The modulation of proteomics and antioxidant stress is involved in the effect of nitazoxanide against Japanese encephalitis virus in vitro.

Japanese encephalitis virus (JEV) is a significant circulating arbovirus flavivirus and the primary cause of viral encephalitis in Asia. Previous studies have demonstrated that nitazoxanide (NTZ), an antiparasitic gastroenteritis medication classified as a thiazolide, exhibits efficacy against JEV both in vitro and in vivo. To explore the potential antiviral mechanisms, we employed Tandem Mass Tag (TMT)-based quantitative proteomics to identify differentially expressed proteins (DEPs) among three groups: Blank cell group, JEV-infected cell group, and JEV-infected cells treated with NTZ. Our analysis revealed that NTZ treatment led to the upregulation of 30 DEPs and downregulation of 54 DEPs in JEV-infected cells. Enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that these DEPs are involved in various biological processes and signaling pathways, including transport, localization, response to wounding, P53 pathway activation, and fatty acid metabolism-related pathways. Moreover, we observed that the expression trend of TMX2, a protein associated with redox homeostasis, was consistent with findings from TMT-based quantitative proteomics. Further investigations into reactive oxygen species (ROS), mitochondrial membrane potential, antioxidant enzyme activity, and the KEAP1-NRF2 pathway demonstrated that NTZ effectively regulates the KEAP1-NRF2 pathway while suppressing oxidative stress induced by JEV infection. In conclusion, the proteomic data along with antioxidant stress results presented herein provide a foundational basis for further research into the molecular mechanisms and potential targets of NTZ against JEV.

A Portable Electrochemical Biosensor Based on an Amino-Modified Ionic Metal-Organic Framework for the One-Site Detection of Multiple Organophosphorus Pesticides.

Constructing stable, portable sensors and revealing their mechanisms is challenging. Ion metal-organic frameworks (IMOFs) are poised to serve as highly effective electrochemical sensors for detecting organophosphorus pesticides (OPs), leveraging their unique charge properties. In this work, an amino-modified IMOF was constructed and combined with near-field communication (NFC) technology to develop a portable, touchless, and battery-free electrochemical biosensor NH2-IMOF@CS@AChE. -NH2 in NH2-IMOF gives the framework a higher electropositivity compared to IMOF, enhancing the electrostatic attraction with acetylcholinesterase (AChE), which is beneficial for immobilizing AChE. Furthermore, the uncoordinated O atoms and the (CH3)2NH2+ groups in NH2-IMOF help to form stronger bonds with AChE through hydrogen bonds. The results showed a wide linear response range of 1 × 10-15 to 1 × 10-9 M and a low detection limit of 1.24 × 10-13 M for glyphosate (Gly) in the practical detection of OPs. Additionally, electrochemical biosensor arrays were constructed to effectively identify and distinguish multiple OPs on the basis of their unique differential pulse voltammetry (DPV) electrochemical signals. This work provides a simple and effective solution for on-site OP analysis and can be widely applied in food safety and water quality monitoring.

Establishment of a Sensitive and Reliable Droplet Digital PCR Assay for the Detection of Bursaphelenchus xylophilus.

Pine wilt disease (PWD), which poses a significant risk to pine plantations across the globe, is caused by the pathogenic agent Bursaphelenchus xylophilus, also referred to as the pine wood nematode (PWN). A droplet digital PCR (ddPCR) assay was developed for the quick identification of the PWN in order to improve detection sensitivity. The research findings indicate that the ddPCR assay demonstrated significantly higher analysis sensitivity and detection sensitivity in comparison to traditional quantitative PCR (qPCR). However, it had a more limited dynamic range. High specificity was shown by both the ddPCR and qPCR techniques in the diagnosis of the PWN. Assessments of reproducibility revealed that ddPCR had lower coefficients of variation at every template concentration. Inhibition tests showed that ddPCR was less susceptible to inhibitors. There was a strong linear association between standard template measurements obtained using ddPCR and qPCR (Pearson correlation = 0.9317; p < 0.001). Likewise, there was strong agreement (Pearson correlation = 0.9348; p < 0.001) between ddPCR and qPCR measurements in the evaluation of pine wood samples. Additionally, wood samples from symptomatic (100% versus 86.67%) and asymptomatic (31.43% versus 2.9%) pine trees were diagnosed with greater detection rates using ddPCR. This study's conclusions highlight the advantages of the ddPCR assay over qPCR for the quantitative detection of the PWN. This method has a lot of potential for ecological research on PWD and use in quarantines.

