Survival benefit of adjuvant TACE for patients with hepatocellular carcinoma and child-pugh B7 or B8 after hepatectomy.

BACKGROUND & AIMS: The benefit of postoperative adjuvant transcatheter arterial chemoembolization (pTACE) for patients with hepatocellular carcinoma (HCC), especially those with Child-Pugh (CP) B, remains controversial. This study aimed to assess the survival benefit of pTACE for HCC patients with CP B. METHODS: Data from 297 HCC patients with CP B7 or B8 were analyzed, dividing them into groups with and without pTACE (70, 23.6% vs. 227, 76.4%). Propensity score matching (PSM) was used to control for confounding bias, and competing-risk regression was applied to address bias from non-cancer-specific death (NCSD). RESULTS: Preliminary findings suggest that pTACE did not increase the incidence of severe complications in HCC patients with CP B7 or B8. Survival analysis indicated that the group receiving pTACE had better overall survival and recurrence-free survival than the group without pTACE after PSM. Furthermore, competitive risk analysis revealed that pTACE was an independent prognostic factor associated with reduced cancer-specific death incidence (subdistribution hazard ratio [SHR] 0.644, 95%CI: 0.378-0.784, P = 0.011) and recurrence (SHR 0.635, 95% CI: 0.379-0.855, P = 0.001). Importantly, pTACE did not increase NCSD. Subgroup analysis corroborated these results. CONCLUSION: Adjuvant TACE demonstrates the potential to significantly enhance the long-term prognosis of HCC patients with CP B7 or B8 following hepatectomy, particularly those with multiple tumors, large tumor size, macrovascular or microvascular invasion, and narrow resection margin. Hence, pTACE should be considered for patients at high risk of recurrence following thorough evaluation.

Antimicrobial activity of novel symmetrical antimicrobial peptides centered on a hydrophilic motif against resistant clinical isolates: in vitro and in vivo analyses.

Antibiotic resistance poses a significant public health threat worldwide. The rise in antibiotic resistance and the sharp decline in effective antibiotics necessitate the development of innovative antibacterial agents. Based on the central symmetric structure of glycine-serine-glycine, combined with tryptophan and arginine, we designed a range of antimicrobial peptides (AMPs) that exhibited broad-spectrum antibacterial activity. Notably, AMP W5 demonstrated a rapid and effective sterilization against methicillin-resistant Staphylococcus aureus (MRSA), displaying both a minimum inhibitory concentration and a minimum bactericidal concentration of 8 µM. Mechanistic studies revealed that AMP W5 killed bacterial cells by disrupting the cytoplasmic membrane integrity, triggering leakage of cell contents. AMP W5 also exhibited excellent biocompatibility in both in vitro and in vivo safety evaluations. AMP W5 treatment significantly reduced skin bacterial load in our murine skin infection model. In conclusion, we designed a novel centrosymmetric AMP representing a promising medical alternative to conventional antibiotics for treating MRSA infections. IMPORTANCE: Increasing antibiotic resistance and the paucity of effective antibiotics necessitate innovative antibacterial agents. Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen causing bacterial infections with high incidence and mortality rates, showing increasing resistance to clinical drugs. Antimicrobial peptides (AMPs) exhibit significant potential as alternatives to traditional antibiotics. This study designed a novel series of AMPs, characterized by a glycine-serine-glycine-centered symmetrical structure, and our results indicated that AMP W5 exhibited a rapid and effective bactericidal effect against MRSA. AMP W5 also demonstrated excellent biocompatibility and a bactericidal mechanism that disrupted membrane integrity, leading to leakage of cellular contents. The notable reduction in skin bacterial load observed in mouse models reinforced the clinical applicability of AMP W5. This study provides a promising solution for addressing the increasing threat of antibiotic-resistant bacteria and heralds new prospects for clinical applications.

EDDS application destabilizes soil organic matter in phytoremediation: Insights from quantity and molecular composition of dissolved organic matter.

