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Abstract Objective This study aimed to evaluate the clinical effect of different vertebral body heights restoration rate after percutaneous kyphoplasty (PKP) for the treatment of osteoporotic vertebral compression fractures (OVCF). Methods The patients were divided into two groups according to the height restoration rate of the anterior edge of the vertebral body fracture after PKP operation using X-Ray imaging. The group A was below 80%, and the group B was above 80%. Clinical preoperative and postoperative efficacy (1st day, 1st month, 6th month, and 12th month after surgery) were evaluated according to VAS, Oswestry Disability Index(ODI), Quality of Life Questionnaire of the European Foundation for Osteoporosis(QUALEFFO), and Back Pain Life Disorder Questionnaire(RQD). Simultaneously, the preoperative and postoperative local Cobb angles and changes in the injured vertebrae in the two groups were calculated and analyzed. Results The postoperative Cobb angle in group A was significantly higher than that in group B. The correction rate in group B was significantly better than that in group A. The VAS, ODI, QUALEFFO, and RQD scores of group B patients were significantly lower than those of patients in group A at each follow-up time point. The correlation coefficients of vertebral body height restoration rate and VAS, ODI, QUALEFFO, and RQD scores at the last follow-up were − 0.607 (P

Abstract Elucidating cellular architecture and cell-type evolution across species is central to understanding immune system function and susceptibility to disease. Adaptive immunity is a shared trait of the common ancestor of cartilaginous and bony fishes. However, evolutionary features of lymphocytes in these two jawed vertebrates remain unclear. Here, we present a single-cell RNA sequencing atlas of immune cells from cartilaginous (white-spotted bamboo shark) and bony (zebrafish and Chinese tongue sole) fishes. Cross-species comparisons show that the same cell types across different species exhibit similar transcriptional profiles. In the bamboo shark, we identify a phagocytic B cell population expressing several pattern recognition receptors, as well as a T cell sub-cluster co-expressing both T and B cell markers. In contrast to a division by function in the bony fishes, we show close linkage and poor functional specialization among lymphocytes in the cartilaginous fish. Our cross-species single-cell comparison presents a resource for uncovering the origin and evolution of the gnathostome immune system.

Abstract Background In recent years, the traditional simulation-based medical teaching approach has faced challenges in meeting the requirements of practical emergency medicine education. This study utilized open-source tools and software to develop immersive panoramic videos using virtual reality technology for emergency medical teaching. It aims to investigate the efficacy of this novel teaching methodology. This transformation shifted the focus from physical simulation to virtual simulation in medical education, establishing a metaverse for emergency medical teaching. Methods In accordance with the curriculum guidelines, the instructors produced panoramic videos demonstrating procedures such as spinal injury management, humeral fracture with abdominal wall intestinal tube prolapse, head and chest composite injuries, cardiopulmonary resuscitation, and tracheal intubation. Using Unity software, a virtual training application for bronchoscopy was developed and integrated into the PICO4 VR all-in-one device to create a metaverse teaching environment. Fourth-year medical undergraduate students were allocated into either an experimental group (n = 26) or a control group (n = 30) based on student IDs. The experimental group received instruction through the metaverse immersive teaching method, while the control group followed the traditional simulation-based medical teaching approach. Both groups participated in theoretical and practical lessons as usual. Subsequently, all students underwent a four-station Objective Structured Clinical Examination (OSCE) to assess the effectiveness of the teaching methods based on their performance. Additionally, students in the experimental group provided subjective evaluations to assess their acceptance of the new teaching approach. Results Before the training commenced, there were no significant statistical differences in the first aid test scores between the experimental and control groups. Following the training, the experimental group outperformed the control group in the four-station OSCE examination, with all P-values being less than 0.05. The satisfaction rate among the experimental group regarding the new teaching method reached 88.46%, reflecting levels of satisfaction and extreme satisfaction. Conclusion The open-source metaverse immersive teaching method has demonstrated a positive impact on enhancing the emergency skills of medical undergraduate students, with a high level of acceptance among students. In comparison to traditional simulated medical teaching methods, this approach requires less time and space, incurring lower costs, and is deemed worthy of wider adoption.

Objective To investigate the use of anti‐osteoporotic agents and refracture incidence in patients with osteoporotic vertebral compression fracture (OVCF) following percutaneous vertebral augmentation (PVA) and to evaluate the real‐world treatment of patients using denosumab following PVA. This study aims to provide spine surgeons with empirical insights derived from real‐world scenarios to enhance the management of bone health in OVCF patients. Methods This retrospective cohort study was based on data from the MarketScan and Optum databases from the USA. Female patients aged 55–90 years who underwent PVA for OVCF between January 2013 and March 2020 were included and followed up from the day after surgery. Patients who received at least one dose of denosumab were included in the denosumab cohort and were further divided into the on‐treatment and off‐treatment groups according to whether they received a second dose of denosumab, with follow‐up beginning on the index day (225 days after the first denosumab dose). In this study, the off‐treatment group was considered as the control group. Refracture incidence after PVA, the proportion of patients using anti‐osteoporotic agents in the total study population, and refracture incidence after the index day in the denosumab cohort were analyzed. Results A total of 13,451 and 21,420 patients from the MarketScan and Optum databases, respectively, were included. In the denosumab cohort, the cumulative incidence of clinical osteoporotic fractures within 3 years after the index day was significantly lower in the on‐treatment group than in the off‐treatment group (MarketScan database: 23.0% vs 39.0%, p = 0.002; Optum database: 28.2% vs 40.0%, p = 0.023). The cumulative incidence of clinical vertebral fractures was also lower in the on‐treatment group than in the off‐treatment group, with a significant difference in the MarketScan database (14.4% vs 25.5%, p = 0.002) and a numerical difference was found in the Optum database (20.2% vs 27.5%, p = 0.084).The proportion of patients using anti‐osteoporotic agents was low at 6 months postoperatively, with only approximately 7% using denosumab and 13%–15% taking oral bisphosphonates. Conclusion Postmenopausal women have a high refracture rate and a low proportion of anti‐osteoporotic drug use after PVA. Continued denosumab treatment after PVA is associated with a lower risk of osteoporotic and clinical vertebral fractures. Therefore, denosumab may be a treatment option for patients with osteoporosis after PVA.