Synthesis and Characterization of Heterodinuclear Indium(III)/Sodium(I) Complexes Containing Benzotriazole-Derived Phenolate Ligands: Effective Catalysts for Ring-Opening Copolymerization of Carbon Dioxide with Epoxides.

This study reported for the first time the facile synthesis of a series of novel structurally well-characterized heterodinuclear indium(III)/sodium(I) dihalide complexes containing benzotriazole-based bis(amino-phenolate) derivatives. All heterobimetallic In(III)/Na(I) complexes were found to be active single-component catalysts for the copolymerization of carbon dioxide (CO2) with cyclohexene oxide (CHO). Noteworthily, In/Na chloro complex 1 has been shown to give high copolymerization selectivity possessing >99% carbonate repeated units for CO2-derived poly(cyclohexene carbonate) production and displayed a turnover number of >1400 under the optimized conditions. Apart from the CO2/CHO copolymerization, the same complex was capable of mediating the CO2-copolymerization of 4-vinyl-1,2-cyclohexene oxide or cyclopentene oxide to deliver the related CO2-based polycarbonates. To the best of our knowledge, complex 1 in this work appears to be the first example of In/Na halide complex-promoted CO2/epoxide copolymerization that enabled the generation of aliphatic polycarbonates with good productivity and high product selectivity.

Effects of time-dependent acupuncture on back muscle endurance in women with chronic nonspecific low back pain: A randomized crossover trial.

BACKGROUND: Chronic nonspecific low back pain (CNLBP) is a leading cause of disability and remains a major burden for many public health systems. Acupuncture is a nonpharmacological treatment for CNLBP that can be effective in improving low back pain; nevertheless, its effect on improving back muscle endurance in patients with CNLBP and its duration of effect have not been studied. OBJECTIVE: The goal of this study was to assess the impact of acupuncture on lower back muscle activity in CNLBP patients. METHODS: This was a single-blind, randomized, crossover experimental study. Thirty female patients were randomized into Group A (15 patients) or Group B (15 patients). Patients in Group A were assigned to receive real acupuncture (RA) in the first phase and sham acupuncture (SA) in the second phase, while those in Group B received SA first and then RA, with a 1-week washout period between phases. Two-way repeated ANOVA was used to evaluate the effect of group and time on isokinetic parameters, Surface electromyography (sEMG) data, and blood data. RESULTS: Significant interaction effects were identified between group * time on the isokinetic parameters of the lumbar extensor muscles, sEMG values of the erector spinae, blood lactate levels, and blood ammonia levels (all p< 0.05). Compared with those of the SA group, the isokinetic parameters of the lumbar extensor muscles, sEMG values of the erector spinae, blood lactate levels, and blood ammonia levels of the RA group were significantly different (all p< 0.05). CONCLUSION: RA improves lumbar extensor endurance in patients with CNLBP and lasts approximately 9 minutes. RA can improve blood circulation to reduce blood lactic acid and blood ammonia produced during exercise.

Spin relaxation dynamics with a continuous spin environment: The dissipaton equation of motion approach.

We investigate the quantum dynamics of a spin coupling to a bath of independent spins via the dissipaton equation of motion (DEOM) approach. The bath, characterized by a continuous spectral density function, is composed of spins that are independent level systems described by the su(2) Lie algebra, representing an environment with a large magnitude of anharmonicity. Based on the previous work by Suarez and Silbey [J. Chem. Phys. 95, 9115 (1991)] and by Makri [J. Chem. Phys. 111, 6164 (1999)] that the spin bath can be mapped to a Gaussian environment under its linear response limit, we use the time-domain Prony fitting decomposition scheme to the bare-bath time correlation function (TCF) given by the bosonic fluctuation-dissipation theorem to generate the exponential decay basis (or pseudo modes) for DEOM construction. The accuracy and efficiency of this strategy have been explored by a variety of numerical results. We envision that this work provides new insights into extending the hierarchical equations of motion and DEOM approach to certain types of anharmonic environments with arbitrary TCF or spectral density.

