A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections.

RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function. A deficiency in RHOH has been linked to epidermodysplasia verruciformis, lung disease, Burkitt lymphoma and T cell defects. Here, we report a novel germline homozygous RHOH c.245G > A (p.Cys82Tyr) variant in a 21-year-old male suffering from recurrent, invasive, opportunistic infections affecting the lungs, eyes, and brain. His sister also succumbed to a lung infection during early adulthood. The patient exhibited a persistent decrease in CD4+ T, B, and NK cell counts, and hypoimmunoglobulinemia. The patient's T cell showed impaired activation upon in vitro TCR stimulation. In Jurkat T cells transduced with RHOHC82Y, a similar reduction in activation marker CD69 up-regulation was observed. Furthermore, the C82Y variant showed reduced RHOH protein expression and impaired interaction with the TCR signaling molecule ZAP70. Together, these data suggest that the newly identified autosomal-recessive RHOH variant is associated with T cell dysfunction and recurrent opportunistic infections, functioning as a hypomorph by disrupting ZAP70-mediated TCR signaling.

Uncoordinated 51-like kinase 1a/b and 2 in fish Megalobrama amblycephala: Molecular cloning, functional characterization, and their potential roles in glucose metabolism.

Uncoordinated (Unc) 51-like kinase (ulk1) and ulk2 are closely involved in autophagy activation, but little is known about their roles in regulating glucose homeostasis. In this study, the genes of ulk1a, ulk1b and ulk2 were cloned and characterized in fish Megalobrama amblycephala. All the three genes shared the approximate N-terminal kinase domain and the C-terminal Atg1-like_tMIT domain structure, while the amino acid sequence identity of them are different between M. amblycephala and other vertebrates. Their transcripts were widely observed in various tissues (brain, muscle, gill, heart, spleen, eye, liver, intestine, abdominal adipose and kidney), but differed in tissue expression patterns. During the glucose tolerance test and the insulin tolerance test, the up-regulated transcriptions of ulk1a, ulk1b and ulk2 were all found despite some differences in the temporal patterns. At the same time, the activities of glycolytic enzymes like hexokinase and phosphofructokinase both showed parallel increases. Furthermore, the feeding of a high-carbohydrate diet decreased the transcriptions of ulk1a, ulk1b and ulk2. Collectively, this study demonstrated that ulk1a, ulk1b and ulk2 in M. amblycephala had similar molecular characterizations, but with different conservation and tissue expression patterns. In addition, ulk1/2 might play important roles in maintaining the glucose homeostasis in fish through regulating the glycolytic pathway.

Finite element study on three osteotomy methods for treating thoracolumbar osteoporotic fracture vertebral collapse complicated with neurological dysfunction.

BACKGROUND: Surgical methods for patients with osteoporotic fracture vertebral collapse complicated with neurological dysfunction are still a topic of debate. We designed an improved osteotomy for the treatment of osteoporotic compression fracture patients with neurological dysfunction. Compared with traditional osteotomy methods such as pedicle subtraction osteotomy (PSO) and bone-disc-bone osteotomy (BDBO), the osteotomy range is reduced. Therefore, we use a finite element method to analyze the biomechanical conditions of these three osteotomy methods and provide a mechanical theoretical basis for the surgical treatment of these three osteotomy methods. METHODS: Based on the CT scan of a patient with L1 osteoporotic fracture vertebral collapse and neurological dysfunction, the finite element model was constructed by importing Mimics software, and three different osteotomy models were established. The forces and displacements of internal fixation device, T1-L5 whole segment, T10 vertebral body, and T10/11 intervertebral disc were recorded under different working conditions. RESULTS: The displacement levels of internal fixation device, T1-L5 spine, T10 vertebral body, and T10/11 intervertebral disc in the modified osteotomy group were between BDBO group and PSO group. The stress in BDBO group was concentrated in titanium mesh and its maximum stress was much higher than that in PSO group and modified osteotomy group. The mechanical distribution of T10/11 intervertebral disc showed that the maximum stress distribution of the three osteotomy methods was similar. CONCLUSION: The relatively simple modified osteotomy has certain advantages in stress and displacement. In contrast, the stability of BDBO group was poor, especially in the lumbar intervertebral disc and lumbar body. For this type of osteotomy patients, it is recommended to avoid postoperative flexion so as not to increase the load.