Clarifying the effects of meteorological factors on the growth and development of fresh maize after delayed sowing is important for selecting appropriate sowing dates and improving yield. Six sowing dates (B1 (March 10); B2 (March 20); B3 (March 30); B4 (April 9); B5 (April 19), and B6 (April 29)) and three fresh maize cultivars (A1 (Wan Nuo 2000); A2 (Nongke Nuo 336), and A3 (Caitian Nuo 6)) were chosen for experiments conducted between 2021 and 2022 in Guiyang, Qingzhen City, China. The results showed that the whole growth period and sowing-silking period were significantly reduced with delayed sowing, while the grain-filling period was relatively stable. Delayed sowing was beneficial in increasing the number of endosperm cells and the weight of the hundred kernels. The graining filling rate and the activities of four key starch synthesis enzymes (sucrose synthase, ADP-glucose pyrophosphorylase, starch branching enzyme, and starch debranching enzyme) were significantly influenced by light, temperature, and precipitation, and they mainly affected the hundred kernel weight. The yield tended to increase with delayed sowing, and the correlation analysis between precipitation and yield at different sowing periods showed a significant effect of precipitation on yield. Delaying the sowing to mid-early April was more favourable for grain filling, enhanced key enzyme activity, and increased the kernel weight and yield. These results highlight the importance of choosing excellent cultivars and matching them with the most suitable sowing date to fully exploit climatic resources and achieve high-yield and high-efficiency cultivation of fresh maize.

Abstract Wireless capsule endoscopy (WCE) offers a non-invasive evaluation of the digestive system, eliminating the need for sedation and the risks associated with conventional endoscopic procedures. Its significance lies in diagnosing gastrointestinal tissue irregularities, especially in the small intestine. However, existing commercial WCE devices face limitations, such as the absence of autonomous lesion detection and treatment capabilities. Recent advancements in micro-electromechanical fabrication and computational methods have led to extensive research in sophisticated technology integration into commercial capsule endoscopes, intending to supersede wired endoscopes. This Review discusses the future requirements for intelligent capsule robots, providing a comparative evaluation of various methods’ merits and disadvantages, and highlighting recent developments in six technologies relevant to WCE. These include near-field wireless power transmission, magnetic field active drive, ultra-wideband/intrabody communication, hybrid localization, AI-based autonomous lesion detection, and magnetic-controlled diagnosis and treatment. Moreover, we explore the feasibility for future “capsule surgeons”.

Abstract Chinese Painting and Calligraphy (ChP&C) holds significant cultural value, representing integral aspects of both Chinese culture and global art. A considerable amount of ChP&C works are dispersed worldwide. With the emergence of digital humanities, a vast collection of cultural artifacts data is now available online. However, the online databases of these artifacts remain decentralized and diverse, posing significant challenges to their effective organization and utilization. Addressing this, our paper focuses on the Wu Men School of Painting and proposes a framework for constructing a multimodal knowledge graph for the ChP&C domain. We construct the domain ontology by analyzing the ChP&C knowledge schema. Then, we acquire knowledge from diverse data sources, including textual and visual information. To enhance data collection around collecting historical context and subject matter, we propose methods for seal extraction and subject extraction specific to ChP&C. We validate the effectiveness of these methods on the constructed dataset. Finally, we construct the Wu Men Multimodal Knowledge Graph (WuMKG) and implement applications such as cross-modal retrieval, knowledge-based question-answering and visualization.

Abstract Chimeric antigen receptor T (CAR-T) cells have been proposed for HIV-1 treatment but have not yet demonstrated desirable therapeutic efficacy. Here, we report newly developed anti-HIV-1 CAR-T cells armed with endogenic broadly neutralizing antibodies (bNAbs) and the follicle-homing receptor CXCR5, termed M10 cells. M10 cells were designed to exercise three-fold biological functions, including broad cytotoxic effects on HIV-infected cells, neutralization of cell-free viruses produced after latency reversal, and B-cell follicle homing. After demonstrating the three-fold biological activities, M10 cells were administered to treat 18 HIV-1 patients via a regimen of two allogenic M10 cell infusions with an interval of 30 days, with each M10 cell infusion followed by two chidamide stimulations for HIV-1 reservoir activation. Consequently, 74.3% of M10 cell infusions resulted in significant suppression of viral rebound, with viral loads declining by an average of 67.1%, and 10 patients showed persistently reduced cell-associated HIV-1 RNA levels (average decrease of 1.15 log10) over the 150-day observation period. M10 cells were also found to impose selective pressure on the latent viral reservoir. No significant treatment-related adverse effects were observed. Overall, our study supported the potential of M10 CAR-T cells as a novel, safe, and effective therapeutic option for the functional cure of HIV-1/AIDS.

The value of Baijiu is affected by its flavor, age, and adulteration. Therefore, a simple and rapid identification method is crucial for the market. In this study, we present a rapid, non-intrusive identification technique for Baijiu utilizing the Tyndall effect combined with chemometrics analysis. Our experiment begins illuminating Baijiu with a 405 nm wavelength laser and recording the resulting bright light path due to the Tyndall effect. To further analyze the color and brightness information, Principal Component Analysis (PCA), Linear Discriminant Analysis (LDA), Hierarchical Cluster Analysis (HCA), and Multilayer Perceptron (MLP) were employed. This study establishes correlations between the brightness of the Tyndall light path and seven trace flavor compounds in Baijiu. The findings demonstrate that this method effectively identifies the flavor, age cellar, and adulteration of Baijiu and also quantitatively detects the concentrations of flavor compounds. Additionally, an analysis platform was developed to enable the rapid identification of Baijiu.

IntroductionLiquiritigenin (LQ), a natural flavonoid found in traditional Chinese medicine and often administered orally, holds potential to affect both the gut and its microbiota, that potentially mediating or influencing its biological and pharmacological effects. However, the effects of LQ on gut microbiota composition and intestinal function remain poorly understood. In this study, we aimed to explore the impact of LQ on gut microbiota and gene expression in both intestinal and extraintestinal tissues.MethodsWe orally inoculated six-week-old SPF C57BL/6 mice with either LQ (a concentration of 4 mg/ml diluted in dimethylsulfoxide, (DMSO)) or DMSO, and administered daily for a duration of 2 weeks. At the end of the experimental period, all mice were euthanized. Fresh fecal samples, as well as samples from the intestine, lung, and liver, were collected for subsequent microbiota analysis, RNA-seq, or histochemical and immunohistochemical (IHC) staining.ResultsFindings show that LQ alters gut microbiota composition, enhancing microbial correlations in the colon but causing some dysbiosis, evidenced by increased pathobionts, decreased beneficial bifidobacteria, and reduced microbiota diversity. Gene expression analysis reveals LQ upregulates mucosal immune response genes and antiinfection genes in both the intestine and lung, with histology confirming increased Paneth cells and antimicrobial peptides in the intestine. Additionally, LQ affects tissue-specific gene expression, triggering hypersensitivity genes in the colon, downregulating metabolic genes in the small intestine, and reducing cell motility and adhesion genes in the lung.DiscussionThese results suggest LQ’s potential to modulate common mucosal immunity but also highlight possible risks of gut dysbiosis and hypersensitivity, particularly in vulnerable individuals. Our study, while informative about the effects of LQ on gut health, lacks direct evidence on whether changes in gut microbiota and gene expression caused by LQ impact inflammatory diseases or are causally linked. Future research should investigate this through fecal microbiota transplantation to explore the causal relationships and LQ’s potential effects on immune responses and disease outcomes in relevant models.

