Trichosporon asahii co-infection with Pneumocystis jiroveci in a renal transplant patient.

Trichosporon asahii is considered an opportunistic pathogen, capable of causing superficial infections in humans and invasive deep-seated infections in immunocompromised hosts. Pneumocystis jirovecii can cause life-threatening pneumonia in immunosuppressed patients. Both Trichosporon and Pneumocystis jirovecii are highly lethal in immunocompromised individuals. Here we present a case of invasive Trichosporon asahii co-infection with Pneumocystis jiroveci in a renal transplant patient.

CADM2 participates in endometriosis development by influencing the epithelial-mesenchymal transition.

Endometriosis (EM) is a common gynecologic condition that often leads to infertility in women of reproductive age. Cell adhesion molecule 2 (CADM2) is involved in maintaining cell adhesion and polarity, as well as suppressing tumors. However, the role and mechanism of CADM2 in endometriosis is unclear. Therefore, this study evaluated the expression levels of CADM2 and epithelial-mesenchymal transition (EMT)-related marker proteins (E-cadherin, α-SMA, and N-cadherin). Compared to normal endometrial tissue, CADM2 was expressed at low levels in ectopic endometrial tissue from patients with EM. We performed clone formation assays, wound healing assays, and Transwell cell invasion assays to investigate the effects of CADM2 on the biological behavior of endometriosis epithelial cells (11Z) and ectopic endometrial stromal cells (EESCs). The growth, migration, and invasion abilities of these cells were significantly inhibited by overexpression of CADM2. The results were reversed after the knockdown of CADM2. Finally, western blotting (WB) was utilized to detect the effect of CADM2 on EMT in endometriosis cells. CADM2 inhibited EMT in endometriosis cells. In conclusion, our study suggests that CADM2 is a negative regulator of endometriosis development and may inhibit endometriosis development by suppressing EMT.

Prevalence and influencing factors of patient delay in stroke patients: a systematic review and meta-analysis.

PURPOSE: Determine the prevalence and influencing factors of patient delay in stroke patients and explore variation in prevalence by country and delayed time. METHODS: PubMed, The Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), Weipu database, and Wanfang database were comprehensively searched for observational studies from inception to April, 2023. The pooled prevalence, odds ratio (OR), and 95% confidence intervals (CI) were calculated with Stata 16.0 software. RESULTS: In total, 2721 articles were screened and data from 70 studies involving 85,468 subjects were used in meta-analysis. The pooled prevalence of patient delay in stroke patients was 59% (95% CI, 0.54-0.64). The estimates of pooled prevalence calculated for African, Asian, and European patient delay in stroke patients were 55% (0.29-0.81), 61% (0.56-0.66), and 49% (0.34-0.64).According to the patient delay time, the prevalence of 6 h, 5 h, 4.5 h, 3.5 h, 3 h and 2 h were 54% (0.47-0.61), 73% (0.61-0.86), 60% (0.49-0.71), 81% (0.68-0.93), 52% (0.42-0.62), 63% (0.19-1.07). Distance from the place of onset to the hospital > 10 km [OR=2.49, 95%CI (1.92, 3.24)], having medical insurance [OR = 0.45, 95%CI (0.26,0.80)], lack of stroke-related knowledge [OR = 1.56, 95%CI (1.08,2.26)], education level below junior high school [OR = 1.69, 95%CI (1.22,2.36)], non-emergency medical services (Non-EMS) [OR = 2.10, 95%CI (1.49,2.97)], living in rural areas [OR = 1.54, 95%CI (1.15,2.07)], disturbance of consciousness [OR = 0.60, 95%CI (0.39,0.93)], history of atrial fibrillation [OR = 0.53, 95%CI (0.47,0.59)], age ≥ 65 years [OR = 1.18, 95%CI (1.02,1.37)], National institutes of health stroke scale (NIHSS) ≤ 4 points [OR= 2.26, 95%CI (1.06,4.79)]were factors for patient delay in stroke patients. CONCLUSIONS: The prevalence of patient delay in stroke patients is high, we should pay attention to the influencing factors of patient delay in stroke patients and provide a theoretical basis for shortening the treatment time of stroke patients.

