Clinical efficacy and pathological outcomes of transanal endoscopic intersphincteric resection for low rectal cancer.

BACKGROUND: Transanal endoscopic intersphincteric resection (ISR) surgery currently lacks sufficient clinical research and reporting. AIM: To investigate the clinical effectiveness of transanal endoscopic ISR, in order to promote the clinical application and development of this technique. METHODS: This study utilized a retrospective case series design. Clinical and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated Hospital of Xiamen University between May 2018 and May 2023 were included. All patients underwent transanal endoscopic ISR as the surgical approach. We conducted this study to determine the perioperative recovery status, postoperative complications, and pathological specimen characteristics of this group of patients. RESULTS: This study included 45 eligible patients, with no perioperative mortalities. The overall incidence of early complications was 22.22%, with a rate of 4.44% for Clavien-Dindo grade ≥ III events. Two patients (4.4%) developed anastomotic leakage after surgery, including one case of grade A and one case of grade B. Postoperative pathological examination confirmed negative circumferential resection margins and distal resection margins in all patients. The mean distance between the tumor lower margin and distal resection margin was found to be 2.30 ± 0.62 cm. The transanal endoscopic ISR procedure consistently yielded high quality pathological specimens. CONCLUSION: Transanal endoscopic ISR is safe, feasible, and provides a clear anatomical view. It is associated with a low incidence of postoperative complications and favorable pathological outcomes, making it worth further research and application.

Role of calcium nutrition in plant Physiology: Advances in research and insights into acidic soil conditions - A comprehensive review.

Plant mineral nutrition has immense significance for crop productivity and human well-being. Soil acidity plays a major role in determining the nutrient availability that influences plant growth. The importance of calcium (Ca) in biological processes, such as signaling, metabolism, and cell growth, underlines its critical role in plant growth and development. This review focuses on soil acidification, a gradual process resulting from cation leaching, fertilizer utilization, and drainage issues. Soil acidification significantly hampers global crop production by modifying nutrient accessibility. In acidic soils, essential nutrients, such as nitrogen (N), phosphorus (P), potassium (K), magnesium (Mg), and Ca become less accessible, establishing a correlation between soil pH and plant nutrition. Cutting-edge Ca nutrition technologies, including nanotechnology, genetic engineering, and genome sequencing, offer the potential to deliver Ca and reduce the reliance on conventional soluble fertilizers. These fertilizers not only contribute to environmental contamination but also impose economic burdens on farmers. Nanotechnology can enhance nutrient uptake, and Ca nanoparticles improve nutrient absorption and release. Genetic engineering enables the cultivation of acid-tolerant crop varieties by manipulating Ca-related genes. High-throughput technologies such as next-generation sequencing and microarrays aid in identifying the microbial structures, functions, and biosynthetic pathways involved in managing plant nutritional stress. The ultimate goal is to shed light on the importance of Ca, problems associated with soil acidity, and potential of emerging technologies to enhance crop production while minimizing the environmental impact and economic burden on farmers.

Targeting dysregulated phago-/auto-lysosomes in Sertoli cells to ameliorate late-onset hypogonadism.

Age-related changes in testicular function can impact health and well-being. The mechanisms underlying age-related testicular dysfunction, such as late-onset hypogonadism (LOH), remain incompletely understood. Using single-cell RNA sequencing on human testes with LOH, we delineated Sertoli cells (SCs) as pivotal metabolic coordinators within the testicular microenvironment. In particular, lysosomal acidity probing revealed compromised degradative capacity in aged SCs, hindering autophagy and phagocytic flux. Consequently, SCs accumulated metabolites, including cholesterol, and have increased inflammatory gene expression; thus, we termed these cells as phago-/auto-lysosomal deregulated SCs. Exposure to a high-fat diet-induced phago-/auto-lysosomal dysregulated-like SCs, recapitulating LOH features in mice. Notably, efferent ductular injection and systemic TRPML1 agonist administration restored lysosomal function, normalizing testosterone deficiency and associated abnormalities in high-fat diet-induced LOH mice. Our findings underscore the central role of SCs in testis aging, presenting a promising therapeutic avenue for LOH.

[Investigation on the current situation and influencing factors of sitting time and health literacy among high school students in China].

