A body map of somatic mutagenesis in morphologically normal human tissues.

Somatic mutations that accumulate in normal tissues are associated with ageing and disease1,2. Here we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies of 9 organs from 5 donors. We found that somatic mutation accumulations and clonal expansions were widespread, although to variable extents, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for in tissues from the oesophagus and cardia. Endogenous mutational processes with the SBS1 and SBS5 mutational signatures are ubiquitous among normal tissues, although they exhibit different relative activities. Exogenous mutational processes operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimetre resolution. In the oesophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometres were frequently seen, whereas in tissues such as the colon, rectum and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue microstructures. Our study depicts a body map of somatic mutations and clonal expansions from the same individual.

Low Pneumoperitoneum Pressure Reduces Gas Embolism During Laparoscopic Liver Resection: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of low and standard pneumoperitoneal pressure (PP) on the occurrence of gas embolism during laparoscopic liver resection (LLR). BACKGROUND: LLR has an increased risk of gas embolism. Although animal studies have shown that low PP reduces the occurrence of gas embolism, clinical evidence is lacking. METHODS: This parallel, dual-arm, double-blind, randomized controlled trial included 141 patients undergoing elective LLR. Patients were randomized into standard ("S," 15 mm Hg; n = 70) or low ("L," 10 mm Hg; n = 71) PP groups. Severe gas embolism (≥ grade 3, based on the Schmandra microbubble method) was detected using transesophageal echocardiography and recorded as the primary outcome. Intraoperative vital signs and postoperative recovery profiles were also evaluated. RESULTS: Fewer severe gas embolism cases (n = 29, 40.8% vs n = 47, 67.1%, P = 0.003), fewer abrupt decreases in end-tidal carbon dioxide partial pressure, shorter severe gas embolism duration, less peripheral oxygen saturation reduction, and fewer increases in heart rate and lactate during gas embolization episodes was found in group L than in group S. Moreover, a higher arterial partial pressure of oxygen and peripheral oxygen saturation were observed, and fewer fluids and vasoactive drugs were administered in group L than in group S. In both groups, the distensibility index of the inferior vena cava negatively correlated with central venous pressure throughout LLR, and a comparable quality of recovery was observed. CONCLUSIONS: Low PP reduced the incidence and duration of severe gas embolism and achieved steadier hemodynamics and vital signs during LLR. Therefore, a low PP strategy can be considered a valuable choice for the future LLR.

Effects of the alpine meadow in different phenological periods on rumen fermentation and gastrointestinal tract bacteria community in grazing yak on the Qinghai-Tibetan Plateau.

BACKGROUND: In this study, we investigated the effects of alpine meadow in different phenological periods on ruminal fermentation, serum biochemical indices, and gastrointestinal tract microbes in grazing yak on the Qinghai-Tibetan Plateau. A total of eighteen female freely grazing yaks with an average age of 3 years old and a body weight of 130 ± 19 kg were selected. According to the plant phenological periods, yaks were randomly allocated to one of three treatments: (1) regreen periods group (RP, n = 6); (2) grassy periods group (GP, n = 6); and (3) hay periods group (HP, n = 6). At the end of the experiment, the blood, rumen fluids, and rectal contents were collected to perform further analysis. RESULTS: The concentrations of total volatile fatty acid (TVFA), acetate, glucose (GLU), triglyceride (TG), cholesterol (CHO), high density lipoprotein (HDL), and low density lipoprotein (LDL) were higher in the GP group than in the HP group (P < 0.05). However, compared with the RP and GP groups, the HP group had higher concentrations of isobutyrate, isovalerate, valerate, and creatinine (CREA) (P < 0.05). The abundance of Prevotella in the rumen, and the abundances of Rikenellaceae_RC9_gut_group, Eubacterium_coprostanoligenes_group, and Prevotellaceae_UCG-004 in the gut were higher in the GP group compared with the HP group (P < 0.05). The HP had higher abundance of Eubacterium_coprostanoligenes_group in the rumen as well as the abundances of Romboutsia and Arthrobacter in the gut compared with the RP and GP groups (P < 0.05). CONCLUSIONS: Based on the results of rumen fermentation, serum biochemical, differential biomarkers, and function prediction, the carbohydrate digestion of grazing yak would be higher with the alpine meadow regreen and grassy due to the gastrointestinal tract microbes. However, the risk of microbe disorders and host inflammation in grazing yak were higher with the alpine meadow wither.