Dearomative [2 + 1] Spiroannulation of Bromophenols with Electron-Deficient Alkenes.

A base-assisted dearomative [2 + 1] spiroannulation of p/o-bromophenols with activated olefins (methylenemalonates) to construct various cyclopropyl spirocyclohexadienone skeletons is reported. Furthermore, several other halophenols (X = Cl, I) were also tolerated in this process. Control experiments reveal a dearomative Michael addition of phenols at their halogenated positions to methylenemalonates, followed by intramolecular radical-based SRN1 dehalogenative cyclopropanation. However, according to the density functional theory (DFT) calculations, an SN2 dehalogenative cyclopropanation with the same low activation energy barrier should not be excluded. The utility of this method is showcased by gram-scale syntheses and transformations of the dearomatized products.

Temporal relationship between hepatic steatosis and blood pressure elevation and the mediation effect in the development of cardiovascular disease.

The temporal relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension remains highly controversial, with ongoing debates on whether NAFLD induces hypertension or vice versa. We employed cross-lagged panel models to investigate the temporal relationship between hepatic steatosis (assessed by Fatty Liver Index [FLI] in the main analysis, and by Proton Density Fat Fraction [PDFF] in the validation study) and blood pressure (systolic and diastolic blood pressure [SBP/ DBP]). Subsequently, we employed causal mediation models to explore the mediation effect in CVD development, including ischemic heart disease and stroke. The main analysis incorporated repeated measurement data of 5,047 participants from the China Multi-Ethnic Cohort (CMEC) and 5,685 participants from the UK Biobank (UKB). In both cohorts, the path coefficients from FLI to blood pressure were significant and greater than the path from blood pressure to FLI, with ßFLI→SBP = 0.081, P < 0.001 versus ßSBP→FLI = 0.020, P = 0.031; ßFLI→DBP = 0.082, P < 0.001 versus ßDBP→FLI = -0.006, P = 0.480 for CEMC, and ßFLI→SBP = 0.057, P < 0.001 versus ßSBP→FLI = -0.001, P = 0.727; ßFLI→DBP = 0.061, P < 0.001, versus ßDBP→FLI = -0.006, P = 0.263 for UKB. The validation study with 962 UKB participants using PDFF consistently supported these findings. In the mediation analyses encompassing 11,108 UKB participants, SBP and DBP mediated 12.2% and 5.2% of the hepatic steatosis-CVD association, respectively. The proportions were lower for ischemic heart disease (SBP: 6.1%, DBP: non-statistically significant -6.8%), and relatively stronger for stroke (SBP: 19.4%, DBP: 26.1%). In conclusion, hepatic steatosis more strongly contributes to elevated blood pressure than vice versa. Blood pressure elevation positively mediates the hepatic steatosis-CVD association, particularly in stroke compared to ischemic heart disease.

Citizen science in action: Time-resolved immunofluorescence-based field detection of antibiotics with portable analytical kit.

Citizen scientist-based environmental monitoring and public education are becoming increasingly popular. However, current technologies for antibiotic-based novel contaminant identification are still restricted to laboratory sample collection and analysis due to detection methodologies and apparatus limitations. This study developed a time-resolved immunofluorescence-based simultaneous field-based assay for ciprofloxacin (CIP) and enrofloxacin (ENR) that matches test results to geographic locations. The assay helps the public understand the potential levels of antibiotic exposures in their environments and helps them take appropriate action to reduce risk. The assay was developed using smartphones and social software in addition to rapid testing. The method uses a portable, low-cost analytical kit with a smartphone app to build a field-based detection platform for the detection and analysis of ENR and CIP in water and aquatic products. The methodological evaluation was good, with detection limits of 0.4 ng/mL and 0.5 ng/g for ENR in water and fish, and quantification limits of 1.2 ng/mL and 1.4 ng/g, with recoveries of 89.0 %-101.0 % and 78.0 %-97.0 %. For CIP in water and fish, the limits of detection were 0.3 ng/mL and 0.4 ng/g, the limits of quantification were 0.9 ng/mL and 1.2 ng/g, and the recoveries were 75.0 %-91.0 % and 72.0 %-89.0 %, both with coefficients of variation <15 %. These limits were sufficient to prevent the two antibiotics from crossing over during simultaneous detection. The assay was validated using real samples to assess the effectiveness of the assay platform in field deployments, and the results were consistent with those obtained through liquid chromatography-tandem mass spectrometry (LC-MS) and enzyme-linked immunoassay (ELISA) techniques. In addition, the TRFIA assay process requires less time, uses more portable instruments, and is less complex than traditional methods. This study provides a new scientific, accurate, and rapid detection method for antibiotic detection by citizen scientists, helping scientists to obtain a wider range of data and providing more opportunities to solve scientific problems.

