Dual-Responsive Near-Infrared BODIPY-Based Fluorescent Probe for the Detection of F- and HClO in Organisms.

Fluoride anions (F-) play a crucial role in human physiological processes. However, excessive intake of F- would affect oxygen metabolism and promote the generation of oxygen-free radicals. Hence, it is essential to develop a precise and efficient fluorescent probe for visualizing F--induced oxidative stress. In this work, we developed the first bifunctional BODIPY-based fluorescent probe dfBDP with p-tert-butyldimethylsilanolate benzyl thioether as the sensing site for the detection of F- and HClO via two distinct reactions, the self-immolative removal and the thioether oxidation, which generate the sensing products with two nonoverlap fluorescence bands: 800-1200 and 500-750 nm, respectively. The probe dfBDP displays rapid response, high specificity, and sensitivity for the detection of F- (LOD, 316.2 nM) and HClO (LOD, 33.9 nM) in vitro. Cellular imaging reveals a correlation between F--induced oxidative stress and the upregulation of HClO. Finally, probe dfBDP was employed to detect F- and HClO in mice under the stimulation of F-. The experimental results display that the level of HClO elevates in the liver of mice.

Arylacryl amides: Design, synthesis and the protection against cisplatin-induced acute kidney injury via TLR4/STING/NF-κB pathway.

Arylpropionic ester scaffold was found as anti-inflammatory agents for the treatment and prevention of acute kidney injury (AKI). To further study the structure-activity relationship (SAR) of this scaffold, a series of acryl amides were designed, synthesized, and evaluated their anti-inflammation. Of these, compound 9d displayed the protective effect on renal tubular epithelial cells to significantly enhance the survival rate through inhibiting NF-κB phosphorylation and promoting cell proliferation in cisplatin-induced HK2 cells. Furthermore, 9d can interact with TLR4 to inhibit TLR4/STING/NF-κB pathway in the RAW264.7 cell. In vivo AKI mice model, 9d significantly downregulated the level of serum creatinine (Scr), blood urea nitrogen (BUN) and the inflammatory factors (IL-1ß, IL-6, TNF-α) to improve kidney function. Morphological and KIM-1 analyses showed that 9d alleviated cisplatin-induced tubular damage. In a word, 9d was a promising lead compound for preventive and therapeutic of AKI.

The Value of Minimal Clinically Important Difference, Substantial Clinical Benefit, and Patient-Acceptable Symptomatic State for Commonly Used Patient-Reported Outcomes in Recurrent Patellar Instability Patients After Medial Patellofemoral Ligament Reconstruction and Tibial Tubercle Transfer.

PURPOSE: To identify the minimal clinically important difference (MCID), substantial clinical benefit (SCB) and patient-acceptable symptomatic state (PASS) for commonly used patient-reported outcomes (PROs) in recurrent patellar instability patients after medial patellofemoral ligament reconstruction (MPFLR) and tibial tubercle transfer (TTT), and to determine the impact of potential prognostic factors on the likelihood of achieving these values. METHODS: From April 2015 to February 2021, patients who underwent MPFLR and TTT were retrospectively reviewed. PROs included Kujala, Knee Injury and Osteoarthritis Outcome (KOOS), Lysholm, International Knee Documentation Committee (IKDC), and Tegner score. Relevant anchor questions were provided. A distribution- or anchor-based method was adopted to determine the MCID, SCB, and PASS. Minimal detectable change (MDC) was included to confirm the validity. Univariate regression analyses were conducted to determine the potential prognostic factors. RESULTS: One hundred forty-two patients were included. The MCID were 9.1 (Kujala), 11.1 (Lysholm), 0.9 (Tegner), 9.9 (IKDC), 9.0 (KOOS-Pain), 10.8 (KOOS-Symptoms), 10.0 (KOOS-Activities of Daily Living [ADL]), 17.8 (KOOS-Sports and Recreation [Sports/Rec]), and 12.7 (KOOS-Quality of Life [QoL]). The SCB were 14.5 (Kujala), 12.5 (Lysholm), 1.5 (Tegner), 14.5 (IKDC), 13.9 (KOOS-Pain), 14.3 (KOOS-Symptoms), 18.4 (KOOS-ADL), 47.5 (KOOS-Sports/Rec), and 15.0 (KOOS-QoL). The PASSs were 85.5 (Kujala), 75.5 (Lysholm), 3.5 (Tegner), 73.2 (IKDC), 87.5 (KOOS-Pain), 73.2 (KOOS-Symptoms), 92.0 (KOOS-ADL), 77.5 (KOOS-Sports/Rec), and 53.1 (KOOS-QoL). All SCBs were valid except KOOS-QoL. All MCIDs were valid at the 95% confidence interval (CI) except KOOS scores, the majority of which were valid at the 90% CI. A younger age was an independent prognostic factor of reaching PASS for Lysholm, IKDC, Tegner, and KOOS-ADL score. A higher baseline score was a negative prognostic factor for achieving MCID or SCB but had a slightly positive influence on the achievement of PASS. CONCLUSIONS: This study established the MCID, SCB, and PASS for commonly used PROs and confirmed their validity in recurrent patellar instability patients after MPFLR and TTT. Younger age and lower baseline scores were prognostic factors of achieving MCID and SCB, whereas patients with higher baseline scores were more likely to report satisfaction. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic trial.