OBJECTIVE: To investigate the current situation of sitting time and health literacy among high school students in China, in order to provide a basis for improving their physical and mental health levels. METHODS: A stratified random cluster sampling method was used to investigate the length of sitting time and health literacy of first and second grade high school students from 31 provinces, cities, and autonomous regions in China(data did not include that of Hong Kong and Macao Special Administrative Region, and Taiwan Province of China). The Kruskal-Wallis H method, independent sample Mann-Whitney U test, and regression model were used to analyze the influencing factors of sitting time and total health literacy score. RESULTS: (1) The total score of health literacy was statistically significant (P < 0.01) in different regions, urban and rural distribution, annual family income, parents' educational background, age, and gender. (2) The length of sitting was statistically significant (P < 0.01) among multiple groups in different regions, family annual income, parental education, and gender. However, there was no statistically significant difference between groups of different ages and urban-rural distribution (P>0.05). (3) The analysis of multiple linear regression model showed that the total score of health literacy was positively correlated with the family' s annual income and the mother' s education, and negatively correlated with the father' s education and the length of sitting. Standardized regression coefficient ß comparison: Father' s education (-0.32) > family annual income (0.15) > mother' s education (0.09) > average daily sitting time (-0.02), with father' s education having the greatest impact, followed by family annual income. The length of sitting was positively related to the family' s annual income and the mother' s educational background, and negatively related to the total score of health literacy. Standardized regression coefficient ß comparison: Annual family income (0.14) > education background of mother (0.13)> total score of health literacy (-0.02), with the impact of annual family income the largest, followed by education background of mother. CONCLUSION: China' s first and second grade high school students generally spend a long time sitting every day, and the level of health literacy is generally low. The level of health literacy and sitting time are negatively correlated with each other, and are most influenced by the educational background of high school students' parents and their family economic levels.

A chromosome-level genome assembly of the spider mite Tetranychus piercei McGregor.

Despite the rapid advances in sequencing technology, limited genomic resources are currently available for phytophagous spider mites, which include many important agricultural pests. One of these pests is Tetranychus piercei (McGregor), a serious banana pest in East Asia exhibiting remarkable tolerance to high temperature. In this study, we assembled a high-quality genome of T. piercei using a combination of PacBio long reads and Illumina short reads sequencing. With the assistance of chromatin conformation capture technology, 99.9% of the contigs were anchored into three pseudochromosomes with a total size of 86.02 Mb. Repetitive elements, accounting for 14.16% of this genome (12.20 Mb), are predominantly composed of long-terminal repeats (30.7%). By combining evidence of ab initio prediction, transcripts, and homologous proteins, we annotated 11,881 protein-coding genes. Both the genome and proteins have high BUSCO completeness scores (>94%). This high-quality genome, along with reliable annotation, provides a valuable resource for investigating the high-temperature tolerance of this species and exploring the genomic basis that underlies the host range evolution of spider mites.

Digital inverse patterning solutions for fabrication of high-fidelity microstructures in spatial light modulator (SLM)-based projection lithography.

Digital mask projection lithography (DMPL) technology is gaining significant attention due to its characteristics of free-mask, flexibility, and low cost. However, when dealing with target layouts featuring sizes smaller than the wavelength scale, accurately producing resist patterns that closely match the target layout using conventional methods to design the modulation coefficients of digital masks produced by spatial light modulators (SLM) becomes challenging. Here, we present digital inversion lithography technology (DILT), which offers what we believe to be a novel approach to reverse engineer the modulation coefficients of digital masks. In the case of binary amplitude modulation, DILT achieves a remarkable reduction in pattern errors (PE), reaching the original 0.26. At the same time, in the case of the gray amplitude modulation, the PE can be reduced to the original 0.05, which greatly improves the high-fidelity transfer of the target layout. This significant improvement enhances the accuracy of target design transfer. By leveraging the capabilities of DILT, DMPL can now attain higher precision and reliability, paving the way for more advanced applications in the field of micro-nano device manufacturing.

Human Seminal Extracellular Vesicles Enhance Endometrial Receptivity Through Leukemia Inhibitory Factor.

