shelf facies" developed in a seaward direction. Conclusion The classification of sedimentary systems can provide a reference for Carboniferous sedimentary environments and oil and gas exploration in the Southwest Tarim Basin.

Aiming at the problems of gas lift reverse circulation shaft washing slag discharge and low drilling efficiency in the application of vertical shaft drilling method in the Jurassic strata coal mines in western China, taking ϕ4.2 m advanced drilling of central return air shaft in the Kekegai coal mine as the engineering background, based on the CFD-DEM (computational fluid dynamics and discrete element method coupling) research method, a gas-liquid-solid multiphase coupling slag discharge numerical model is established, which reveals the velocity and pressure distribution law of the flow field in the slag discharge pipe and the bottom hole. Based on the self-developed gas lift reverse circulation slag discharge test device, the correctness of the flow field distribution is verified by PIV (Particle Image Velocimetry) test technology. The evaluation index and method of optimizing cutter head suction port are put forward. The number, length-diameter ratio, area ratio and total area ratio of slag suction outlets are optimized. The best way and related parameters of cutter head suction port arrangement of advanced bit are optimized. The effects of main factors such as bit speed, gas injection rate, submerged ratio of air duct and mud viscosity on slag discharge flow field are discussed. The research results show that ① the fluid in the slag discharge pipe mainly moves in the axial direction, and when passing through the gas injection end, the velocity increases sharply. The migration of bottom hole fluid is mainly horizontal flow, and the vertical upward flow of fluid only exists near the slag suction port. The horizontal flow at the bottom of the shaft is mainly tangential flow, and the radial flow is obvious only on both sides of the slag suction port, and it is far away from the slag suction port, so the runoff speed is small and it is easy to produce cuttings deposition. ② When the number of slag suction ports of cutter head is 2, the length-diameter ratio is 0.4, the area ratio is 1, and the total area ratio is 1.94%, the layout of slag suction ports is the best, and the slag removal rate is increased by 66% compared with the current layout of slag suction ports. ③ Increasing the bit speed can significantly enhance the adsorption of the slag suction port. The gas injection rate and the submerged ratio of the air duct are positively correlated with the axial velocity of the fluid in the bottom hole and the slag discharge pipe. The mud with low viscosity and low density is easy to obtain high return velocity, but its rock carrying capacity is poor. The research results can provide a useful theoretical reference for solving the technical problems of washing, slag removal and low drilling efficiency of deep and large vertical shaft drilling in the Jurassic strata.

Abstract Chemical structure segmentation constitutes a pivotal task in cheminformatics, involving the extraction and abstraction of structural information of chemical compounds from text-based sources, including patents and scientific articles. This study introduces a deep learning approach to chemical structure segmentation, employing a Vision Transformer (ViT) to discern the structural patterns of chemical compounds from their graphical representations. The Chemistry-Segment Anything Model (ChemSAM) achieves state-of-the-art results on publicly available benchmark datasets and real-world tasks, underscoring its effectiveness in accurately segmenting chemical structures from text-based sources. Moreover, this deep learning-based approach obviates the need for handcrafted features and demonstrates robustness against variations in image quality and style. During the detection phase, a ViT-based encoder-decoder model is used to identify and locate chemical structure depictions on the input page. This model generates masks to ascertain whether each pixel belongs to a chemical structure, thereby offering a pixel-level classification and indicating the presence or absence of chemical structures at each position. Subsequently, the generated masks are clustered based on their connectivity, and each mask cluster is updated to encapsulate a single structure in the post-processing workflow. This two-step process facilitates the effective automatic extraction of chemical structure depictions from documents. By utilizing the deep learning approach described herein, it is demonstrated that effective performance on low-resolution and densely arranged molecular structural layouts in journal articles and patents is achievable.

Abstract In vivo cardiac diffusion tensor imaging (cDTI) is a promising Magnetic Resonance Imaging (MRI) technique for evaluating the microstructure of myocardial tissue in living hearts, providing insights into cardiac function and enabling the development of innovative therapeutic strategies. However, the integration of cDTI into routine clinical practice poses challenging due to the technical obstacles involved in the acquisition, such as low signal-to-noise ratio and prolonged scanning times. In this study, we investigated and implemented three different types of deep learning-based MRI reconstruction models for cDTI reconstruction. We evaluated the performance of these models based on the reconstruction quality assessment, the diffusion tensor parameter assessment as well as the computational cost assessment. Our results indicate that the models discussed in this study can be applied for clinical use at an acceleration factor (AF) of $$\times 2$$ × 2 and $$\times 4$$ × 4 , with the D5C5 model showing superior fidelity for reconstruction and the SwinMR model providing higher perceptual scores. There is no statistical difference from the reference for all diffusion tensor parameters at AF $$\times 2$$ × 2 or most DT parameters at AF $$\times 4$$ × 4 , and the quality of most diffusion tensor parameter maps is visually acceptable. SwinMR is recommended as the optimal approach for reconstruction at AF $$\times 2$$ × 2 and AF $$\times 4$$ × 4 . However, we believe that the models discussed in this study are not yet ready for clinical use at a higher AF. At AF $$\times 8$$ × 8 , the performance of all models discussed remains limited, with only half of the diffusion tensor parameters being recovered to a level with no statistical difference from the reference. Some diffusion tensor parameter maps even provide wrong and misleading information.