Unraveling the immunogenic cell death pathways in gastric adenocarcinoma: A multi-omics study.

BACKGROUND: Gastric cancer (GC) is a prevalent malignant tumor of the gastrointestinal (GI) system. However, the lack of reliable biomarkers has made its diagnosis, prognosis, and treatment challenging. Immunogenic cell death (ICD) is a type of programmed cell death that is strongly related to the immune system. However, its function in GC requires further investigation. METHOD: We used multi-omics and multi-angle approaches to comprehensively explore the prognostic features of ICD in patients with stomach adenocarcinoma (STAD). At the single-cell level, we screened genes associated with ICD at the transcriptome level, selected prognostic genes related to ICD using weighted gene co-expression network analysis (WGCNA) and machine learning, and constructed a prognostic model. In addition, we constructed nomograms that incorporated pertinent clinical features and provided effective tools for prognostic prediction in clinical settings. We also investigated the sensitivity of the risk subgroups to both immunotherapy and drugs. Finally, in addition to quantitative real-time polymerase chain reaction, immunofluorescence was used to validate the expression of ICD-linked genes. RESULTS: Based on single-cell and transcriptome WGCNA analyses, we identified 34 ICD-related genes, of which 11 were related to prognosis. We established a prognostic model using the least absolute shrinkage and selection operator (LASSO) algorithm and identified dissimilarities in overall survival (OS) and progression-free survival (PFS) in risk subgroups. The nomograms associated with the ICD-related signature (ICDRS) demonstrated a good predictive value for clinical applications. Moreover, we detected changes in the tumor microenvironment (TME), including biological functions, mutation landscapes, and immune cell infiltration, between the high- and low-risk groups. CONCLUSION: We constructed an ICD-related prognostic model that incorporated features related to cell death. This model can serve as a useful tool for predicting the prognosis of GC, targeted prevention, and personalized medicine.

Construction of Nitrogen-Doped Biphasic Transition-Metal Sulfide Nanosheet Electrode for Energy-Efficient Hydrogen Production via Urea Electrolysis.

Urea-assisted hybrid water splitting is a promising technology for hydrogen (H2 ) production, but the lack of cost-effective electrocatalysts hinders its extensive application. Herein, it is reported that Nitrogen-doped Co9 S8 /Ni3 S2 hybrid nanosheet arrays on nickel foam (N-Co9 S8 /Ni3 S2 /NF) can act as an active and robust bifunctional catalyst for both urea oxidation reaction (UOR) and hydrogen evolution reaction (HER), which could drive an ultrahigh current density of 400 mA cm-2 at a low working potential of 1.47 V versus RHE for UOR, and gives a low overpotential of 111 mV to reach 10 mA cm-2 toward HER. Further, a hybrid water electrolysis cell utilizing the synthesized N-Co9 S8 /Ni3 S2 /NF electrode as both the cathode and anode displays a low cell voltage of 1.40 V to reach 10 mA cm-2 , which can be powered by an AA battery with a nominal voltage of 1.5 V. The density functional theory (DFT) calculations decipher that N-doped heterointerfaces can synergistically optimize Gibbs free energy of hydrogen and urea, thus accelerating the catalytic kinetics of HER and UOR. This work significantly advances the development of the promising cobalt-nickel-based sulfide as a bifunctional electrocatalyst for energy-saving electrolytic H2 production and urea-rich innocent wastewater treatment.