Arginine and tryptophan-rich dendritic antimicrobial peptides that disrupt membranes for bacterial infection in vivo.

The potent antibacterial activity and low resistance of antimicrobial peptides (AMPs) render them potential candidates for treating multidrug-resistant bacterial infections. Herein, a minimalist design strategy was proposed employing the "golden partner" combination of arginine (R) and tryptophan (W), along with a dendritic structure to design AMPs. By extension, the α/ε-amino group and the carboxyl group of lysine (K) were utilized to link R and W, forming dendritic peptide templates αRn(εRn)KWm-NH2 and αWn(εWn)KRm-NH2, respectively. The corresponding linear peptide templates R2nKWm-NH2 and W2nKRm-NH2 were used as controls. Their physicochemical properties, activity, toxicity, and stability were compared. Among these new peptides, the dendritic peptide R2(R2)KW4 was screened as a prospective candidate owing to its preferable antibacterial properties, biocompatibility, and stability. Additionally, R2(R2)KW4 not only effectively restrained the progression of antibiotic resistance, but also demonstrated synergistic utility when combined with conventional antibiotics due to its unique membrane-disruptive mechanism. Furthermore, R2(R2)KW4 possessed low toxicity (LD50 = 109.31 mg/kg) in vivo, while efficiently clearing E. coli in pulmonary-infected mice. In conclusion, R2(R2)KW4 has the potential to become an antimicrobial regent or adjuvant, and the minimalist design strategy of dendritic peptides provides innovative and encouraging thoughts in designing AMPs.

Vitamin D Deficiency Exacerbates Poor Sleep Outcomes with Endocrine-Disrupting Chemicals Exposure: A Large American Population Study.

Phthalates and bisphenol A are recognized as the predominant endocrine-disrupting substances (EDCs) in the environment, but their impact on sleep health remains unclear. Vitamin D has often been reported to play a role in sleep health and may be affected by endocrine-disrupting compounds. The study utilized data from 5476 individuals in the NHANES project to investigate the correlation between combined exposure to environmental EDCs and sleep duration through modeling various exposures. Furthermore, it emphasizes the importance of vitamin D in the present scenario. Preliminary analyses suggested that vitamin D-deficient individuals generally slept shorter than individuals with normal vitamin D (p < 0.05). Exposure to Mono-ethyl phthalate (MEP), triclosan (TRS), and Mono-benzyl phthalate (MZP), either alone or in combination, was associated with reduced sleep duration and a greater risk of vitamin D deficiency. Individuals with low vitamin D levels exposed to TRS experienced shorter sleep duration than those with normal vitamin D levels (p < 0.05). TRS and MZP were identified as crucial factors in patient outcomes when evaluating mixed exposures (p < 0.05). The results provide new data supporting a link between exposure to EDCs and insufficient sleep length. Additionally, they imply that a vitamin D shortage may worsen the sleep problems induced by EDCs.

Cohort profile: the Adverse Childhood Experiences cohort of the Malawi Longitudinal Study of Families and Health.