Combined contamination of tire and road wear microplastics with heavy metals in expressway tunnels: occurrence characteristics and risk assessment.

Tire and road wear microplastics (TRWMPs), as an important type of microplastics, have attracted increasing attention. However, current studies on their contamination within expressway tunnels remain limited. Therefore, we investigated the occurrence characteristics of TRWMPs in dusts from various tunnels, and combined contamination with heavy metals (HMs). The results showed that the abundance of TRWMPs in expressway tunnel dust (53,778 n/kg) was much higher than that sampled from other land use types (1360-4960 n/kg) in the same region. A large amount of polyamide was released into the environment along with wear particles from the vehicles. Also, the abundance of TRWMPs inside tunnels was greater than outside, and the proportion of large-size TRWMPs was higher inside tunnels. TRWMPs was symmetrically distributed with respect to the center of expressway tunnel. The pollution load index (PLI) and ecological risk index (H) indicated that study area was heavily contaminated with TRWMPs. There was a significant positive correlation between the abundance of TRWMPs and concentration of Cr (p < 0.01) in dust, and their risk assessment and health risk fluctuations were almost identical. Thus, the study is of great significance for elucidating the synergistic contamination and potential risk of TRWMPs and HMs in expressway tunnels.

High-Power Battery Electrodes Fabricated by Acupuncture-Inspired Microneedle Processing.

Advancing battery electrode performance is essential for high-power applications. Traditional fabrication methods for porous electrodes, while effective, often face challenges of complexity, cost, and environmental impact. Inspired by acupuncture, here we introduce an eco-friendly and cost-effective microneedle process for fabricating lithium iron phosphate electrodes. This technique employs commercial cosmetic microneedle molds to create low-curvature holes on electrode surfaces, significantly enhancing electrolyte infiltration and ion transport kinetics. The punctured electrodes were prepared and characterized, with comparisons to pristine electrodes conducted using scanning electron microscopy, 3D metallurgical microscopy, and detailed electrochemical evaluations. Our results show that the microneedle-processed electrodes exhibit superior rate performance and diffusion properties. Simulations and experimental data reveal that the low-curvature holes reduce Li-ion concentration polarization and improve Li-ion transport within the electrode. This enhancement leads to higher specific capacities and better rate capabilities in the punctured electrodes. The findings highlight the potential of this innovative microneedle technique for large-scale production of high-performance electrodes, offering a promising avenue for the development of high-power-density batteries.

Advanced Li-S Battery Configuration Featuring Sulfur-Coated Separator and Interwoven rGO/CNT Fabric Current Collector.

The development of lithium-sulfur batteries (LSBs) marks a crucial milestone in advancing energy storage solutions essential for sustainable energy transitions. With high theoretical specific capacity, cost-effectiveness, and reduced ecological footprint, LSBs promise to enhance electric vehicle ranges, extend portable electronics' operational times, and stabilize grids integrated with renewable energy. However, challenges like complex processing, electrode instability, and poor cycling stability hinder their commercialization. This study introduces a novel battery design that addresses these issues by coating sulfur directly onto the separator instead of the current collector, demonstrating that active sulfur can be effectively utilized without being incorporated into the electrode structure. Using an interwoven substrate made from carbon nanotube (CNT) fabric adorned with reduced graphene oxide (rGO), this setup enhances manufacturing scalability, supports optimal sulfur utilization, and improves battery performance. The rGO decoration provides multiple highly conductive polysulfide trapping sites, enhancing active material reutilization, while the flexibility and mechanical strength of CNT fabric contribute to electrode integrity. This combination boosts electrical conductivity and polysulfide-capturing capability, effectively managing migrating sulfur species during charge-discharge cycles and mitigating sulfur loss and polysulfide shuttling. The results demonstrate superior cycling stability and efficiency, highlighting the potential of this approach in advancing LSB technology.

Environmental sustainable treatment and disposal technologies for reservoir wastes: a review.