Choline and trimethylamine N-oxide supplementation in normal chow diet and western diet promotes the development of atherosclerosis in Apoe -/- mice through different mechanisms.

Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, has been shown to aggravate cardiovascular disease. However, the mechanisms of TMAO in the setting of cardiovascular disease progress remain unclear. Here, we aim to investigate the effects of TMAO on atherosclerosis (AS) development and the underlying mechanisms. Apoe -/- mice received choline or TMAO supplementation in a normal diet and a western diet for 12 weeks. Choline or TMAO supplementation in both normal diet and western diet significantly promoted plaque progression in Apoe-/- mice. Besides, serum lipids levels and inflammation response in the aortic root were enhanced by choline or TMAO supplementation. In particular, choline or TMAO supplementation in the western diet changed intestinal microbiota composition and bile acid metabolism. Therefore, choline or TMAO supplementation may promote AS by modulating gut microbiota in mice fed with a western diet and by other mechanisms in mice given a normal diet, even choline or TMAO supplementation in a normal diet can promote AS.

Phase-Selective Synthesis of Ruthenium Phosphide in Hybrid Structure Enables Efficient Hybrid Water Electrolysis Under pH-Universal Conditions.

Hydrazine-assisted hybrid water electrolysis is an energy-saving approach to produce high-purity hydrogen, whereas the development of pH-universal bifunctional catalysts encounters a grand challenge. Herein, a phase-selective synthesis of ruthenium phosphide compounds hybrid with carbon forming pancake-like particles (denoted as Rux P/C-PAN, x = 1 or 2) is presented. The obtained RuP/C-PAN exhibits the highest catalytic activity among the control samples, delivering ultralow cell voltages of 0.03, 0.27, and 0.65 V to drive 10 mA cm-2 using hybrid water electrolysis corresponding to pH values of 14, 7, and 0, respectively. Theoretical calculation deciphers that the RuP phase displays optimized free energy for hydrogen adsorption and reduced energy barrier for hydrazine dehydrogenation. This work may not only open up a new avenue in exploring universally compatible catalyst to transcend the limitation on the pH value of electrolytes, but also push forward the development of an energy-saving hydrogen generation technique based on emerging hybrid water electrolysis.

High level of complement factor Ba within first prenatal test of gestation increases the risk of subsequent gestational diabetes: a propensity score-matched study.

OBJECTIVE: This study was to assess the alteration of circulating complement factor Ba (CFBa) within 11 to 17 weeks of gestation and its association with subsequent gestational diabetes mellitus (GDM) and its delivery outcome. METHODS: Biochemical parameters and blood samples were collected from 399 pregnant women within 11 to 17 weeks of gestation. At 24 to 28 weeks of gestation, all participants underwent 75-g oral glucose tolerance test and were assigned to GDM group (n = 80) and normal control group (n = 319). Perinatal data were collected after delivery. A propensity score-matched (PSM) analysis was performed to reduce the impact of confounding factors on glucose metabolism during pregnancy between the two groups. RESULTS: Two groups of 74 well-matched patients who maintained balance in terms of baseline characteristics. The levels of CFBa in pregnant women who later developed GDM were significantly higher than those in healthy pregnant women [0.4(0.1-0.8) vs. 0.2(0.2-0.3), p = 0.024]. Logistic regression analysis results confirmed that the level of CFBa was an independent impact factor for the occurrence of GDM (OR = 1.57, 95% CI: 1.118-2.210, p = 0.009). Further grouping according to the median level of CFBa, it was found that the incidence of GDM in category two (>0.23 ng/ml, n = 74) was markedly higher than that in the first category (≤0.23 ng/ml, n = 74) (p = 0.021). CONCLUSIONS: High level of the CFBa within 11 to 17 weeks of gestation increases the risk of subsequent GDM, and maybe a biomarker for predicting GDM.

Dual Nanoislands on Ni/C Hybrid Nanosheet Activate Superior Hydrazine Oxidation-Assisted High-Efficiency H2 Production.