25-hydroxycholesterol promotes proliferation and metastasis of lung adenocarcinoma cells by regulating ERß/TNFRSF17 axis.

Lung adenocarcinoma is the main type of lung cancer in women. Our previous findings have evidenced that 25-hydroxycholesterol (25-HC) promotes migration and invasion of lung adenocarcinoma cells (LAC), during which LXR as a 25-HC receptor plays an important role. Estrogen receptor beta (ERß) is a receptor of 27-hydroxycholesterol that is structurally analogous to 25-HC, but its role in the functional actions of 25-HC remained largely unknown. In this study, we demonstrated that 25-HC treatment triggered ERß expression in LAC. Knockdown of ERß inhibited 25-HC-mediated proliferation, migration and invasion, and reduced 25-HC-induced LAC metastasis in vivo. Further investigation revealed that ERß knockdown restrained the expression of TNFRSF17 (BCMA). In vivo experiments also confirmed that ERß knockdown blocked 25-HC-induced TNFRSF17 expression. TNFRSF17 knockdown also restrained 25-HC-induced proliferation, migration and invasion. Bioinformatic analysis showed that the levels of ERß and TNFRSF17 were elevated in lung adenocarcinoma, and were closely related to tumor stages and nodal metastasis status. These results suggested that 25-HC promoted the proliferation and metastasis of LAC by regulating ERß/TNFRSF17 axis.

IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities.

Stimulator of interferon genes (STING) is a crucial innate immune sensor responsible for distinguishing pathogens and cytosolic DNA, mediating innate immune signaling pathways to defend the host. Recent studies have revealed additional regulatory functions of STING beyond its innate immune-related activities, including the regulation of cellular metabolism, DNA repair, cellular senescence, autophagy and various cell deaths. These findings highlight the broader implications of STING in cellular physiology beyond its role in innate immunity. Currently, approximately 10 STING agonists have entered the clinical stage. Unlike inhibitors, which have a maximum inhibition limit, agonists have the potential for infinite amplification. STING signaling is a complex process that requires precise regulation of STING to ensure balanced immune responses and prevent detrimental autoinflammation. Recent research on the structural mechanism of STING autoinhibition and its negative regulation by adaptor protein complex 1 (AP-1) provides valuable insights into its different effects under physiological and pathological conditions, offering a new perspective for developing immune regulatory drugs. Herein, we present a comprehensive overview of the regulatory functions and molecular mechanisms of STING beyond innate immune regulation, along with updated details of its structural mechanisms. We discuss the implications of these complex regulations in various diseases, emphasizing the importance and feasibility of targeting the immunity-dependent or immunity-independent functions of STING. Moreover, we highlight the current trend in drug development and key points for clinical research, basic research, and translational research related to STING.

Factors Influencing Time to First Medical Contact in Patients with Acute ST-Segment Elevation Myocardial Infarction: A Retrospective Analysis.