Seminal extracellular vesicles (EVs) contain different subgroups that have diverse effects on sperm function. However, the effect of seminal EVs-especially their subgroups-on endometrial receptivity is largely unknown. Here, we found that seminal EVs could be divided into high-density EVs (EV-H), medium density EVs, and low-density EVs after purification using iodixanol. We demonstrated that EV-H could promote the expression and secretion of leukemia inhibitor factor (LIF) in human endometrial cells. In EV-H-treated endometrial cells, we identified 1274 differentially expressed genes (DEGs). DEGs were enriched in cell adhesion and AKT and STAT3 pathways. Therefore, we illustrated that EV-H enhanced the adhesion of human choriocarcinoma JAr cell spheroids to endometrial cells through the LIF-STAT3 pathway. Collectively, our findings indicated that seminal EV-H could regulate endometrial receptivity through the LIF pathway, which could provide novel insights into male fertility.

Association between multipollutant exposure and thyroid hormones in elderly people: A cross-sectional study in China.

Environmental chemicals have been indicated to cause disruption of thyroid homeostasis in human populations. However, previous studies mostly focused on single group of chemicals. Herein, we investigate the independent and combined effects of multiple pollutants on thyroid homeostasis, including thyroid-stimulating hormone (TSH), total and free thyroxine (tT4 and fT4) and total and free triiodothyronine (tT3 and fT3) in elderly people. These environmental pollutants (n = 144) are from ten categories, including phenols, parabens, perfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs), phthalate esters (PAEs), polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), synthetic pyrethroids (SPs), herbicides, and metals. Few studies have evaluated the health risks of these 144 chemicals, especially their joint effects. In single-pollutant evaluations, multiple linear regression (MLR) models were used to estimate the independent associations between multiple exposures and thyroid biomarkers. In multi-pollutant evaluations, elastic net regression and Bayesian kernel machine regression (BKMR) models were used to estimate the combined associations. The MLR models showed that 41 chemicals were significantly related to THs levels. BKMR models revealed the most important chemical groups: metals for TSH, PAHs, SPs and PCBs for tT4, herbicides and SPs for tT3. This study will contribute to the understanding of multipollutant exposure and help prioritize specific chemical groups related to thyroid hormone disruption.

MD investigation on the differences in the dynamic interactions between the specific ligand azamulin and two CYP3A isoforms, 3A4 and 3A5.

The unmarked potential drug molecule azamulin has been found to be a specific inhibitor of CYP3A4 and CYP3A5 in recent years, but this molecule also shows different binding ability and affinity to the two CYP3A isoforms. In order to explore the microscopic mechanism, conventional molecular dynamics (MD) simulation methods were performed to study the dynamic interactions between two isoforms and azamulin. The simulation results show that the binding of the ligand leads to different structural properties of two CYP3A proteins. First of all, compared with apo-CYP3A4, the binding of the ligand azamulin can lead to changes in the structural flexibility of CYP3A4, i.e., holo-CYP3A4 is more flexible than apo-CYP3A4. The structural changes of CYP3A5 are just the opposite. The ligand binding increases the rigidity of CYP3A5. Furthermore, the representative structures of the production phase in the MD simulation were in details analyzed to obtain the microscopic interactions between the ligand azamulin and two CYP3A isoforms at the atomic level. It is speculated that the difference of composition and interaction of the active sites is the fundamental cause of the change of structural properties of the two proteins.Communicated by Ramaswamy H. Sarma.

Phylogenomics resolves the higher-level phylogeny of herbivorous eriophyoid mites (Acariformes: Eriophyoidea).

BACKGROUND: Eriophyoid mites (Eriophyoidea) are among the largest groups in the Acariformes; they are strictly phytophagous. The higher-level phylogeny of eriophyoid mites, however, remains unresolved due to the limited number of available morphological characters-some of them are homoplastic. Nevertheless, the eriophyoid mites sequenced to date showed highly variable mitochondrial (mt) gene orders, which could potentially be useful for resolving the higher-level phylogenetic relationships. RESULTS: Here, we sequenced and compared the complete mt genomes of 153 eriophyoid mite species, which showed 54 patterns of rearranged mt gene orders relative to that of the hypothetical ancestor of arthropods. The shared derived mt gene clusters support the monophyly of eriophyoid mites (Eriophyoidea) as a whole and the monophylies of six clades within Eriophyoidea. These monophyletic groups and their relationships were largely supported in the phylogenetic trees inferred from mt genome sequences as well. Our molecular dating results showed that Eriophyoidea originated in the Triassic and diversified in the Cretaceous, coinciding with the diversification of angiosperms. CONCLUSIONS: This study reveals multiple molecular synapomorphies (i.e. shared derived mt gene clusters) at different levels (i.e. family, subfamily or tribe level) from the complete mt genomes of 153 eriophyoid mite species. We demonstrated the use of derived mt gene clusters in unveiling the higher-level phylogeny of eriophyoid mites, and underlines the origin of these mites and their co-diversification with angiosperms.