Vascular stent with immobilized anti-inflammatory chemerin 15 peptides mitigates neointimal hyperplasia and accelerates vascular healing.

Endovascular stenting is a safer alternative to open surgery for use in treating cerebral arterial stenosis and significantly reduces the recurrence of ischemic stroke, but the widely used bare-metal stents (BMSs) often result in in-stent restenosis (ISR). Although evidence suggests that drug-eluting stents are superior to BMSs in the short term, their long-term performances remain unknown. Herein, we propose a potential vascular stent modified by immobilizing clickable chemerin 15 (C15) peptides on the stent surface to suppress coagulation and restenosis. Various characterization techniques and an animal model were used to evaluate the surface properties of the modified stents and their effects on endothelial injury, platelet adhesion, and inflammation. The C15-immobilized stent could prevent restenosis by minimizing endothelial injury, promoting physiological healing, restraining the platelet-leukocyte-related inflammatory response, and inhibiting vascular smooth muscle cell proliferation and migration. Furthermore, in vivo studies demonstrated that the C15-immobilized stent mitigated inflammation, suppressed neointimal hyperplasia, and accelerated endothelial restoration. The use of surface-modified, anti-inflammatory, endothelium-friendly stents may be of benefit to patients with arterial stenosis. STATEMENT OF SIGNIFICANCE: Endovascular stenting is increasingly used for cerebral arterial stenosis treatment, aiming to prevent and treat ischemic stroke. But an important accompanying complication is in-stent restenosis (ISR). Persistent inflammation has been established as a hallmark of ISR and anti-inflammation strategies in stent modification proved effective. Chemerin 15, an inflammatory resolution mediator with 15-aa peptide, was active at picomolar through cell surface receptor, no need to permeate cell membrane and involved in resolution of inflammation by inhibiting inflammatory cells adhesion, modulating macrophage polarization into protective phenotype, and reducing inflammatory factors release. The implications of this study are that C15 immobilized stent favors inflammation resolution and rapid re-endothelialization, and exhibits an inhibitory role of restenosis. As such, it helps the decreased incidence of ISR.

Activating CD8+ T Cells by Pt(IV) Prodrug-Based Nanomedicine and aPD-L1 Antibody for Enhanced Cancer Immunotherapy.

Recent years have witnessed substantial progress in cancer immunotherapy, specifically T cell-based therapies. However, the application of T cell therapies has been primarily limited to hematologic malignancies, with limited success in the treatment of solid tumors. The main challenge in treating solid tumor is immune escape, which is characterized by reduced antigenicity, diminished immunogenicity, and the development of suppressive tumor immune microenvironments. To address these obstacles and restore T cell-mediated anti-tumor responses, a novel nanoparticle formulation known as PRA@Oxa-c16 is developed. This innovative approach combines retinoic acid and Pt(IV) to specifically target and overcome immune escape. Notably, the therapeutic efficacy of PRA@Oxa-c16 primarily relies on its ability to induce anti-tumor T cell responses, in contrast to the cytotoxicity associated with conventional chemotherapeutic agents. When combined with an immune checkpoint blockade, anti-programmed death-ligand 1 antibody, PRA@Oxa-c16 effectively eliminates solid tumors and induces immune memory responses, which prevent tumor metastasis and recurrence. This promising approach holds great potential for enhancing the treatment of solid tumors with T cell-based immunotherapy.

Chestnut-Inspired Hollow Hydroxyapatite 3D Printing Scaffolds Accelerate Bone Regeneration by Recruiting Calcium Ions and Regulating Inflammation.

This study aims to overcome the drawbacks associated with hydroxyapatite (HAP) dense structures after sintering, which often result in undesirable features such as large grain size, reduced porosity, high crystallinity, and low specific surface area. These characteristics hinder osseointegration and limit the clinical applicability of the material. To address these issues, a new method involving the preparation of hollow hydroxyapatite (hHAP) microspheres has been proposed. These microspheres exhibit distinctive traits including weak crystallization, high specific surface area, and increased porosity. The weak crystallization aligns more closely with early mineralization products found in the human body and animals. Moreover, the microspheres' high specific surface area and porosity offer advantages for protein loading and facilitating osteoblast attachment. This innovative approach not only mitigates the limitations of conventional HAP structures but also holds the potential for improving the effectiveness of hydroxyapatite in biomedical applications, particularly in enhancing osseointegration. Three-dimensional printed hHAP/chitosan (CS) scaffolds with different hHAP concentration gradients were manufactured, and the physical and biological properties of each group were systematically evaluated. In vitro and in vivo experiments show that the hHAP/CS scaffold has excellent performance in bone remodeling. Furthermore, in-scaffold components, hHAP and CS were cocultured with bone marrow mesenchymal stem cells to explore the regulatory role of hHAP and CS in the process of bone healing and to reveal the cell-level specific regulatory network activated by hHAP. Enrichment analysis showed that hHAP can promote bone regeneration and reconstruction by recruiting calcium ions and regulating inflammatory reactions.