Objective: Proteus syndrome, a rare disorder with an incidence of one in a million, is characterized by connective tissue nevi, asymmetric limb overgrowth, and abnormal subcutaneous adipose tissue distribution. Limited awareness of this condition often hinders accurate clinical diagnosis. We report a case of Proteus syndrome with concurrent progressive paralysis in the unilateral lower limb, aiming to enhance understanding of the disease and its associated complications. Methods: The patient, an 11-year-old male, has been conclusively diagnosed with Proteus Syndrome. This diagnosis was established by analyzing clinical manifestations, imaging studies, and laboratory tests. In addition, a literature review was conducted to systematically elucidate the etiology, diagnosis, treatment, and prognosis of this condition. Results: According to the clinical manifestations, we confirmed a case of Proteus syndrome. This example exhibits the general characteristics of patients with severe hemihypertrophy of the bilateral lower limbs, anomalies in hypodermic and adipose distribution, and unilateral lower limb progressive paralysis. Pathological biopsy confirmed the right chest wall mass as a lipoma. Notably, the patient experiences lower limb movement disorders caused by intraspinal disease. At the same time, the gene sequencing results of this Proteus syndrome patient showed mutations in the IDUS gene and SPECC1L gene, which have not been reported before. Conclusion: We diagnosed Proteus Syndrome with lower limb sensorimotor abnormalities, which may be caused by mutations in the IDUS gene or SPECC1L gene. This is the first report of these kinds of gene mutations in association with Proteus Syndrome.

This study comprehensively investigates the impact of varying red-to-blue light ratios on the growth of Spanish lettuce. The research considers various factors such as growth morphology, photosynthetic parameters, and chlorophyll fluorescence. Lettuce was cultivated in an environment with a photosynthetic photon flux density (PPFD) of 200 ± 20 μmol/m2/s and a photoperiod of 16 h per day. The experiment incorporated eight distinct light treatment methodologies, with the red-to-blue light ratios ranging from 2:8 (R2B8) to 9:1 (R9B1). The data implies that during the initial 20 days of growth, groups exposed to a higher proportion of red light demonstrated superior growth. In particular, the R9B1 group exhibited the highest increase in plant height. The photosynthetic performance of leaves (net photosynthetic rate, stomatal conductance, and transpiration rate) showed a tendency to rise with a decreasing red-to-blue ratio within a particular range, peaking at R3B7. However, both the dry matter content and fresh weight were relatively lower under the R3B7 light quality ratio. The results indicate that cultivating lettuce under the R8B2 ratio led to optimal outcomes. This group significantly outperformed the other test groups in terms of weight and exhibited higher photosynthetic rates. Despite exhibiting lower stomatal conductance, this group reduced energy consumption and ultimately achieved the highest overall weight.

“Synthetic” allopolyploids recreated by interspecific hybridization play an important role in providing novel genomic variation for crop improvement. Such synthetic allopolyploids often undergo rapid genomic structural variation (SV). However, how such SV arises, is inherited and fixed, and how it affects important traits, has rarely been comprehensively and quantitively studied in advanced generation synthetic lines. A better understanding of these processes will aid breeders in knowing how to best utilize synthetic allopolyploids in breeding programs. Here, we analyzed three genetic mapping populations (735 DH lines) derived from crosses between advanced synthetic and conventional Brassica napus (rapeseed) lines, using whole-genome sequencing to determine genome composition. We observed high tolerance of large structural variants, particularly toward the telomeres, and preferential selection for balanced homoeologous exchanges (duplication/deletion events between the A and C genomes resulting in retention of gene/chromosome dosage between homoeologous chromosome pairs), including stable events involving whole chromosomes (“pseudoeuploidy”). Given the experimental design (all three populations shared a common parent), we were able to observe that parental SV was regularly inherited, showed genetic hitchhiking effects on segregation, and was one of the major factors inducing adjacent novel and larger SV. Surprisingly, novel SV occurred at low frequencies with no significant impacts on observed fertility and yield-related traits in the advanced generation synthetic lines. However, incorporating genome-wide SV in linkage mapping explained significantly more genetic variance for traits. Our results provide a framework for detecting and understanding the occurrence and inheritance of genomic SV in breeding programs, and support the use of synthetic parents as an important source of novel trait variation.

Abstract Autophagy is a cellular self-degradation process that plays a crucial role in maintaining metabolic functions in cells and organisms. Dysfunctional autophagy has been linked to various diseases, including cancer. In cancer, dysregulated autophagy is closely associated with the development of cancer and drug resistance, and it can have both oncogenic and oncostatic effects. Research evidence supports the connection between m6A modification and human diseases, particularly cancer. Abnormalities in m6A modification are involved in the initiation and progression of cancer by regulating the expression of oncogenes and oncostatic genes. There is an interaction between m6A modification and autophagy, both of which play significant roles in cancer. However, the molecular mechanisms underlying this relationship are still unclear. m6A modification can either directly inhibit autophagy or promote its initiation, but the complex relationship between m6A modification, autophagy, and cancer remains poorly understood. Therefore, this paper aims to review the dual role of m6A and autophagy in cancer, explore the impact of m6A modification on autophagy regulation, and discuss the crucial role of the m6A modification-autophagy axis in cancer progression and treatment resistance.

Abstract Cone‐beam computed tomography (CBCT) system can provide real‐time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Interleukin-21 (IL-21) is produced mainly by activated CD4+ T cells and promotes the proliferation, survival and differentiation of immune cells. This study characterised a high affinity binding receptor of IL-21 (IL-21 Rα) from grass carp (Ctenopharyngodon idella, Ci) and analyzed the expression of CiIL-21 and CiIL-21 Rα. It has been shown that they were modulated by PAMPs and during infection with bacterial and viral pathogens. Recombinant CiIL-21 protein produced in bacteria was active in inducing the expression of genes involved in Th responses. A monoclonal CiIL-21 antibody was generated against the rCiIL-21 and showed good reactive specificity with the rCiIL-21 proteins expressed in E. coli cells, and HEK293 T cells and the native protein from PHA-stimulated kidney leukocytes. In addition, the IL-21-producing cells detected by the CiIL-21 monoclonal antibody were found to be increased to in the kidney, spleen and hindgut after infection with Flavobacterium columnare. Our data indicate that IL-21 is involved in the regulation of immune response to bacterial and viral infection.