BACKGROUND Exploring the factors that impact the time from symptom onset to first medical contact (S2FMC) is crucial for improving outcomes in elderly patients diagnosed with acute ST-segment elevation myocardial infarction (STEMI). This study conducted a retrospective analysis on 282 patients who underwent emergency percutaneous coronary intervention (PCI) or percutaneous transluminal coronary angioplasty (PTCA) in Guangzhou City District to identify significant factors affecting S2FMC. MATERIAL AND METHODS A retrospective analysis was conducted on 282 patients with STEMI who underwent emergency percutaneous coronary intervention (PCI). Descriptive statistics, univariate and multivariate Cox regression analyses were used to identify significant factors affecting S2FMC. Additionally, interactions between risk factors were examined using multivariate logistic regression and the structural equation model (SEM). RESULTS Age (HR=0.984, 95% CI: 0.975-0.993), nature of chest pain (HR=2.561, 95% CI: 1.900-3.458), admission mode (HR=1.805, 95% CI: 1.358-2.400), and vascular characteristics (HR=1.246, 95% CI: 1.069-1.451) were independent influencing factors for S2FMC. Persistent chest tightness/pain, EMS admission, and vascular characteristics (RCADL or LCADL) played a protective role in S2FMC. Among the influencing factors, vascular characteristics (OR=1.072, 95% CI: 1.008-1.141) had an independent effect on the nature of chest pain. Meanwhile, the nature of chest pain (OR=1.148, 95% CI: 1.015-1.298) was an independent influencing factor in the admission mode. CONCLUSIONS Patients with persistent chest tightness/pain, EMS admission, and vascular characteristics (RCADL or LCADL) experienced shorter S2FMC and higher compliance rate (S2FMC ≤180 min). At the same time, age and other vascular features played an inverse role. This study proposes enhancing follow-up and monitoring measures, and shows the consequences of intermittent chest pain should not be disregarded.

Different classes of small RNAs are essential for head regeneration in the planarian Dugesia japonica.

BACKGROUND: Planarians reliably regenerate all body parts after injury, including a fully functional head and central nervous system. But until now, the expression dynamics and functional role of miRNAs and other small RNAs during the process of head regeneration are not well understood. Furthermore, little is known about the evolutionary conservation of the relevant small RNAs pathways, rendering it difficult to assess whether insights from planarians will apply to other taxa. RESULTS: In this study, we applied high throughput sequencing to identify miRNAs, tRNA fragments and piRNAs that are dynamically expressed during head regeneration in Dugesia japonica. We further show that knockdown of selected small RNAs, including three novel Dugesia-specific miRNAs, during head regeneration induces severe defects including abnormally small-sized eyes, cyclopia and complete absence of eyes. CONCLUSIONS: Our findings suggest that a complex pool of small RNAs takes part in the process of head regeneration in Dugesia japonica and provide novel insights into global small RNA expression profiles and expression changes in response to head amputation. Our study reveals the evolutionary conserved role of miR-124 and brings further promising candidate small RNAs into play that might unveil new avenues for inducing restorative programs in non-regenerative organisms via small RNA mimics based therapies.

A novel RhoA-related gene, DjRhoA, contributes to the regeneration of brain and intestine in planarian Dugesia japonica.

A small GTPase, RhoA, plays a variety of functions in the regulation of cellular and developmental events via its downstream effectors, including cytokinesis, cell migration, and phagocytosis. In this study, a novel RhoA-related gene from the planarian Dugesia japonica, DjRhoA, was cloned and characterized. The full-length cDNA of DjRhoA is 869 bp, and the open reading frame encodes a poly-peptide of 194 amino acids. Phylogenetic analysis revealed that DjRhoA clustered with another RhoA-related protein, DjRho2, and located on the base of phylogenetic tree. Whole-mount in situ hybridization results indicated that DjRhoA was expressed in the brain primordia and intestine during regeneration. Knockdown of DjRhoA induces defects in the brain and intestine. These results suggested that DjRhoA was responsible for the regeneration of brain and intestine in Dugesia japonica.

Effect of Al Content on Microstructure and Mechanical Property of Nanocomposite TiAlSiN Thin Films.