DLP fabrication of HA scaffold with customized porous structures to regulate immune microenvironment and macrophage polarization for enhancing bone regeneration.

The immune microenvironment plays a pivotal role in osteoanagenesis. Biomaterials can modulate osteogenic efficacy by inducing specific local immune reactions. As 3D-printing technology advances, digital light projection printing has emerged as a promising method for creating large scale, high-precision biomaterial scaffolds. By adjusting the solid content and the sintering conditions during printing, the pore size of biomaterials can be meticulously controlled. Yet, the systematic influence of pore size on the immune microenvironment remains uncharted. We fabricated 3D-printed hydroxyapatite bioceramic scaffolds with three distinct pore sizes: 400 µm, 600 µm, and 800 µm. Our study revealed that scaffolds with a pore size of 600 µm promote macrophage M2 polarization, which is achieved by upregulating interferon-beta and HIF-1α production. When these materials were implanted subcutaneously in rats and within rabbit skulls, we observed that the 600 µm scaffolds notably improved the long-term inflammatory response, fostered vascular proliferation, and augmented new bone growth. This research paves the way for innovative therapeutic strategies for treating large segmental bone defects in clinical settings.

Programmable and Weldable Superelastic EGaIn/TPU Composite Fiber by Wet Spinning for Flexible Electronics.

As an essential component of flexible electronics, superelastic conductive fibers with good mechanical and electrical properties have drawn significant attention, especially in their preparation. In this study, we prepared a superelastic conductive fiber composed of eutectic gallium-indium (EGaIn) and thermoplastic polyurethane (TPU) by simple wet spinning. The composite conductive fiber with a liquid metal (LM) content of 85 wt % achieved a maximum strain at a break of 659.2%, and after the conductive pathway in the porous structure of the composite fibers was fully activated, high conductivity (1.2 × 105 S/m) was achieved with 95 wt % LM by mechanical sintering and training processes. The prepared conductive fibers exhibited a stable resistive response as the fibers were strained and could be sewn into fabrics and used as wearable strain sensors to monitor various human motions. These conductive fibers can be molded into helical by heating, and they have excellent electrical properties at a maximum mechanical strain of 3400% (resistance change <0.27%) with a helical index of 11. Moreover, the conductive fibers can be welded to various two or three-dimensional conductors. In summary, with a scalable manufacturing process, weldability, superelasticity, and high electrical conductivity, EGaIn/TPU composite fibers fabricated by wet spinning have considerable potential for flexible electronics.

The association between basal metabolic rate and osteoarthritis: a Mendelian randomization study.

BACKGROUND: The role of the basal metabolic rate (BMR) in osteoarthritis (OA) remains unclear, as previous retrospective studies have produced inconsistent results. Therefore, we performed a Mendelian randomization (MR) study to systematically investigate the causal relationship between the BMR and OA. METHODS: Single-nucleotide polymorphism (SNP) data related to BMR and OA were collected in a genome-wide association study. Using OA as the outcome variable and BMR as the exposure factor, SNPs with strong correlation with the BMR as the tool variable were screened. The correlation between the BMR and OA risk was evaluated using the inverse-variance weighted method, and heterogeneity and pleiotropy were evaluated using a sensitivity analysis. RESULTS: There was a potential causal relationship between the BMR and OA risk (odds ratio [OR], 1.014; 95% confidence interval [CI], 1.008-1.020; P = 2.29e - 6). A causal relationship was also revealed between the BMR and knee OA (OR, 1.876; 95% CI, 1.677-2.098; P = 2.98e - 28) and hip OA (OR, 1.475; 95% CI, 1.290-1.686; P = 1.26e - 8). Sensitivity analysis confirmed the robustness of these results. CONCLUSION: Here, we identified a latent causal relationship between the BMR and the risk of OA. These results suggest that the risk of OA in the hip or knee joint may be reduced by controlling the BMR.