The stability of soil organic matter (SOM) is crucial for metal transport and carbon cycling. S,S-ethylenediaminedisuccinic acid (EDDS) is widely used to enhance phytoremediation efficiency for heavy metals in contaminated soils, yet its specific impacts on SOM have been underexplored. This study investigates the effects of EDDS on SOM stability using a rhizobox experiment with ryegrass. Changes in soil dissolved organic matter (DOM) quantity and molecular composition were analyzed via Fourier transform ion cyclotron resonance mass spectrometry. Results showed that the use of EDDS increased the uptake of Cu, Cd and Pb by ryegrass, but simultaneously induced the destabilization and transformation of SOM. After 7 days of EDDS application, dissolved organic carbon (DOC) and nitrogen (DON) concentrations in rhizosphere soils increased significantly by 3.44 and 10.2 times, respectively. In addition, EDDS reduced lipids (56.3%) and proteins/amino sugars-like compounds (52.1%), while increasing tannins (9.11%) and condensed aromatics-like compounds (24.4%) in the rhizosphere DOM. These effects likely stem from EDDS's dual action: extracting Fe/Al from SOM-mineral aggregates, releasing SOM into the DOM pool, and promoting microbial degradation of bioavailable carbon through chain scission and dehydration. Our study firstly revealed that the application of EDDS in phytoremediation increased the mineralization of SOM and release of CO2 from soil to the atmosphere, which is important to assess the carbon budget of phytoremediation and develop climate-smart strategy in future.

Efficacy and prognostic factors of stereotactic body radiotherapy combined with immunotherapy for pulmonary oligometastases: a preliminary retrospective cohort study.

Background: Stereotactic body radiotherapy (SBRT) combined immunotherapy has a synergistic effect on patients with stage IV tumors. However, the efficacy and prognostic factors analysis of SBRT combined immunotherapy for patients with pulmonary oligometastases have rarely been reported in the studies. The purpose of this study is to explore the efficacy and prognostic factors analysis of SBRT combined immunotherapy for patients with oligometastatic lung tumors. Methods: A retrospective analysis was conducted on 43 patients with advanced tumors who received SBRT combined with immunotherapy for pulmonary oligometastases from October 2018 to October 2021. Local control (LC), progression-free survival (PFS), and overall survival (OS) were assessed using the Kaplan-Meier method. Univariate and multivariate analyses of OS were performed using the Cox regression model, and the P value <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve of neutrophil-to-lymphocyte ratio (NLR) after SBRT was generated. Spearman correlation analysis was used to determine the relationship of planning target volume (PTV) with absolute lymphocyte count (ALC) before and after SBRT and with neutrophil count (NE) after SBRT. Additionally, linear regression was used to examine the relationship between ALC after SBRT and clinical factors. Results: A total of 43 patients with pulmonary oligometastases receiving SBRT combined with immunotherapy were included in the study. The change in NLR after SBRT was statistically significant (P<0.001). At 1 and 2 years, respectively, the LC rates were 90.3% and 87.5%, the OS rates were 83.46% and 60.99%, and the PFS rates were 69.92% and 54.25%, with a median PFS of 27.00 (17.84-36.13) months. Univariate and multivariate Cox regression analyses showed that a shorter interval between radiotherapy and immunization [≤21 days; hazard ratio (HR) =1.10, 95% confidence interval (CI): 0.06-0.89; P=0.02] and a low NLR after SBRT (HR =0.24, 95% CI: 1.01-1.9; P=0.03) were associated with improved OS. The ROC curve identified 4.12 as the cutoff value for predicting OS based on NLR after SBRT. NLR after SBRT ≤4.12 significantly extended OS compared to NLR after SBRT >4.12 (log-rank P=0.001). Spearman correlation analysis and linear regression analysis showed that PTV was negatively correlated with ALC after SBRT. Conclusions: Our preliminary research shows that SBRT combined with immunotherapy has a good effect, and NLR after SBRT is a poor prognostic factor for OS. Larger PTV volume is associated with decreased ALC after SBRT.

