Association between organophosphate esters exposure and all-cause and cause-specific mortality: a national population-based cohort study.

Exposure to organophosphate esters (OPEs) is associated with several chronic diseases, but the relationship with mortality risk is unclear. Therefore, we used the National Health and Nutrition Examination Survey 2011-2018 data to evaluate these relationships. 6,869 participants aged 18 years or older were included. Survival status information was obtained through the National Death Index through 31 December 2019. Multivariable COX regression model was adopted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships of urinary OPEs metabolites with mortality risk. During an average of 5.0 years of follow-up, 406 deaths were documented. After adjusting for confounders, bis(2-chloroethyl) phosphate was associated with an increased risk of all-cause mortality [HR (95%CI) = 1.12(1.05-1.20)] and cardiovascular mortality [HR (95%CI) = 1.15(1.04-1.26)]. Our study found that exposure to OPEs was significantly associated with increased risks of all-cause and cardiovascular mortality. Consequently, controlling OPEs exposure is needed to alleviate the health-related burden.

Repurposing of halogenated organic pollutants via alkyl bromide-catalysed transfer chlorination.

Halogenated organic pollutants (HOPs) are causing a significant environmental and human health crisis due to their high levels of toxicity, persistence and bioaccumulation. Urgent action is required to develop effective approaches for the reduction and reuse of HOPs. Whereas current strategies focus primarily on the degradation of HOPs, repurposing them is an alternative approach, albeit a challenging task. Here we discover that alkyl bromide can act as a catalyst for the transfer of chlorine using alkyl chloride as the chlorine source. We demonstrate that this approach has a wide substrate scope, and we successfully apply it to reuse HOPs that include dichlorodiphenyltrichloroethane, hexabromocyclododecane, chlorinated paraffins, chloromethyl polystyrene and poly(vinyl chloride) (PVC). Moreover, we show that the synthesis of essential non-steroidal anti-inflammatory drugs can be achieved using PVC and hexabromocyclododecane, and we demonstrate that PVC waste can be used directly as a chlorinating agent. Overall, this methodology offers a promising strategy for repurposing HOPs.

Feasibility and effect of cognitive-based board game and multi-component exercise interventions on older adults with dementia.

BACKGROUND: Taiwan is an aging society, and the number of people with dementia is rapidly increasing. Due to a decline in cognitive and physical function, older adults with dementia not only gradually lose the ability to complete daily living tasks on their own, but are also at a higher risk of falls and injurious falls. It is important to develop interventions that combine cognitive and exercise training for older adults with dementia to promote or maintain their cognitive and physical functions and reduce their risk of falls. This study aimed to investigate the feasibility and effect of cognitive-based board games and multi-component exercise interventions on cognitive function, physical fitness, and fall risk in older adults with dementia. METHODS: This was a quasi-experimental study with a single-group pretest and post-test design. The study participants were 41 community-dwelling older adults with mild to moderate dementia. They received cognitive-based board games and multi-component exercise interventions once a week for 12 weeks. The interventions included 1 hour of exercise training and 1 hour of cognitive training. Scores for the Taiwan version of the Montreal Cognitive Assessment (MoCA-T), physical fitness, and the St. Thomas Risk Assessment Tool for Falling Elderly Inpatients (STRATIFY) were measured as outcome indicators at baseline and after the 12-week period. RESULTS: The overall MoCA-T score increased significantly (effect size = 0.402), with participants with mild dementia showing a greater increase (effect size = 0.522) than those with moderate dementia (effect size = 0.310). Participants' physical fitness performance improved. Female participants exhibited significant improvements in the 30-second chair stand test (effect size = 0.483) and 8-foot up-and-go test (effect size = 0.437). The fall risk score decreased by 0.05 points, the change was not significant. CONCLUSION: The cognitive-based board game and multi-component exercise interventions used in this study are beneficial for improving cognitive function and physical fitness in older adults with dementia. These interventions are feasible and suitable for promotion among community-dwelling and institution-dwelling older adults with mild cognitive impairment or dementia to delay the decline in cognitive and physical function.