CD4 T helper cells are an important group of cells in the immune system of vertebrates and express CD4 receptor on the cell surface. In mammals, the CD4 receptor is encoded by a single copy gene, whilst in fish, two copies of cd4 genes, namely cd4-1 and cd4-2, are found. In this study, the ectodomains of grass carp (Ctenopharyngodon idella, Ci) CD4-1 and CD4-2 were expressed in the E. coli cells and used to generate monoclonal antibodies in mice. Western blotting, confocal microscopy and flow cytometry were performed to characterize the monoclonal antibodies. It has been shown that the CiCD4-1 and CiCD4-2 monoclonal antibodies had good specificity to react with the recombinant ectodomains of CiCD4-1 and CiCD4-2 expressed in the CHO–S cells and the native CD4 molecules of grass carp. The CiCD4-1 monoclonal antibody did not recognize CiCD4-2 and verse versa. In addition, the CD4-1 and CD4-2 monoclonal antibodies specifically recognized the CD4-1 and CD4-2 receptors expressed in the HEK293 cells and native molecules of fish cells. Further, the percentages of lymphocytes in immune tissues of healthy fish were analyzed by flow cytometry. It was found that 17.6% of lymphocytes were CD4-1+ cells and 22.5% were CD4-2+ in the head kidney. In the spleen, 13.1% of lymphocytes were CD4-1+ and 18.6% were CD4-2+ while 7.3% of blood lymphocytes were CD4-1+ cells and 8.8% were CD4-2+ cells. The availability of the CD4-1 and CD4-2 monoclonal antibodies provides antibody-based tools for further elucidation of the functions of CD4 T cells in grass carp.

A cell line, termed ZFIN, was established from the caudal fin of zebrafish and was shown to be susceptible to spring viremia of carp virus (SVCV). The ZFIN cells are epithelial like cells and have a moderate plasmid transfection efficiency of 13.9%. Using an RNA-seq approach, differentially expressed genes (DEGs) regulated by SVCV were identified. Infection of SVCV gave rise to 3931 DEGs and up-regulated DEGs were mostly enriched into the biological regulation and cellular processes, among which pathways for the type I interferon signaling and the response to exogenous dsRNA were the top two GO terms. Several KEGG signaling pathways including TLR signaling pathway, RLR receptor signaling pathway, cytosolic DNA-sensing pathway, NLR signaling pathway, cytokine-cytokine receptor interaction and ferroptosis were significantly enriched. Antiviral genes including ifnφ1, isg15 and mx were significantly up-regulated. In addition, key DEGs involved in autophagy were identified. The results indicate that the ZFIN cell line provides a useful in vitro tool for study on the gene functions and cellular responses to viral infection in fish.

Low-fat conversion of high-fat products met consumers' pursuit of health, and was one of the future development directions of meat products. In this study, the effects of two forms of tea seed oil (TSO) and nano tea seed oil microcapsules (NTM) on the physical and chemical properties of pork mince products were investigated, with no tea seed oil fat replacing pork mince as the control group. The water retention, cooking yield, water distribution, texture, microstructure, and fat oxidation level of different fat replacing pork mince products were studied. The results showed that the addition of 50% and 70% NTM could improve the water retention ability of pork minced meat products caused by TSO replacement. The T21 relaxation time and proportion of the NTM replacement group were not significantly different from those of the non-replacement control group (P>0.05), while the proportion of non-flowable water in the TSO replacement group was significantly decreased (P

Background Idiopathic Pulmonary Fibrosis (IPF) presents a severe respiratory challenge with a poor prognosis due to the lack of reliable biomarkers. Recent evidence suggests that Endoplasmic Reticulum Stress (ERS) may be associated with IPF pathogenesis. This study focuses on uncovering ERS-associated biomarkers for IPF.Methods Sequencing data from diverse datasets were analyzed, utilizing differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Endoplasmic Reticulum Stress (ERS)-related genes were extracted from the GeneCards database. Hub genes were identified through Protein-Protein Interaction (PPI) analysis. Diagnostic and prognostic models were developed using machine learning algorithms and validated across both training and validation sets. Additionally, techniques such as Cell-type Identification by Estimating Relative Subsets of RNA Transcripts and single-cell RNA sequencing were employed to identify potential IPF-related cells. These findings were further investigated to elucidate their underlying mechanisms through in vitro experiments.Results Differentially expressed genes, WGCNA-identified blue module genes, and ERS-related genes extracted from the GeneCards database were intersected, and the resulting genes were used to construct diagnostic and prognostic models. Validation using multiple datasets indicated that both the diagnostic and prognostic models possess strong predictive capabilities. PPI analysis highlighted SPP1 as a potential hub gene in IPF. Moreover, M2 macrophages were found in higher quantities in the lung tissue of IPF patients, with a significant increase in SPP1-expressing M2 macrophages compared to the control group. In vitro experiments demonstrated that exogenous SPP1 inhibited the proliferation and migration of M2 macrophages and promoted apoptosis within a certain concentration range.Conclusion This study identifies ERS-related biomarkers in IPF, highlighting SPP1 and M2 macrophages. The resulting diagnostic and prognostic models offer strong predictive capabilities, unveiling new therapeutic avenues.

Recurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral therapy (ART). To address this gap, we developed an HLA-mismatched allogeneic adoptive immune therapy (AAIT) specifically targeting this patient population. The safety and efficacy of this novel therapeutic approach were preliminarily confirmed in our phase 1 trial. Subsequently, a multicenter, open-label, controlled, phase 2a trial was conducted to evaluate the efficacy of AAIT in combination with ART compared with the conventional ART-only regimen. No difference in the incidence of adverse events (AEs) was observed between the two groups at the 96-week follow-up. AAIT treatment improved CD4+ T cell recovery at weeks 72 (P = 0.048) and 96 (P = 0.024) compared to the Control Group. Additionally, stratified analysis of patients in the AAIT Group showed that donor/recipient sex mismatch was significantly associated with the likelihood of patients achieving an immunological response (OR = 8.667; 95% CI, 2.010–37.377; P = 0.004). These findings suggest that AAIT serves as a promising adjunct therapy for improving the outcomes of patients with severely immunosuppressed AIDS. Further studies are needed to elucidate the immunological mechanisms underlying AAIT and identify the subpopulations that respond optimally to this therapeutic approach. This trial is registered at www.clinicaltrials.gov (NCT04098770).Trial registration: ClinicalTrials.gov identifier: NCT04098770.Trial registration: ClinicalTrials.gov identifier: NCT02651376.