TiAlSiN thin films exhibit high hardness due to the multicomponent and multiphase structures. Effects of Si on TiAlSiN microstructure and mechanical properties have been well studied. However, there is insufficient information on the effects of Al. Thus, in this work, Al-contained nanocomposite nc-TiN/a-SiNx thin films with Al up to 10 at.% were prepared by magnetron co-sputtering Ti, Al and Si3N4 targets in Ar/N2 gas atmosphere. The effects of Al on TiAlSiN microstructure and mechanical property were well studied. Adjusting Al/(Ti+Al) target power ratio tuned chemical composition, microstructure and consequently mechanical properties. With increase of Al/(Ti+Al) target power ratio from 0 to 0.2, Al content increased from 0 to 10 at.%. X-ray photoelectron spectroscope results showed that aluminum nitride was formed. X-ray diffraction results confirmed that the nanocrystalline phase TiN was with Si and Al in its structure, or (Ti, Al, Si) N. The matrix was amorphous silicon nitride containing aluminum nitride. Nanoindentation hardness of the thin films remained at about 28 GPa till Al addition was increased to 3.1 at.%.

A new N-methoxyl-carbonyl benzylisoquinoline from Litsea cubeba.

A new benzylisoquinoline alkaloid (•)-N-methoxycarbonyl-norjuziphine (1) was isolated from Litsea cubeba. Its structure was identified by extensively spectroscopic techniques and confirmed by the single-crystal X-ray diffraction analysis. Compound 1 showed cytotoxicity against HL-60 and MCF-7 cells, with IC50 values of 18.1 and 15.0 µM, respectively, comparable to 3.1 and 17.5 µM of the cisplatin (positive control).

Thoracic epidural analgesia (TEA) vs. patient controlled analgesia (PCA) in laparoscopic colectomy: a meta-analysis.

BACKGROUND/AIMS: Use of thoracic epidural analgesia (TEA) in laparoscopic colorectal surgery is still controversial. Previous clinical trials have conflicting findings in terms of bowel function return, length of hospital stay and postoperative complications. This meta-analysis aims to assess the effect of TEA on clinical outcomes of laparoscopic colorectal surgery compared with patient controlled analgesia (PCA). METHODOLOGY: Randomized, controlled trials (RCTs) compared the effect of thoracic epidural analgesia (TEA) and patient controlled analgesia (PCA) on outcomes of laparoscopic colorectal surgery was searched. The effects on pain relief, bowel function return, length of hospital stay and post-operative complications were compared. RESULTS: Seven RCTs were included in this meta-analysis. Compared with PEA, TEA contributed significantly lower visual analog scale (VAS) or verbal rate scale (VRS) pain score during the initial period after surgery. No significant difference was observed in time to return of bowel function and length of hospital stay between the two groups. TEA group was associated with lower risk in nausea and vomiting, but with similar risk in urinary retention, urinary tract infection, wound infection, ileus and anastomotic leakage compared with PCA group. CONCLUSIONS: Use of epidural analgesia in laparoscopic colorectal surgery helps to provide better pain alleviation during the initial period after operation. This benefit is not at the expense of increased risks of any major complications, or significantly longer hospital stay. No significant benefits in return of bowel function were observed.

The characteristics and influencing factors of farmland soil microplastic in Hetao Irrigation District, China.

Microplastic pollution, a major global concern, has garnered increasing attention in agricultural ecosystem research. China's Hetao Irrigation District, vital for grain production in the Yellow River Basin, lacks sufficient research on microplastic pollution of agricultural soils. This study, based on a detailed background investigation and testing of 47 samples, is the first to elucidate the characteristics and potential influencing factors of microplastics in the Hetao Irrigation District. The abundance of microplastics in the farmland soil ranged from 1810 to 86331 items/kg, with 90% measuring below 180 µm and mainly in film and fragment forms. Predominant polymers were polyethylene (PE, 43.0%) and polyamide (PA, 27.8%). Key pollution influencers were identified as agricultural inputs, with low-density polyethylene (LDPE) being the most extensively used plastic type. The carbonyl index and hydroxyl indices of the detected LDPE microplastics ranged from 0.041 to 0.96 and 0.092 to 1.20, respectively. The study highlights the significance of mulching management and agronomic practices in shaping microplastic characteristics. Potential pollution sources include agricultural inputs, irrigation equipment, domestic waste, and tire wear. Proposed effective strategies include responsible plastic use, robust waste management, and irrigation system upgrades, establishing a foundation for future ecological risk assessments and effective management approaches in the Hetao Irrigation District. ENVIRONMENTAL IMPLICATION: The harmful substances studied in this paper are microplastics, which are widely distributed in the environment and have potential ecological risks. This study is the first to investigate the characteristics of microplastics in farmland soil within the Hetao Irrigation Area, a region that is of critical importance to agricultural production in the Yellow River Basin of China. The study provides comprehensive insights into the factors influencing the characteristics of microplastics and speculates on their sources. These findings offer a novel perspective on the assessment of microplastic contamination in the area and provide valuable recommendations for prevention and control measures.