A salivary urea sensor based on a microsieve disposable gate AlGaN/GaN high electron mobility transistor.

The abundant bio-markers in saliva provide a new option for non-invasive testing. However, due to the presence of impurities in the saliva background, most of the existing saliva testing methods rely on pre-processing, which limits the application of saliva testing as a convenient means of testing in daily life. Herein, a disposable-gate AlGaN/GaN high electron mobility transistor (HEMT) biosensor integrated with a micro-sieve was introduced to solve the problem of signal interference caused by charged impurities in saliva for HEMT based biosensors, where the micro-sieve was utilized as a pre-treatment unit to remove large particles of impurities from saliva through the size effect and thus greatly improving the accuracy of detection. The experimental results showed that the HEMT based biosensor has excellent linearity (R2 = 0.9977) and a high sensitivity of 6.552 µA dec-1 for urea sensing from 1 fM to 100 mM in 0.1× PBS solution. When it comes to artificial saliva detection, compared to the HEMT sensor without the micro-sieve (sensitivity = 3.07432 µA dec-1), the sensitivity of the HEMT sensor integrated with the micro-sieve showed almost no change. Moreover, to verify that urea can be detected in actual saliva, urea is sensed directly in human saliva. The addition of the microsieve module provides a new way for biosensors to detect specific markers in saliva in real time, and the designed HEMT biosensor with the microsieve function has a wide range of application potential in rapid saliva detection.

Comparative effectiveness of eHealth interventions on the exercise endurance and quality of life of patients with COPD: A systematic review and network meta-analysis.

AIMS: To compare the effectiveness of different types of eHealth interventions in improving exercise endurance and quality of life in chronic obstructive pulmonary disease (COPD) patients. BACKGROUND: COPD is a chronic airway disease characterized by persistent respiratory symptoms and airflow limitation. eHealth interventions have been accepted and recognized by healthcare professionals and COPD patients as an effective alternative to pulmonary rehabilitation. However, it is not clear which eHealth interventions are effective and preferred for exercise endurance and quality of life in COPD patients. DESIGN: A systematic review and network meta-analysis based on PRISMA-NMA. METHODS: We searched nine electronic databases to identify randomized controlled trials addressing the effect of eHealth interventions on the exercise endurance and quality of life of COPD patients from their inception to 30 October 2022. First, a random-effects model was chosen to conduct a traditional meta-analysis to directly investigate the efficacy of different eHealth interventions. Next, a network meta-analysis was performed to evaluate the relative efficacy of the eHealth interventions for COPD. The quality of the data was assessed using the Cochrane Risk of Bias tool. RESULTS: Fifty-one studies containing six eHealth interventions (telemonitoring, application [APP], web-based interventions, phone calls, virtual reality and combined interventions [≥two types]) were included in the final analysis. Network meta-analysis showed that telemonitoring, APP, web-based interventions and combined interventions improved exercise endurance in COPD patients, with telemonitoring being the most effective. Web-based interventions and apps are effective in improving the quality of life, and web-based interventions are the most effective. CONCLUSIONS: This study confirms that eHealth interventions can improve exercise endurance and quality of life in COPD patients. In the future, healthcare professionals can promote the use of telemedicine in COPD patients to enhance their exercise endurance and quality of life according to their individual needs. RELEVANCE TO CLINICAL PRACTICE: This evidence suggests that eHealth interventions can improve exercise endurance and quality of life in COPD patients. Therefore, in the future, eHealth interventions could be used to maximize their effectiveness in improving exercise endurance and quality of life in COPD patients.

New-Onset Hidradenitis Suppurativa in Psoriasis Patients: A Multi-Center, Retrospective Cohort Study.

