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Objective: This project aims to identify the top 30 drugs most commonly associated with constipation and their signal values within the FDA Adverse Event Reporting System database. Methods: We extracted adverse drug events (ADEs) related to constipation from the FAERS database spanning from January 1, 2004, to September 30, 2023. We compiled the 30 most frequently reported drugs based on the frequency of constipation events. We employed signal detection methodologies to ascertain whether these drugs elicited significant signals, including reporting odds ratio, proportional reporting ratio, multi-item gamma Poisson shrinker, and information component given by the Bayesian confidence propagation neural network. Furthermore, we conducted a time-to-onset (TTO) analysis for drugs generating significant signals using the medians, quartiles, and the Weibull shape parameter test. Results: We extracted a total of 50, 659, 288 ADEs, among which 169,897 (0.34%) were related to constipation. We selected and ranked the top 30 drugs. The drug with the highest ranking was lenalidomide (7,730 cases, 4.55%), with the most prevalent drug class being antineoplastic and immunomodulating agents. Signal detection was performed for the 30 drugs, with constipation risk signals identified for 26 of them. Among the 26 drugs, 22 exhibited constipation signals consistent with those listed on the FDA-approved drug labels. However, four drugs (orlistat, nintedanib, palbociclib, and dimethyl fumarate) presented an unexpected risk of constipation. Ranked by signal values, sevelamer carbonate emerged as the drug with the strongest risk signal [reporting odds ratio (95% CI): 115.51 (110.14, 121.15); PRR (χ2): 83.78 (191,709.73); EBGM (EB05): 82.63 (79.4); IC (IC025): 6.37 (4.70)]. A TTO analysis was conducted for the 26 drugs that generated risk signals, revealing that all drugs exhibited an early failure type. The median TTO for orlistat was 3 days, the shortest of all the drugs, while the median TTO for clozapine was 1,065 days, the longest of all the drugs. Conclusion: Our study provides a list of drugs potentially associated with drug-induced constipation (DIC). This could potentially inform clinicians about some alternative medications to consider when managing secondary causes of constipation or caring for patients prone to DIC, thereby reducing the incidence and mortality associated with DIC.

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Hermetia illucens larvae showcases remarkable bioremediation capabilities for both antibiotics and heavy metal contaminants. However, the distinctions in larval intestinal microbiota arising from the single and combined effects of antibiotics and heavy metals remain poorly elucidated. In this study, we delved into the details of larval intestinal bacterial communities and microbial metabolites when exposed to single and combined contaminants of oxytetracycline (OTC) and hexavalent chromium (Cr(VI)). After conversion, single contaminant-spiked substrate showed 75.5% of OTC degradation and 95.2% of Cr(VI) reductiuon, while combined contaminant-spiked substrate exhibited 71.3% of OTC degradation and 93.4% of Cr(VI) reductiuon. Single and combined effects led to differences in intestinal bacterial communities, mainly reflected in the genera of Enterococcus, Pseudogracilibacillus, Gracilibacillus, Wohlfahrtiimonas, Sporosarcina, Lysinibacillus, and Myroide. Moreover, these effects also induced differences across various categories of microbial metabolites, which categorized into amino acid and its metabolites, benzene and substituted derivatives, carbohydrates and its metabolites, heterocyclic compounds, hormones and hormone-related compounds, nucleotide and its metabolites, and organic acid and its derivatives. In particular, the differences induced OTC was greater than that of Cr(VI), and combined effects increased the complexity of microbial metabolism compared to that of single contaminant. Correlation analysis indicated that the bacterial genera, Preudogracilibacillus, Enterococcus, Sporosarcina, Lysinibacillus, Wohlfahrtiimonas, Ignatzschineria, and Fusobacterium exhibited significant correlation with significant differential metabolites, these might be used as indicators for the resistance and bioremediation of OTC and Cr(VI) contaminants. These findings are conducive to further understanding that the metabolism of intestinal microbiota determines the resistance of Hermetia illucens to antibiotics and heavy metals.