Point-based risk score for the risk stratification and prediction of hepatocellular carcinoma: a population-based random survival forest modeling study.

Background: The precise associations between common clinical biomarkers and hepatocellular carcinoma (HCC) risk remain unclear but hold valuable insights for HCC risk stratification and prediction. Methods: We examined the linear and nonlinear associations between the baseline levels of 32 circulating biomarkers and HCC risk in the England cohort of UK Biobank (UKBB) (n = 397,702). The participants were enrolled between 2006 and 2010 and followed up to 31st October 2022. The primary outcome is incident HCC cases. We then employed random survival forests (RSF) to select the top ten most informative biomarkers, considering their association with HCC, and developed a point-based risk score to predict HCC. The performance of the risk score was evaluated in three validation sets including UKBB Scotland and Wales cohort (n = 52,721), UKBB non-White-British cohort (n = 29,315), and the Taizhou Longitudinal Study in China (n = 17,269). Findings: Twenty-five biomarkers were significantly associated with HCC risk, either linearly or nonlinearly. Based on the RSF model selected biomarkers, our point-based risk score showed a concordance index of 0.866 in the England cohort and varied between 0.814 and 0.849 in the three validation sets. HCC incidence rates ranged from 0.95 to 30.82 per 100,000 from the lowest to the highest quintiles of the risk score in the England cohort. Individuals in the highest risk quintile had a 32-73 times greater risk of HCC compared to those in the lowest quintile. Moreover, over 70% of HCC cases were detected in individuals within the top risk score quintile across all cohorts. Interpretation: Our simple risk score enables the identification of high-risk individuals of HCC in the general population. However, including some biomarkers, such as insulin-like growth factor 1, not routinely measured in clinical practice may increase the model's complexity, highlighting the need for more accessible biomarkers that can maintain or improve the predictive accuracy of the risk score. Funding: This work was supported by the National Natural Science Foundation of China (grant numbers: 82204125) and the Science and Technology Support Program of Taizhou (TS202224).

Phase II control charts for monitoring the depth-ratio of ball-bearings involving three normal variables.

This paper investigates the problem of monitoring the ratio involving three variables, jointly distributed as trivariate normal. The Shewhart-type and two exponentially weighted moving average (EWMA) type schemes for monitoring depth ratio are proposed. The ratio of a normal variable to the average of two other normal variables has wide applications in natural science, production, and engineering. It is defined with slightly different terminology in various contexts, such as depth or aspect ratios. In modern bearing manufacturing, the aspect ratio of width to the average of inner and outer diameters can be an essential indicator of product quality and process stability. While there are many helpful existing charts for monitoring the three components separately or jointly when these characteristics follow a normal distribution, the ratio aspect is often ignored. The Shewhart-type schemes' exact and approximated control limits are considered and analyzed. Numerical results based on Monte-Carlo are conducted using the average run length as a metric with different values of in-control ratio and correlation between the three variables. An application based on the parts manufacturing data illustrates the implementation design of the two control charts. The real-life data analysis shows the efficacy of the proposed monitoring schemes in practice.

Use of high-resolution fluorescence in situ hybridization for fast and robust detection of SARS-CoV-2 RNAs.

Early, rapid, and accurate diagnostic tests play critical roles not only in the identification/management of individuals infected by SARS-CoV-2, but also in fast and effective public health surveillance, containment, and response. Our aim has been to develop a fast and robust fluorescence in situ hybridization (FISH) detection method for detecting SARS-CoV-2 RNAs by using an HEK 293 T cell culture model. At various times after being transfected with SARS-CoV-2 E and N plasmids, HEK 293 T cells were fixed and then hybridized with ATTO-labeled short DNA probes (about 20 nt). At 4 h, 12 h, and 24 h after transfection, SARS-CoV-2 E and N mRNAs were clearly revealed as solid granular staining inside HEK 293 T cells at all time points. Hybridization time was also reduced to 1 h for faster detection, and the test was completed within 3 h with excellent results. In addition, we have successfully detected 3 mRNAs (E mRNA, N mRNA, and ORF1a (-) RNA) simultaneously inside the buccal cells of COVID-19 patients. Our high-resolution RNA FISH might significantly increase the accuracy and efficiency of SARS-CoV-2 detection, while significantly reducing test time. The method can be conducted on smears containing cells (e.g., from nasopharyngeal, oropharyngeal, or buccal swabs) or smears without cells (e.g., from sputum, saliva, or drinking water/wastewater) for detecting various types of RNA viruses and even DNA viruses at different timepoints of infection.