BACKGROUND: Previous research has indicated a potential correlation between hidradenitis suppurativa (HS) and psoriasis (PSO), two chronic inflammatory dermatological diseases. However, there is a lack of comprehensive evaluations that consider a variety of clinical and demographic factors, and the risk of developing HS in PSO patients remains unclear. Our study aims to examine HS risk over time among PSO patients versus matched controls while considering the influence of confounders to provide insights into the potential link between these two diseases. METHOD: In this multi-institutional cohort study using the TriNetX database, we matched 202,318 patients with PSO with an equivalent number of individuals without PSO, using propensity score matching. The study period extended from 1 January 2005 to 31 December 2018. We computed hazard ratios and their respective 95% confidence intervals (CIs) to evaluate the probability of HS manifestation over a period of 5 years in patients with PSO in comparison to those without PSO. RESULTS: PSO patients demonstrated a consistently higher risk of developing HS than matched controls across all analytic models with the hazard ratios (HR) ranging from 1.43 (95% CI 1.30-1.56) to 5.91 (95% CI 2.49-14.04). Stratified analyses showed the increased HS risk was observed in both genders but only significant in those aged 18-64 years. Kaplan-Meier analysis indicated PSO patients had a higher cumulative probability of developing HS over time (HR 1.77, 95% CI 1.49-1.89). CONCLUSIONS: PSO was associated with increased HS risk, highlighting the importance of considering HS as a potential comorbidity in PSO patients and may have implications for early detection, prevention, and management strategies for both conditions. Shared inflammatory pathways, genetic components, and skin dysbiosis may contribute. Further research should elucidate underlying mechanisms.

Influence of Si Addition on the Microstructures, Phase Assemblages and Properties in CoCrNi Medium-Entropy Alloy.

The effects of Si addition on the microstructures and properties of CoCrNi medium-entropy alloy (MEA) were systematically investigated. The CrCoNiSix MEA possesses a single face-centered cubic (FCC) phase when x is less than 0.3 and promotes solution strengthening, while the crystal structure shows a transition to the FCC+σ phase structure when x = 0.4 and the volume fraction of the σ phase increases with a microstructure evolution as the Si content increases. The Orowan mechanism from σ precipitation effectively enhances the strength, hardness, and stain hardening of CrCoNiSix MEA, which also exhibits superior hardness at high temperatures. Furthermore, a large amount of σ phase decreases the wear resistance because of the transformation of the main wear mechanism from abrasion wear for σ-free CrCoNiSix MEA to adhesion wear for σ-contained CrCoNiSix MEA. This work contributes to the understanding of the effect of Si addition on FCC structured alloys and provides guidance for the development of novel Si-doped alloys.

Resistant starch from yam: Preparation, nutrition, properties and applications in the food sector.

Yam is a significant staple food and starch source, particularly in tropical and subtropical regions, holding the fourth position among the world's top ten tuber crops. Yam tubers are rich in essential nutrients and a diverse range of beneficial plant compounds, which contribute to their multifaceted beneficial functions. Furthermore, the abundant starch and resistant starch (RS) content in yam can fulfil the market demand for RS. The inherent and modified properties of yam starch and RS make them versatile ingredients for a wide range of food products, with the potential to become one of the most cost-effective raw materials in the food industry. In recent years, research on yam RS has experienced progressive expansion. This article provides a comprehensive summary of the latest research findings on yam starch and its RS, elucidating the feasibility of commercial RS production and the technology's impact on the physical and chemical properties of starch. Yam has emerged as a promising reservoir of tuber starch for sustainable RS production, with thermal, chemical, enzymatic and combination treatments proving to be effective manufacturing procedures for RS. The adaptability of yam RS allows for a wide range of food applications.

First Report of Leaf Spot Disease on Lonicera japonica Caused by Nigrospora oryzae in China.

