Metabolomics reveals changes in soil metabolic profiles during vegetation succession in karst area.

Soil metabolites are critical in regulating the dynamics of ecosystem structure and function, particularly in fragile karst ecosystems. Clarification of response of soil metabolism to vegetation succession in karst areas will contribute to the overall understanding and management of karst soils. Here, we investigated the metabolite characteristics of karst soils with different vegetation stages (grassland, brushwood, secondary forest and primary forest) based on untargeted metabolomics. We confirmed that the abundance and composition of soil metabolites altered with vegetation succession. Of the 403 metabolites we found, 157 had significantly varied expression levels across vegetation soils, including mainly lipids and lipid-like molecules, phenylpropanoids and polyketides, organic acids and derivatives. Certain soil metabolites, such as maltotetraose and bifurcose, were sensitive to vegetation succession, increasing significantly from grassland to brushwood and then decreasing dramatically in secondary and primary forests, making them possible indicators of karst vegetation succession. In addition, soil metabolic pathways, such as galactose metabolism and biosynthesis of unsaturated fatty acids, also changed with vegetation succession. This study characterized the soil metabolic profile in different vegetation stages during karst secondary succession, which would provide new insights for the management of karst soils.

Nomogram for predicting the probability of rectal anastomotic re-leakage after stoma closure: a retrospective study.

BACKGROUND: In this study, we aimed to identify the risk factors in patients with rectal anastomotic re-leakage and develop a prediction model to predict the probability of rectal anastomotic re-leakage after stoma closure. METHODS: This study was a single-center retrospective analysis of patients with rectal cancer who underwent surgery between January 2010 and December 2020. Among 3225 patients who underwent Total or Partial Mesorectal Excision (TME/PME) surgery for rectal cancer, 129 who experienced anastomotic leakage following stoma closure were enrolled. Risk factors for rectal anastomotic re-leakage were analyzed, and a prediction model was established for rectal anastomotic re-leakage. RESULTS: Anastomotic re-leakage after stoma closure developed in 13.2% (17/129) of patients. Multivariable analysis revealed that neoadjuvant chemoradiotherapy (odds ratio, 4.07; 95% confidence interval, 1.17-14.21; p = 0.03), blood loss > 50 ml (odds ratio, 4.52; 95% confidence interval, 1.31-15.63; p = 0.02), and intersphincteric resection (intersphincteric resection vs. low anterior resection: odds ratio, 6.85; 95% confidence interval, 2.01-23.36; p = 0.002) were independent risk factors for anastomotic re-leakage. A nomogram was constructed to predict the probability of anastomotic re-leakage, with an area under the receiver operating characteristic curve of 0.828 in the cohort. Predictive results correlated with the actual results according to the calibration curve. CONCLUSIONS: Neoadjuvant chemoradiotherapy, blood loss > 50 ml, and intersphincteric resection are independent risk factors for anastomotic re-leakage following stoma closure. The nomogram can help surgeons identify patients at a higher risk of rectal anastomotic re-leakage.

Chaotic RIME optimization algorithm with adaptive mutualism for feature selection problems.

The RIME optimization algorithm is a newly developed physics-based optimization algorithm used for solving optimization problems. The RIME algorithm proved high-performing in various fields and domains, providing a high-performance solution. Nevertheless, like many swarm-based optimization algorithms, RIME suffers from many limitations, including the exploration-exploitation balance not being well balanced. In addition, the likelihood of falling into local optimal solutions is high, and the convergence speed still needs some work. Hence, there is room for enhancement in the search mechanism so that various search agents can discover new solutions. The authors suggest an adaptive chaotic version of the RIME algorithm named ACRIME, which incorporates four main improvements, including an intelligent population initialization using chaotic maps, a novel adaptive modified Symbiotic Organism Search (SOS) mutualism phase, a novel mixed mutation strategy, and the utilization of restart strategy. The main goal of these improvements is to improve the variety of the population, achieve a better balance between exploration and exploitation, and improve RIME's local and global search abilities. The study assesses the effectiveness of ACRIME by using the standard benchmark functions of the CEC2005 and CEC2019 benchmarks. The proposed ACRIME is also applied as a feature selection to fourteen various datasets to test its applicability to real-world problems. Besides, the ACRIME algorithm is applied to the COVID-19 classification real problem to test its applicability and performance further. The suggested algorithm is compared to other sophisticated classical and advanced metaheuristics, and its performance is assessed using statistical tests such as Wilcoxon rank-sum and Friedman rank tests. The study demonstrates that ACRIME exhibits a high level of competitiveness and often outperforms competing algorithms. It discovers the optimal subset of features, enhancing the accuracy of classification and minimizing the number of features employed. This study primarily focuses on enhancing the equilibrium between exploration and exploitation, extending the scope of local search.