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Hermetia illucens larvae can enhance the degradation of oxytetracycline (OTC) through its biotransformation. However, the underlying mechanisms mediated by gut metabolites and proteins are unclear. To gain further insights, the kinetics of OTC degradation, the functional structures of gut bacterial communities, proteins, and metabolites were investigated. An availability-adjusted first-order model effectively evaluated OTC degradation kinetics, with degradation half-lives of 4.18 and 21.71 days for OTC degradation with and without larval biotransformation, respectively. Dominant bacteria in the larval guts were Enterococcus, Psychrobacter, Providencia, Myroides, Enterobacteriaceae, and Lactobacillales. OTC exposure led to significant differential expression of proteins, with functional classification revealing involvement in digestion, transformation, and adaptability to environmental stress. Upregulated proteins, such as aromatic ring hydroxylase, acted as oxidoreductases modifying the chemical structure of OTC. Unique metabolites, aclarubicin and sancycline identified were possible OTC metabolic intermediates. Correlation analysis revealed significant interdependence between gut bacteria, metabolites, and proteins. These findings reveal a synergistic mechanism involving gut microbial metabolism and enzyme structure that drives the rapid degradation of OTC and facilitates the engineering applications of bioremediation.

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Hermetia illucens larvae are recognized for their ability to mitigate or eliminate contaminants by biodegradation. However, the biodegradation characteristics of microplastics and phthalic acid esters plasticizers, as well as the role of larval gut microorganisms, have remained largely unrevealed. Here, the degradation kinetics of plasticizers, and biodegradation characteristics of microplastics were examined. The role of larval gut microorganisms was investigated. For larval development, microplastics slowed larval growth significantly (P < 0.01), but the effect of plasticizer was not significant. The degradation kinetics of plasticizers were enhanced, resulting in an 8.11 to 20.41-fold decrease in degradation half-life and a 3.34 to 3.82-fold increase in final degradation efficiencies, compared to degradation without larval participation. The depolymerization and biodeterioration of microplastics were conspicuously evident, primarily through a weight loss of 17.63 %-25.52 %, variation of chemical composition and structure, bio-oxidation and bioerosion of microplastic surface. The synergistic effect driven by larval gut microorganisms, each with various functions, facilitated the biodegradation. Specifically, Ignatzschineria, Paenalcaligenes, Moheibacter, Morganella, Dysgonomonas, Stenotrophomonas, Bacteroides, Sphingobacterium, etc., appeared to be the key contributors, owing to their xenobiotic biodegradation and metabolism functions. These findings offered a new perspective on the potential for microplastics and plasticizers biodegradation, assisted by larval gut microbiota.

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Background: Existing studies confirm the importance of dietary factors in developing autism spectrum disorder (ASD) and disease progression. Still, these studies are primarily observational, and their causal relationship is unknown. Moreover, due to the extensive diversity of food types, the existing research remains somewhat limited in comprehensiveness. The inconsistency of the results of some studies is very disruptive to the clinic. This study infers a causal relationship between dietary factors on the risk of developing ASD from a genetic perspective, which may lead to significant low-cost benefits for children with ASD once the specificity of dietary factors interfering with ASD is confirmed. Methods: We performed a two-sample Mendelian randomization (MR) analysis by selecting single nucleotide polymorphisms (SNPs) for 18 common dietary factors from the genome-wide association study (GWAS) database as instrumental variables (IVs) and obtaining pooled data for ASD (Sample size = 46,351) from the iPSYCH-PGC institution. Inverse variance weighted (IVW) was used as the primary analytical method to estimate causality, Cochran's Q test to assess heterogeneity, the Egger-intercept test to test for pleiotropy and sensitivity analysis to verify the reliability of causal association results. Results: The MR analysis identified four dietary factors with potential causal relationships: poultry intake (fixed-effects IVW: OR = 0.245, 95% CI: 0.084-0.718, P < 0.05), beef intake (fixed-effects IVW: OR = 0.380, 95% CI: 0.165-0.874, P < 0.05), cheese intake (random-effects IVW: OR = 1.526, 95% CI: 1.003-2.321, P < 0.05), and dried fruit intake (fixed-effects IVW: OR = 2.167, 95% CI: 1.342-3.501, P < 0.05). There was no causal relationship between the remaining 14 dietary factors and ASD (P > 0.05). Conclusion: This study revealed potential causal relationships between poultry intake, beef intake, cheese intake, dried fruit intake, and ASD. Poultry and beef intake were associated with a reduced risk of ASD, while cheese and dried fruit intake were associated with an increased risk. Other dietary factors included in this study were not associated with ASD.

