Detecting and characterizing new endofungal bacteria in new hosts: Pandoraea sputorum and Mycetohabitans endofungorum in Rhizopus arrhizus.

The fungus Rhizopus arrhizus (=R. oryzae) is commonly saprotrophic, exhibiting a nature of decomposing organic matter. Additionally, it serves as a crucial starter in food fermentation and can act as a pathogen causing mucormycosis in humans and animals. In this study, two distinct endofungal bacteria (EFBs), associated with individual strains of R. arrhizus, were identified using live/dead staining, fluorescence in situ hybridization, transmission electron microscopy, and 16S rDNA sequencing. The roles of these bacteria were elucidated through antibiotic treatment, pure cultivation, and comparative genomics. The bacterial endosymbionts, Pandoraea sputorum EFB03792 and Mycetohabitans endofungorum EFB03829, were purified from the host fungal strains R. arrhizus XY03792 and XY03829, respectively. Notably, this study marks the first report of Pandoraea as an EFB genus. Compared to its free-living counterparts, P. sputorum EFB03792 exhibited 28 specific virulence factor-related genes, six specific CE10 family genes, and 74 genes associated with type III secretion system (T3SS), emphasizing its pivotal role in invasion and colonization. Furthermore, this study introduces R. arrhizus as a new host for EFB M. endofungorum, with EFB contributing to host sporulation. Despite a visibly reduced genome, M. endofungorum EFB03829 displayed a substantial number of virulence factor-related genes, CE10 family genes, T3SS genes, mobile elements, and significant gene rearrangement. While EFBs have been previously identified in R. arrhizus, their toxin-producing potential in food fermentation has not been explored until this study. The discovery of these two new EFBs highlights their potential for toxin production within R. arrhizus, laying the groundwork for identifying suitable R. arrhizus strains for fermentation processes.

Predictors of Serum Per- and Polyfluoroalkyl Substances Concentrations among U.S. Couples Attending a Fertility Clinic.

Previous studies have examined the predictors of PFAS concentrations among pregnant women and children. However, no study has explored the predictors of preconception PFAS concentrations among couples in the United States. This study included 572 females and 279 males (249 couples) who attended a U.S. fertility clinic between 2005 and 2019. Questionnaire information on demographics, reproductive history, and lifestyles and serum samples quantified for PFAS concentrations were collected at study enrollment. We examined the PFAS distribution and correlation within couples. We used Ridge regressions to predict the serum concentration of each PFAS in females and males using data of (1) socio-demographic and reproductive history, (2) diet, (3) behavioral factors, and (4) all factors included in (1) to (3) after accounting for temporal exposure trends. We used general linear models for univariate association of each factor with the PFAS concentration. We found moderate to high correlations for PFAS concentrations within couples. Among all examined factors, diet explained more of the variation in PFAS concentrations (1-48%), while behavioral factors explained the least (0-4%). Individuals reporting White race, with a higher body mass index, and nulliparous women had higher PFAS concentrations than others. Fish and shellfish consumption was positively associated with PFAS concentrations among both females and males, while intake of beans (females), peas (male), kale (females), and tortilla (both) was inversely associated with PFAS concentrations. Our findings provide important data for identifying sources of couples' PFAS exposure and informing interventions to reduce PFAS exposure in the preconception period.

Repositioning baloxavir marboxil as VISTA agonist that ameliorates experimental asthma.

V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA), a novel negative checkpoint regulator, plays an essential role in allergic pulmonary inflammation in mice. Treatment with a VISTA agonistic antibody could significantly improve asthma symptoms. Thus, for allergic asthma treatment, VISTA targeting may be a compelling approach. In this study, we examined the functional mechanism of VISTA in allergic pulmonary inflammation and screened the FDA-approved drugs for VISTA agonists. By using mass cytometry (CyTOF), we found that VISTA deficiency primarily increased lung macrophage infiltration in the OVA-induced asthma model, accompanied by an increased proportion of M1 macrophages (CD11b+F4/80+CD86+) and a decreased proportion of M2 macrophages (CD11b+F4/80+CD206+). Further in vitro studies showed that VISTA deficiency promoted M1 polarization and inhibited M2 polarization of bone marrow-derived macrophages (BMDMs). Importantly, we discovered baloxavir marboxil (BXM) as a VISTA agonist by virtual screening of FDA-approved drugs. The surface plasmon resonance (SPR) assays revealed that BXM (KD = 1.07 µM) as well as its active form, baloxavir acid (BXA) (KD = 0.21 µM), could directly bind to VISTA with high affinity. Notably, treatment with BXM significantly ameliorated asthma symptoms, including less lung inflammation, mucus secretion, and the generation of Th2 cytokines (IL-5, IL-13, and IL-4), which were dramatically attenuated by anti-VISTA monoclonal antibody treatment. BXM administration also reduced the pulmonary infiltration of M1 macrophages and raised M2 macrophages. Collectively, our study indicates that VISTA regulates pulmonary inflammation in allergic asthma by regulating macrophage polarization and baloxavir marboxil, and an old drug might be a new treatment for allergic asthma through targeting VISTA.

Exposure to haloacetic acid disinfection by-products and male steroid hormones: An epidemiological and in vitro study.