Mechanism and kinetics of thermal decomposition of decabromobiphenyl: Reaction with reactive radicals and formation chemistry of polybrominated dibenzofurans.

Although the production and usage of polybrominated biphenyls (PBBs) as brominated flame retardants have already been prohibited, they still pose a threat to the environment and human health. However, the evolutionary behaviors and decomposition mechanisms of PBBs during thermal treatment of waste remain unclear. In the present work, the mechanism and kinetics of thermal decomposition of decabromobiphenyl (deca-BB), one of the most frequently-used PBB congeners, are studied in detail using quantum chemical calculations. Results indicate that the high bond dissociation energies and large energy gap of deca-BB make its self-decomposition reaction difficult to occur, while its reactions with several reactive radicals (including hydrogen, bromine, and hydroxyl radicals) in the combustion environment are universally carried out at low energy barriers. Hydrogen, bromine, and hydroxyl radicals all exhibit a high selectivity for the para-C/Br atoms of deca-BB, resulting in the generation of several debromination products or intermediates. This study also investigates the formation mechanism of polybrominated dibenzofurans (PBDFs) from deca-BB and the effect of polymeric materials on this process. We found that the oxidation of ortho-phenyl-type radical, followed by evolution into PBDFs, is a very exothermic and relatively low-barrier process. Thus, the emergence of ortho-phenyl-type radicals from the loss of ortho-Br atoms is a critical step in the formation of PBDFs. Influence of polymeric materials on the formation of PBDFs is reflected in that various alkyl radicals and diradicals produced by their decomposition can readily abstract ortho-Br atoms to generate ortho-phenyl-type radicals, thus facilitating the formation of PBDFs. The mechanistic pathways and kinetic parameters presented in this study can offer theoretical guidance for controlling contaminant emissions in the thermal treatment of deca-BB-containing waste.

Genome-wide analysis of the CCT gene family and functional characterization of SlCCT6 in response to drought stress in tomato.

CCT transcription factors are important for photoperiod and abiotic stress regulation in Arabidopsis and rice. However, the CCT gene family has not been reported in tomato. Here, we systematically analyzed this. Thirty-one SlCCT genes were identified and divided into five groups (CMF, TIFY, PRR, S8, and COL), with members unevenly distributed across 12 chromosomes and the third chromosome exhibiting the most distribution. SlCCT was found to interact with an interacting protein (SlGI), transcription factor (MYB), and non-coding RNA (sly-miR156-5p) to jointly regulate the tomato stress response. cis-Acting element analysis of the SlCCT promoter region indicated large stress- and hormone-response elements in this family. Real-time PCR results indicated that SlPRR subfamily genes respond to various abiotic stresses and hormones. Tissue expression analysis revealed that several PRR subfamily genes are highly expressed in flowers, and subcellular localization analysis indicated an SlCCT6 nuclear location. Notably, SlCCT6 expression was significantly induced by drought, and its silencing reduced drought stress tolerance. Moreover, SlCCT6 overexpression enhanced tomato drought resistance by increasing antioxidant enzyme activity and activating stress-related genes, whereas SlCCT6 knockout decreased drought resistance. In conclusion, this provides valuable insights for future research on SlCCT functions.

Fecal microbiota transplantation as a new way for OVA-induced atopic dermatitis of juvenile mice.