Clean hydrogen evolution through electrochemical water splitting underpins various innovative approaches to the pursuit of sustainable energy conversion technologies, but it is blocked by the sluggish anodic oxygen evolution reaction (OER). The hydrazine oxidation reaction (HzOR) has been considered as one of the most promising substitute for OER to improve the efficiency of hydrogen evolution reaction (HER). Herein, we construct novel dual nanoislands on Ni/C hybrid nanosheet array: one kind of island represents the part of bare Ni particle surface, while the other stands for the part of core-shell Ni@C structure (denoted as Ni-C HNSA), in which exposed Ni atoms and Ni-decorated carbon shell perform as active sites for HzOR and HER respectively. As a result, when the current density reaches 10 mA cm-2 , the working potentials are merely -37 mV for HER and -20 mV for HzOR. A two-electrode electrolyzer exhibits superb activity that only requires an ultrasmall cell voltage of 0.14 V to achieve 50 mA cm-2 .

The biological and chemical contents of atmospheric particulate matter and implication of its role in the transmission of bacterial pathogenesis.

Atmospheric particulate matter (APM) is an environmental hazard that endangers human health and causes a variety of diseases. In this work, the microbial community composition, chemical element composition and antimicrobial resistance gene (ARG) prevalence, along with their relationships with environmental parameters were analysed using APM samples collected in Jinan, China. Pathogenic Klebsiella and Aeromonas were found to be significantly correlated with PM2.5 and temperature, suggesting their proliferation on APM. PM2.5 and PM10 have similar microbial community compositions but different chemical element compositions, suggesting they have different origins, which have little impact on microbial community structures. This finding, together with analysis of the timing of microbial community structure changes, suggests that microbial community composition is impacted by anthropic activities. Further investigations showed that rare metals including lanthanides are significantly negatively correlated with pathogens in APM, suggesting their inhibitory role. ARGs were observed for every class of antibiotic except for carbapenems in APM, suggesting high ARG prevalence in APM, and APM functions in transmission of antimicrobial resistance. Results obtained in this study suggest that APM can act as a transmission vehicle for pathogenic bacteria and ARGs and lead to the implication of a new transmission route for bacterial pathogenesis by APM.

Superhydrophilic Ni-based Multicomponent Nanorod-Confined-Nanoflake Array Electrode Achieves Waste-Battery-Driven Hydrogen Evolution and Hydrazine Oxidation.

The low thermodynamic potential (-0.33 V) and safe by-product of N2 /H2 O, make utilizing hydrazine oxidation reaction (HzOR) to replace thermodynamically-unfavorable and kinetically-sluggish oxygen evolution reaction a promising tactic for energy-efficient hydrogen production. However, the complexity of bifunctionality increases difficulties for effective material design, thus hindering the large-scale hydrogen generation. Herein, we present the rationally designed synthesis of superhydrophilic Ni-based multicomponent arrays (Ni NCNAs) composed of 1D nanorod-confined-nanoflakes (2D), which only needs -26 mV of working potential and 47 mV of overpotential to reach 10 mA cm-2 for HzOR and HER, respectively. Impressively, this Ni NCNA electrode exhibits the top-level bifunctional activity for overall hydrazine splitting (OHzS) with an ultralow voltage of 23 mV at 10 mA cm-2 and a record-high current density of 892 mA cm-2 at just 0.485 V, also achieves the high-speed hydrogen yield driven by a waste AAA battery for OHzS.

In Vitro Assessment of Antimicrobial Resistance Dissemination Dynamics during Multidrug-Resistant-Bacterium Invasion Events by Using a Continuous-Culture Device.