The three most common kinds of urologic malignancies are prostate, bladder, and kidney cancer, which typically cause substantial morbidity and mortality. Early detection and effective treatment are essential due to their high fatality rates. As a result, there is an urgent need for innovative research to improve the clinical management of patients with urologic cancers. A type of small noncoding RNAs of 22 nucleotides, microRNAs (miRNAs) are well-known for their important roles in a variety of developmental processes. Among these, microRNA-21 (miR-21) stands out as a commonly studied miRNA with implications in tumorigenesis and cancer development, particularly in urological tumors. Recent research has shed light on the dysregulation of miR-21 in urological tumors, offering insights into its potential as a prognostic, diagnostic, and therapeutic tool. This review delves into the pathogenesis of miR-21 in prostate, bladder, and renal cancers, its utility as a cancer biomarker, and the therapeutic possibilities of targeting miR-21.

The micro-mechanical properties of asphalt surfaces are significantly impacted by short-term aging during construction and long-term aging in service. This, in turn, affects macroscopic characteristics such as asphalt-aggregate adhesion and water stability of asphalt mixtures. The study investigated different aging processes had different impacts on the micromechanical properties of the asphalt on the surface. The short-term aging process had the most significant effects, while the subsequent long-term aging had similar but less important effects. The adhesion, surface energy, and Young's modulus of five different types of asphalt using atomic force microscopy (AFM) in their original state, after short-term aging through the Rolling Thin Film Oven Test (RTFOT), and after long-term aging through the RTFOT+Pressure Aging Vessel (PAV). The results showed that ZH and SK asphalts had a distinct ''bee structure'', and aging had varying effects on adhesion, surface energy, and Young's modulus in different areas (peak, valley, and other region). Before and after asphalt aging, the adhesion and surface energy approximately followed the order other region > peak > valley, while Young's modulus approximately followed the peak>valley> other region. This indicates that the bumpy ''bee structure'' does not always correspond to higher modulus or lower adhesion. It was also found that ZH asphalt and SK asphalt with a ''bee structure'' exhibited better aging resistance compared to KL asphalt without a ''bee structure''. The study also revealed that aging led to decreased adhesion and surface energy, while increasing Young's modulus. This finding indicates that as asphalt ages, adhesion decreases and asphalt elasticity increases. Additionally, it was observed that the modified asphalt showed less change in adhesion, surface energy, and Young's modulus after aging compared to the matrix asphalt, indicating that SBS modifiers contribute to improving the aging resistance of asphalt. These results will provide a good reference for understanding the microscopic changes in asphalt aging properties.

Artificial optoelectronic synaptic transistors have attracted extensive research interest as an essential component for neuromorphic computing systems and brain emulation applications. However, performance challenges still remain for synaptic devices, including low energy consumption, high integration density, and flexible modulation. Employing trapping and detrapping relaxation, a novel optically stimulated synaptic transistor enabled by the AlGaN/GaN hetero-structure metal-oxide semiconductor high-electron-mobility transistor has been successfully demonstrated in this study. Synaptic functions, including excitatory postsynaptic current (EPSC), paired-pulse facilitation index, and transition from short-term memory to long-term memory, are well mimicked and explicitly investigated. In a single EPSC event, the AlGaN/GaN synaptic transistor shows the characteristics of low energy consumption and a high signal-to-noise ratio. The EPSC of the synaptic transistor can be synergistically modulated by both optical stimulation and gate/drain bias. Moreover, utilizing a convolution neural network, hand-written digit images were used to verify the data preprocessing capability for neuromorphic computing applications.

Summary: Ferroptosis is an iron-dependent cell death mechanism characterized by the accumulation of toxic lipid peroxides and cell membrane rupture. GPX4 (glutathione peroxidase 4) prevents ferroptosis by reducing these lipid peroxides into lipid alcohols. Ferroptosis induction by GPX4 inhibition has emerged as a vulnerability of cancer cells, highlighting the need to identify ferroptosis regulators that may be exploited therapeutically. Through genome-wide CRISPR activation screens, we identify the SWI/SNF (switch/sucrose non-fermentable) ATPases BRM (SMARCA2) and BRG1 (SMARCA4) as ferroptosis suppressors. Mechanistically, they bind to and increase chromatin accessibility at NRF2 target loci, thus boosting NRF2 transcriptional output to counter lipid peroxidation and confer resistance to GPX4 inhibition. We further demonstrate that the BRM/BRG1 ferroptosis connection can be leveraged to enhance the paralog dependency of BRG1 mutant cancer cells on BRM. Our data reveal ferroptosis induction as a potential avenue for broadening the efficacy of BRM degraders/inhibitors and define a specific genetic context for exploiting GPX4 dependency.

Urologic oncology is a significant public health concern on a global scale. Recent research indicates that long chain non-coding RNAs (lncRNAs) and autophagy play crucial roles in various cancers, including urologic malignancies. This article provides a summary of the latest research findings, suggesting that lncRNA-mediated autophagy could either suppress or promote tumors in prostate, kidney, and bladder cancers. The intricate network involving different lncRNAs, target genes, and mediated signaling pathways plays a crucial role in urological malignancies by modulating the autophagic process. Dysregulated expression of lncRNAs can disrupt autophagy, leading to tumorigenesis, progression, and enhanced resistance to therapy. Consequently, targeting particular lncRNAs that control autophagy could serve as a dependable diagnostic tool and a promising prognostic biomarker in urologic oncology, while also holding potential as an effective therapeutic approach.

Summary: Interleukin (IL)-22 promotes host-microbiota homeostasis. We sought to identify microbiota metabolite(s) that drive intestinal IL-22 production. We observed that exposing Peyer’s patch cells (PPCs), ex vivo, to fecal supernatants (FSs) recapitulates fermentable fiber- and microbiota-dependent IL-22 production, and cellular sources thereof, thus supporting the use of this model. An interrogation of FSs generated from mice fed the fermentable fiber inulin (FS-Inu) revealed that its IL-22-inducing activity is mediated by heat-labile protein. Fractionation of FS-Inu by ion-exchange chromatography, and subsequent proteomic analysis of IL-22-inducing fractions, indicates that outer membrane protein A (OmpA) might be a microbial driver of IL-22 expression. Concomitantly, recombinant OmpA from Parabacteroides goldsteinii, which is enriched by an inulin diet, induces IL-22 production and expression of the IL-22-dependent genes REG3γ and -β, in PPCs and mice. Thus, OmpA is one bacterial inducer of IL-22 expression, potentially linking diet, mucosal immune homeostasis, and gut health.