Children all over the world suffer from atopic dermatitis (AD), a prevalent condition that impairs their health. Corticosteroids, which have long-term negative effects, are frequently used to treat AD. There has been a growing body of research on the gut microbiota's function in AD. Nevertheless, the function and underlying mechanisms of fecal microbiota transplantation (FMT) in AD children remain to be established. Therefore, in order to assess the preventive effects of FMT treatment on AD and investigate the mechanisms, we constructed an ovalbumin (OVA)-induced juvenile mouse AD model in this investigation. This study explored the role and mechanism of FMT treatment in AD through 16S RNA sequencing, pathological histological staining, molecular biology, and Flow cytometry. Results demonstrated that the FMT treatment improved the gut microbiota's diversity and composition, bringing it back to a level similar to that of a close donor. Following FMT treatment, OVA-specific antibodies were inhibited, immunoglobulin (Ig) E production was decreased, the quantity of mast cells and eosinophils was decreased, and specific inflammatory markers in the skin and serum were decreased. Further mechanistic studies revealed that FMT treatment induced CD103+ DCs and programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression in skin-draining lymph nodes and promoted Treg production to induce immune tolerance and suppress skin inflammation. Meanwhile, changes in the gut microbiota were substantially correlated with Th2 cytokines, OVA-specific antibodies, and PD-L1/PD-1. In conclusion, FMT regulates the Th1/Th2 immunological balance and the gut microbiota. It may also inhibit AD-induced allergy responses through the PD-L1/PD-1 pathway, and providing a unique idea and possibly a fresh approach to the treatment of AD.

Pan-Cancer Screening and Validation of CALU's Role in EMT Regulation and Tumor Microenvironment in Triple-Negative Breast Cancer.

Purpose: Cancer-associated fibroblasts (CAFs) significantly contribute to tumor progression and the development of resistance to therapies across a range of malignancies, notably breast cancer. This study aims to elucidate the specific role and prognostic relevance of CALU across multiple cancer types. Patients and Methods: The association between CALU expression and prognosis, along with clinical characteristics in BRCA, HNSC, KIRP, LGG, and LIHC, was analyzed using data from the TCGA, GTEx, and GEO databases. Transcriptomic analysis of TCGA BRCA project data provided insights into the interaction between CALU and epithelial-mesenchymal transition (EMT) marker genes. Using TIMER and TISCH databases, the correlation between CALU expression and tumor microenvironment infiltration was assessed, alongside an evaluation of CALU expression across various cell types. Furthermore, CALU's influence on TNBC BRCA cell lines was explored, and its expression in tumor tissues was confirmed through immunohistochemical analysis of clinical samples. Results: This study revealed a consistent upregulation of CALU across several tumor types, including BRCA, KIRP, LIHC, HNSC, and LGG, with elevated CALU expression being associated with unfavorable prognoses. CALU expression was particularly enhanced in clinical contexts linked to poor outcomes. Genomic analysis identified copy number alterations as the principal factor driving CALU overexpression. Additionally, a positive correlation between CALU expression and CAF infiltration was observed, along with its involvement in the EMT process in both CAFs and malignant cells. In vitro experiments demonstrated that CALU is highly expressed in TNBC-BRCA cell lines, and knockdown of CALU effectively reversed EMT progression and inhibited cellular migration. Immunohistochemical analysis of clinical samples corroborated the elevated expression of CALU in tumors, along with alterations in EMT markers. Conclusion: This comprehensive pan-cancer analysis underscores CALU's critical role in modulating the tumor microenvironment and facilitating cell migration via the EMT pathway, identifying it as a potential therapeutic target.

The role of lipoprotein­associated phospholipase A2 in inflammatory response and macrophage infiltration in sepsis and the regulatory mechanisms.