Antimicrobial-resistant pathogens display significant public health threats by causing difficulties in clinical treatment of bacterial infection. Antimicrobial resistance (AMR) is transmissible between bacteria, significantly increasing the appearance of antimicrobial-resistant pathogens and aggravating the AMR problem. In this work, the dissemination dynamics of AMR from invading multidrug-resistant (MDR) Escherichia coli to a community of pathogenic Salmonella enterica was investigated using a continuous-culture device, and the behaviors of dissemination dynamics under different levels of antibiotic stress were investigated. Three MDR E. coli invasion events were analyzed in this work: MDR E. coli-S. enterica cocolonization, MDR E. coli invasion after antibiotic treatment of S. enterica, and MDR E. coli invasion before antibiotic treatment of S. enterica It was found that both horizontal gene transfer (HGT) and vertical gene transfer (VGT) play significant roles in AMR dissemination, although different processes contribute differently under different circumstances, that environmental levels of antibiotics promote AMR dissemination by enhancing HGT rather than leading to selective advantage for resistant bacteria, and that early invasion of MDR E. coli completely and quickly sabotages the effectiveness of antibiotic treatment. These findings contribute to understanding the drivers of AMR dissemination under different antibiotic stresses, the detrimental impact of environmental tetracycline contamination, and the danger of nosocomial presence and dissemination of MDR nonpathogens.IMPORTANCE Antimicrobial resistance poses a grave threat to public health and reduces the effectiveness of antimicrobial drugs in treating bacterial infections. Antimicrobial resistance is transmissible, either by horizontal gene transfer between bacteria or by vertical gene transfer following inheritance of genetic traits. The dissemination dynamics and behaviors of this threat, however, have not been rigorously investigated. In this work, with a continuous-culture device, we studied antimicrobial resistance dissemination processes by simulating antimicrobial-resistant Escherichia coli invasion to a pathogenic Salmonella enterica community. Using this novel tool, we provide evidence on the drivers of antimicrobial resistance dissemination, on the detrimental impact of environmental antibiotic contamination, and on the danger of antimicrobial resistance in hospitals, even if what harbors the antimicrobial resistance is not a pathogen. This work furthers our understanding of antimicrobial resistance and its dissemination between bacteria and of antibiotic therapy, our most powerful tool against bacterial infection.

The role of complement factor H in gestational diabetes mellitus and pregnancy.

BACKGROUND: Complement factor H (CFH) has been found to be associated with insulin resistance. This study assessed the correlation between CFH and other clinical parameters, and determined whether CFH played a role in gestational diabetes mellitus (GDM) and adverse pregnancy outcomes. METHODS: A total of 397 pregnant women were included for analysis in this nested case-control study. Clinical parameters and serum were collected within the 11-17th gestational age at the first prenatal visit. At 24-28 weeks of gestation, a 75 g oral glucose tolerance test was performed and subjects were divided into a GDM (n = 80) and a non-GDM control group (n = 317). The delivery data were also followed. The serum CFH level was assayed by ELISA. RESULTS: CFH was higher in GDM than in non-GDM controls (280.02 [58.60] vs. 264.20 [68.77]; P = 0.014). CFH level was moderately associated with pre-pregnancy body mass index (BMI), BMI and total triglycerides (TG), and slightly associated with gestational age, low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) in GDM and non-GDM (all P <  0.05). Moreover, CFH level was moderately correlated with alkaline phosphatase (ALP) and slightly correlated with age, uric acid (UA) and total bilirubin (TB) in non-GDM (all P <  0.05). After adjustment for clinical confounding factors, BMI, TG, gestational age, ALP, TB, age and UA were independent risk factors for log10 CFH levels (all P <  0.05) in all subjects. In addition, overweight or obese pregnant women, women with hypertriglyceridemia and women in the second trimester had significantly higher CFH levels than normal weight and underweight group (P <  0.001), the non-hypertriglyceridemia group (P <  0.001) and women in the first trimester group (P < 0.05) in all pregnant women respectively. Following binary logistic regression, CFH was not independently associated with GDM and related pregnant outcomes. CONCLUSIONS: The CFH in 11-17th weeks of gestation might be affected by many factors, including BMI, TG, gestational age, ALP, TB, age and UA. CFH was not an independent risk factor for GDM and avderse pregnancy outcomes.

Artificial Heterointerfaces Achieve Delicate Reaction Kinetics towards Hydrogen Evolution and Hydrazine Oxidation Catalysis.