PURPOSE: The Adverse Childhood Experiences (ACE) cohort of the Malawi Longitudinal Study of Families and Health (MLSFH-ACE) is a study of adolescents surveyed during 2017-2021. It provides an important opportunity to examine the longitudinal impact of ACEs on health and development across the early life course. The MLSFH-ACE cohort provides rich data on adolescents, their children and adult caregivers in a low-income, high-HIV-prevalence context in sub-Saharan Africa (SSA). PARTICIPANTS: The MLSFH-ACE cohort is a population-based study of adolescents living in three districts in rural Malawi. Wave 1 enrolment took place in 2017-2018 and included 2061 adolescents aged 10-16 years and 1438 caregivers. Wave 2 took place in 2021 and included data on 1878 adolescents and 208 offspring. Survey instruments captured ACEs during childhood and adolescence, HIV-related behavioural risk, mental and physical health, cognitive development and education, intimate partner violence (IPV), marriage and aspirations, early transitions to adulthood and protective factors. Biological indicators included HIV, herpes simplex virus and anthropometric measurements. FINDINGS TO DATE: Key findings include a high prevalence of ACEs among adolescents in Malawi, a low incidence of HIV and positive associations between ACE scores and composite HIV risk scores. There were also strong associations between ACEs and both IPV victimisation and perpetration. FUTURE PLANS: MLSFH-ACE data will be publicly released and will provide a wealth of information on ACEs and adolescent outcomes in low-income, HIV-endemic SSA contexts. Future expansions of the cohort are planned to capture data during early adulthood.

Development of a new caged intein for multi-input conditional translation of synthetic mRNA.

mRNA medicines can be used to express therapeutic proteins, but the production of such proteins in non-target cells has a risk of adverse effects. To accurately distinguish between therapeutic target and nontarget cells, it is desirable to utilize multiple proteins expressed in each cell as indicators. To achieve such multi-input translational regulation of mRNA medicines, in this study, we engineered Rhodothermus marinus (Rma) DnaB intein to develop "caged Rma DnaB intein" that enables conditional reconstitution of full-length translational regulator protein from split fragments. By combining the caged Rma DnaB intein, the split translational regulator protein, and target protein-binding domains, we succeeded in target protein-dependent translational repression of mRNA in human cells. In addition, the caged Rma intein showed orthogonality to the previously reported Nostoc punctiforme (Npu) DnaE-based caged intein. Finally, by combining these two orthogonal caged inteins, we developed an mRNA-based logic gate that regulates translation based on the expression of multiple intracellular proteins. This study provides important information to develop safer mRNA medicines.

Performance evaluation of a newly developed 2019-nCoV nucleic acid detection kit based on Ion Proton sequencing platform and its comparison with the MGI Tech (DNBSEQ-G99) platform.

PURPOSE: To evaluate the performance of a newly developed 2019-nCoV nucleic acid detection kit based on Ion Proton sequencing platform and make comparation with MGI Tech (DNBSEQ-G99) platform. METHODS: References and clinical samples were used to evaluate the precision, agreement rate, limit of detection (LOD), anti-interference ability and analytical specificity. Twenty-seven clinical specimens were used to make comparison between two platforms. RESULTS: The kit showed good intra-assay, inter-assay, inter-day precision between different operators and laboratories, fine agreement rate with references, a relatively low LOD of 1 × 103 copies/ml, anti-interference capability of 5 % whole blood and 1mg/ml mucin and no cross reaction with twenty-nine common clinical pathogens. Consistency of variant classification was observed between two platforms. The WGS from Ion Proton tended to have higher coverage and less missing data. CONCLUSIONS: The newly developed kit has shown satisfactory performances and excellent consistency with DNBSEQ-G99, making it a good alternative choice clinically.

NEK2 promotes the development of ovarian endometriosis and impairs decidualization by phosphorylating FOXO1.

