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The relationship between simple appendicitis and inflammatory bowel disease (IBD) is not clear. In this study, we approach the issue from a genetic perspective, using Mendelian randomization (MR) tools to explore the potential causal connection between the two. We used GWAS data from 12,882 IBD patients (21,770 controls), 5956 crohn’s disease (CD) patients (14,927 controls), 6968 ulcerative colitis (UC) patients (20,464 controls), and 4604 simple appendicitis patients (481,880 controls). These statistical data were derived from a large-scale whole-genome association study of individuals with European ancestry. The primary analytical method for inferring the causal relationship between the conditions involved the use of the Inverse Variance Weighting (IVW) method as the main approach for bidirectional MR analysis. The MR analysis results predicted IBD was associated with a lower risk of simple appendicitis (OR: 0.947 (0.911, 0.984), p  = 0.005). The results for CD (OR: 0.948 (0.916, 0.981), p  = 0.002) and UC (OR: 0.954 (0.917, 0.992), p  = 0.020) are consistent with this finding. In the reverse MR analysis, there is no significant association between simple appendicitis and the occurrence of IBD ( p  > 0.05), and the same holds true for CD and UC ( p  > 0.05). Our MR study results suggest a potential negative causal effect of IBD on the occurrence of simple appendicitis. Conversely, there does not appear to be a significant causal relationship between simple appendicitis and the risk of developing IBD.

Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up to 6 mg in Chinese overweight adults or adults with obesity, as an interim analysis of a randomised, two-part (low doses up to 6 mg and high dose of 9 mg), double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov, NCT04904913). Overweight adults (body-mass index [BMI] ≥24 kg/m 2 ) accompanied by hyperphagia and/or at least one obesity-related comorbidity or adults with obesity (BMI ≥ 28 kg/m 2 ) were randomly assigned (3:1:3:1:3:1) to once-weekly mazdutide 3 mg, 4.5 mg, 6 mg or matching placebo at 20 hospitals in China. The primary endpoint was the percentage change from baseline to week 24 in body weight. A total of 248 participants were randomised to mazdutide 3 mg ( n  = 62), 4.5 mg ( n  = 63), 6 mg ( n  = 61) or placebo ( n  = 62). The mean percentage changes from baseline to week 24 in body weight were −6.7% (SE 0.7) with mazdutide 3 mg, −10.4% (0.7) with 4.5 mg, −11.3% (0.7) with 6 mg and 1.0% (0.7) with placebo, with treatment difference versus placebo ranging from −7.7% to −12.3% (all p  < 0.0001). All mazdutide doses were well tolerated and the most common adverse events included diarrhoea, nausea and upper respiratory tract infection. In summary, in Chinese overweight adults or adults with obesity, 24-week treatment with mazdutide up to 6 mg was safe and led to robust and clinically meaningful body weight reduction. Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. Here, the authors show mazdutide was well tolerated over 24 weeks and demonstrated significant and clinically meaningful body weight loss, compared with placebo, in Chinese overweight adults or adults with obesity.

Background: Both extreme heat and air pollution exposure during pregnancy have been associated with preterm birth; however, their combined effects are unclear. Objectives: Our goal was to estimate the independent and joint effects of heatwaves and fine particulate matter [PM <2.5μm in aerodynamic diameter (PM2.5 )], exposure during the final gestational week on preterm birth. Methods: Using birth registry data from Guangzhou, China, we included 215,059 singleton live births in the warm season (1 May–31 October) between January 2015 and July 2017. Daily meteorological variables from 5 monitoring stations and PM2.5 concentrations from 11 sites were used to estimate district-specific exposures. A series of cut off temperature thresholds and durations (2, 3, and 4 consecutive d) were used to define 15 different heatwaves. Cox proportional hazard models were used to estimate the effects of heatwaves and PM2.5 exposures during the final week on preterm birth, and departures from additive joint effects were assessed using the relative excess risk due to interaction (RERI). Results: Numbers of preterm births increased in association with heatwave exposures during the final gestational week. Depending on the heatwave definition used, hazard ratios (HRs) ranged from 1.10 (95% CI: 1.01, 1.20) to 1.92 (1.39, 2.64). Associations were stronger for more intense heatwaves. Combined effects of PM2.5 exposures and heatwaves appeared to be synergistic (RERIs>0 ) for less extreme heatwaves (i.e., shorter or with relatively low temperature thresholds) but were less than additive (RERIs<0 ) for more intense heatwaves. Conclusions: Our research strengthens the evidence that exposure to heatwaves during the final gestational week can independently trigger preterm birth. Moderate heatwaves may also act synergistically with PM2.5 exposure to increase risk of preterm birth, which adds new evidence to the current understanding of combined effects of air pollution and meteorological variables on adverse birth outcomes.

Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR , RBM10 , BRAF , ERBB2 , TP53 , KRAS , MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53 , arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment. The genomic and immune landscape of pre-invasive lung adenocarcinoma is poorly understood. Here, the authors perform exome and transcriptome sequencing on precursor legions and invasive lung adenocarcinomas, identifying recurrently mutated genes in pre/minimally invasive cases, and arm level alteration events linked to immune infiltration.

To develop a reference of population-based gestational age-specific birth weight percentiles for contemporary Chinese. Birth weight data was collected by the China National Population-based Birth Defects Surveillance System. A total of 1,105,214 live singleton births aged ≥28 weeks of gestation without birth defects during 2006-2010 were included. The lambda-mu-sigma method was utilized to generate percentiles and curves. Gestational age-specific birth weight percentiles for male and female infants were constructed separately. Significant differences were observed between the current reference and other references developed for Chinese or non-Chinese infants. There have been moderate increases in birth weight percentiles for Chinese infants of both sexes and most gestational ages since 1980s, suggesting the importance of utilizing an updated national reference for both clinical and research purposes.

The acquisition of exogenous mobile genetic material imposes an adaptive burden on bacteria, whereas the adaptational evolution of virulence plasmids upon entry into carbapenem-resistant Klebsiella pneumoniae (CRKP) and its impact remains unclear. To better understand the virulence in CRKP, we characterize virulence plasmids utilizing a large genomic data containing 1219  K. pneumoniae from our long-term surveillance and publicly accessible databases. Phylogenetic evaluation unveils associations between distinct virulence plasmids and serotypes. The sub-lineage ST11-KL64 CRKP acquires a pK2044-like virulence plasmid from ST23-KL1 hypervirulent K. pneumoniae , with a 2698 bp region deletion in all ST11-KL64. The deletion is observed to regulate methionine metabolism, enhance antioxidant capacity, and further improve survival of hypervirulent CRKP in macrophages. The pK2044-like virulence plasmid discards certain sequences to enhance survival of ST11-KL64, thereby conferring an evolutionary advantage. This work contributes to multifaceted understanding of virulence and provides insight into potential causes behind low fitness costs observed in bacteria. Plasmid acquisition imposes an adaptive burden, which can be ameliorated by host-plasmid coevolution. Here, the authors characterise virulence plasmids of carbapenem-resistant Klebsiella pneumoniae , and show the discard of certain sequences to enhance survival, conferring an evolutionary advantage.

Accurate segmentation of key tobacco structures is essential for enabling automated harvesting. However, complex backgrounds, variable lighting conditions, and blurred boundaries between the stem and petiole significantly hinder segmentation accuracy in field environments. To overcome these challenges, we propose an enhanced instance segmentation approach based on YOLOv8-seg, incorporating depth-based background filtering and architectural improvements. Specifically, depth information from RGB-D images is employed to spatially filter non-target background regions, thereby enhancing foreground clarity. In addition, a Hybrid Dilated Residual Attention Block (HDRAB) is integrated into the YOLOv8-seg backbone to improve boundary discrimination between petioles and stems, while a Lightweight Shared Detail-Enhanced Convolution Detection Head (LSDECD) is designed to efficiently capture fine-grained texture features. Experimental results demonstrate that depth filtering increases mAP50 bb and mAP50 seg by 7.9% and 6.3%, respectively, while the architectural enhancements further raise them to 89.5% and 91.1%, surpassing the YOLOv8-seg baseline by 5.2% and 10.0%. Compared with mainstream models such as Mask R-CNN and SOLOv2, the proposed method achieves superior segmentation accuracy with low computational cost, highlighting its potential for practical deployment in automated tobacco harvesting