Electrochemical water splitting for H2 production is limited by the sluggish anode oxygen evolution reaction (OER), thus using hydrazine oxidation reaction (HzOR) to replace OER has received great attention. Here we report the hierarchical porous nanosheet arrays with abundant Ni3 N-Co3 N heterointerfaces on Ni foam with superior hydrogen evolution reaction (HER) and HzOR activity, realizing working potentials of -43 and -88 mV for 10 mA cm-2 , respectively, and achieving an industry-level 1000 mA cm-2 at 200 mV for HzOR. The two-electrode overall hydrazine splitting (OHzS) electrolyzer requires the cell voltages of 0.071 and 0.76 V for 10 and 400 mA cm-2 , respectively. The H2 production powered by a direct hydrazine fuel cell (DHzFC) and a commercial solar cell are investigated to inspire future practical applications. DFT calculations decipher that heterointerfaces simultaneously optimize the hydrogen adsorption free energy (ΔGH* ) and promote the hydrazine dehydrogenation kinetics. This work provides a rationale for advanced bifunctional electrocatalysts, and propels the practical energy-saving H2 generation techniques.

Microbial communities, antibiotic resistance genes, and virulence factors in urinary infectious stone-associated urinary tract infections.

Urinary infectious stones are challenging due to bacterial involvement, necessitating a comprehensive understanding of these conditions. Antibiotic-resistant urease-producing bacteria further complicate clinical management. In this study, analysis of urine and stone samples from urinary tract infection (UTI) patients revealed microbial shifts, gene enrichment in stones, and metabolic pathway disparities; antibiotic resistance gene trends were phylum-specific, urease-producing bacteria are at risk of acquiring AMR carried by Enterobacteriaceae under antibiotic, emphasizing potential AMR dissemination between them; Correlations of key pathogenic species in kidney stone and urine microbial communities highlight the need for targeted therapeutic strategies to manage complexities in UTIs; Stones and urine contain a variety of deleterious genes even before antibiotic use, and piperacillin/tazobactam better reduced the abundance of antibiotic resistance genes in stones and urine. The presence of diverse antibiotic resistance and virulence genes underscores challenges in clinical management and emphasizes the need for effective treatment strategies to mitigate risks associated with UTIs and urinary infectious stone formation. Ongoing research is vital for advancing knowledge and developing innovative approaches to address these urological conditions.

Prodigiosin: unveiling the crimson wonder - a comprehensive journey from diverse bioactivity to synthesis and yield enhancement.

Prodigiosin (PG) is a red tripyrrole pigment from the prodiginine family that has attracted widespread attention due to its excellent biological activities, including anticancer, antibacterial and anti-algal activities. The synthesis and production of PG is of particular significance, as it has the potential to be utilized in a number of applications, including those pertaining to clinical drug development, food safety, and environmental management. This paper provides a systematic review of recent research on PG, covering aspects like chemical structure, bioactivity, biosynthesis, gene composition and regulation, and optimization of production conditions, with a particular focus on the biosynthesis and regulation of PG in Serratia marcescens. This provides a solid theoretical basis for the drug development and production of PG, and is expected to promote the further development of PG in medicine and other applications.

Cerebellar gray matter and white matter damage among older adults with prediabetes.

AIMS: To investigate alterations in cerebrum and cerebellum in prediabetes. Cerebellar injury in diabetes is traceable, but it has not been systematically studied, and whether cerebellar injury occurs and the degree of damage in prediabetes are not known. METHODS: The current study investigated cerebral and cerebellar gray matter volume, white matter volume, white matter microstructure and white matter hyperintensity on T1-weighted, T2-weighted fluid-attenuated inversion recovery and diffusion tensor imaging scans in 78 individuals with normal glucose metabolism, 92 with prediabetes, and 108 with type 2 diabetes. RESULTS: Participants with prediabetes showed significant gray matter and white matter atrophy, microstructural damage in the cerebellar and cerebral regions. Additionally, widespread structural alterations were observed in the diabetic stage. The function of the damaged brain area was further decoded in Neurosynth, and the damaged cerebellar area with prediabetic lesions was closely related to motor function, while the area affected by diabetes was related to complex cognitive function in addition to motor function. CONCLUSIONS: Cerebellar injury had already appeared in the prediabetic stage, and cerebellar injury was aggravated in the diabetic stage; therefore, the cerebellum is a key area that is damaged early in the development of diabetes.

Synergistic horizontal transfer of antibiotic resistance genes and transposons in the infant gut microbial genome.