Integrative analysis identifies cancer cell-intrinsic RARRES1 as a predictor of prognosis and immune response in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and limited treatment options. Although immune checkpoint inhibitors (ICIs) have been proven to improve outcomes in TNBC patients, the potential mechanisms and markers that determine the therapeutic response to ICIs remains uncertain. Revealing the relationship and interaction between cancer cells and tumor microenvironment (TME) could be helpful in predicting treatment efficacy and developing novel therapeutic agents. By analyzing single-cell RNA sequencing dataset, we comprehensively profiled cell types and subpopulations as well as identified their signatures in the TME of TNBC. We also proposed a method for quantitatively assessment of the TME immune profile and provided a framework for identifying cancer cell-intrinsic features associated with TME through integrated analysis. Using integrative analyses, RARRES1 was identified as a TME-associated gene, whose expression was positively correlated with prognosis and response to ICIs in TNBC. In conclusion, this study characterized the heterogeneity of cellular components in TME of TNBC patients, and brought new insights into the relationship between cancer cells and TME. In addition, RARRES1 was identified as a potential predictor of prognosis and response to ICIs in TNBC.

Multi-omics reveal the gut microbiota-mediated severe foraging environment adaption of small wild ruminants in the Three-River-Source National Park, China.

The Tibetan antelope (Pantholops hodgsonii), blue sheep (Pseudois nayaur), and Tibetan sheep (Ovis aries) are the dominant small ruminants in the Three-River-Source National Park (TRSNP). However, knowledge about the association between gut microbiota and host adaptability remains poorly understood. Herein, multi-omics sequencing approaches were employed to investigate the gut microbiota-mediated forage adaption in these ruminants. The results revealed that although wild ruminants (WR) of P. hodgsoni and P. nayaur were faced with severe foraging environments with significantly low vegetation coverage and nutrition, the apparent forage digestibility of dry matter, crude protein, and acid detergent fiber was significantly higher than that of O. aries. The 16s rRNA sequencing showed that the gut microbiota in WR underwent convergent evolution, and alpha diversity in these two groups was significantly higher than that in O. aries. Moreover, indicator species, including Bacteroidetes and Firmicutes, exhibited positive relationships with apparent forage digestibility, and their relative abundances were enriched in the gut of WR. Enterotype analysis further revealed that enterotype 1 belonged to WR, and the abundance of fatty acid synthesis metabolic pathway-related enzyme genes was significantly higher than enterotype 2, represented by O. aries. Besides, the metagenomic analysis identified 14 pathogenic bacterial species, among which 10 potentially pathogenic bacteria were significantly enriched in the gut microbiota of O. aries. Furthermore, the cellulolytic strains and genes encoding cellulase and hemicellulase were significantly enriched in WR. In conclusion, our results provide new evidence of gut microbiota to facilitate wildlife adaption in severe foraging environments of the TRSNP, China.

Insight into the differences in meat quality among three breeds of sheep on the Qinghai-Tibetan plateau from the perspective of metabolomics and rumen microbiota.