Abstract Miniaturized fiber-Bragg-grating (FBG) interrogators are of interest for applications in the areas where weight and size controlling is important, e.g., airplanes and aerospace or in-situ monitoring. An ultra-compact high-precision on-chip interrogator is proposed based on a tailored arrayed waveguide grating (AWG) on a silicon-on-insulator (SOI) platform. The on-chip interrogator enables continuous wavelength interrogation from 1 544 nm to 1 568 nm with the wavelength accuracy of less than 1 pm [the root-mean-square error (RMSE) is 0.73 pm] over the whole wavelength range. The chip loss is less than 5 dB. The 1 × 16 AWG is optimized to achieve a large bandwidth and a low noise level at each channel, and the FBG reflection peaks can be detected by multiple output channels of the AWG. The fabricated AWG is utilized to interrogate FBG sensors through the center of gravity (CoG) algorithm. The validation of an on-chip FBG interrogator that works with sub-picometer wavelength accuracy in a broad wavelength range shows large potential for applications in miniaturized fiber optic sensing systems.

Abstract To investigate the role and potential mechanism of serine/threonine kinase 36 (STK36) in docetaxel resistance-prostate cancer (PCa). The expression of STK36 in PCa and the correlation with clinicopathological characteristics of PCa patients were analyzed using the data from different databases and tissue microarrays. To investigate the role of STK36 on cell proliferation, invasion, and migration, STK36 was overexpressed and silenced in DU-145 and PC-3 cell lines. Cell counting kit-8 (CCK8) was used to test cell proliferation. Cell invasion and migration were detected by cell wound scratch assay and trans well, respectively. The expression profile of STK36, E-Cadherin, and Vimentin was analyzed by Western blot. Cell apoptosis was detected by the TUNEL assay. STK36 expression was upregulated in PCa tissue compared with adjacent benign PCa tissue; it was higher in patients with advanced stages compared with lower stages and was significantly correlated with decreased overall survival. Up-regulation of STK36 significantly promoted the proliferation, invasion, and migration of DU-145 and PC-3 cells and compensated for the suppression caused by docetaxel treatment in vitro. A striking apoptosis inhibition could be observed when dealing with docetaxel, although the apoptosis of DU-145 and PC-3 cells was not affected by the STK36 exclusive overexpression. Besides, E-Cadherin expression was restrained while the expression levels of vimentin were all enhanced. The knockdown of STK36 reversed the above process. STK36 up-regulation could accelerate the biological behavior and docetaxel resistance of PCa by epithelial-mesenchymal transition (EMT) activation. STK36 may be potentially used as a target in PCa resolvent with docetaxel.

Abstract Background Interplay between gut microbiota and heart, termed “gut-heart” axis, has a crucial role in the pathogenesis of atherosclerosis. Our previous study showed that lycopene possesses anti-inflammatory and anti-atherosclerotic effects, but its link to the gut microbiota is poorly understood. Herein, we surmised that lycopene could regulate the gut microbiota, exert anti-atherosclerotic effect by regulating the “gut-heart” axis. Methods Male ApoE−/− mice were fed a high-fat diet (HFD) with or without lycopene (0.1% w/w) for 19 weeks. Gut microbiota was analyzed by 16 S rRNA sequencing, the protein levels of zonula occludens-1 (ZO-1), occludin, toll-like receptor 4 (TLR4) and phospho-nuclear factor-κB (NF-κB) p65 were measured by Western blotting, the levels of serum inflammatory factors including monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 were assayed using ELISA kits. Also, the concentrations of serum lipopolysaccharide (LPS), D-lactic acid (D-LA) and diamine peroxidase (DAO) were measured through ELISA method. Results The aortic sinus sections revealed that lycopene supplementation significantly reduced the extent of atherosclerotic lesions and inhibited atherosclerosis development caused by HFD. The analysis of gut microbiota showed that lycopene reduced the ratio of Firmicutes/Bacteroides and increased the relative abundance of Verrucomicrobia, Akkermansia and Alloprevotella, which were related to elevated intestinal barrier function and reduced inflammation. Moreover, lycopene up-regulated the expression of intestinal ZO-1 and occludin and decreased serum LPS, D-LA and DAO levels. In addition, lycopene inhibited the expression of TLR4 and phospho-NF-κB p65 in aortic sinus plaque, serum MCP-1, TNF-α, IL-1β, and IL-6 levels were also lowered by lycopene treatment. Conclusions Our results indicated the protective effect of lycopene against atherosclerosis induced by HFD and further revealed that its mechanism might be its prebiotic effect on maintaining gut microbiota homeostasis and improving intestinal barrier function, consequently reducing serum LPS-triggered inflammatory response in the heart.

Due to the limited payload and power of drones, the computational overhead, storage overhead and communication overhead that can be used for secure communication are restricted, making it difficult to apply some complex but fairly secure authentication protocols on drones. In this paper, we propose a low-complexity protocol for storing identity information in a resource-unconstrained device that does not require the UAV to store the information, thereby enhancing the UAV’s resistance to capture. The protocol in this paper mainly consists of quasi-cyclic low-density parity-check (QC-LDPC) codes, physical unclonable functions (PUFs) based on random-access memory (RAM), “XOR” operations, and hash computation. The protocol in this paper is an authentication architecture in which the drone is guided by the ground station to read its identity information, and the drone does not store any identity information in advance. The protocol is divided into two phases: 1. fuzzy authentication of fingerprint PUF and 2. uniqueness authentication accomplished while guiding the recovery of identity PUF. Recovering identity PUF in this paper, QC-LDPC is used as the error control module, and the optimization of bit-flip decoding significantly reduces the probability of decoding failure. After the comparative security analysis and comparative overhead analysis of this paper’s protocol, it can be concluded that this paper’s protocol can withstand common attacks (including attacks attempting to pass authentication, attacks attempting to interfere with authentication, and physical capture attacks), and the storage and communication overhead is small in the case of large time overhead.

This article reports the fine-tuning of the optical resonance wavelength (ORW) of surface-micromachined optical ultrasound transducer (SMOUT) arrays to enable ultrasound data readout with non-tunable interrogation light sources for photoacoustic computed tomography (PACT). Permanent ORW tuning is achieved by material deposition onto or subtraction from the top diaphragm of each element with sub-nanometer resolution. For demonstration, a SMOUT array is first fabricated, and its ORW is tuned for readout with an 808 nm laser diode (LD). Experiments are conducted to characterize the optical and acoustic performances of the elements within the center region of the SMOUT array. Two-dimensional and three-dimensional PACT (photoacoustic computed tomography) is also performed to evaluate the imaging performance of the ORW-tuned SMOUT array. The results show that the ORW tuning does not degrade the optical, acoustic, and overall imaging performances of the SMOUT elements. As a result, the fine-tuning method enables new SMOUT-based PACT systems that are low cost, compact, powerful, and even higher speed, with parallel readout capability.