The process of dredging reservoirs serves the purpose of preserving water storage capacity and ensuring the functionality of navigational channels. Additionally, it has the potential to mitigate the presence of pollutants and chemicals that pose risks to both the environment and human well-being. This review article examines the many ways of disposal and treatment of dredged sediment, as well as the ecological and economic advantages associated with these approaches. Algae and reed-based treatment methods have the potential to effectively and economically remediate and sustainably manage dredged sediments. Landfills and ocean dumping are widely utilized methods for the disposal of excavated materials. However, other approaches such as land reclamation, the use of fill material, and the preservation of wetlands can offer cost-effective solutions while also contributing to environmental conservation. The implementation of sediment cleaning, stabilization, and solidification techniques has the potential to effectively mitigate waste and improve the quality of sediment, hence facilitating its reuse. Algae and reed-based treatment systems have been found to effectively mitigate disposal costs and contribute to environmental enhancement. Additionally, the practice of reusing dredged sediments has been recognized as a valuable strategy in promoting a circular economy.

Evaluation of traditional Chinese medicine tea bag TBDESJS in patients with Sjögren's syndrome and dry eye syndrome: A phase II pilot study.

ETHNOPHARMACOLOGICAL RELEVANCE: Sjögren's syndrome (SJS) and dry eye syndrome (DES) are characterized by ocular dryness from inadequate tear production or excessive evaporation. To evaluate the effectiveness of TBDESJS (Chun-Yu-Ching-Hua-Yin, CYCHY), a TCM tea bag, in treating SJS and DES patients compared with healthy controls (NHC). MATERIALS AND METHODS: This phase II pilot study included 100 participants (60 SJS, 30 DES, 10 NHC) across 8 weeks, assessing changes in Schirmer's test, OSDI, ESSPRI, PSQI, FIRST, and artificial tear usage, using repeated measurement ANOVA and Tukey's honestly significant difference (HSD) for analysis. RESULTS: Total 97 subjects completed the trial, for the left eye (OS) of Schirmer's test, significant improvements at 4, and 8 weeks were observed in SJS (0.13 ± 0.43-5.77 ± 2.87, and 7.60 ± 4.84 mm) and DES (0.21 ± 0.41-6.21 ± 2.97, and 7.86 ± 3.47 mm) (all p < .001). For the right eye (OD), significant improvements were observed in SJS (0.13 ± 0.39-6.77 ± 4.53, and 8.79 ± 5.92 mm) and DES (0.34 ± 0.55-6.59 ± 2.50, and 8.24 ± 3.42 mm) (all p < .001). Secondary outcomes showed reduced the dryness of ESSPRI scores in SJS (6.37 ± 1.97-5.57 ± 1.79, p < .001) and DES (6.10 ± 1.97-5.28 ± 2.23, p < .05). PSQI global scores improved significantly in all groups at 8 weeks (p < .05). Artificial tear usage decreased in SJS (4.93 ± 2.45-1.00 ± 0.82 times/day), DES (4.47 ± 1.99-0.66 ± 0.67 times/day) (all p < .001). No serious adverse events in this study. CONCLUSION: TBDESJS significantly improved tear production, ocular dryness, and sleep quality, indicating potential neural regulation, anti-inflammatory and immunomodulatory benefits. These findings advocate for TBDESJS (Chun-Yu-Ching-Hua-Yin, CYCHY)'s comprehensive therapeutic value in SJS and DES treatment, emphasizing the need for further research to understand long-term effects and mechanisms.

Fatal Zargar grade 3b corrosive injury after hydrochloric acid ingestion: A case report.