SMC1A facilitates gastric cancer cell proliferation, migration, and invasion via promoting SNAIL activated EMT.

BACKGROUND: Structural maintenance of chromosomes protein 1 A (SMC1A) is a crucial subunit of the cohesion protein complex and plays a vital role in cell cycle regulation, genomic stability maintenance, chromosome dynamics. Recent studies demonstrated that SMC1A participates in tumorigenesis. This reseach aims to explore the role and the underlying mechanisms of SMC1A in gastric cancer (GC). MATERIALS AND METHODS: RT-qPCR and western blot were used to examine the expression levels of SMC1A in GC tissues and cell lines. The role of SMC1A on GC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were analyzed. Furthermore,the mechanism of SMC1A action was investigated. RESULTS: SMC1A was highly expressed in GC tissues and cell lines. The high expression of SMC1A indicated the poor overall survival of GC patients from Kaplan-Meier Plotter. Enhancing the expression of SMC1A in AGS cells remarkably promoted cell proliferation in vitro and in vivo, migration and invasion, Conversely, knockdown of SMC1A in HGC27 cells inhibited cell proliferation, migration and invasion. Moreover, it's observed that SMC1A promoted EMT and malignant cell behaviors via regulating SNAIL. CONCLUSION: Our study revealed that SMC1A promotes EMT process by upregulating SNAIL, which contributes to gastric cancer cell proliferation, migration and invasion. Therefore, targeting SMC1A may be a potential strategy to improve GC therapy.

Flexible BaTiO3-PDMS Capacitive Pressure Sensor of High Sensitivity with Gradient Micro-Structure by Laser Engraving and Molding.

The significant potential of flexible sensors in various fields such as human health, soft robotics, human-machine interaction, and electronic skin has garnered considerable attention. Capacitive pressure sensor is popular given their mechanical flexibility, high sensitivity, and signal stability. Enhancing the performance of capacitive sensors can be achieved through the utilization of gradient structures and high dielectric constant media. This study introduced a novel dielectric layer, employing the BaTiO3-PDMS material with a gradient micro-cones architecture (GMCA). The capacitive sensor was constructed by incorporating a dielectric layer GMCA, which was fabricated using laser engraved acrylic (PMMA) molds and flexible copper-foil/polyimide-tape electrodes. To examine its functionality, the prepared sensor was subjected to a pressure range of 0-50 KPa. Consequently, this sensor exhibited a remarkable sensitivity of up to 1.69 KPa-1 within the pressure range of 0-50 KPa, while maintaining high pressure-resolution across the entire pressure spectrum. Additionally, the pressure sensor demonstrated a rapid response time of 50 ms, low hysteresis of 0.81%, recovery time of 160 ms, and excellent cycling stability over 1000 cycles. The findings indicated that the GMCA pressure sensor, which utilized a gradient structure and BaTiO3-PDMS material, exhibited notable sensitivity and a broad linear pressure range. These results underscore the adaptability and viability of this technology, thereby facilitating enhanced flexibility in pressure sensors and fostering advancements in laser manufacturing and flexible devices for a wider array of potential applications.

Associating Multimodal Neuroimaging Abnormalities With the Transcriptome and Neurotransmitter Signatures in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Schizophrenia is a multidimensional disease. This study proposes a new research framework that combines multimodal meta-analysis and genetic/molecular architecture to solve the consistency in neuroimaging biomarkers of schizophrenia and whether these link to molecular genetics. STUDY DESIGN: We systematically searched Web of Science, PubMed, and BrainMap for the amplitude of low-frequency fluctuations (ALFF) or fractional ALFF, regional homogeneity, regional cerebral blood flow, and voxel-based morphometry analysis studies investigating schizophrenia. The pooled-modality, single-modality, and illness duration-dependent meta-analyses were performed using the activation likelihood estimation algorithm. Subsequently, Spearman correlation and partial least squares regression analyses were conducted to assess the relationship between identified reliable convergent patterns of multimodality and neurotransmitter/transcriptome, using prior molecular imaging and brain-wide gene expression. STUDY RESULTS: In total, 203 experiments comprising 10 613 patients and 10 461 healthy controls were included. Multimodal meta-analysis showed that brain regions of significant convergence in schizophrenia were mainly distributed in the frontotemporal cortex, anterior cingulate cortex, insula, thalamus, striatum, and hippocampus. Interestingly, the analyses of illness-duration subgroups identified aberrant functional and structural evolutionary patterns: Lines from the striatum to the cortical core networks to extensive cortical and subcortical regions. Subsequently, we found that these robust multimodal neuroimaging abnormalities were associated with multiple neurobiological abnormalities, such as dopaminergic, glutamatergic, serotonergic, and GABAergic systems. CONCLUSIONS: This work links transcriptome/neurotransmitters with reliable structural and functional signatures of brain abnormalities underlying disease effects in schizophrenia, which provides novel insight into the understanding of schizophrenia pathophysiology and targeted treatments.