Lonicera japonica Thunb. is a traditional Chinese medicinal plant, which widely cultivated in China, Japan and Korea. From August to October in 2021 and 2022, severe leaf spots symptoms were observed on L. japonica in medicinal botanical garden of Shandong University of Traditional Chinese Medicine (36°55'89"N, 116°79'91"E), Jinan, Shandong Province, China. The disease incidence was above 80% in the 25 acre cultivation area. Early symptoms were small brown spots on the leaves. Then the number of small spots gradually increased and spread over the entire leaves. The small brown spots seldom merge together to form larger lesions. Leaves with typical symptoms were collected from twenty individual plants, and cut into small 5×5 mm fragments in the junction of infected and healthy tissues. The fragments were sterilized in 75% ethanol for 30 s and 1% NaClO for 60 s, rinsed three times in sterile water, and then placed on potato dextrose agar (PDA). After 3 days of incubation at 25°C, fungal plugs along the edge of the colony were cut and transferred to new PDA for purification. A total number of 23 colonies with similar morphological characteristics were obtained, and three representative strains (Lj14, Lj18 and Lj20) were selected for subsequent study. The colonies grew rapidly on PDA and covered the entire petri dish in 4 days. Colonies had abundant aerial hyphae, initially white, round, later turning gray and black. Conidia were oblate or nearly spherical, single-celled, black, and measured in size from 9.6 to 13.2 µm × 7.9 to 16.1 µm in diameter (n=150) (Figure S1). The observed characteristics were close to those of Nigrospora spp. ( Wang et al. 2017). The genomic DNA was extracted, and PCR amplification of the rDNA internal transcribed spacer (ITS), ß-tubulin gene (TUB), and translation elongation factor 1-alpha gene (TEF1) were completed by primers ITS1/ITS4, Bt2a/Bt2b and EF1-728F/EF1-986R (Carbone and Kohn, 1999). Sequences were deposited in GenBank (accession nos. OR936661, OR936662, OR936671 for ITS, OR947626, OR947627, OR947628 for TUB, and OR947629, OR947630, OR947631 for TEF1 sequences, respectively). BLAST analyses of ITS (OR936661), TUB(OR947626) and TEF1 (OR947629) sequences exhibited 100% (487 bp out of 487 bp), 99.48% (380 bp out of 382 bp), and 99.6% (248 bp out of 249 bp) similarity to the sequences of N. oryzae strains KoLRI_053384 (MZ855426), LC2991 (KY019496) and LC7307 (KY019409), respectively. Lj14, Lj18 and Lj20 formed a clade with N. oryzae LC6763 and LC2991 in phylogenetic tree (Figure S2). Based on morphological and molecular evidence, the pathogen was identified as N. oryzae (Berk. &Broome) Petch. To fulfill Koch's postulates, the pathogenicity was tested in vivo experiments. Thirty non-wounded healthy leaves of ten intact plants were inoculated with 10 µl spore suspension (106 spores/ml) of three strains, respectively. As negative control, thirty leaves of ten healthy plants were inoculated with sterile water. The inoculated plants were placed at 28°C in the growth chamber with high relative humidity. The pathogenicity tests were repeated three times. Distinct symptoms similar to that of natural conditions were observed on the leaves of inoculated plants after 4 to 7 days. The strain was reisolated from the lesions and identified as N. oryzae by morphological features and ITS sequence. The pathogen has been reported to cause leaf spot disease on tobacco (Wang et al. 2022) and asiatic dayflower (Qiu et al. 2022). To our knowledge, this is the first report of leaf spot caused by N. oryzae on Lonicera japonica in China. The research will be helpful for leaf spot disease control.

ClinOleic Impairs ROS Production and Phagocytosis in M1 Macrophages Without Affecting M1 Differentiation.