The value of audiovisual sexual stimulation with virtual reality in diagnosing erectile dysfunction.

Background: The traditional audiovisual sexual stimulation (AVSS) test may experience limitations including low erectile response rate and lack of unified diagnostic criteria. Aim: We aimed to explore the clinical value of AVSS with virtual reality (VR-AVSS) test in assessing erectile function and diagnosing erectile dysfunction (ED). Methods: Participants 18 to 60 years of age were screened for analysis in 3 clinical centers from June 2020 to March 2022. Demographic data, 5-item International Index of Erectile Function (IIEF-5), erectile hardness score (EHS), and self-reported symptom questions were collected. The ED patients and control patients were confirmed according to the IIEF-5 and EHS. All subjects watched a 60-minute erotic video by VR device during RigiScan recording. The parameters including tip average rigidity, tip effective erectile duration (duration of rigidity ≥60%, tip effective erectile duration), base average rigidity, and base effective erectile duration were evaluated. Outcomes: The main outcome of interest was the application of VR immersion technology to improve the traditional AVSS test. Results: A total of 301 ED cases and 100 eligible control patients were included for final analysis. Compared with control patients, ED cases had significantly lower IIEF-5 scores, EHS, positive response rate, and erectile rigidity and duration. The positive response rate of ED and control patients were 75.5% and 90.9%, respectively. The cutoff points of tip average rigidity, tip effective erectile duration, base average rigidity, and base effective erectile duration were 40.5% (sensitivity: 77.6%, specificity: 70.2%; P < .001), 4.75 minutes (sensitivity: 75.9%, specificity: 75.4%; P < .001), 48.5% (sensitivity: 77.6%, specificity: 75.1%; P < .001), and 7.75 minutes (sensitivity: 79.3%, specificity: 75.7%; P < .001). Clinical Implications: The technological superiority of VR will enable the VR-AVSS immersion test to be a more accurate detection than traditional AVSS modes. Strengths and Limitations: Our study applied VR immersion technology to establish the standard operation procedure for the AVSS test, which could effectively reduce the interference of adverse factors and minimize the detecting errors. However, the test data only included positive response subjects, so the true erectile status of men with a negative response to the AVSS test cannot be obtained. Conclusions: The VR-AVSS test can effectively improve the diagnostic accuracy of ED. The average rigidity and effective erectile duration were the optimal diagnostic parameters for excluding ED.

Lycopene inhibits apoptosis of mouse spermatocytes in varicocele via miR-23a/b-induced downregulation of PROK2.

Context The varicocele is the leading cause of male infertility and can impair sperm quality and testicular function through various mechanisms. In our previous study, we found that lycopene could attenuate hypoxia-induced testicular injury. Aims To illustrate the detailed mechanism of lycopene on spermatocytes. Methods The effect of lycopene on GC-2 cells under hypoxia were detected by flow cytometry and western blot assay. miR-seq was used to determine miRNA expression in varicocele rat model testes. The function of miR-23a/b were determined by flow cytometry and western blot assay. Key results We demonstrate that lycopene could alleviate hypoxia-induced GC-2 cell apoptosis and could elevate miR-23a/b expression of the hypoxia model in vivo and in vitro . The miR-23a and -23b mimics could reduce the hypoxia-induced GC-2 cell apoptosis. Both miR-23a and -23b could directly bind with prokineticin 2 (PROK2) mRNA and downregulate its expression. Conclusions Lycopene could attenuate hypoxia-induced spermatocyte injury through the miR-23a/b-PROK2 pathway. Implications Lycopene may be an effective treatment for varicocele to improve testicular impairment.

Gut microbiota-derived LCA mediates the protective effect of PEDV infection in piglets.

BACKGROUND: The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics. RESULTS: Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids' deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8+ CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8+ CTLs to exert antiviral effects. CONCLUSIONS: Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract.