TrueTH: A user-friendly deep learning approach for robust dopaminergic neuron detection.

Parkinson's disease (PD) entails the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc), leading to movement-related impairments. Accurate assessment of DA neuron health is vital for research applications. Manual analysis, however, is laborious and subjective. To address this, we introduce TrueTH, a user-friendly and robust pipeline for unbiased quantification of DA neurons. Existing deep learning tools for tyrosine hydroxylase-positive (TH+) neuron counting often lack accessibility or require advanced programming skills. TrueTH bridges this gap by offering an open-sourced and user-friendly solution for PD research. We demonstrate TrueTH's performance across various PD rodent models, showcasing its accuracy and ease of use. TrueTH exhibits remarkable resilience to staining variations and extreme conditions, accurately identifying TH+ neurons even in lightly stained images and distinguishing brain section fragments from neurons. Furthermore, the evaluation of our pipeline's performance in segmenting fluorescence images shows strong correlation with ground truth and outperforms existing models in accuracy. In summary, TrueTH offers a user-friendly interface and is pretrained with a diverse range of images, providing a practical solution for DA neuron quantification in Parkinson's disease research.

miR-142-3p alleviates neuronal apoptosis in Parkinson's disease via negatively regulating C9orf72.

Although microRNA (miRNA) have important clinical prospects in the early diagnosis and treatment of PD, the functions and mechanisms of miRNAs in PD models remain poorly defined. In this study, we screened 9 miRNAs that differently expressed in PD patients and found that miR-142-3p expression was downregulated in both animal and cell models of PD. We showed that overexpression of miR-142-3p significantly alleviates the neuronal damage induced by MPP+, while knockdown of miR-142-3p exacerbates the neuronal damage caused by MPP+. We further found that miR-142-3p targets and inhibits the expression of C9orf72. Knockdown of C9orf72 mitigated neuronal autophagy dysfunction by reducing excessive activation of the AKT/mTOR pathway after MPP+ stimulation, thereby exerted neuroprotective effects. This study reveals that miR-142-3p protects neuron in PD pathogenesis via negatively regulating C9orf72 and enhancing autophagy. Our findings provides an insight into the development of potential biomarkers and therapeutic targets for PD.

Causal effects of 731 immune cell phenotypes on autism spectrum disorder: a Mendelian randomization study.

Objective: The role of different immune cells in autism spectrum disorders (ASD) is still controversial. The purpose of this study was to evaluate the causal effects of different immune cell phenotypes on ASD via Mendelian randomization (MR). Methods: Datasets of immune cell phenotypes were obtained from the European Bioinformatics Institute, and datasets of ASD were obtained from the IEU Open GWAS project. Single nucleotide polymorphisms were selected based on the assumptions of association, independence, and exclusivity. Inverse variance weighted was utilized as the main method for MR analysis. MR-Egger was employed to assess the horizontal pleiotropy of the results. Cochran's Q and leave-one-out method were used for heterogeneity analysis and sensitivity analysis of the results, respectively. Results: MR analysis showed that TD CD8br AC [odds ratio (OR), 1.137; 95% confidence interval (CI), 1.031-1.254; p = 0.010], CD8br %leukocyte (OR, 1.142; 95% CI, 1.067-1.223; p < 0.001), CD8br and CD8dim %leukocyte (OR, 1.117; 95% CI, 1.032-1.210; p = 0.006), naive CD8br %T cell (OR, 1.052; 95% CI, 1.004-1.104; p = 0.035), CD28- CD8dim %T cell (OR, 1.097; 95% CI, 1.038-1.158; p < 0.001), CD127- CD8br AC (OR, 1.086; 95% CI, 1.006-1.171; p = 0.034), CD45 on CD8br (OR, 1.059; 95% CI, 1.021-1.099; p = 0.002), CD3 on HLA DR+ CD8br (OR, 1.098; 95% CI, 1.041-1.158; p < 0.001), CD4 on activated Treg (OR, 1.048; 95% CI, 1.001-1.096; p = 0.046), CD3 on CD39+ resting Treg (OR, 1.070; 95% CI, 1.012-1.131; p = 0.018), IgD+ CD38- %lymphocyte (OR, 1.103; 95% CI, 1.023-1.190; p = 0.011), CD62L- plasmacytoid DC %DC (OR, 1.046; 95% CI, 1.001-1.093; p = 0.046), and FSC-A on plasmacytoid DC (OR, 1.075; 95% CI, 1.003-1.153; p = 0.042) were associated with increased genetic susceptibility to ASD. MR-Egger displayed no horizontal pleiotropy (p ≥ 0.05). Cochran's Q revealed no heterogeneity of results (p ≥ 0.05). Sensitivity analysis indicated that the results were robust. Conclusion: This MR analysis revealed 13 immune cell phenotypes associated with increased genetic susceptibility to ASD and emphasized the importance of CD8 T cells and Tregs, which provides new directions for the pathogenesis and drug research of ASD.