Lipoproteinassociated phospholipase A2 (Lp-PLA2), encoded by the phospholipase A2 group VII (Pla2g7) gene, has been pertinent to inflammatory responses. This study investigates the correlation between Lp-PLA2 and inflammatory injury in septic mice and explores its regulatory mechanism. Lp-PLA2 was found to be upregulated in the serum of septic mice induced by cecal ligation and puncture and in the culture supernatant of RAW264.7 cells following lipopolysaccharide and adenosine triphosphate treatments. The contents of Lp-PLA2 were positively correlated with increased concentrations of proinflammatory cytokines in patients with sepsis. Both animal and cellular models showed increased concentrations of proinflammatory cytokines. Spi-1 proto-oncogene (Spi1), highly expressed in these models, was found to activate Pla2g7 transcription. Knockdown of Pla2g7 or Spi1 reduced the proinflammatory cytokine production, mitigated organ damage in mice, and suppressed macrophage migration in vitro. Retinoblastoma binding protein 6 (Rbbp6), poorly expressed in both models, was found to reduce Spi1 protein stability through ubiquitination modification. Rbbp6 overexpression similarly suppressed inflammatory activation of RAW264.7 cells, which was counteracted by Pla2g7 or Spi1 upregulation. In summary, this study demonstrates that the Pla2g7 loss and Spi1 upregulation participate in inflammatory responses in sepsis by elevating the Lp-PLA2 levels.

Menopausal Hormone Therapy and Osteoarthritis Risk: Retrospective Population-Based Study in South Korea.

OBJECTIVES: This study aimed to investigate the risk of osteoarthritis associated with menopausal hormone therapy (MHT). METHODS: This population-based retrospective cohort study used a database of Korean health insurance claims (2007-2020). Females aged ≥ 40 who initiated menopause-related healthcare visits between 2011 and 2014 were identified. The MHT group comprised females aged ≥ 40 who initiated MHT for ≥ 6 months during this period. The non-MHT group comprised females aged ≥ 40 who attended menopause-related healthcare visits but did not receive MHT. To account for potential confounding factors, the two groups were matched at a 1:1 ratio using propensity score matching. RESULTS: A cohort of 453,040 postmenopausal females aged ≥ 40 years was identified, with 26,354 assigned to either the MHT or non-MHT group after propensity matching. The median age was 49 years, and the median follow-up was 8.2 years. The Cox proportional hazards model demonstrated an elevated risk of osteoarthritis with MHT (hazard ratio [HR], 1.154; 95% confidence interval [CI], 1.117-1.193) for knee (HR, 1.148; 95% CI, 1.102-1.195) and other arthritis (HR, 1.205; 95% CI, 1.151-1.261), although not statistically significant for hip arthritis. Tibolone (HR, 1.211; 95% CI, 1.161-1.263), estrogen-progestogen therapy (EPT) (HR, 1.092; 95% CI, 1.048-1.137), and estrogen therapy (ET) (HR, 1.235; 95% CI, 1.148-1.329) were associated with a higher risk of osteoarthritis compared to non-MHT users. CONCLUSIONS: MHT was associated with an increased risk of osteoarthritis, consistently observed across tibolone, EPT, and ET, particularly affecting joints other than the hip, with a trend toward an elevated risk of hip osteoarthritis.

A novel small molecule ZYZ384 targeting SMYD3 for hepatocellular carcinoma via reducing H3K4 trimethylation of the Rac1 promoter.

SMYD3 (SET and MYND domain-containing 3) is a histone lysine methyltransferase highly expressed in different types of cancer(s) and is a promising epigenetic target for developing novel antitumor therapeutics. No selective inhibitors for this protein have been developed for cancer treatment. Therefore, the current study describes developing and characterizing a novel small molecule ZYZ384 screened and synthesized based on SMYD3 structure. Virtual screening was initially used to identify a lead compound and followed up by modification to get the novel molecules. Several technologies were used to facilitate compound screening about these novel molecules' binding affinities and inhibition activities with SMYD3 protein; the antitumor activity has been assessed in vitro using various cancer cell lines. In addition, a tumor-bearing nude mice model was established, and the activity of the selected molecule was determined in vivo. Both RNA-seq and chip-seq were performed to explore the antitumor mechanism. This work identified a novel small molecule ZYZ384 targeting SMYD3 with antitumor activity and impaired hepatocellular carcinoma tumor growth by reducing H3K4 trimethylation of the Rac1 promoter triggering the tumor cell cycle arrest through the AKT pathway.