Mutton is one of the most popular meats among the general public due to its high nutritional value. This study evaluated the differences in meat quality among Chaka (CK), Black Tibetan (BT) and Oula (OL) sheep and investigated the metabolic mechanisms affecting meat quality using targeted and untargeted metabolomics and 16S rRNA. The results showed that the meat quality of CK sheep was superior to that of BT and OL sheep in terms of meat color, muscle fiber characteristics and nutritional quality. Pseudobutyrivibrio, Alloprevotella, Methanobrevibacter, unidentified_Christensenellaceae, and unidentified_Bacteroidales were key microbes involved in regulating meat color, muscle fiber characteristics, amino acid and fatty acid content. Protein digestion/absorption, pentose phosphate metabolism, carbon metabolism, and glyoxylate and dicarboxylate metabolism were important metabolic pathways involved in meat quality regulation. Our study is important for the development of sheep breeding strategy and sheep meat industry in Qinghai-Tibetan Plateau.

Targeted and untargeted metabolomics reveals meat quality in grazing yak during different phenology periods on the Qinghai-Tibetan Plateau.

Yak meat is more popular among consumers because of its high nutritional value, but little attention has been paid to its meat quality, which is affected by different phenology periods grass. We hypothesized that seasonal variations in grass composition influenced the ruminal bacteria community, and eventually affected the meat quality of yaks. This study aims to investigate the relationship of meat quality in grazing yak as well as the key rumen bacteria using targeted and untargeted metabolomics and 16S rRNA during different phenology periods. The main three altered metabolic pathways in grazing yak, including amino acids biosynthesis, glutathione metabolism, and fatty acids biosynthesis, were found in the grass period (GP) group compared to the regreen period (RP) and hay period (HP) groups. The GP group had higher concentrations of flavor amino acids (FAA), polyunsaturated fatty acids (PUFA), and a lower ratio of n-6/n-3 compared with the RP group. Correlation analysis results showed that Rikenellaceae_RC9_gut_group was positively correlated with fatty acids and lipid metabolites, which might be involved in lipid metabolism. Pediococcus had a positive correlation with biological peptides, which could be involved in the metabolism of bioactive compounds. In conclusion, grass in different phenology periods was associated with modified amino acids and fatty acids composition of yak meat as well as altered regulation of biological pathways, which was correlated with changes in rumen bacterial communities.

Evaluation of the Longissimus Thoracis et Lumborum Muscle Quality of Chaka and Tibetan Sheep and the Analysis of Possible Mechanisms Regulating Meat Quality.

This study aimed to comprehensively evaluate the characteristics in the longissimus thoracis et lumborum (LTL) muscle of Chaka (CK) sheep and Tibetan (TB) sheep, and transcriptomics-metabolomics association analysis was used to find the possible genes, differential metabolites, and significant differential metabolic pathways that lead to meat quality differences. Based on the researched results, the nutritional quality of meat, including the contents of ether extract (11.95% vs. 10.56%), unsaturated fatty acid (51.20% vs. 47.69%), and polyunsaturated fatty acid (5.71% vs. 3.97%), were better in TB sheep than in CK sheep, while the CK sheep has better muscle fiber characteristics, such as the total number (62 vs. 45) and muscle fiber density (1426.54 mm2 vs. 1158.77 mm2) and flavor. Omics research has shown that the key differential metabolites and metabolic pathways were dominated by amino acid metabolism, particularly the glutathione metabolism, taurine and hypotaurine metabolism, and lipid metabolism-related pathways, such as glycerophospholipid metabolism and the sphingolipid signaling pathway. The intermediate metabolite sn-Glycerol 3-phosphoethanolamine played a key role in determining sheep meat quality, which was regulated by GPAT2, PLPP2, AGPAT1, PNPLA2, and GPAT4 and correlated with meat color, texture, and flavor. Overall, these results will provide effective information and more evidence to support further exploration of valuable biomarkers of meat quality.

A modified primary culture method of rat pulmonary vein smooth muscle cells.