Optical proximity correction of hot-spot patterns with subwavelength size in DMD maskless projection lithography.

When the critical dimension (CD) of resist patterns nears the resolution limit of the digital micromirror device (DMD) maskless projection lithography (DMD-MPL), significant distortion can emerge in the silicon wafer due to the optical proximity effect (OPE). The significant distortion (breakpoints, line-end scaling, corner rounding, etc.) between resist patterns and target patterns results in reduced lithographic quality. To address this issue, we have proposed a pixel-based optical proximity correction (PB-OPC) method used for the hot-spot patterns with subwavelength sizes specifically designed for DMD-MPL. Employing an end-to-end learning neural network, the PB-OPC algorithm is both straightforward and efficient. A well-trained U-net framework facilitates the mapping from unoptimized masks to optimized masks. Experimental exposure trials have demonstrated that this method not only corrects OPC in general patterns but also effectively rectifies hot-spot patterns. The pattern error (PE) value can be reduced by about 30% in the design layouts. We believe this approach holds the potential to enhance the resolution and fidelity of resist patterns in DMD maskless lithography.

Oligomeric HIV-1 Integrase Structures Reveal Functional Plasticity for Intasome Assembly and RNA Binding.

Integrase (IN) performs dual essential roles during HIV-1 replication. During ingress, IN functions within an oligomeric "intasome" assembly to catalyze viral DNA integration into host chromatin. During late stages of infection, tetrameric IN binds viral RNA and orchestrates the condensation of ribonucleoprotein complexes into the capsid core. The molecular architectures of HIV-1 IN assemblies that mediate these distinct events remain unknown. Furthermore, the tetramer is an important antiviral target for allosteric IN inhibitors. Here, we determined cryo-EM structures of wildtype HIV-1 IN tetramers and intasome hexadecamers. Our structures unveil a remarkable plasticity that leverages IN C-terminal domains and abutting linkers to assemble functionally distinct oligomeric forms. Alteration of a newly recognized conserved interface revealed that both IN functions track with tetramerization in vitro and during HIV-1 infection. Collectively, our findings reveal how IN plasticity orchestrates its diverse molecular functions, suggest a working model for IN-viral RNA binding, and provide atomic blueprints for allosteric IN inhibitor development.

Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer.

BACKGROUND: Laparoscopic radical gastrectomy is widely used, and perioperative complications have become a highly concerned issue. AIM: To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery, guide perioperative treatment strategies for gastric cancer patients, and prevent serious complications. METHODS: In total, 998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model, and 398 patients were included in the validation group. The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected. Three machine learning methods, lasso regression, random forest, and artificial neural networks, were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy, and their prediction efficacy and accuracy were evaluated. RESULTS: The constructed complication model, particularly the random forest model, could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy. It exhibited stable performance in external validation and is worthy of further promotion in more centers. CONCLUSION: Using the risk factors identified in multicenter datasets, highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established. We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

Associations of chronic exposure to a mixture of pesticides and type 2 diabetes mellitus in a Chinese elderly population.

Epidemiological studies have related exposure to pesticides to increased risk of diabetes. However, few studies have evaluated the health effects of mixed pesticides exposure, especially in an elderly population. Here, we utilized gas chromatography-tandem mass spectrometry to quantify the levels of 39 pesticides in 4 categories in a Chinese elderly population. Then we used general linear models to explore the association between individual pesticide exposure and type 2 diabetes mellitus (T2DM). Restricted cubic spline (RCS) models were fitted to identify potential non-linearities between those associations. Furthermore, stratified analysis by gender was conducted to explore the gender-specific associations. Finally, we used weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR) to evaluate the effects of mixed exposure to 39 pesticides. The results showed that exposure to pesticides was associated with high risk of T2DM, with ß-Hexachlorocyclohexane (ß-BHC) and oxadiazon being the most significant independent contributors, which was pronounced among elderly women. Moreover, the association of ß-BHC and oxadiazon with T2DM was linear. These indicated that it is an urgent need to take practical measures to control these harmful pesticides.

Theoretical prediction of two-dimensional ferromagnetic Mn2X2 (X = As, Sb) with strain-controlled magnetocrystalline anisotropy.