Lipid emulsions are the primary source of calories and fatty acids that are used to provide essential energy and nutrients to patients suffering from severe intestinal failure and critical illness. However, their use has been linked to adverse effects on patient outcomes, notably affecting immune defenses and inflammatory responses. ClinOleic is a lipid emulsion containing a mixture of olive oil and soybean oil (80:20). The effect of ClinOleic on the differentiation of M1 macrophages remains unclear. In this study, we isolated human monocytes and added ClinOleic to differentiation culture media to investigate whether it affects monocyte polarization into M1 macrophages and macrophage functions, such as reactive oxygen species (ROS) production and phagocytosis. ROS production was stimulated by live S. aureus and detected with L-012, a chemiluminescence emission agent. Phagocytic capacity was assayed using pHrodo™ Green S. aureus Bioparticles® Conjugate. We found that M1 cell morphology, surface markers (CD80 and CD86), and M1-associated cytokines (TNF-α and IL-6) did not significantly change upon incubation with ClinOleic during M1 polarization. However, S. aureus-triggered ROS production was significantly lower in M1 macrophages differentiated with ClinOleic than in those not treated with ClinOleic. The inhibitory effect of ClinOleic on macrophage function also appeared in the phagocytosis assay. Taken together, these findings reveal that ClinOleic has a limited impact on the M1 differentiation phenotype but obviously reduces ROS production and phagocytosis.

An integrated electronic tag-based vertical flow assay (e-VFA) with micro-sieve and AlGaN/GaN HEMT sensors for multi-target detection in actual saliva.

Vertical flow assay (VFA) is an effective point-of-care (POC) diagnostic tool for widespread application. Nevertheless, the lack of multi-target detection and multi-signal readout capability still remains a challenge. Herein, a brand new VFA scheme for multi-target saliva detection based on electronic tags was proposed, where AlGaN/GaN HEMT sensors modified with different bio-receptors as electronic tags endowed the VFA with multi-target detection capability. In addition, the use of electronic tags instead of optical tags allowed the VFA to simultaneously carry out direct multi-target readouts, which ensure effective POC diagnostics for saliva analysis. Moreover, by integrating a hydrophilically optimized micro-sieve, impurities like sticky filaments, epidermal cells and other large-scale charged particles in saliva were effectively screened, which enabled the direct detection of saliva using AlGaN/GaN HEMT sensors. Glucose, urea, and cortisol were selected to verify the feasibility of the multi-target e-VFA scheme, and the results showed that the limit of detection (LOD) was as low as 100 aM. The linear response was demonstrated in the dynamic range of 100 aM to 100 µM, and the specificity, long-term stability and validity of the actual saliva test were also verified. These results demonstrated that the as-proposed e-VFA has potential for application in saliva detection for simultaneous multi-target detection, and it is expected to achieve the real-time detection of more biological targets in saliva.

Survival benefits of postoperative radiotherapy in patients with cT1 - 2N1M0 breast cancer after neoadjuvant chemotherapy: a SEER-based population study.

BACKGROUND: Whether patients with cT1 - 2N1M0 breast cancer can benefit from postoperative radiotherapy (RT) after receiving neoadjuvant chemotherapy (NAC) has been controversial. Therefore, the purpose of this study was to explore whether postoperative RT can benefit this group of patients in terms of survival. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) data to conduct a retrospective review of women with cT1 - 2N1M0 breast cancer diagnosed between 20 and 80 years of age who received NAC between 2010 and 2015. Our study compared the impact of postoperative RT on overall survival (OS) and cancer-specific survival (CSS) in breast cancer patients using propensity score matching (PSM) and performed subgroup analysis. RESULTS: This study finally included 1092 cT1 - 2N1M0 breast cancer patients. Regardless of the patient's PSM status, postoperative RT was significantly associated with OS of cT1-2N1M0 breast cancer patients who received NAC. Specifically, the 10-year OS rate was 78.7% before PSM matching, compared with 71.1% in patients who did not receive postoperative RT, and the difference was more significant after PSM matching, which was 83.1% and 71.1% respectively. However, postoperative RT did not significantly benefit CSS in patients with cT1 - 2N1M0 breast cancer who received NAC. The 10-year CSS rate was 81.4% VS 76.2% (P = 0.085) before PSM matching and 85.8% VS 76.2%(P = 0.076) after matching. Due to the intersection of OS and CSS curves, this restricted mean survival time (RMST) method was chosen as a supplement. After 60 months, the OS difference in RMST between the postoperative RT group and the non-radiotherapy (noRT) group was 7.37 months (95%CI: 0.54-14.21; P = 0.034), and the CSS difference was 5.18 months (95%CI: -1.31-11.68; P = 0.118). Subgroup analysis found that in patients with right-sided breast cancer, postoperative RT improved the patient's OS (HR = 0.45, 95%CI: 0.21-0.95, P = 0.037) and CSS (HR = 0.42, 95%CI: 0.18-0.98, P = 0.045). CONCLUSIONS: Our results showed that additional postoperative RT improved the OS of cT1 - 2N1M0 breast cancer patients who received NAC, but failed to improve their CSS. It is worth noting that in the subgroup analysis of patients with right-sided breast cancer, we observed significant improvements in OS and CSS. And further prospective studies are still needed to verify the effect of postoperative RT in different subgroups.