The success of glucagon-like peptide-1 (GLP-1) receptor agonists to treat type 2 diabetes (T2D) and obesity has sparked considerable efforts to develop next-generation co-agonists that are more effective. We conducted a randomised, placebo-controlled phase 1b study (ClinicalTrials.gov: NCT04466904) to evaluate the safety and efficacy of IBI362 (LY3305677), a GLP-1 and glucagon receptor dual agonist, in Chinese patients with T2D. A total of 43 patients with T2D were enrolled in three cohorts in nine study centres in China and randomised in each cohort to receive once-weekly IBI362 (3.0 mg, 4.5 mg or 6.0 mg), placebo or open-label dulaglutide (1.5 mg) subcutaneously for 12 weeks. Forty-two patients received the study treatment and were included in the analysis, with eight receiving IBI362, four receiving placebo and two receiving dulaglutide in each cohort. The patients, investigators and study site personnel involved in treating and assessing patients in each cohort were masked to IBI362 and placebo allocation. Primary outcomes were safety and tolerability of IBI362. Secondary outcomes included the change in glycated haemoglobin A 1c (HbA 1c ), fasting plasma glucose (FPG) and post-mixed-meal tolerance test (post-MTT) glucose levels. IBI362 was well tolerated. Most commonly-reported treatment-emergent adverse events were diarrhoea (29.2% for IBI362, 33.3% for dulaglutide, 0% for placebo), decreased appetite (25.0% for IBI362, 16.7% for dulaglutide, 0% for placebo) and nausea (16.7% for IBI362, 16.7% for dulaglutide and 8.3% for placebo). HbA 1c , FPG and post-MTT glucose levels were reduced from baseline to week 12 in patients receiving IBI362 in all three cohorts. IBI362 showed a favourable safety profile and clinically meaningful reductions in blood glucose in Chinese patients with T2D. Glucagon-like peptide-1 receptor (GLP1R) agonists are used to treat type 2 diabetes (T2D), and polyagonists targeting multiple hormone receptors are investigated as potential therapeutics for T2D. Here the authors report that IBI362 (LY3305677), a balanced once-weekly GLP-1 and glucagon receptor dual agonist, showed favourable safety and tolerability in Chinese patients with type 2 diabetes in a randomized controlled phase 1b clinical trial.

Chelation-assisted olefinic C–H functionalization has been demonstrated to be a powerful method of constructing multi-substituted alkenes from simpler ones. This strategy produces complex alkenes in a regio- and stereoselective manner, followed by C–H endo- and exo-cyclometallation. Among the various directing groups developed, N,N- and N,O-bidentate directing groups are the most widely used to selectively promote C–H functionalization due to their fine, tunable, and reversible coordination with the metal center. In this review, we discuss various N,N- and N,O-bidentate directing group-assisted olefinic C–H bond functionalization reactions, including alkenylation, alkylation, arylation, thiolation, silylation, halogenation, and cyclization.

As a natural potential resource, Tamarix ramosissima has been widely used as barbecue skewers for a good taste and unique flavor. The polyphenolics in the branch bark play a key role in the quality improvement. The purposes of the present work were to explore the polyphenolic composition of T. ramosissima bark extract and assess their potential antioxidant and antimicrobial activities. Hispidulin and cirsimaritin from T. ramosissima bark extract were first identified in the Tamarix genus reported with UPLC-MS analysis. Isorhamnetin (36.91 μg/mg extract), hispidulin (28.79 μg/mg extract) and cirsimaritin (13.35 μg/mg extract) are rich in the bark extract. The extract exhibited promising antioxidant activity with IC50 values of 117.05 μg/mL for 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 151.57 μg/mL for hydroxyl radical scavenging activities, as well as excellent reducing power with an EC50 of 93.77 μg/mL. The bark extract showed appreciable antibacterial properties against foodborne pathogens. Listeria monocytogenes was the most sensitive microorganism with the lowest minimum inhibitory concentration (MIC) value of 5 mg/mL and minimum bactericidal concentration (MBC) value of 10 mg/mL followed by S. castellani and S. aureus among the tested bacteria. The T. ramosissima bark extract showed significantly stronger inhibitory activity against Gram-positive than Gram-negative bacteria. Nevertheless, this extract failed to show any activity against tested fungi. Overall, these results suggested that T. ramosissima shows potential in improving food quality due to its highly efficacious antioxidant and antibacterial properties.