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To evaluate the causal relationship between genetically determined telomere length (TL) and atherosclerosis (AS). We performed a 2-sample Mendelian randomization (MR) study to assess the potential causal relationship between TL and AS (coronary AS, cerebral AS, peripheral atherosclerosis (PAD), and AS, excluding cerebral, coronary, and PAD). The TL phenotype contained 472,174 participants, and the 4 subtypes of AS had 361,194, 218,792, 168,832, and 213,140 participants, all of European ancestries. The single nucleotide polymorphisms (SNPs) of TL strongly associated with the 4 atherosclerotic subtypes included in this study were 101, 92, 91, and 92, respectively. The odds ratios (ORs) and 95% confidence interval (CI) between TL and coronary AS calculated using inverse variance weighted (IVW) were 0.993 (0.988, 0.997), and the results were statistically significant (P < .05). The results between TL and cerebral AS, PAD, and AS (excluding cerebral, coronary, and PAD) were not statistically significant (P > .05). "Egger-intercept test" showed that there was no horizontal pleiotropy (P > .05); "leave-one-out analysis" sensitivity analysis showed that the results were stable and there were no instrumental variables with strong effects on the results; "MR- pleiotropy residual sum and outlier (PRESSO) test" showed 1 outlier for coronary AS and no outliers for the remaining subgroups. The results of the 2-sample MR analysis showed a causal association between TL and coronary AS but not with cerebral AS, PAD, and AS (excluding cerebral, coronary, and PAD). This may elucidate the observation that various vascular regions can be affected by AS but highlights the propensity of coronary arteries to be more susceptible to AS development.

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Black soldier fly larvae (larvae) can digest organic wastes and degrade contaminants such as oxytetracycline (OTC). However, compared to the kinetic processes and enhanced mechanisms used in the traditional microbial degradation of OTC, those employed by larvae are largely uncharacterized. To obtain further details, a combined analysis of larval development, larval nutritional values (crude protein, crude fat and the composition of fatty acids) and the expression of tetracycline resistance genes (TRGs) in the larval gut was performed for the degradation of OTC added to substrates and for oxytetracycline bacterial residue (OBR). When the larvae were exposed to the substrates, the degradation processes were enhanced significantly (P < 0.01), with a 4.74-7.86-fold decrease in the degradation half-life (day-1) and a 3.34-5.74-fold increase in the final degradation efficiencies. This result was attributed to the abundant TRGs (with a detection rate of 35.90%∼52.14%) in the larval gut. The TRGs presented the resistance mechanisms of cellular protection and efflux pumps, which ensured that the larvae could tolerate elevated OTC concentrations. Investigation of the TRGs indicated that enzymatic inactivation enhanced OTC degradation by larvae. These findings demonstrate that the larval degradation of antibiotic contaminants is an efficient method based on abundant TRGs in the larval gut, even though OTC degradation results in OBR. In addition, a more optimized system for higher reductions in antibiotic levels and the expansion of larval bioremediation to other fields is necessary.