Two-dimensional (2D) magnetic materials with large and tunable magnetocrystalline anisotropy (MCA) provide unique opportunities to develop various spintronic devices. We, herein, propose an experimentally feasible 2D material platform, Mn2X2 (X = As, Sb), which is a family of intrinsic ferromagnet. Using first-principles calculations, we show that 2D Mn2X2 (X = As, Sb) with a robust ferromagnetic ground state exhibits not only a large perpendicular magnetic anisotropy (PMA), but also significant strain-driven modulation behaviors under external biaxial strain. The analysis of the results demonstrates that the dominant contribution to the change of MCA of Mn2As2 and Mn2Sb2 primarily arises from the Mn and Sb atoms, respectively. Moreover, we reveal that the underlying origin is the competitive mechanism for the spin-orbit coupling (SOC) between different orbitals and spin channels. These findings indicate that 2D Mn2X2 (X = As, Sb) provides a promising material platform for the next generation of ultra-low energy memory devices.

Combined effects of organochlorine pesticides on type 2 diabetes mellitus: Insights from endocrine disrupting effects of hormones.

Association between organochlorine pesticides (OCPs) exposure and type 2 diabetes mellitus (T2DM) remains contradictory, and the evidence is mostly focused on a single exposure. Here, we assessed the associations between individual and combined OCPs exposure and T2DM, and explored the underlying mechanism of sex hormones and the methylation levels of sex hormone receptors in above associations. A case-control study with 1812 participants was performed. Gas chromatography mass spectrometry, liquid chromatography-tandem mass spectrometry, and pyrosequencing were used to measure plasma OCPs, serum sex hormones, and whole blood methylation levels of sex hormone receptors, respectively. Generalized linear models were used to analyze the relationships between OCPs, sex hormones, the methylation levels of sex hormone receptors, and T2DM. Quantile based g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) were employed to assess the combined OCPs exposure. The roles of sex hormones and the methylation levels of their receptors were evaluated by moderating mediation models. After adjusting for covariates, each unit (2.718 ng/ml) increase in p,p'-DDE was associated with a higher risk of T2DM in males (odds ratio (OR) and 95% confidence interval (CI): 1.066 (1.023, 1.112)). QGC and BKMR showed a positive combined effect in the associations of OCPs mixtures on T2DM among premenopausal females, and positive effects but not statistically significant among males and postmenopausal females. p,p'-DDE was the largest contributor for the positive associations. Furthermore, testosterone mediated 21.149% of the associations of p,p'-DDE with T2DM moderated by the androgen receptor methylation (ARm) located in CpG island 1. Individual and mixtures of OCPs exposure were positively linked to elevated risk of T2DM. Testosterone and ARm may participate in the related processes of OCPs with T2DM, providing new insights into the adverse endocrine effects caused by OCPs and specific pathways for the etiology and control of diabetes.

Sustainable valorizing high-protein feather waste utilization through solid-state fermentation by keratinase-enhanced Streptomyces sp. SCUT-3 using a novel promoter.

Feather waste, a rich source of proteins, has traditionally been processed through high-temperature puffing and acid-base hydrolysis, contributing to generation of greenhouse gases and H2S. To address this issue, we employed circular economy techniques to recover the nutritional value of feather waste. Streptomyces sp. SCUT-3, an efficient proteolytic and chitinolytic bacterium, was isolated for feather degradation previously. This study aimed to valorize feather waste for feed purposes by enhancing its feather transformation ability through promoter optimization. Seven promoters were identified through omics analysis and compared to a common Streptomyces promoter ermE*p. The strongest promoter, p24880, effectively enhanced the expression of three candidate keratinases (Sep39, Sep40, and Sep53). The expression efficiency of double-, triple-p24880 and sandwich p24880-sep39-p24880 promoters were further verified. The co-overexpression strain SCUT-3-p24880-sep39-p24880-sep40 exhibited a 16.21-fold increase in keratinase activity compared to the wild-type. Using this strain, a solid-state fermentation process was established that increased the feather/water ratio (w/w) to 1:1.5, shortened the fermentation time to 2.5 days, and increased soluble peptide and free amino acid yields to 0.41 g/g and 0.14 g/g, respectively. The resulting has high protein content (90.49 %), with high in vitro digestibility (94.20 %). This method has the potential to revolutionize the feather waste processing industry.