Ovarian endometriosis is a common gynecological disease, and one of its most significant symptoms is infertility. In patients with endometriosis, defects in endometrial decidualization lead to impaired endometrial receptivity and embryo implantation, thus affecting early pregnancy and women's desire to have children. However, the mechanisms underlying the development of endometriosis and its associated defective decidualization are unclear. We find that NEK2 expression is increased in the ectopic and eutopic endometrium of patients with endometriosis. Meanwhile, NEK2 interacts with FOXO1 and phosphorylates FOXO1 at Ser184, inhibiting the stability of the FOXO1 protein. Importantly, NEK2-mediated phosphorylation of FOXO1 at Ser184 promotes cell proliferation, migration, invasion and impairs decidualization. Furthermore, INH1, an inhibitor of NEK2, inhibits the growth of ectopic lesions in mouse models of endometriosis and promotes endometrial decidualization in mouse models of artificially induced decidualization. Taken together, these findings indicate that NEK2 regulates the development of endometriosis and associated disorders of decidualization through the phosphorylation of FOXO1, providing a new therapeutic target for its treatment.

Phosphorus accumulation during the ice-on season in macrophyte-dominated eutrophic lakes and its implications.

Macrophyte overgrowth in eutrophic lakes can hasten the decline of shallow water bodies, yet the impact of macrophyte deposition on sediment phosphorus (P) accumulation in the ice-on season remains unclear. Comparative analyses of P variations among 13 semi-connected sub-lakes in Wuliangsu Lake in China, a typical MDE lake, considered external flow and macrophyte decomposition as driving forces. Sediment P fractions and water total phosphorus (TP) were analyzed at 35 sampling points across three ice-on season stages, along with macrophyte TP content to assess debris contributions. Our findings reveal that phosphorus accumulation occurs during the ice-on season in the MDE lake, with an average TP content increase of 16 mg/kg. However, we observed a surprisingly small sediment nutrient accumulation ratio (ΔTP/ΔTN=0.006) compared to macrophyte nutrient levels before decomposition. Further analysis of the dominant species, Potamogeton pectinatus, indicates that a significant portion (55%) of macrophyte phosphorus is released before the ice-on season. This highlights the critical importance of timing macrophyte harvesting to precede the phosphorus leaching process, which has implications for lake management and ecosystem restoration efforts. Additionally, our research demonstrates similar transformations among different sediment fractions as previously reported. Macrophyte debris decomposition likely serves as the primary source of Residual P (Res-P) or TP accumulation. In addition, Ca-bound P (Ca-P) generally showed a decrease, which mainly caused by its transformation to Fe/Al-bound P (Fe/Al-P), Exchange-P (Ex-P), and sometimes to Res-P. However, we emphasize the significant impacts of flow dynamics on Ca-P transport and transformations. Its hydrodynamic action increases water dissolved oxygen, which accelerates the transformation of Ca-P to more easily released Fe/Al-P and Ex-P. Furthermore, hydrodynamic transport also leads to upstream Ca-P transport to downstream. This underscores the necessity of considering flow dynamics when estimating phosphorus variations and formulating phosphorus restoration strategies.

A novel hybrid model for species distribution prediction using neural networks and Grey Wolf Optimizer algorithm.

Neural networks are frequently employed to model species distribution through backpropagation methods, known as backpropagation neural networks (BPNN). However, the complex structure of BPNN introduces parameter settings challenges, such as the determination of connection weights, which can affect the accuracy of model simulation. In this paper, we integrated the Grey Wolf Optimizer (GWO) algorithm, renowned for its excellent global search capacity and rapid convergence, to enhance the performance of BPNN. Then we obtained a novel hybrid algorithm, the Grey Wolf Optimizer algorithm optimized backpropagation neural networks algorithm (GNNA), designed for predicting species' potential distribution. We also compared the GNNA with four prevalent species distribution models (SDMs), namely the generalized boosting model (GBM), generalized linear model (GLM), maximum entropy (MaxEnt), and random forest (RF). These models were evaluated using three evaluation metrics: the area under the receiver operating characteristic curve, Cohen's kappa, and the true skill statistic, across 23 varied species. Additionally, we examined the predictive accuracy concerning spatial distribution. The results showed that the predictive performance of GNNA was significantly improved compared to BPNN, was significantly better than that of GLM and GBM, and was even comparable to that of MaxEnt and RF in predicting species distributions with small sample sizes. Furthermore, the GNNA demonstrates exceptional powers in forecasting the potential non-native distribution of invasive plant species.