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Soil carbon dioxide (CO2) and nitrous oxide (N2O) emissions are two main greenhouse gases that play important roles in global warming. Studies have shown that microplastics, biochar, and earthworms can significantly affect soil greenhouse gas emissions. However, few studies have explored how their interactions affect soil CO2 and N2O emissions. A mesocosm experiment was conducted to investigate their interactive effects on soil greenhouse gases and soil microbial functional genes in vegetable-growing soil under different incubation times. Biochar alone or combined with microplastics significantly decreased soil CO2 emissions but had no effect on soil N2O emissions. Microplastics and biochar inhibited CO2 emissions and promoted N2O emissions in the soil with earthworms. The addition of microplastics, biochar, and earthworms had significant effects on soil chemical properties, including dissolved organic carbon, ammonia nitrogen, nitrate nitrogen, total nitrogen, and pH. Microplastics and earthworms selectively influenced microbial abundances and led to a fungi-prevalent soil microbial community, while biochar led to a bacteria-prevalent microbial community. The interactions of microplastics, biochar, and earthworms could alleviate the reduction of the bacteria-to-fungi ratio and the abundance of microbial functional genes caused by microplastics and earthworms alone. Microplastics significantly inhibited microorganisms as well as C and N cycling functional genes in earthworm guts, while biochar obviously stimulated them. The influence of the addition of exogenous material on soil greenhouse gas emissions, soil chemical properties, and functional microbes differed markedly with soil incubation time. Our results indicated that biochar is a promising amendment for soil with microplastics or earthworms to simultaneously mitigate CO2 emissions and regulate soil microbial community composition and function. These findings contribute to a better understanding of the interaction effects of microplastics, biochar, and earthworms on soil carbon and nitrogen cycles, which could be used to help conduct sustainable environmental management of soil.

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BACKGROUND: Western medicine has played an essential role in treating poststroke insomnia (PSI) in China, and traditional Chinese medicine therapy based on Chinese characteristics is also effective. Combined with China's national conditions, we plan to conduct this systematic review and meta-analysis to compare the efficacy of integrated traditional Chinese medicine and Western medicine (INTEGRATED TCM and WM) therapy and Western medicine alone for PSI. METHODS: We will search the following 5 electronic databases: PubMed, Wanfang, Chinese biomedical literature database, the Chongqing VIP Chinese Science and Technology Periodical, and China national knowledge infrastructure. Randomized controlled trials that compared the efficacy of INTEGRATED TCM and WM with Western medicine alone in the treatment of PSI will be considered. Primary outcomes have Treatment effectiveness rate, and Pittsburgh sleep quality index. Secondary outcomes include traditional Chinese medicine syndrome score, Athens insomnia scale, the incidence of adverse reactions, and outcome follow-up. Based on the eligibility criteria, we will conduct literature screening and data extraction. The quality of the included literature will be evaluated using the Cochrane risk of bias tools. We will use Review Manager software (Version 5.3) for data synthesis and statistical analyses. If sources of heterogeneity exist, we will perform a subgroup analysis or sensitivity analysis. A funnel plot will be used to analyze publication bias. RESULTS: This study will provide evidence-based medicine evidence for treatment of PSI with INTEGRATED TCM and WM in terms of its efficacy. CONCLUSION: This systematic review aims to provide new options for INTEGRATED TCM and WM treatment of PSI in terms of its efficacy.

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Antibiotic bacterial residue is a unique hazardous waste, and its safe and effective disposal has always been a concern of pharmaceutical enterprises. This report presents the effective treatment of hazardous waste-antibiotic bacterial residue-by black soldier fly larvae (larvae), oxytetracycline bacterial residue (OBR), and soya meal with mass ratios of 0:1 (soya), 1:20 (OBRlow), and 1:2 (OBRhigh), which were used as substrates for larval bioconversion. Degradation of OBR and oxytetracycline, the bacterial community, the incidence of antibiotic resistance genes (ARGs) and the bacterial function in the gut were examined. When the larvae were harvested, 70.8, 59.3, and 54.5% of the substrates had been consumed for soya, OBRlow and OBRhigh; 65.9 and 63.3% of the oxytetracycline was degraded effectively in OBRlow and OBRhigh, respectively. The larval bacterial communities were affected by OBR, abundant and various ARGs were discovered in the gut, and metabolism was the major predicted function of the gut. These findings show that OBR can be digested and converted by larvae with gut bacteria, and the larvae can be used as a bioremediation tool for the treatment of hazardous waste. Finally, the abundant ARGs in the gut deserve further attention and consideration in environmental health risk assessments.