RATIONALE: Caustic substance ingestion is an emergency and life-threatening condition as it leads to tissue damage, acidosis, and multiorgan failure. This study presents a case report of hydrochloric acid ingestion and notably dark-red urine output due to acute tubular necrosis. PATIENT CONCERNS: A 59-year-old male presented with attempted suicide by ingesting 500 mL of hydrochloric acid (37%), and complained of severe abdominal pain and shortness of breath. Upon arrival, his vital signs showed a temperature of 34.3°C, blood pressure of 104/77 mm Hg, a pulse rate of 135 beats per minute, and the Glasgow Coma Scale E4V2M6. Following Foley catheter insertion, dark, bloody urine resulting from acute tubular necrosis was observed. His creatinine level was 1.1 mg/dL, and urinalysis showed 38 red blood cells per high-power field. Arterial blood gas analysis revealed metabolic acidosis. DIAGNOSES: The patient's condition rapidly deteriorated in the emergency room, revealing diffuse circumferential ulceration with necrosis in the esophagus (Zargar score grade 3b). An exploratory laparotomy was performed for acidosis with intractable shock, revealing up to 1500 mL of bloody ascites, and ischemic changes with loss of peristalsis throughout the small bowel to the cecum. INTERVENTIONS: Esophagostomy with T-tube insertion was performed. Notably, stomach necrosis with perforation was identified, prompting a surgical consultation for primary perforation closure. OUTCOMES: During the operation, the patient experienced hemodynamic instability. The family confirmed the "Do Not Resuscitate" status, and he died in a critical state. LESSONS: For corrosive injuries, early endoscopy was crucial in assessing the extent of the damage and guiding treatment in this patient. It is essential to perform an early endoscopic examination in cases of acute nephrotoxic tubular necrosis following hydrochloric acid ingestion. Surgical intervention is warranted if necrosis is detected in the corrosive tissue.

Host genotype and age shape the microbial community in the rhizosphere soils of Camellia forests.

Microbiota living in the rhizosphere influences plant growth and fitness, from the opposite perspective; whether host genotypes control its root microbiota is of great interest to forest breeders and microbiologists. To improve low-yield plantations and promote sustainable management of Camellia oleifera, high-throughput sequencing was used to study the chemical properties and microbiome in rhizosphere soil of Camellia forests under three genotypes (common C. oleifera, local C. gauchowensis, and C. chekiangoleosa) and three growth stages (sapling stage at 4-year-old, primary fruit stage at 7-year-old, and full fruiting stage at 11-year-old). The results showed that the rhizosphere soil organic matter (OM), nutrient concentrations, diversity, and community composition of the microbiome were significantly varied among different Camellia genotypes. The relative abundance of symbiotic and pathotrophic fungi in the rhizosphere soil of C. chekiangoleosa was significantly higher than that of C. gauchowensis. Concentrations of OM, available phosphorus (AP), and bacterial alpha diversity increased with tree age. Fungi of Saitozyma, Mortierella, and Glomeromycota and bacteria of Burkholderia-Caballeronia-Paraburkholderia and Vicinamibacterales had potential for fertilizer development for Camellia plantation. Camellia genotypes and growth stages were significantly correlated with the rhizosphere soil pH, OM, and available potassium (AK). Soil pH and OM were key factors that affected the microbiome in the Camellia rhizosphere soils. In conclusion, tree genotypes and growth stages shaped microbial communities in Camellia rhizosphere soils, and some plant growth-promoting rhizobacteria were identified as preliminary candidates for improving Camellia plantation growth.

Survival prediction of colorectal liver metastases underwent surgical resection after neoadjuvant chemotherapy: Tumor response combined with the genetic and morphological evaluation score.

INTRODUCTION: Neoadjuvant chemotherapy is becoming routine for colorectal liver metastasis (CRLM) in patients with high risks of recurrence or in whom resection is difficult. This retrospective study aimed to establish a modified survival prediction model for patients with CRLM who underwent hepatectomy after neoadjuvant chemotherapy. MATERIALS AND METHODS: A total of 619 patients who received neoadjuvant chemotherapy followed by hepatectomy between 2006 and 2021 were included and divided into training and validation groups at a ratio of 2:1. The model was established in training group and validated in validation group. Chemotherapy response was integrated into the genetic and morphological evaluation (GAME) score as a new NeoGAME model, with assigned points based on the hazard ratio in the multivariate Cox regression. The NeoGAME score grouping cutoff was divided using X-tile, and the predictive power was compared with that of traditional models. RESULTS: The 5-year overall survival were significantly different in the NeoGAME low-risk (0-2 points), medium-risk (3-4 points) and high-risk (≥5 points) groups (training group, P < 0.001; validation group, P = 0.0012). The area under the curve in predicting 5-year survival was 0.67 and 0.66 for the training and validation groups, respectively. Time-dependent receiver operating characteristic curve showed better discrimination ability of NeoGAME than the GAME score in predicting 5-year survival. CONCLUSIONS: The newly established NeoGAME score can predict survival more precisely for patients with CRLM receiving neoadjuvant chemotherapy. Moreover, the model offers a useful tool for assessing tumor behavior and selecting a benefiting population for liver resection.