Habitual use of glucosamine and adverse liver outcomes among patients with type 2 diabetes and MASLD.

BACKGROUND: Glucosamine is a dietary supplement commonly used to support joint health. However, there has been interest in exploring other effects of glucosamine on health outcomes due to its ant-inflammation effect. OBJECTIVE: This study compared the risks of major adverse liver outcomes (MALOs) between regular users and non-users of glucosamine among patients with type 2 diabetes and metabolic dysfunction associated steatotic liver disease (MASLD) using the data from a large prospective cohort study. METHODS: Demographic, anthropometric, laboratory and medication prescription information among 18 753 patients with type 2 diabetes and MASLD was obtained from the UK Biobank. MASLD was identified based on hepatic steatosis defined by fatty liver index ≥60 plus the presence of any clues of metabolic dysregulation and cardio-metabolic risk factors, excluding patients with moderate to severe alcohol consumption. RESULTS: During a mean follow-up of 11.4 years, 826 incident MALOs events were recorded. Patients not regularly using glucosamine compared with patients using glucosamine showed a significantly higher risk of the composite MALOs (HR 1.36, 95% confidence interval [CI] 1.09-1.69) as well as most individual MALOs except for ascites. The multivariable-adjusted HRs of MALOs within 3, 5 and 10 years among non-users of glucosamine compared with regular users were 1.79 (95% CI .69-2.03), 1.88 (95% CI 1.21-2.54) and 1.32 (95% CI 1.05-1.72), respectively. Further subgroup analyses in participants with different baseline characteristics and sensitivity analyses excluding participants who regularly took any other supplements and participants who used self-reports to diagnose diabetes confirmed the findings. CONCLUSIONS: The present study indicated that habitual use of glucosamine was associated with a low risk of individual and composite MALOs among patients with type 2 diabetes and MASLD.

A Mendelian randomization study of the effect of mental disorders on cardiovascular disease.

Objective: The effect of mental disorders (MD) on cardiovascular disease (CVD) remains controversial, and this study aims to analyze the causal relationship between eight MD and CVD by Mendelian randomization (MR). Methods: Single nucleotide polymorphisms of attention-deficit/hyperactivity disorder (ADHD), anorexia nervosa (AN), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), depression, obsessive-compulsive disorder (OCD), schizophrenia (SCZ), and CVD were obtained from UK Biobank and FinnGen. Exposure-outcome causality was tested using inverse variance weighted (IVW), MR-Egger, and weighted median. Horizontal pleiotropy and heterogeneity were assessed by MR-Egger intercept and Cochran's Q, respectively, while stability of results was assessed by leave-one-out sensitivity analysis. Results: MR analysis showed that ANX (IVW [odds ratio (OR) 1.11, 95% confidence intervals (CI) 1.07-1.15, p < 0.001]; MR-Egger [OR 1.03, 95% CI 0.92-1.14, p = 0.652]; weighted median [OR 1.09, 95% CI 1.03-1.14, p = 0.001]), ASD (IVW [OR 1.05, 95% CI 1.00-1.09, p = 0.039]; MR-Egger [OR 0.95, 95% CI 0.84-1.07, p = 0.411]; weighted median [OR 1.01, 95% CI 0.96-1.06, p = 0.805]), depression (IVW [OR 1.15, 95% CI 1.10-1.19, p < 0.001]; MR-Egger [OR 1.10, 95% CI 0.96-1.26, p = 0.169]; weighted median [OR 1.13, 95% CI 1.08-1.19, p < 0.001]) were significantly associated with increased risk of CVD, whereas ADHD, AN, BD, OCD, and SCZ were not significantly associated with CVD (p > 0.05). Intercept analysis showed no horizontal pleiotropy (p > 0.05). Cochran's Q showed no heterogeneity except for BD (p = 0.035). Sensitivity analysis suggested that these results were robust. Conclusions: ANX, ASD, and depression are associated with an increased risk of CVD, whereas AN, ADHD, BD, OCD, and SCZ are not causally associated with CVD. Active prevention and treatment of ANX, ASD, and depression may help reduce the risk of CVD.