Due to the joint influence of climate change and human activities, the hydrological rhythm of Poyang Lake has changed in recent years, leading to an increasingly severe drought problem during autumn and winter in this region. Notably, the extreme drought that occurred in 2022 had profound impacts on shipping, water supply and the ecological environment of the wetlands in the Poyang Lake Delta, sparking widespread concern. Based on the historical hydrometeorological data of Poyang Lake, we used statistical models (such as Chow test, correlation analysis, etc.) to analyze the cause of the extreme drought in the Poyang Lake Delta from the perspectives of natural factors and human activity. Through correlation analysis, we found that the water level, discharge, and drought duration of the Poyang Lake Delta were all significantly affected by climate change, particularly rainfall in the Poyang Lake basin. Furthermore, combining the results of Chow test and correlation analysis, we also found that the operation of the Three Gorges Reservoir had a notable impact on the water level of the Poyang Lake Delta. Based on remote sensing images, ecological and environmental sampling monitoring, the damage inflicted by the extreme drought event on the Poyang Lake Delta was analyzed. The results show that the inundated area of the delta wetlands in the extreme-drought year (2022) decreased by 45.75% compared with that in a normal year (2017). In addition, the ecological environment of the wetlands deteriorated significantly. The water quality parameters (TN, TP, NH4+-N) increased by 50.2%, 240% and 64.7%, respectively. The concentrations of TN and TP were 3.8 mg/L and 0.17 mg/L, respectively, while the context values in the delta were 1.2 mg/L and 0.075 mg/L. The density and biomass of algae increased by 87.2% and 557.9%, respectively. In contrast, the density and biomass of benthos decreased by 59.9% and 78.5%, respectively. The control strategy for the Poyang Lake Delta under extreme drought was studied through an experiment on the operation of hydraulic controllers. The results show that under extreme drought conditions, the newly built hydraulic controllers could raise the water level of the delta from 9.1 ± 0.7 m to 14.2 ± 1.8 m, thus effectively solving the water cut-off problem in the four branches of the delta. Furthermore, by adjusting the distributive ratio of the main, north, middle and south branches of the delta to 50%, 4%, 24% and 22% through newly built hydraulic controllers, the water area can be increased by 56%.

Objective: This study aims to introduce a configurable standard-type (CST) coil design methodology that can accommodate different stimulation needs through the overlapping of standard coil components, while ensuring the performance of CST coil approaches the existing optimal physical limit as closely as possible. Approach: The study utilizes planar, spherical, and hemispherical stream function to represent the spatial geometry of the coils. Singular value decomposition is employed to design the standard coil components while minimizing the number of coil components. Initially, this study delineates the relationship between singular vectors and coil geometry, defining a multi-objective optimization problem for the research. By contrasting the decay characteristics of singular values in the inductance and electric field matrices of the stream functions, the singular vectors of the electric field matrix are utilized as the foundation for CST coil optimization. Subsequently, the relationships between the number of singular vectors and the coil’s Pareto fronts are determined through the optimization algorithms, and the geometric patterns of the singular vectors, i.e., the standard coil components, are analyzed. Main results: By constructing the CST coil components using seven singular vectors and comparing with the Pareto front of the performance of over 50 existing coil types, the stimulation depth range of the CST coil based on the planar stream function decreased by only 7.7%; the focality performance of the CST coil based on the spherical stream function improved by 22.4%; the focality performance of the CST coil based on the hemispherical stream function decreased by only 1.6%. Significance: The construction of CST coils with a minimal number of components is explored to approximate the performance at any discrete point on the physical limit curve. This approach overcomes the limitation of one coil associating with one performance point in traditional designs, presenting a novel perspective on coil design.

Abstract Soft metamaterials have attracted extensive attention due to their remarkable properties. These materials hold the potential to program and control the morphing behavior of soft machines, however, their combination is limited by the poor reprogrammability of metamaterials and incompatible communication between them. Here, printable and recyclable soft metamaterials possessing reprogrammable embedded intelligence to regulate the morphing of soft machines are introduced. These metamaterials are constructed from interconnected and periodically arranged logic unit cells that are able to perform compound logic operations coupling multiplication and negation. The scalable computation capacity of the unit cell empowers it to simultaneously process multiple fluidic signals with different types and magnitudes, thereby allowing the execution of sophisticated and high‐level control operations. By establishing the laws of physical Boolean algebra and formulating a universal design route, soft metamaterials capable of diverse logic operations can be readily created and reprogrammed. Besides, the metamaterials' potential of directly serving as fluidic processors for soft machines is validated by constructing a soft latched demultiplexer, soft controllers capable of universal and customizable morphing programming, and a reprogrammable processor without reconnection. This work provides a facile way to create reprogrammable soft fluidic control systems to meet on‐demand requirements in dynamic situations.

Introduction Alport syndrome (AS) is one of the most common fatal hereditary renal diseases in human, with a high risk of progressing to end-stage renal disease without effective treatments. Mesenchymal stem cells (MSCs) have recently emerged as a promising therapeutic strategy for chronic kidney disease. However, the safety and therapeutic potential of MSC transfusion for patients with AS are still need to be confirmed. Therefore, we have designed a clinical trial to evaluate the hypothesis that intravenous infusion of human umbilical cord-derived MSC (hUC-MSC) is safe, feasible, and well-tolerated in children with AS.Methods and analysis We report the protocol of the first prospective, open-label, single-arm clinical trial to evaluate the safety and preliminary efficacy of hUC-MSC transfusion in children with early-stage AS. Paediatric patients diagnosed with AS who have persistent albuminuria will be candidates for screening. Twelve eligible patients are planned to recruit and will receive hUC-MSC infusions under close safety monitoring, and complete the efficacy assessments at scheduled follow-up visits. The primary endpoints include the occurrence of adverse events to assess safety and the albuminuria level for efficacy evaluation. Secondary endpoint assessments are based on haematuria and glomerular filtration measurements. Each patient’s efficacy endpoints will be evaluated against their baseline levels. Additionally, the underlying mechanism of hUC-MSC therapy will be explored through transcriptomic and proteomic analysis of blood and urine samples.Ethics and dissemination The protocol (V.1.0, date 17 January 2015) was approved by the institutional review board of the Affiliated Taihe Hospital of Hubei University of Medicine (ethical approval 03 March 2015). Written informed consent will be obtained from the patient and/or guardians before study specific process. In addition to publication in a peer-reviewed scientific journal, a lay summary of study will be available for participants and the public on the Chinese Organization for Rare Disorders website (http://www.cord.org.cn/).Trial registration number ISRCTN62094626.