The Protective Effect of Astragalus Polysaccharide on Experimental Autoimmune Encephalomyelitis in Mice by Activating the AMPK/JAK/STAT3/Arginase-1 Signaling Pathway.

OBJECTIVE: This study aimed to investigate the protective effect and mechanism of Astragalus polysaccharide (APS) on autoimmune encephalomyelitis. METHODS: C57BL/6 mice were randomly divided into the blank control group, EAE group, and APS intervention group (n=15/group). The Experimental Autoimmune Encephalomyelitis (EAE) mouse model was established by active immunization. The pathological changes in the spinal cord were evaluated by Hematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining. The number of CD11b+ Gr-1+ myeloid-derived suppressor cells (MDSCs) in the spleen tissues of mice in each group was determined by immunofluorescence staining. The expression of Arginase-1 in the spinal cord and spleen of each group was detected by immunofluorescence double staining. The TNF-α, IL-6, and Arginase-1 levels in the spleen were detected by ELISA assay. A western blot was used to detect the protein expression of the AMPK/JAK/STAT3/Arginase-1 signaling pathway. RESULTS: After the intervention of APS, the incidence of autoimmune encephalomyelitis in mice of the APS group was significantly lower than that in the EAE group, and the intervention of APS could significantly delay the onset time in the EAE mice, and the score of neurological function deficit in mice was significantly lower than that in EAE group (P < 0.05). APS intervention could reduce myelin loss and improve the inflammatory response of EAE mice. Moreover, it could induce the expression of CD11b+ GR-1 + bone MDSCs in the spleen and increase the expression of Arginase-1 in the spinal cord and spleen. This study further demonstrated that APS can protect EAE mice by activating the AMPK/JAK/STAT3/Arginase-1 signaling pathway. CONCLUSION: After the intervention of APS, myelin loss and inflammatory response of EAE mice were effectively controlled. APS promoted the secretion of Arginase-1 by activating MDSCs and inhibited CD4+T cells by activating AMPK/JAK/STAT3/Arginase-1 signaling pathway, thus improving the clinical symptoms and disease progression of EAE mice.

Spatial and temporal attention embedded spatial temporal graph convolutional networks for skeleton based gait recognition with multiple IMUs.

Gait recognition is one of the key technologies for exoskeleton robot control, while the current IMU-based gait recognition methods only use inertial data and do not fully consider the interconnections of human spatial structure and human joints. In this regard, a skeleton-based gait recognition approach with inertial measurement units using spatial temporal graph convolutional networks with spatial and temporal attention is proposed. A human forward kinematics solver module was used for constructing different human skeleton models and a temporal attention module was added for capturing the more important time frames in the gait cycle. Moreover, the two-stream structure was used to construct spatial temporal graph convolutional networks with spatial and temporal attention for gait recognition, and an average accuracy of about 99% was obtained in user experiments, which is the best performance compared to other algorithms, provides certain reference for gait recognition and real-time control of exoskeleton robots.

Unraveling the role of BMI and blood markers in the relationship between plant-based diets and osteoporosis: A prospective cohort study.

BACKGROUND: The potential adverse effects of plant-based diets on bone health have raised significant concern, while the prospective evidence is limited. This study aimed to evaluate the association between plant-based diet indexes and incident osteoporosis while exploring the underlying mechanisms involved in this relationship. METHODS: The analysis included 202,063 UK Biobank participants conducted between 2006 and 2022. Plant-based diet indexes (hPDI and uPDI) were calculated using the 24-h dietary questionnaire. Cox proportional risk regression and mediation analysis were used to explore the associations of plant-based diet indexes with osteoporosis, estimating the contribution of BMI and blood markers. RESULTS: We found the highest quintile for hPDI (HR = 1.16; 95% CI: 1.05 to 1.28) and uPDI (HR = 1.15; 95% CI: 1.05 to 1.26) were associated with an increased risk of osteoporosis. BMI was identified as an important mediator in the association between hPDI and osteoporosis, with mediation proportions of 46.17%. For blood markers, the mediating (suppressing) effects of C-reactive protein, alkaline phosphatase, and insulin-like growth factor-1 on the association between uPDI (hPDI) and osteoporosis were significant, ranging from 5.63%-16.87% (4.57%-6.22%). CONCLUSION: Adherence to a plant-based diet is associated with a higher risk of osteoporosis, with BMI and blood markers potentially contributing to this relationship. Notably, even a healthy plant-based diet necessitates attention to weight management to mitigate its impact on bone loss. These findings emphasize the importance of personalized dietary recommendations and lifestyle interventions to decrease the risk of osteoporosis.