Hollow Hydroxyapatite Microspheres Loaded with rhCXCL13 to Recruit BMSC for Osteogenesis and Synergetic Angiogenesis to Promote Bone Regeneration in Bone Defects.

Introduction: Bone tissue engineering is a promising method to treat bone defects. However, the current methods of preparing composite materials that mimic the complex structure and biological activity of natural bone are challenging for recruitment of bone marrow mesenchymal stem cells (BMSCs), which affects the application of these materials in situ bone regeneration. Hollow hydroxyapatite microspheres (HHMs) possess a natural porous bone structure, good adsorption, and slow release of chemokines, but have low ability to recruit BMSCs and induce osteogenesis. In this study, The HHM/chitosan (CS) and recombinant human C-X-C motif chemokine ligand 13 (rhCXCL13)-HHM/CS biomimetic scaffolds that optimize bone regeneration and investigated their mechanism of BMSC recruitment and osteogenesis through cell and animal experiments and transcriptomic sequencing. Methods: Evaluate the physical characteristics of the HHM/CS and rhCXCL13-HHM/CS biomimetic scaffolds through Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), and the cumulative release curve of rhCXCL13. Transwell migration experiments and co-culture with BMSCs were conducted to study the recruitment ability and osteogenic differentiation of the scaffolds. Transcriptomic sequencing was performed to analyze the osteogenic differentiation mechanism. The osteogenesis and bone healing performance were evaluated using a rabbit radial defect model. Results: SEM demonstrated that the rhCXCL13-HHM/CS scaffold comprised hydroxyapatite microspheres in a porous three-dimensional network. The rhCXCL13 showed excellent sustained release capability. The rhCXCL13-HHM/CS scaffold could recruit BMSCs and induce bone regeneration. Transcriptome sequencing and experimental results showed that the osteogenesis mechanism of rhCXCL13-HHM/CS was through the PI3K-AKT pathway. In vivo, the rhCXCL13-HHM/CS scaffold significantly promoted osteogenesis and angiogenesis at 12 weeks after surgery. Conclusion: The rhCXCL13-HHM/CS scaffold demonstrates excellent potential for BMSC recruitment, osteogenesis, vascularized tissue-engineered bone reconstruction, and drug delivery, providing a theoretical basis for material osteogenesis mechanism study and promising clinical applications for treating large bone defects.

Progressive trajectories of schizophrenia across symptoms, genes, and the brain.

BACKGROUND: Schizophrenia is characterized by complex psychiatric symptoms and unclear pathological mechanisms. Most previous studies have focused on the morphological changes that occur over the development of the disease; however, the corresponding functional trajectories remain unclear. In the present study, we aimed to explore the progressive trajectories of patterns of dysfunction after diagnosis. METHODS: Eighty-six patients with schizophrenia and 120 healthy controls were recruited as the discovery dataset. Based on multiple functional indicators of resting-state brain functional magnetic resonance imaging, we conducted a duration-sliding dynamic analysis framework to investigate trajectories in association with disease progression. Neuroimaging findings were associated with clinical symptoms and gene expression data from the Allen Human Brain Atlas database. A replication cohort of patients with schizophrenia from the University of California, Los Angeles, was used as the replication dataset for the validation analysis. RESULTS: Five stage-specific phenotypes were identified. A symptom trajectory was characterized by positive-dominated, negative ascendant, negative-dominated, positive ascendant, and negative surpassed stages. Dysfunctional trajectories from primary and subcortical regions to higher-order cortices were recognized; these are associated with abnormal external sensory gating and a disrupted internal excitation-inhibition equilibrium. From stage 1 to stage 5, the importance of neuroimaging features associated with behaviors gradually shifted from primary to higher-order cortices and subcortical regions. Genetic enrichment analysis identified that neurodevelopmental and neurodegenerative factors may be relevant as schizophrenia progresses and highlighted multiple synaptic systems. CONCLUSIONS: Our convergent results indicate that progressive symptoms and functional neuroimaging phenotypes are associated with genetic factors in schizophrenia. Furthermore, the identification of functional trajectories complements previous findings of structural abnormalities and provides potential targets for drug and non-drug interventions in different stages of schizophrenia.