Effects of a Multicomponent Intervention With Cognitive Training and Lifestyle Guidance for Older Adults at Risk of Dementia: A Randomized Controlled Trial.

Objective: This study examined the effects of a multicomponent intervention program on cognitive function in community-dwelling older adults with mild cognitive impairment (MCI) and subjective cognitive decline (SCD).Methods: This was a 2-arm, randomized controlled trial in which a multicomponent intervention was applied. Participants were recruited from June 2020 to August 2020, randomization and intervention began in August 2020, and the entire program ended in January 2021. It included cognitive training (mnemonic strategy training) and lifestyle guidance (diet, sleep, and exercise guidance) for 7 weeks. A total of 123 Chinese community-dwelling older adults experiencing MCI or SCD were randomly divided into a multicomponent intervention group (n = 62) and a health education group (n = 61). The global cognitive function was measured using the Mini-Mental State Examination (MMSE). The cognitive domains outcomes included memory functions measured using the immediate and delayed tests of the Auditory Verbal Learning Test (AVLT) and Logical Memory Test (LMT), and executive function and attention measured using the Digital Symbol Substitution Test (DSST) and Digit Span Test (DST). Data were collected at baseline and postintervention.Results: For cognitive outcome, the results of linear mixed-effect model showed significant time × group effects in the MMSE (Cohen d =0.63 [95% CI, 0.27 to 1.00], F = 10.25, P = .002). This study found significant time × group effects in AVLT-immediate (Cohen d = 0.47 [95% CI, 0.11 to 0.83], F = 8.18, P = .005), AVLT delayed (Cohen d = 0.45 [95% CI, 0.10 to 0.81], F = 4.59, P = .034), LMT-delayed (Cohen d = 0.71 [95% CI, 0.34 to 1.07], F = 4.59, P = .034), DSST (Cohen d = 0.27 [95% CI, -0.08 to 0.63], F = 4.83, P = .030), and DST (Cohen d =0.69 [95% CI, 0.33 to 1.05], F = 8.58, P = .004).Conclusions and Implications: The results support the feasibility and effectiveness of the multicomponent intervention program in improving cognitive function in community dwelling older adults at risk of dementia. The high adherence of this program shows its potential for promotion in the community and supports a larger and longer trial.Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200061420).

Nomogram for predicting early hypophosphatemia in term infants.

BACKGROUND: Physiological processes rely on phosphate, which is an essential component of adenosine triphosphate (ATP). Hypophosphatasia can affect nearly every organ system in the body. It is crucial to monitor newborns with risk factors for hypophosphatemia and provide them with the proper supplements. We aimed to evaluate the risk factors and develop a nomogram for early hypophosphatemia in term infants. METHODS: We conducted a retrospective study involving 416 term infants measured serum phosphorus within three days of birth. The study included 82 term infants with hypophosphatemia (HP group) and 334 term infants without hypophosphatemia (NHP group). We collected data on the characteristics of mothers, newborn babies, and childbirth. Furthermore, univariate and multivariate logistic regression analyses were performed to identify independent risk factors for hypophosphatemia in term infants, and a nomogram was developed and validated based on the final independent risk factors. RESULTS: According to our analysis, the multivariate logistic regression analysis showed that male, maternal diabetes, cesarean delivery, lower serum magnesium, and lower birth weight were independent risk factors for early hypophosphatemia in term infants. In addition, the C-index of the developed nomogram was 0.732 (95% CI = 0.668-0.796). Moreover, the calibration curve indicated good consistency between the hypophosphatemia diagnosis and the predicted probability, and a decision curve analysis (DCA) confirmed the clinical utility of the nomogram. CONCLUSIONS: The analysis revealed that we successfully developed and validated a nomogram for predicting early hypophosphatemia in term infants.

Inhibition of autophagosome-lysosome fusion contributes to TDCIPP-induced Aß1-42 production in N2a-APPswe cells.