Serum tumor marker and CT body composition scoring system predicts outcomes in colorectal cancer surgical patients.

OBJECTIVE: To investigate the prognostic value of preoperative body composition and serum tumor markers (STM) in patients undergoing surgical treatment for colorectal cancer (CRC) and to establish the prognostic score for patients with CRC. METHODS: This study enrolled 365 patients (training set 245, validation set 120) with CRC who underwent surgical resection. The predictive value of various body composition features and STM for determining CRC prognosis were compared. A novel index score based on the independent risk factors from Cox regression for CRC patients was established and evaluated for its usefulness. RESULTS: Multivariate Cox regression showed that low skeletal muscle radiodensity (SMD) (p = 0.020), low subcutaneous fat area (SFA) (p = 0.029), high carcinoembryonic antigen (CEA) (p = 0.008), and high alpha-fetoprotein (AFP) (p = 0.039) were all independent prognostic factors for poor overall survival (OS). The multifactorial analysis indicated that high intermuscular fat area (IMFA) (p = 0.033) and high CEA (p = 0.009) were independent prognostic factors for poor disease-free survival (DFS). Based on these findings, two scoring systems for OS and DFS were established in the training datasets. CRC patients who scored higher on the new scoring systems had lower OS and DFS (both p < 0.001) as shown in the Kaplan-Meier survival curves in the training and validation datasets. CONCLUSION: In predicting the prognosis of CRC patients, SFA and SMD are superior to other body composition measurements. A scoring system based on body composition and STM can have prognostic value and clinical applicability. CLINICAL RELEVANCE STATEMENT: This scoring system, combining body composition and serum tumor markers, may help predict postoperative survival of CRC patients and help clinicians make well-informed decisions regarding the treatment of patients. KEY POINTS: Colorectal cancer prognosis can be related to body composition. High intermuscular fat area and CEA were independent prognostic factors for poor disease-free survival. This scoring system, based on body composition and tumor markers, can prognosticate for colorectal cancer patients.

DRPSO:A multi-strategy fusion particle swarm optimization algorithm with a replacement mechanisms for colon cancer pathology image segmentation.

Colon adenocarcinoma (COAD) is a type of colon cancers with a high mortality rate. Its early symptoms are not obvious, and its late stage is accompanied by various complications that seriously endanger patients' lives. To assist in the early diagnosis of COAD and improve the detection efficiency of COAD, this paper proposes a multi-level threshold image segmentation (MIS) method based on an enhanced particle swarm algorithm for segmenting COAD images. Firstly, this paper proposes a multi-strategy fusion particle swarm optimization algorithm (DRPSO) with a replacement mechanism. The non-linear inertia weight and sine-cosine learning factors in DRPSO help balance the exploration and exploitation phases of the algorithm. The population reorganization strategy incorporating MGO enhances population diversity and effectively prevents the algorithm from stagnating prematurely. The mutation-based final replacement mechanism enhances the algorithm's ability to escape local optima and helps the algorithm to obtain highly accurate solutions. In addition, comparison experiments on the CEC2020 and CEC2022 test sets show that DRPSO outperforms other state-of-the-art algorithms in terms of convergence accuracy and speed. Secondly, by combining the non-local mean 2D histogram and 2D Renyi entropy, this paper proposes a DRPSO algorithm based MIS method, which is successfully applied to the segments the COAD pathology image problem. The results of segmentation experiments show that the above method obtains relatively higher quality segmented images with superior performance metrics: PSNR = 23.556, SSIM = 0.825, and FSIM = 0.922. In conclusion, the MIS method based on the DRPSO algorithm shows great potential in assisting COAD diagnosis and in pathology image segmentation.