Transposons, plasmids, bacteriophages, and other mobile genetic elements facilitate horizontal gene transfer in the gut microbiota, allowing some pathogenic bacteria to acquire antibiotic resistance genes (ARGs). Currently, the relationship between specific ARGs and specific transposons in the comprehensive infant gut microbiome has not been elucidated. In this study, ARGs and transposons were annotated from the Unified Human Gastrointestinal Genome (UHGG) and the Early-Life Gut Genomes (ELGG). Association rules mining was used to explore the association between specific ARGs and specific transposons in UHGG, and the robustness of the association rules was validated using the external database in ELGG. Our results suggested that ARGs and transposons were more likely to be relevant in infant gut microbiota compared to adult gut microbiota, and nine robust association rules were identified, among which Klebsiella pneumoniae, Enterobacter hormaechei_A, and Escherichia coli_D played important roles in this association phenomenon. The emphasis of this study is to investigate the synergistic transfer of specific ARGs and specific transposons in the infant gut microbiota, which can contribute to the study of microbial pathogenesis and the ARG dissemination dynamics.IMPORTANCEThe transfer of transposons carrying antibiotic resistance genes (ARGs) among microorganisms accelerates antibiotic resistance dissemination among infant gut microbiota. Nonetheless, it is unclear what the relationship between specific ARGs and specific transposons within the infant gut microbiota. K. pneumoniae, E. hormaechei_A, and E. coli_D were identified as key players in the nine robust association rules we discovered. Meanwhile, we found that infant gut microorganisms were more susceptible to horizontal gene transfer events about specific ARGs and specific transposons than adult gut microorganisms. These discoveries could enhance the understanding of microbial pathogenesis and the ARG dissemination dynamics within the infant gut microbiota.

Temporal development and potential interactions between the gut microbiome and resistome in early childhood.

Antimicrobial resistance-associated infections have become a major threat to global health. The gut microbiome serves as a major reservoir of bacteria with antibiotic resistance genes; whereas, the temporal development of gut resistome during early childhood and the factors influencing it remain unclear. Moreover, the potential interactions between gut microbiome and resistome still need to be further explored. In this study, we found that antibiotic treatment led to destabilization of the gut microbiome and resistome structural communities, exhibiting a greater impact on the resistome than on the microbiome. The composition of the gut resistome at various developmental stages was influenced by the abundance and richness of different core microbes. First exposure to antibiotics led to a dramatic increase in the number of opportunistic pathogens carrying multidrug efflux pump encoding genes. Multiple factors could influence the gut microbiome and resistome formation. The data may provide new insights into early-life research.IMPORTANCEIn recent years, the irrational or inappropriate use of antibiotics, an important life-saving medical intervention, has led to the emergence and increase of drug-resistant and even multidrug-resistant bacteria. It remains unclear how antibiotic exposure affects various developmental stages of early childhood and how gut core microbes under antibiotic exposure affect the structural composition of the gut resistome. In this study, we focused on early antibiotic exposure and analyzed these questions in detail using samples from infants at various developmental stages. The significance of our research is to elucidate the impact of early antibiotic exposure on the dynamic patterns of the gut resistome in children and to provide new insights for early-life studies.

Causal relationship between endometrial cancer and risk of breast cancer: A 2-sample Mendelian randomization study.

Several studies have confirmed the important role of endometrial cancer (EC) in the development and progression of breast cancer (BC), and this study will explore the causal relationship between EC and BC by 2-sample Mendelian randomization analysis. Pooled data from published genome-wide association studies were used to assess the association between EC and BC risk in women using 5 methods, namely, inverse variance weighting (IVW), MR-Egger, weighted median (WME), simple multimaximetry (SM) and weighted multimaximetry (WM) with the EC-associated genetic loci as the instrumental variables (IV) and sensitivity analyses were used to assess the robustness of the results. The statistical results showed a causal association between EC and BC (IVW: OR = 1.07, 95% CI = 1.01-1.32, P = .02; MR-Egger: OR = 1.21, 95% CI = 0.71-1.51, P = .11; weighted median: OR = 1.05, 95% CI = 0.97-1.31, P = .19; simple plurality method: OR = 0.98, 95% CI = 0.81-1.15, P = .78; weighted plurality method: OR = 0.98, 95% CI = 0.81-1.14, P = .75), and the results of the sensitivity analyses showed that there was no significant heterogeneity or multiplicity, and the results were stable. EC is associated with an increased risk of developing BC. The results of this MR analysis can be used as a guideline for screening for BC in women with EC and to help raise awareness of screening for early detection and treatment.