Alzheimer's disease is the most common form of dementia and is characterized by cognitive impairment. The disruption of autophagosome-lysosome function has been linked to the pathogenesis of Alzheimer's disease. Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphorus flame retardant that has the potential to cause neuronal damage. We found that TDCIPP significantly increased the expression of ß-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), presenilin-1 (PS1) and Aß42. Proteomic studies with TMT labeling revealed changes in the profiles of N2a-APPswe cells after exposure to TDCIPP. Proteomic and bioinformatics analyses revealed that lysosomal proteins were dysregulated in N2a-APPswe cells after treatment with TDCIPP. The LC3, P62, CTSD, and LAMP1 levels were increased after TDCIPP exposure, and dysregulated protein expression was validated by Western blotting. The exposure to TDCIPP led to the accumulation of autophagosomes, and this phenomenon was enhanced in the presence of chloroquine (CQ). Our results revealed for the first time that TDCIPP could be a potential environmental risk factor for AD development. The inhibition of autophagosome-lysosome fusion may have a significant impact on the generation of Aß1-42 in response to TDCIPP.

Expression, purification, and crystal structure of mpox virus A41 protein.

Mpox is a zoonotic disease that was once endemic in Africa countries caused by mpox virus. However, cases recently have been confirmed in many non-endemic countries outside of Africa. The rapidly increasing number of confirmed mpox cases poses a threat to the international community. In-depth studies of key viral factors are urgently needed, which will inform the design of multiple antiviral agents. Mpox virus A41L gene encodes a secreted protein, A41, that is nonessential for viral replication, but could affect the host response to infection via interacting with chemokines. Here, mpox virus A41 protein was expressed in Sf9 cells, and purified by affinity chromatography followed by gel filtration. Surface plasmon resonance spectroscopy showed that purified A41 binds a certain human chemokine CXCL8 with the equilibrium dissociation constant (KD) being 1.22 × 10-6 M. The crystal structure of mpox virus A41 protein was solved at 1.92 Å. Structural analysis and comparison revealed that mpox virus A41 protein adopts a characteristic ß-sheet topology, showing minor differences with that of vaccinia virus. These preliminary structural and functional studies of A41 protein from mpox virus will help us better understand its role in chemokine subversion, and contributing to the knowledge to viral chemokine binding proteins.

Associations between residential greenness and obesity phenotypes among adults in Southwest China.

BACKGROUND: Although exposure to greenness has generally benefited human metabolic health, the association between greenness exposure and metabolic obesity remains poorly studied. We aimed to investigate the associations between residential greenness and obesity phenotypes and the mediation effects of air pollutants and physical activity (PA) level on the associations. METHODS: We used the baseline of the China Multi-Ethnic Cohort (CMEC) study, which enrolled 87,613 adults. Obesity phenotypes were defined based on obesity and metabolic status, including metabolically unhealthy obesity (MUO), non-obesity (MUNO), metabolically healthy obesity (MHO), and non-obesity (MHNO). Greenness exposure was measured as the 3-year mean values of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) within the 500-m buffer zones around the participants' residence. Multivariable logistic regression was used to estimate the associations between greenness and obesity phenotypes. Stratified analyses by age, sex, educational level, and urbanicity were performed to identify how the effect varies across different subgroups. Causal mediation analysis was used to examine the mediation effects of air pollutants and PA level. RESULTS: Compared with MHNO, each interquartile range (IQR) increase in greenness exposure was associated with reduced risks of MHO (ORNDVI [95% CI] = 0.87 [0.81, 0.93]; OREVI = 0.91 [0.86, 0.97]), MUO (ORNDVI = 0.83 [0.78, 0.88]; OREVI = 0.86 [0.81, 0.91]), and MUNO (ORNDVI = 0.88 [0.84, 0.91]; OREVI = 0.89 [0.86, 0.92]). For each IQR increase in both NDVI and EVI, the risks of MHO, MUO, and MUNO were reduced more in men, participants over 60 years, those with a higher level of education, and those living in urban areas, compared to their counterparts. Concentrations of particulate matter (PM) and PA level partially mediated the associations between greenness exposure and obesity phenotypes. CONCLUSIONS: Exposure to residential greenness was associated with decreased risks of MHO, MUO, and MUNO, which was mediated by concentrations of PM and PA level, and modified by sex, age, educational level, and urbanicity.