Optimizing the combination of chemotherapeutic drugs along with radiotherapy for extranodal NK/T-cell lymphoma.

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) has a unique treatment principle. However, the optimal combination of drugs along with radiotherapy (RT) is unknown. Design: Retrospective cohort study. Objectives: We screened multiple drug combinations to identify the most efficacious therapeutic combinations. Methods: We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of 9 drug classes and/or RT. Least absolute shrinkage and selection operator and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens. Results: Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drug. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/platinum-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens was associated with significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, p = 0.001), ASP/methotrexate-based (63.5%, p = 0.011), or ASP/not otherwise specified-based (63.2%, p < 0.001) regimens. The survival benefit of ASP/GEM-based regimens over other ASP-based regimens was substantial across risk-stratified and advanced-stage subgroups. The survival benefits of a combination of RT, ASP, and GEM were consistent after adjustment for confounding factors by IPTW. Conclusion: These results suggest that combining ASP/GEM with RT for ENKTCL is an efficacious and feasible therapeutic option and provides a rationale and strategy for developing combination therapies.

Physical health challenges faced by elders with severe mental illness: population-based retrospective cohort study.

BACKGROUND: Severe mental illness (SMI), which includes schizophrenia, schizoaffective disorder and bipolar disorder, has profound health impacts, even in the elderly. AIMS: To evaluate relative risk of hospital admission and length of hospital stay for physical illness in elders with SMI. METHOD: To construct a population-based retrospective cohort observed from April 2007 to March 2016, data from a case registry with full but de-identified electronic health records were retrieved for patients of the South London and Maudsley NHS Foundation Trust, the single secondary mental healthcare service provider in south-east London. We compared participants with SMI aged >60 years old with the general population of the same age and residing in the same areas through data linkage by age-, sex- and fiscal-year-standardised admission ratios (SARs) for primary diagnoses at hospital discharge. Furthermore, we compared the duration of hospital stay with an age-, sex- and cause-of-admission-matched random group by linear regression for major causes of admission. RESULTS: In total, records for 4175 older people with SMI were obtained, relating to 10 342 admission episodes, showing an overall SAR for all physical illnesses of 5.15 (95% CI: 5.05, 5.25). Among the top causes of admission, SARs ranged from 3.87 for circulatory system disorders (ICD-10 codes: I00-I99) to 6.99 for genitourinary system or urinary conditions (N00-N39). Specifically, the diagnostic group of 'symptoms, signs and findings, not elsewhere classified' (R00-R99) had an elevated SAR of 6.56 (95% CI: 6.22, 6.90). Elders with SMI also had significantly longer hospital stays than their counterparts in the general population, especially for digestive system illnesses (K00-K93), after adjusting for confounding. CONCLUSIONS: Poorer overall physical health and specific patterns were identified in elders with SMI.

Evolution and maintenance of a large multidrug-resistant plasmid in a Salmonella enterica Typhimurium host under differing antibiotic selection pressures.