Posterior cingulate and medial prefrontal excitation-inhibition balance in euthymic bipolar disorder.

BACKGROUND: Persistent cognitive deficits and functional impairments are associated with bipolar disorder (BD), even during the euthymic phase. The dysfunction of default mode network (DMN) is critical for self-referential and emotional mental processes and is implicated in BD. The current study aims to explore the balance of excitatory and inhibitory neurotransmitters, i.e. glutamate and γ-aminobutyric acid (GABA), in hubs of the DMN during the euthymic patients with BD (euBD). METHOD: Thirty-four euBD and 55 healthy controls (HC) were recruited to the study. Using proton magnetic resonance spectroscopy (1H-MRS), glutamate (with PRESS sequence) and GABA levels (with MEGAPRESS sequence) were measured in the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and the posterior cingulate gyrus (PCC). Measured concentrations of excitatory glutamate/glutamine (Glx) and inhibitory GABA were used to calculate the excitatory/inhibitory (E/I) ratio. Executive and attentional functions were respectively assessed using the Wisconsin card-sorting test and continuous performance test. RESULTS: euBD performed worse on attentional function than controls (p = 0.001). Compared to controls, euBD had higher E/I ratios in the PCC (p = 0.023), mainly driven by a higher Glx level in the PCC of euBD (p = 0.002). Only in the BD group, a marginally significant negative association between the mPFC E/I ratio (Glx/GABA) and executive function was observed (p = 0.068). CONCLUSIONS: Disturbed E/I balance, particularly elevated Glx/GABA ratio in PCC is observed in euBD. The E/I balance in hubs of DMN may serve as potential biomarkers for euBD, which may also contribute to their poorer executive function.

The fertility research of "Huajin 6", a new variety of honeysuckle.

The aim of this study was to investigate the fertility of "Huajin 6" and the effect of exogenous methyl jasmonate on its fertility. In this study, "Huajin 6", "Huajin 6" treated with methyl jasmonate and "Damaohua" were used as the research objects, the stamen phenotypes and the shape of pollen grains were observed, pollen viability and stigma receptivity were measured. The results showed that the pistil structure and function were normal, and although the stamen anthers did not dehisce, they were still capable of producing pollen with a certain amount of vigor. Methyl jasmonate could promote the opening of the flowers of "Huajin 6" and improve the development of pollen grains to a certain extent, but it could not promote anthers dehiscence of "Huajin 6". This study can provide theoretical guidance for the cultivation of new honeysuckle varieties using "Huajin 6".

New-onset Fibromyalgia After Total Knee Replacement in Patients With Osteoarthritis: A Propensity-score-matched Cohort Study in the United States.