Investigating the link between gut microbiome and bone mineral density: The role of genetic factors.

Osteoporosis is a complex metabolic bone disease that severely undermines the quality of life and overall health of the elderly. While previous studies have established a close relationship between gut microbiome and host bone metabolism, the role of genetic factors has received less scrutiny. This research aims to identify potential taxa associated with various bone mineral density states, incorporating assessments of genetic factors. Fecal microbiome profiles from 605 individuals (334 females and 271 males) aged 55-65 from the Taizhou Imaging Study with osteopenia (n = 270, 170 women) or osteoporosis (n = 94, 85 women) or normal (n = 241, 79 women) were determined using shotgun metagenomic sequencing. The linear discriminant analysis was employed to identify differentially enriched taxa. Utilizing the Kyoto Encyclopedia of Genes and Genomes for annotation, functional pathway analysis was conducted to identify differentially metabolic pathways. Polygenic risk score for osteoporosis was estimated to represent genetic susceptibility to osteoporosis, followed by stratification and interaction analyses. Gut flora diversity did not show significant differences among various bone mineral groups. After multivariable adjustment, certain species, such as Clostridium leptum, Fusicatenibacter saccharivorans and Roseburia hominis, were enriched in osteoporosis patients. Statistically significant interactions between the polygenic risk score and taxa Roseburia faecis, Megasphaera elsdenii were observed (P for interaction = 0.005, 0.018, respectively). Stratified analyses revealed a significantly negative association between Roseburia faecis and bone mineral density in the low-genetic-risk group (ß = -0.045, P < 0.05), while Turicimonas muris was positively associated with bone mineral density in the high-genetic-risk group (ß = 4.177, P < 0.05) after multivariable adjustments. Functional predictions of the gut microbiome indicated an increase in pathways related to structural proteins in high-genetic-risk patients, while low-genetic-risk patients exhibited enrichment in enzyme-related pathways. This study emphasizes the association between gut microbes and bone mass, offering new insights into the interaction between genetic background and gut microbiome.

Genomic dynamics of the Lower Yellow River Valley since the Early Neolithic.

The Yellow River Delta played a vital role in the development of the Neolithic civilization of China. However, the population history of this region from the Neolithic transitions to the present remains poorly understood due to the lack of ancient human genomes. This especially holds for key Neolithic transitions and tumultuous turnovers of dynastic history. Here, we report genome-wide data from 69 individuals dating to 5,410-1,345 years before present (BP) at 0.008 to 2.49× coverages, along with 325 present-day individuals collected from 16 cities across Shandong. During the Middle to Late Dawenkou period, we observed a significant influx of ancestry from Neolithic Yellow River farmers in central China and some southern Chinese ancestry that mixed with local hunter-gatherers in Shandong. The genetic heritage of the Shandong Longshan people was found to be most closely linked to the Dawenkou culture. During the Shang to Zhou Dynasties, there was evidence of genetic admixture of local Longshan populations with migrants from the Central Plain. After the Qin to Han Dynasties, the genetic composition of the region began to resemble that of modern Shandong populations. Our genetic findings suggest that the middle Yellow River Basin farmers played a role in shaping the genetic affinity of neighboring populations in northern China during the Middle to Late Neolithic period. Additionally, our findings indicate that the genetic diversity in the Shandong region during the Zhou Dynasty may be linked with their complex ethnicities.