Nocardioides imazamoxiresistens sp. nov. Isolated from the Activated Sludge.

A Gram-staining-positive actinomycete named YZH12T was isolated from the sediment of the Yangtze River in Nanjing, Jiangsu province, China. Cells were aerobic, non-spore forming, non-motile, short rod (0.4-0.6 × 0.5-1.0 µm) or coccus (0.4-0.6 µm in diameter). Colonies were circular, smooth, and beige to yellowish. Growth occurred at 15-42 °C (optimal 28 °C), pH 5.0-9.0 (optimal 7.0), and 0-10% (w/v) NaCl (optimal 2%). The strain could tolerate 1500 mg/L of imazamox. Strain YZH12T showed 98.7% 16S rRNA gene sequence similarity Nocardioides zeae JM-1068T and less than 97% similarities with other type strains in the genus Nocardioides. Phylogenetic analysis based on genome and 16S rRNA gene sequences indicated that strain YZH12T was phylogenetically affiliated to the genus Nocardioides and formed a subclade with N. zeae JM-1068T and N. alkalitolerans DSM 16699T. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between YZH12T and closely related type strain N. zeae JM-1068T were 79.9% and 35.2%, respectively. The major fatty acids (> 5%) were C18: 1ω9c, iso-C16: 0, C16: 0, C17: 1ω8cand C18: 0; the major respiratory quinone was MK-8(H4); and the polar lipids profiles were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), glycolipid (GL), two aminophospholipids (APL1, APL2), and an unknown polar lipid (L). The genomic DNA G + C content is 73.5%. Based on the phenotypic, chemotaxonomic, phylogenetic analyses, and genomic data, strain YZH12T represents a novel species of the genus Nocardioides, for which the name Nocardioides imazamoxiresistens YZH12T is proposed, with strain YZH12T (= KCTC 49964T = MCCC 1K0892T) as the type strain.

Cellulose aerogel beads and monoliths from CO2-based reversible ionic liquid solution.

The CO2-based reversible ionic liquid solution of 1,1,3,3-tetramethylguanidine (TMG) and ethylene glycol (EG) in dimethyl sulfoxide (DMSO) after capturing CO2, (2[TMGH]+[O2COCH2CH2OCO2]2-/DMSO (χRILs = 0.1), provides a sustainable and effective platform for cellulose dissolution and homogeneous utilization. Highly porous cellulose aerogel beads and monoliths were successfully prepared via a sol-gel process by extruding cellulose solution into different coagulation baths (NaOH aqueous solution or alcohols) and exposing the cellulose solution in open environment, respectively, and followed by different drying techniques, including supercritical CO2-drying, freeze-drying and air-drying. The effect of the coagulation baths and drying protocols on the multi-scale structure of the as-prepared cellulose aerogel beads and monoliths were studied in detail, and the sol-gel transition mechanism was also studied by the solvatochromic parameters determination. High specific surface area of 252 and 207 m2/g for aerogel beads and monoliths were achieved, respectively. The potential of cellulose aerogels in dye adsorption was demonstrated.

LINC01572 promotes the malignant progression of lung adenocarcinoma by modulating p53 mediated by miRNA-338-5p/TTK axis.

OBJECTIVES: Lung cancer is one of the malignant tumors that threaten human health seriously. Long non-coding RNA (lncRNA) is an important factor affecting tumorigenesis and development. However, the mechanism of lncRNA in lung cancer progression remains to be further explored. METHODS: In this study, the TCGA database was analyzed, and LINC01572 was found to be increased in lung adenocarcinoma (LUAD) tissues. Thereafter, with the help of databases including lncBase, TargetScan, and mirDIP, as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, LINC01572/miRNA-338-5p/TTK regulatory axis and downstream p53 signaling pathway were excavated. qRT-PCR was adopted to detect levels of LINC01572, miRNA-338-5p, and TTK in LUAD cells. The role that LINC01572 played in LUAD cells was validated by CCK-8 assay, flow cytometry, colony formation, Transwell, and scratch healing assays. The binding ability between LINC01572/TTK and miRNA-338-5p was then verified by dual-luciferase and RIP analysis. KEY FINDINGS: The results of this study demonstrated that LINC01572 was elevated in LUAD cells compared with normal cells. The overexpression of LINC01572 promoted the proliferative and migratory properties of LUAD cells but inhibited cell apoptosis. The inhibition of LINC01572 resulted in the opposite result. In addition, rescue experiments revealed that LINC01572, as a molecular sponge of miRNA-338-5p, targeted TTK to manipulate p53 for facilitating LUAD cell malignant progression. Apart from this, we constructed a mouse xenograft model and confirmed that the knockdown of LINC01572 hindered the growth of LUAD solid tumors in vivo. CONCLUSIONS: Our findings illuminated the molecular mechanism of LINC01572 influencing LUAD and provided new insights for targeted therapy of LUAD cells.