BACKGROUND: Although the pressure of pulmonary vein increases before pulmonary artery in pulmonary hypertension due to left heart disease (PH-LHD), only a few studies have assessed pulmonary vein smooth muscle cells (PVSMCs) because of the lack of a simple and feasible isolation method. METHODS: In this study, we introduced a simple method to obtain PVSMCs. Primary pulmonary veins were removed by puncture needle cannula guidance. Then, PVSMCs were cultured by the tissue explant method and purified by the differential adhesion method. The cells were characterized by hematoxylin-eosin (HE) staining, immunohistochemistry, western blotting, and immunofluorescence to observe the morphology and verify the expression of alpha-smooth muscle actin (α-SMA). RESULTS: The HE staining results showed that the pulmonary vein media was thinner than the pulmonary artery, the intima and adventitia of the pulmonary vein were removed by this method, and the obtained cells with good activity exhibited morphological characteristics of smooth muscle cells. In addition, higher α-SMA expression was observed in the cells obtained by our isolation method than in the traditional method. CONCLUSION: This study established a simple and feasible method to isolate and culture PVSMCs that might facilitate the cytological experiments for PH-LHD.

Age at menopause is inversely related to the prevalence of common gynecologic cancers: a study based on NHANES.

Background: The fluctuation or even loss of estrogen level caused by menopause in women, and most gynecological cancers often occur before and after menopause, so the age of menopause may be related to the occurrence of gynecological cancer. Aim: To investigate whether the age at menopause is independently associated with the incidence of gynecological cancers and to analyze the possible influencing factors. Methods: We selected the NHANES public database to conduct the study, and by excluding relevant influencing factors, we finally included 5706 NHANES participants who had full data on age at menopause and the occurrence of gynecologic cancers to analyze the relationship between the amount of age at menopause and gynecologic cancers based on univariate or multifactorial logistic regression analysis. Further, the relationship between age at menopause and the prevalence of different gynecologic cancers was investigated, and changes in the prevalence of different gynecologic cancers by age at menopause subgroups were observed. Finally, other relevant factors affecting the prevalence of gynecologic cancers were further investigated by subgroup analysis as well as subcluster analysis. Results: Univariate logistic regression analysis between age at menopause and gynecologic tumor prevalence revealed a negative association between age at menopause and the prevalence of common gynecologic cancers ovarian and cervical cancer, and after adjusting for the effects of covariates, a higher risk of gynecologic tumors was found with statistically significant differences at earlier age at menopause. The regression results showed a negative association between age at menopause and gynecologic cancer prevalence in cervical and ovarian cancer patients (P<0.01,P<0.01). Cervical cancer (OR: 0.91, 95% CI: 0.87,0.94) and ovarian cancer (OR: 0.90, 95% CI: 0.86, 0.95) were more prevalent among those with younger age at menopause. Conclusion: Age at menopause is negatively associated with the prevalence of cervical and ovarian cancers, and the earlier the age at menopause, the greater the risk of developing gynecological cancers.

Mitigation of greenhouse gas emissions and improved yield by plastic mulching in rice production.

Soil mulching technologies are effective practices which alleviate non-point source pollution and carbon emissions, while ensuring grain production security and increasing water productivity. However, the lack of comprehensive understanding of the impacts of mulching technologies on rice fields has hindered progress in global implementation due to the varying environments and application conditions under which they are implemented. This study conducted a meta-analysis based on 2412 groups of field experiment data from 313 studies to evaluate the effects of soil mulching methods on rice production, greenhouse gas (GHG) emissions and water use efficiency. The results show that plastic mulching, straw mulching and no mulching (PM, SM and NM) have reduced CH4 emissions (68.8 %, 61.4 % and 57.2 %), increased N2O emissions (84.8 %, 89.1 % and 96.6 %), reduced global warming potentials (50.7 %, 47.5 % and 46.8 %) and improved water use efficiency (50.2 %, 40.9 % and 34.0 %) compared with continuous flooding irrigation. However, PM increased rice yield (1.6 %), while SM and NM decreased yield (4.3 % and 9.2 %). Furthermore, analysis using random forest models revealed that rice yield, GHG emissions and WUE response to soil mulching were related to climate, soil properties, fertilizer and rice varieties. Our findings can guide the implementation of plastic mulching technology in priority areas, contribute to agricultural carbon neutrality and support the development of practical guidelines for farmers.