Abstract Soft fluidic robots have attracted a lot of attention and have broad application prospects. However, poor fluidic power source and easy to damage have been hindering their development, while the lack of intelligent self-protection also brings inconvenience to their applications. Here, we design diversified self-protection soft fluidic robots that integrate soft electrohydrodynamic pumps, actuators, healing electrofluids, and E-skins. We develop high-performance soft electrohydrodynamic pumps, enabling high-speed actuation and large deformation of untethered soft fluidic robots. A healing electrofluid that can form a self-healed film with excellent stretchability and strong adhesion is synthesized, which can achieve rapid and large-areas-damage self-healing of soft materials. We propose multi-functional E-skins to endow robots intelligence, making robots realize a series of self-protection behaviors. Moreover, our robots allow their functionality to be enhanced by the combination of electrodes or actuators. This design strategy enables soft fluidic robots to achieve their high-speed actuation and intelligent self-protection, opening a door for soft robots with physical intelligence.

Abstract Curcumin is a polyphenol extracted from the rhizome of turmeric, and our previous research showed that curcumin inhibited cholesterol absorption and had cholesterol‐lowering effect. Bisphenol A (BPA), a common plasticizer, is widely used in the manufacture of food packaging and is associated with non‐alcoholic fatty liver disease (NAFLD). We hypothesized that curcumin could protect against BPA‐induced hepatic steatosis by inhibiting cholesterol absorption and synthesis. Male CD‐1 mice fed BPA‐contaminated diet with or without curcumin for 24 weeks were used to test our hypothesis. We found that chronic low‐dose BPA exposure significantly increased the levels of serum triglyceride (TG), total cholesterol (TC), and low‐density lipoprotein cholesterol and the contents of liver TG and TC, resulting in liver fat accumulation and hepatic steatosis while curcumin supplementation could alleviate BPA‐induced dyslipidemia and hepatic steatosis. Moreover, the anti‐steatosis and cholesterol‐lowering effects of curcumin against BPA coincided with a significant reduction in intestinal cholesterol absorption and liver cholesterol synthesis, which was modulated by suppressing the expression of sterol regulatory element‐binding protein‐2 (SREBP‐2), Niemann–Pick C1‐like 1 (NPC1L1), and 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMGCR) in the small intestine and liver. In addition, the expression levels of liver lipogenic genes such as liver X receptor alpha (LXRα), SREBP‐1c, acetyl‐CoA carboxylase 1 (ACC1), and ACC2 were also markedly down‐regulated by curcumin. Overall, our findings indicated that curcumin inhibited BPA‐induced intestinal cholesterol absorption and liver cholesterol synthesis by suppressing SREBP‐2, NPC1L1, and HMGCR expression, subsequently reducing liver cholesterol accumulation and fat synthesis, thereby preventing hepatic steatosis and NAFLD.

Bone metabolism is a process in which osteoclasts continuously clear old bone and osteoblasts form osteoid and mineralization within basic multicellular units, which are in a dynamic balance. The process of bone metabolism is affected by many factors, including diet. Reasonable dietary patterns play a vital role in the prevention and treatment of bone-related diseases. In recent years, dietary patterns have changed dramatically. With the continuous improvement in the quality of life, high amounts of sugar, fat and protein have become a part of people’s daily diets. However, people have gradually realized the importance of a healthy diet, intermittent fasting, calorie restriction, a vegetarian diet, and moderate exercise. Although these dietary patterns have traditionally been considered healthy, their true impact on bone health are still unclear. Studies have found that caloric restriction and a vegetarian diet can reduce bone mass, the negative impact of a high-sugar and high-fat dietary (HSFD) pattern on bone health is far greater than the positive impact of the mechanical load, and the relationship between a high-protein diet (HPD) and bone health remains controversial. Calcium, vitamin D, and dairy products play an important role in preventing bone loss. In this article, we further explore the relationship between different dietary patterns and bone health, and provide a reference for how to choose the appropriate dietary pattern in the future and for how to prevent bone loss caused by long-term poor dietary patterns in children, adolescents, and the elderly. In addition, this review provides dietary references for the clinical treatment of bone-related diseases and suggests that health policy makers should consider dietary measures to prevent and treat bone loss.

In this study, a compact and low-power-consumption quantum random number generator (QRNG) based on a laser diode and a hybrid chip with integrated silicon photonics is proposed and verified experimentally. The hybrid chip’s size is 8.8 × 2.6 × 1 mm3, and the power of the entropy source is 80 mW. A common-mode rejection ratio greater than 40 dB was achieved using an optimized 1 × 2 multimode interferometer structure. A method for optimizing the quantum-to-classical noise ratio is presented. A quantum-to-classical noise ratio of approximately 9 dB was achieved when the photoelectron current is 1 μA using a balance homodyne detector with a high dark current GeSi photodiode. The proposed QRNG has the potential for use in scenarios of moderate MHz random number generation speed, with low power, small volume, and low cost prioritized.

Abstract Background Acquired immunodeficiency syndrome (AIDS) is associated with a high rate of pulmonary infections (bacteria, fungi, and viruses). To overcome the low sensitivity and long turnaround time of traditional laboratory-based diagnostic strategies, we adopted metagenomic next-generation sequencing (mNGS) technology to identify and classify pathogens. Results This study enrolled 75 patients with AIDS and suspected pulmonary infections who were admitted to Nanning Fourth People’s Hospital. Specimens were collected for traditional microbiological testing and mNGS-based diagnosis. The diagnostic yields of the two methods were compared to evaluate the diagnostic value (detection rate and turn around time) of mNGS for infections with unknown causative agent. Accordingly, 22 cases (29.3%) had a positive culture and 70 (93.3%) had positive valve mNGS results (P value

Abstract CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH.

Osteosarcoma (OS) patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis. Magnetic hyperthermia therapy (MHT) combined with immunotherapy is an effective strategy to treat solid and metastatic tumors. Here, we combined biodegradable magnesium (Mg) macroscale rods, which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field, and immunotherapy to achieve a radical cure for OS. The eddy thermal effect (ETE) of the Mg rods (MgR) showed outstanding cytotoxic effects and enhanced the maturation of dendritic cells (DCs), and the mild MHT induced the immunogenic cell death (ICD) in the OS cells. Combined with immune checkpoint blockade (ICB) therapy, we obtained an excellent curative effect against OS, and a further evaluation demonstrated that the local MHT induced by the MgR increased T cells infiltration and the polarization of M1 macrophages. Interestingly, the biodegradable MgR also promoted bone osteogenesis. Our work highlighted the uneven ETE mediated by the biodegradable MgR induced a comprehensive immunologic activation in the OS tumor microenvironment (TME), which would inspire the application of MHT for the effective treatment of OS.

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.