Muscularis macrophages controlled by NLRP3 maintain the homeostasis of excitatory neurons.

Peristaltic movements in gut are essential to propel ingested materials through the gastrointestinal tract. Intestinal resident macrophages play an important role in this physiological function through protecting enteric neurons. However, it is incompletely clear how individuals maintain the homeostasis of gut motility. Here we found that NLRP3 is a critical factor in controlling loss of muscularis resident macrophages (MMs), and demonstrate that MMs are involved in the homeostasis of excitatory neurons such as choline acetyltransferase (ChAT)+ and vesicular glutamate transporter 2 (VGLUT2)+ but not inhibitory neuronal nitric oxide synthase (nNOS)+ neurons. NLRP3 knockout (KO) mice had enhanced gut motility and increased neurons, especially excitatory ChAT+ and VGLUT2+ neurons. Single cell analyses showed that there had increased resident macrophages, especially MMs in NLRP3 KO mice. The MM proportion in the resident macrophages was markedly higher than those in wild-type (WT) or caspase 1/11 KO mice. Deletion of the MMs and transplantation of the NLRP3 KO bone marrow cells showed that survival of the gut excitatory ChAT+ and VGLUT2+ neurons was dependent on the MMs. Gut microbiota metabolites ß-hydroxybutyrate (BHB) could promote gut motility through protecting MMs from pyroptosis. Thus, our data suggest that MMs regulated by NLRP3 maintain the homeostasis of excitatory neurons.

Prognostic stratification of patients with pT4bN0M0 colorectal cancer following multivisceral resection: a multi-institutional case series analysis.

BACKGROUND: Colorectal cancer (CRC) patients with stage pT4b are a complex group as they show differences in tumor-infiltrated organs. Patients with the same stage often exhibit differences in prognosis after multivisceral resection (MVR). Thus far, some important prognostic factors have not been thoroughly investigated. Here, we identified the prognostic factors influencing CRC patients at pT4bN0M0 stage to better stratify the prognostic differences among patients. MATERIALS AND METHODS: A retrospective analysis was conducted on patients diagnosed to have locally advanced CRC and who underwent MVR at three medical institutions from January 2010 to December 2021. The prognostic factors affecting the survival of CRC patients at pT4bN0M0 stage were identified by multivariate Cox proportional hazard models. We then classified the prognosis into different grades on the basis of these independent prognostic factors. RESULTS: We enrolled 690 patients with locally advanced CRC who underwent MVR; of these, 172 patients with pT4bN0M0 were finally included. Patients with digestive system (OS: hazard ratio [HR]=0.441; 95% confidence interval [CI]=0.217-0.900; P=0.024; DFS: HR=0.416; 95% CI=0.218-0.796; P=0.008) or genitourinary system invasion (OS: HR=0.405; 95% CI=0.193-0.851; P=0.017; DFS: HR=0.505; 95% CI=0.267-0.954; P=0.035) exhibited significantly better overall survival (OS) and disease-free survival (DFS) as compared to those with gynecological system invasion, while the OS and DFS were similar between the diggestive system and genitourinary system invasion groups (OS: HR=0.941; 95% CI=0.434-2.042; P=0.878; DFS: HR=1.211; 95% CI=0.611-2.403; P=0.583). Multivariate analysis showed that age (OS: HR=2.121; 95% CI=1.157-3.886; P=0.015; DFS: HR=1.869; 95% CI=1.116-3.131; P=0.017) and type of organs invaded by CRC (OS: HR=3.107; 95% CI=1.121-8.609; P=0.029; DFS: HR=2.827; 95% CI=1.142-6.997; P=0.025) were the independent prognostic factors that influenced the overall survival (OS) and disease-free survival (DFS) of CRC patients with pT4bN0M0 disease. The OS and DFS of patients showing invasion of the gynecological system group were significantly worse (P=0.004 and P=0.003, respectively) than those of patients with invasion of non-gynecological system group. On the basis of the above-mentioned two independent prognostic factors, patients were assigned to high-, medium-, and low-risk groups. Subgroup analysis showed that the OS and DFS of the medium- and high-risk groups were significantly worse (P=0.001 and P=0.001, respectively) than those of the low-risk group. CONCLUSION: Patients with pT4bN0M0 CRC show significant differences in their prognosis. The type of organs invaded by CRC is a valuable indicator for prognostic stratification of CRC patients with pT4bN0M0.