BACKGROUND/AIM: The risk of new-onset fibromyalgia after total knee replacement (TKR) in osteoarthritis patients is not well-established. This study aimed to assess the risk of developing fibromyalgia post-TKR, considering potential variations across age and sex. PATIENTS AND METHODS: Utilizing a multicenter retrospective cohort design and data from the TriNetX research network, electronic health records of osteoarthritis patients who underwent TKR and the same number of matched controls were analyzed. Propensity-score matching was performed by matching critical confounders. Hazard ratios were evaluated to assess fibromyalgia risk in the TKR cohort compared to non-TKR controls. RESULTS: The hazard ratio of future fibromyalgia for the TKR cohort was 2.08 (95% confidence interval=1.74-2.49) for 1 year after the index date, 1.81 (95% confidence interval=1.62-2.02) for 3 years, and 1.69 (95% confidence interval=1.54-1.86) for 5 years compared with non-TKR controls. The significant association remained in sensitivity models and stratification analyses in different age and sex subgroups. CONCLUSION: Clinicians should be vigilant about the potential for fibromyalgia development post-TKR and consider tailored interventions; our findings emphasize the need for further research to elucidate underlying mechanisms and identify modifiable risk factors.

Increased Risk of New-Onset Rheumatoid Arthritis Among Osteoarthritis Patients Received Total Knee Arthroplasty: a global federated health network analysis.

Background: Complications of total knee arthroplasty (TKA) had been widely discussed. However, whether TKA influence risk of rheumatoid arthritis (RA) in osteoarthritis patients remained uncertain. We intend to evaluate the risk of RA in osteoarthritis patients underwent TKA. Methods: In this retrospective cohort study, data was retrieved from the US collaborative networks in TriNetX research network. Within the study period between 2005 and 2017, osteoarthritis patients underwent TKA were enrolled as case cohort whereas osteoarthritis patients never underwent TKA were enrolled as control cohort. Covariates were matched via propensity score matching. Risk of RA in TKA patients were valuated under various follow-up time and sensitivity models. Results: Under 1-year, 3-year and 5-year of follow-up, TKA patients were associated with significantly elevated risk of RA, especially under 1-year follow-up (HR=1.74; 95% CI, 1.39-2.18). Subgroup analysis demonstrated a significant increase in the risk of RA following TKA in the female subgroup (HR=1.42; 95% CI, 1.24-1.63), the subgroup aged 18-64 years (HR=1.48; 95% CI, 1.11-1.97), and the subgroup aged greater than 65 years old (HR=1.38; 95% CI, 1.21-1.58) based on 5-year follow-up. Conclusion: Clinicians should be concerned about uncharted association between TKA and RA reported our current study. Additional prospective studies and in-depth mechanistic inquiries were warranted to determine the causation.

Molecular epidemiology and antimicrobial resistance profiles of Klebsiella pneumoniae isolates from hospitalized patients in different regions of China.

Introduction: The increasing incidence of Klebsiella pneumoniae and carbapenem-resistant Klebsiella pneumoniae (CRKP) has posed great challenges for the clinical anti-infective treatment. Here, we describe the molecular epidemiology and antimicrobial resistance profiles of K. pneumoniae and CRKP isolates from hospitalized patients in different regions of China. Methods: A total of 219 K. pneumoniae isolates from 26 hospitals in 19 provinces of China were collected during 2019-2020. Antimicrobial susceptibility tests, multilocus sequence typing were performed, antimicrobial resistance genes were detected by polymerase chain reaction (PCR). Antimicrobial resistance profiles were compared between different groups. Results: The resistance rates of K. pneumoniae isolates to imipenem, meropenem, and ertapenem were 20.1%, 20.1%, and 22.4%, respectively. A total of 45 CRKP isolates were identified. There was a significant difference in antimicrobial resistance between 45 CRKP and 174 carbapenem-sensitive Klebsiella pneumoniae (CSKP) strains, and the CRKP isolates were characterized by the multiple-drug resistance phenotype.There were regional differences among antimicrobial resistance rates of K. pneumoniae to cefazolin, chloramphenicol, and sulfamethoxazole,which were lower in the northwest than those in north and south of China.The mostcommon sequence type (ST) was ST11 (66.7% of the strains). In addition, we detected 13 other STs. There were differences between ST11 and non-ST11 isolates in the resistance rate to amikacin, gentamicin, latamoxef, ciprofloxacin, levofloxacin, aztreonam, nitrofurantoin, fosfomycin, and ceftazidime/avibactam. In terms of molecular resistance mechanisms, the majority of the CRKP strains (71.1%, 32/45) harbored blaKPC-2, followed by blaNDM (22.2%, 10/45). Strains harboring blaKPC or blaNDM genes showed different sensitivities to some antibiotics. Conclusion: Our analysis emphasizes the importance of surveilling carbapenem-resistant determinants and analyzing their molecular characteristics for better management of antimicrobial agents in clinical use.