HLA-DQA1 expression is associated with prognosis and predictable with radiomics in breast cancer.

BACKGROUND: High HLA-DQA1 expression is associated with a better prognosis in many cancers. However, the association between HLA-DQA1 expression and prognosis of breast cancer and the noninvasive assessment of HLA-DQA1 expression are still unclear. This study aimed to reveal the association and investigate the potential of radiomics to predict HLA-DQA1 expression in breast cancer. METHODS: In this retrospective study, transcriptome sequencing data, medical imaging data, clinical and follow-up data were downloaded from the TCIA ( https://www.cancerimagingarchive.net/ ) and TCGA ( https://portal.gdc.cancer.gov/ ) databases. The clinical characteristic differences between the high HLA-DQA1 expression group (HHD group) and the low HLA-DQA1 expression group were explored. Gene set enrichment analysis, Kaplan‒Meier survival analysis and Cox regression were performed. Then, 107 dynamic contrast-enhanced magnetic resonance imaging features were extracted, including size, shape and texture. Using recursive feature elimination and gradient boosting machine, a radiomics model was established to predict HLA-DQA1 expression. Receiver operating characteristic (ROC) curves, precision-recall curves, calibration curves, and decision curves were used for model evaluation. RESULTS: The HHD group had better survival outcomes. The differentially expressed genes in the HHD group were significantly enriched in oxidative phosphorylation (OXPHOS) and estrogen response early and late signalling pathways. The radiomic score (RS) output from the model was associated with HLA-DQA1 expression. The area under the ROC curves (95% CI), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the radiomic model were 0.866 (0.775-0.956), 0.825, 0.939, 0.7, 0.775, and 0.913 in the training set and 0.780 (0.629-0.931), 0.659, 0.81, 0.5, 0.63, and 0.714 in the validation set, respectively, showing a good prediction effect. CONCLUSIONS: High HLA-DQA1 expression is associated with a better prognosis in breast cancer. Quantitative radiomics as a noninvasive imaging biomarker has potential value for predicting HLA-DQA1 expression.

Study on the influence of scaffold morphology and structure on osteogenic performance.

The number of patients with bone defects caused by various bone diseases is increasing yearly in the aging population, and people are paying increasing attention to bone tissue engineering research. Currently, the application of bone tissue engineering mainly focuses on promoting fracture healing by carrying cytokines. However, cytokines implanted into the body easily cause an immune response, and the cost is high; therefore, the clinical treatment effect is not outstanding. In recent years, some scholars have proposed the concept of tissue-induced biomaterials that can induce bone regeneration through a scaffold structure without adding cytokines. By optimizing the scaffold structure, the performance of tissue-engineered bone scaffolds is improved and the osteogenesis effect is promoted, which provides ideas for the design and improvement of tissue-engineered bones in the future. In this study, the current understanding of the bone tissue structure is summarized through the discussion of current bone tissue engineering, and the current research on micro-nano bionic structure scaffolds and their osteogenesis mechanism is analyzed and discussed.

Effect of basal metabolic rate on osteoporosis: A Mendelian randomization study.

Purpose: Basal metabolic rate may play a key role in the pathogenesis and progression of osteoporosis. We performed Mendelian random analysis to evaluate the causal relationship between basal metabolic rate and osteoporosis. Methods: Instrumental variables for the basal metabolic rate were selected. We used the inverse variance weighting approach as the main Mendelian random analysis method to estimate causal effects based on the summary-level data for osteoporosis from genome-wide association studies. Results: A potential causal association was observed between basal metabolic rate and risks of osteoporosis (odds ratio = 0.9923, 95% confidence interval: 0.9898-0.9949; P = 4.005e - 09). The secondary MR also revealed that BMR was causally associated with osteoporosis (odds ratio = 0.9939, 95% confidence interval: 0.9911-0.9966; P = 1.038e - 05). The accuracy and robustness of the findings were confirmed using sensitivity tests. Conclusion: Basal metabolic rate may play a causal role in the development of osteoporosis, although the underlying mechanisms require further investigation.