Long-term risk of overweight in offspring of Chinese women with gestational diabetes defined by IADPSG's but not by WHO's criteria.

AIMS: To examine long-term risk of overweight in offspring of women with gestational diabetes mellitus (GDM) defined by the International Association of Diabetes and Pregnancy Study Group (IADPSG)'s criteria but not by the 1999 World Health Organization (WHO)'s criteria. METHODS: We followed up 1681 mother-child pairs for 8 years in Tianjin, China. Overweight in children aged 1-5 and 6-8 were respectively defined as body mass index-for-age and -sex above the 2 z-score and 1 z-score curves of the WHO's child growth standards. Logistic regression was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of hyperglycemia indices at oral glucose tolerance test and GDMs defined by different criteria for offspring overweight at different ages. RESULTS: Offspring of women with fasting plasma glucose ≥5.1 mmol/L were at increased risk of overweight at 6-8 years old (OR:1.45, 95% CI: 1.09-1.93). GDM defined by the IADPSG's criteria only was associated with increased risk of childhood overweight at 6-8 years old (1.65, 1.13-2.40), as compared with non-GDM by either of the two sets of criteria. CONCLUSIONS: Newly defined GDM by the IADPSG's criteria increased the risk of offspring overweight aged 6-8 years.

Love-hate relationship between hepatitis B virus and type 2 diabetes: a Mendelian randomization study.

Objective: The impact of hepatitis B virus (HBV) on the risk of type 2 diabetes (T2D) remains a controversial topic. This study aims to analyze the causal relationship between HBV and T2D using Mendelian randomization (MR). Methods: Single nucleotide polymorphisms on chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis, and T2D were obtained from BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Mendelian randomization was utilized to evaluate exposure-outcome causality. Inverse variance weighted was used as the primary method for MR analysis. To assess horizontal pleiotropy and heterogeneity, we conducted MR-Egger intercept analysis and Cochran's Q test, and the robustness of the MR analysis results was evaluated through leave-one-out sensitivity analysis. Results: MR analysis revealed that CHB was associated with a decreased genetic susceptibility to T2D (OR, 0.975; 95% CI, 0.962-0.989; p < 0.001) while liver cirrhosis (OR, 1.021; 95% CI, 1.007-1.036; p = 0.004) as well as liver cirrhosis and liver fibrosis (OR, 1.015; 95% CI, 1.002-1.028; p = 0.020) were associated with an increased genetic susceptibility to T2D. MR-Egger intercept showed no horizontal pleiotropy (p > 0.05). Cochran's Q showed no heterogeneity (p > 0.05). Leave-one-out sensitivity analysis showed that the results were robust. Conclusion: CHB has the potential to act as a protective factor for T2D, but its effectiveness is constrained by viral load and disease stage. This protective effect diminishes or disappears as viral load decreases, and it transforms into a risk factor with the progression to liver fibrosis and cirrhosis.

Focusing on mitochondria in the brain: from biology to therapeutics.

Mitochondria have multiple functions such as supplying energy, regulating the redox status, and producing proteins encoded by an independent genome. They are closely related to the physiology and pathology of many organs and tissues, among which the brain is particularly prominent. The brain demands 20% of the resting metabolic rate and holds highly active mitochondrial activities. Considerable research shows that mitochondria are closely related to brain function, while mitochondrial defects induce or exacerbate pathology in the brain. In this review, we provide comprehensive research advances of mitochondrial biology involved in brain functions, as well as the mitochondria-dependent cellular events in brain physiology and pathology. Furthermore, various perspectives are explored to better identify the mitochondrial roles in neurological diseases and the neurophenotypes of mitochondrial diseases. Finally, mitochondrial therapies are discussed. Mitochondrial-targeting therapeutics are showing great potentials in the treatment of brain diseases.