The dissemination of antibiotic resistance genes (ARGs) through plasmids is a major mechanism for the development of bacterial antimicrobial resistance. The adaptation and evolution mechanisms of multidrug-resistant (MDR) plasmids with their hosts are not fully understood. Herein, we conducted experimental evolution of a 244 kb MDR plasmid (pJXP9) under various conditions including no antibiotics and mono- or combinational drug treatments of colistin (CS), cefotaxime (CTX), and ciprofloxacin (CIP). Our results showed that long-term with or without positive selections for pJXP9, spanning approximately 600 generations, led to modifications of the plasmid-encoded MDR and conjugative transfer regions. These modifications could mitigate the fitness cost of plasmid carriage and enhance plasmid maintenance. The extent of plasmid modifications and the evolution of plasmid-encoded antibiotic resistance depended on treatment type, particularly the drug class and duration of exposure. Interestingly, prolonged exposure to mono- and combinational drugs of CS and CIP resulted in a substantial loss of the plasmid-encoded MDR region and antibiotic resistance, comparable to the selection condition without antibiotic. By contrast, combinational treatment with CTX contributed to the maintenance of the MDR region over a long period of time. Furthermore, drug selection was able to maintain and even amplify the corresponding plasmid-encoded ARGs, with co-selection of ARGs in the adjacent regions. In addition, parallel mutations in chromosomal arcA were also found to be associated with pJXP9 plasmid carriage among endpoint-evolved clones from diverse treatments. Meanwhile, arcA deletion improved the persistence of pJXP9 plasmid without drugs. Overall, our findings indicated that plasmid-borne MDR region deletion and chromosomal arcA inactivation mutation jointly contributed to co-adaptation and co-evolution between MDR IncHI2 plasmid and Salmonella Typhimurium under different drug selection pressure.IMPORTANCEThe plasmid-mediated dissemination of antibiotic resistance genes has become a significant concern for human health, even though the carriage of multidrug-resistant (MDR) plasmids is frequently associated with fitness costs for the bacterial host. However, the mechanisms by which MDR plasmids and bacterial pairs evolve plasmid-mediated antibiotic resistance in the presence of antibiotic selections are not fully understood. Herein, we conducted an experimental evolution of a large multidrug-resistant plasmid in a Salmonella enterica Typhimurium host under single and combinatorial drug selection pressures. Our results show the adaptive evolution of plasmid-encoded antibiotic resistance through alterations of the MDR region in the plasmid, in particular substantial loss of the MDR region, in response to different positive selections, especially mono- and combinational drugs of colistin and ciprofloxacin. In addition, strong parallel mutations in chromosomal arcA were associated with pJXP9 carriage in Salmonella Typhimurium from diverse treatments. Our results thus highlight promoting the loss of the plasmid's MDR region could offer an alternative approach for combating plasmid-encoded antibiotic resistance.

Age- and gender-dependent impact of titanium vertebral augmentation implants combined with cementing on subsequent vertebral fracture incidence: A comparative study with cementing alone.

PURPOSE: To compare vertebroplasty (VP) and kyphoplasty (KP) with a titanium implantable vertebral augmentation device (TIVAD) in symptomatic subsequent vertebral compression fracture (SVCF) incidence among osteoporotic vertebral compression fracture (OVCF) patients stratified by age and sex. METHODS: This retrospective cohort study involved OVCF patients aged ≥ 50, who underwent KP with TIVAD or VP in our hospital from 2014 to 2019. Subgroup analysis was conducted to evaluate the efficacy of KP with TIVAD and VP in patients stratified by age and sex. RESULTS: The study included 472 patients (VP group: 303; TIVAD group: 169). SVCF incidence rates were 15.2% for VP group and 14.8% for TIVAD group (P = 0.87). In subgroup analysis, TIVAD group showed significantly lower SVCF incidence than VP group in women aged 50-70 (2.1% vs 14.3%; P = 0.03) and had significantly higher SVCF incidence than VP group in women aged > 70 (24.2% vs 13.1%; P = 0.02). In men, adjacent SVCF incidence was significantly lower in TIVAD group than VP group (0% vs 14.1%; P = 0.03). CONCLUSION: Compared to VP, TIVAD is associated with lower symptomatic SVCF rate in men and younger women aged 50-70 but not in older women aged > 70. Age and gender may influence SVCF incidence. LEVEL OF EVIDENCE: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Characterization of additive gene-environment interactions for colorectal cancer risk.

BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. METHODS: Using resources from colorectal cancer consortia including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score including 141 variants associated with CRC risk. RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking [RERI = 0.24, 95% confidence interval, CI, (0.13, 0.36)], ever smoking [0.11 (0.05, 0.16)], high BMI [female 0.09 (0.05, 0.13), male 0.10 (0.05, 0.14)], or high red meat intake [highest versus lowest quartile 0.18 (0.09, 0.27)] was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/NSAID use [-0.16 (-0.20, -0.11)] or higher intake of fruit, fiber, or calcium [highest quartile versus lowest quartile -0.12 (-0.18, -0.050); -0.16 (-0.23, -0.09); -0.11 (-0.18, -0.05), respectively] than those with average genetic susceptibility. CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.