High-accuracy calibration method for an underwater one-mirror galvanometric laser scanner.

Three-dimensional (3D) perception of deep-sea targets is the key to autonomous operation of underwater equipment (e.g., underwater robots). Underwater one-mirror galvanometric line-laser scanner has advantages for short-range measurement, but it is difficult to achieve high calibration accuracy due to installation errors and refraction effects. For this reason, in this paper, a high-accuracy refraction-considered and installation-error-independent calibration method is proposed for the vision system. Firstly, to address the difficulty of aligning the incident light plane with the galvanometer shaft, a high-accuracy land-based installation-error-independent model is proposed, which avoids the influence of the installation errors and allows the real shaft axis and the light-plane cluster poses to be calculated using only three light planes. Subsequently, considering the underwater refraction, a 3D model is established for simulating refractive behaviors of the light-plane cluster, and then a partition-based method is proposed for calibrating the underwater light-plane cluster, which further improves the calibration accuracy of the scanner in underwater measurement scenarios. Finally, a one-mirror galvanometric laser scanner is developed in the laboratory to verify the calibration accuracy and to perform the 3D measurement experiments of underwater targets. The results show that the calibration accuracy of the proposed land-based installation-error-independent model is improved 2 times more compared with the traditional installation-error-dependent model. Additionally, the measurement accuracy of the scanner for the standard sphere is 11.98 µm and 12.75 µm in the air and underwater measurement scenarios, and the two measurements are in good agreement. The above results comprehensively verify the high accuracy of the calibration method proposed in this paper.

Ginsenoside Rg3 Ameliorates DSS-Induced Colitis by Inhibiting NLRP3 Inflammasome Activation and Regulating Microbial Homeostasis.

Ulcerative colitis (UC) is a recurrent inflammatory disease without a specific cure or treatment for improvement. Here, we investigated the potential therapeutic effect and mechanism of ginsenoside Rg3 (Gin Rg3) on UC. We constructed an in vitro cellular inflammatory model and a dextran sulfate sodium (DSS)-induced UC mouse model. We also used Gin Rg3, MCC950 (NLRP3 inhibitor), MSU (NLRP3 activator), and fecal transplantation (FMT) to intervene the model. The results showed that Gin Rg3 inhibited NLRP3 inflammasome activation, pyroptosis, and apoptosis in vitro and in vivo. DSS-induced changes in the abundance of gut microbiota at the phylum or genus level were partially restored by Gin Rg3. Furthermore, gin Rg3 affected intestinal metabolism in mice by inhibiting the activation of NLRP3 inflammasome. The gut microbiota treated with Gin Rg3 was sufficient to alleviate DSS-induced UC. In summary, Gin Rg3 alleviated DSS-induced UC by inhibiting NLRP3 inflammasome activation and regulating gut microbiota homeostasis.

Intrinsic Therapeutic Link between Recuperative Cerebellar Con-Nectivity and Psychiatry Symptom in Schizophrenia Patients with Comorbidity of Metabolic Syndrome.

Components of metabolic syndrome might be predictors of the therapeutic outcome of psychiatric symptom in schizophrenia, whereas clinical results are inconsistent and an intrinsic therapeutic link between weaker psychiatric symptoms and emergent metabolic syndrome remains unclear. This study aims to reveal the relationship and illustrate potential mechanism by exploring the alteration of cerebellar functional connectivity (FC) in schizophrenia patients with comorbidity metabolic syndrome. Thirty-six schizophrenia patients with comorbidity of metabolic syndrome (SCZ-MetS), 45 schizophrenia patients without metabolic syndrome (SCZ-nMetS) and 39 healthy controls (HC) were recruited in this study. We constructed FC map of cerebello-cortical circuit and used moderation effect analysis to reveal complicated relationship among FC, psychiatric symptom and metabolic disturbance. Components of metabolic syndrome were significantly correlated with positive symptom score and negative symptom score. Importantly, the dysconnectivity between cognitive module of cerebellum and left middle frontal gyrus in SCZ-nMetS was recuperative increased in SCZ-MetS, and was significantly correlated with general symptom score. Finally, we observed significant moderation effect of body mass index on this correlation. The present findings further supported the potential relationship between emergence of metabolic syndrome and weaker psychiatric symptom, and provided neuroimaging evidence. The mechanism of intrinsic therapeutic link involved functional change of cerebello-cortical circuit.