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Rice straw is considered as a renewable biomass energy source and its efficient utilization is still a topic worthy of attention. Black soldier fly larvae, Hermetia illucens (L.), (Diptera: Stratiomydiae) is a kind of saprophytic insect, which can effectively digest organic wastes. Here we report that alkaline peroxide-pretreatment improves the digestion of rice straw by these larvae, especially the decomposition of cellulose, which was at 70.9% compared to 58.2% without pretreatment. After conversion, the effective conversion rates of rice straw to larvae were 10.7% and 11.4%, for raw rice straw and rice straw with pretreatment, respectively. With pretreatment the composition of larval gut microorganisms was altered where Actinomyces, Dysgonomonas, Devosia and Pelagibacterium were the dominant flora for digesting rice straw. In addition, metabolism, environmental information processing and genetic information processing were the major gut microbial functions. These findings demonstrate that chemical pretreatment for the removal of lignin and hemicellulose was an effective measure for the digestion and consumption of rice straw by black soldier fly larvae.

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As a saprophytic insect, the black soldier fly can digest organic waste efficiently in an environmentally friendly way. However, the ability and efficiency of this insect, and the microbial mechanisms involved, in the degradation of antibiotics are largely uncharacterized. To obtain further details during the degradation of OTC (oxytetracycline) by black soldier fly larvae (larvae), the changes in intestinal bacterial communities were examined. Both ARGs (antibiotic resistance genes) and MGEs (mobile genetic elements) were found within the larval guts. At the end of the degradation period, 82.7%, 77.6% and 69.3% of OTC was degraded by larvae when the initial concentrations were 100, 1000 and 2000 mg kg-1 (dry weight), respectively, which was much higher than the degradation efficiencies (19.3-22.2%) without larvae. There was no obvious effect of OTC on the development of the larvae. Although the larval gut microorganisms were affected by OTC, they adapted to the altered environment. Enterococcus, Ignatzschineria, Providencia, Morganella, Paenalcaligenes and Actinomyces in the gut responded strongly to antibiotic exposure. Interestingly, numerous ARGs (specifically, 180 ARGs and 10 MGEs) were discovered, and significantly correlated with those of both integron-integrase gene and transposases in the larval gut. Of all the detected ARGs, tetracycline resistance genes expressed at relatively high levels and accounted for up to 67% of the total ARGs. In particular, Enterococcus, Ignatzschineria, Bordetella, Providencia and Proteus were all hosts of enzymatic modification genes of tetracycline in the guts that enabled effective degradation of OTC. These findings demonstrate that OTC can be degraded effectively and prove that the bioremediation of antibiotic contamination is enhanced by larvae. In addition, the abundance of ARGs and MGEs formed should receive attention and be considered in environmental health risk assessment systems.

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The black soldier fly, Hermetia illucens (L.) (Diptera: Stratiomyidae), is a saprophytic insect that can digest organic wastes, such as animal manure, plant residues, and food and agricultural wastes. In the degradation process, organic wastes are converted into protein, grease, and polypeptides, which can be applied in medicine, the refining of chemicals, and the manufacturing of feedstuffs. After their conversion by the H. illucens, organic wastes not only become useful but also environmentally friendly. To date, the H. illucens has been widely used to treat food waste and to render manure harmless. The protein and grease obtained via this insect have been successfully used to produce livestock feed and biodiesel. In this article, the biological characteristics, resource utilization of protein and grease, and environmental functions of the H. illucens are summarized. This article provides a theoretical basis for investigating potential applications of the H. illucens.