Antiviral activity of Vigna radiata extract against feline coronavirus in vitro.

Feline infectious peritonitis (FIP) is a fatal illness caused by a mutated feline coronavirus (FCoV). This disease is characterized by its complexity, resulting from systemic infection, antibody-dependent enhancement (ADE), and challenges in accessing effective therapeutics. Extract derived from Vigna radiata (L.) R. Wilczek (VRE) exhibits various pharmacological effects, including antiviral activity. This study aimed to investigate the antiviral potential of VRE against FCoV, addressing the urgent need to advance the treatment of FIP. We explored the anti-FCoV activity, antiviral mechanism, and combinational application of VRE by means of in vitro antiviral assays. Our findings reveal that VRE effectively inhibited the cytopathic effect induced by FCoV, reduced viral proliferation, and downregulated spike protein expression. Moreover, VRE blocked FCoV in the early and late infection stages and was effective under in vitro ADE infection. Notably, when combined with VRE, the polymerase inhibitor GS-441524 or protease inhibitor GC376 suppressed FCoV more effectively than monotherapy. In conclusion, this study characterizes the antiviral property of VRE against FCoV in vitro, and VRE possesses therapeutic potential for FCoV treatment.

Nobiletin derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone, inhibits neuroinflammation through the inhibition of TLR4/MyD88/MAPK signaling pathways and STAT3 in microglia.

OBJECTIVE: Microglia in the central nervous system regulate neuroinflammation that leads to a wide range of neuropathological alterations. The present study investigated the anti-neuroinflammatory properties of nobiletin (Nob) derivative, 5-acetoxy-6,7,8,3',4'-pentamethoxyflavone (5-Ac-Nob), in lipopolysaccharide (LPS)-activated BV2 microglia. MATERIALS AND METHODS: By using the MTT assay, Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), we determined the cell viability, the levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors (interleukin 1 beta; IL-1ß, interleukin 6; IL-6, tumor necrosis factor alpha; TNF-α and prostaglandin E2; PGE2) in LPS-stimulated BV2 microglia. Toll-like receptor 4 (TLR4)-mediated myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK) signaling pathway and signal transducer and activator of transcription 3 (STAT3) were measured by western blotting. Analysis of NO generation and mRNA of pro-inflammatory cytokines was confirmed in the zebrafish model. RESULTS: 5-Ac-Nob reduced cell death, the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and pro-inflammatory factors in LPS-activated BV-2 microglial cells. TLR4-mediated MyD88/NF-κB and MAPK pathway (p38, ERK and JNK) after exposure to 5-Ac-Nob was also suppressed. Moreover, 5-Ac-Nob inhibited phosphorylated STAT3 proteins expression in LPS-induced BV-2 microglial cells. Furthermore, we confirmed that 5-Ac-Nob decreased LPS-induced NO generation and mRNA of pro-inflammatory cytokines in the zebrafish model. CONCLUSIONS: Our findings suggest that 5-Ac-Nob represses neuroinflammatory responses by inhibiting TLR4-mediated signaling pathway and STAT3. As a result of these findings, 5-Ac-Nob has potential as an anti-inflammatory agent against microglia-mediated neuroinflammatory disorders.