Haloacetic acids (HAAs) are ubiquitous in drinking water and have been associated with impaired male reproductive health. However, epidemiological evidence exploring the associations between HAA exposure and reproductive hormones among males is scarce. In the current study, the urinary concentrations of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the internal exposure markers of HAAs, as well as sex hormones (testosterone [T], progesterone [P], and estradiol [E2]) were measured among 449 Chinese men. Moreover, in vitro experiments, designed to simulate the real-world scenarios of human exposure, were conducted to assess testosterone synthesis in the Leydig cell line MLTC-1 and testosterone metabolism in the hepatic cell line HepG2 in response to low-dose HAA exposure. The DCAA and TCAA urinary concentrations were found to be positively associated with urinary T, P, and E2 levels (all p < 0.001), but negatively associated with the ratio of urinary T to E2 (p < 0.05). Combined with in vitro experiments, the results suggest that environmentally-relevant doses of HAA stimulate sex hormone synthesis and steroidogenesis pathway gene expression in MLTC-1 cells. In addition, the inhibition of the key gene CYP3A4 involved in the testosterone phase Ⅰ catabolism, and induction of the gene UGT2B15 involved in testosterone phase Ⅱ glucuronide conjugation metabolism along with the ATP-binding cassette (ABC) transport genes (ABCC4 and ABCG2) in HepG2 cells could play a role in elevation of urinary hormone excretion upon low-dose exposure to HAAs. Our novel findings highlight that exposure to HAAs at environmentally-relevant concentrations is associated with increased synthesis and excretion of sex hormones in males, which potentially provides an alternative approach involving urinary hormones for the noninvasive evaluation of male reproductive health following exposure to DBPs.

Association of urinary and seminal plasma vanadium concentrations with semen quality: A repeated-measures study of 1135 healthy men.

Although animal studies have shown the reproductive toxicity of vanadium, less is known about its effects on semen quality in humans. Among 1135 healthy men who were screened as potential semen donors, we investigated the relationships of semen quality with urinary and seminal plasma vanadium levels via inductively coupled plasma-mass spectrometry (ICP-MS). Spearman rank correlation tests and linear regression models were used to assess the correlations between average urinary and within-individual pooled seminal plasma vanadium concentrations (n = 1135). We utilized linear mixed-effects models to evaluate the associations of urinary and seminal plasma vanadium levels (n = 1135) with repeated sperm quality parameters (n = 5576). Seminal plasma vanadium concentrations were not significantly correlated with urinary vanadium concentrations (r = 0.03). After adjusting for possible confounders, we observed inverse relationships of within-individual pooled seminal plasma vanadium levels with total count, semen volume, and sperm concentration (all P values for trend < 0.05). Specifically, subjects in the highest (vs. lowest) tertile of seminal plasma vanadium concentrations had - 11.3% (-16.4%, -5.9%), - 11.1% (-19.1%, -2.4%), and - 20.9% (-29.0%, -11.8%) lower sperm volume, concentration, and total count, respectively; moreover, urinary vanadium levels appeared to be negatively associated with sperm motility. These relationships showed monotonically decreasing dose-response patterns in the restricted cubic spline analyses. Our results demonstrated a poor correlation between urinary and seminal plasma levels of vanadium, and elevated vanadium concentrations in urine and seminal plasma may be adversely related to male semen quality.

Association between per- and polyfluoroalkyl substances exposure and thyroid function biomarkers among females attending a fertility clinic.

Per- and polyfluoroalkyl substances (PFAS) exposure was associated with changes in thyroid function in pregnant mothers and the general population. Limited such evidence exists in other susceptible populations such as females with fertility problems. This cross-sectional study included 287 females seeking medically assisted reproduction at a fertility clinic in Massachusetts, United States, between 2005 and 2019. Six long-alkyl chain PFAS, thyroid hormones, and autoimmune antibodies were quantified in baseline serum samples. We used generalized linear models and quantile g-computation to evaluate associations of individual PFAS and their total mixture with thyroid biomarkers. Most females were White individuals (82.7%), had graduate degrees (57.8%), and nearly half had unexplained subfertility (45.9%). Serum concentrations of all examined PFAS and their mixture were significantly associated with 2.6%-5.6% lower total triiodothyronine (TT3) concentrations. Serum concentrations of perfluorononanoate (PFNA), perfluorodecanoate (PFDA), and perfluoroundecanoate (PFUnDA), and of the total mixture were associated with higher ratios of free thyroxine (FT4) to free triiodothyronine (FT3). No associations were found for PFAS and TSH or autoimmune antibodies. Our findings support the thyroid-disrupting effect of long alkyl-chain PFAS among a vulnerable population of subfertile females.

Prediction Model of Ocular Metastases in Gastric Adenocarcinoma: Machine Learning-Based Development and Interpretation Study.

Background: Although gastric adenocarcinoma (GA) related ocular metastasis (OM) is rare, its occurrence indicates a more severe disease. We aimed to utilize machine learning (ML) to analyze the risk factors of GA-related OM and predict its risks. Methods: This is a retrospective cohort study. The clinical data of 3532 GA patients were collected and randomly classified into training and validation sets in a ratio of 7:3. Those with or without OM were classified into OM and non-OM (NOM) groups. Univariate and multivariate logistic regression analyses and least absolute shrinkage and selection operator were conducted. We integrated the variables identified through feature importance ranking and further refined the selection process using forward sequential feature selection based on random forest (RF) algorithm before incorporating them into the ML model. We applied six ML algorithms to construct the predictive GA model. The area under the receiver operating characteristic (ROC) curve indicated the model's predictive ability. Also, we established a network risk calculator based on the best performance model. We used Shapley additive interpretation (SHAP) to identify risk factors and to confirm the interpretability of the black box model. We have de-identified all patient details. Results: The ML model, consisting of 13 variables, achieved an optimal predictive performance using the gradient boosting machine (GBM) model, with an impressive area under the curve (AUC) of 0.997 in the test set. Utilizing the SHAP method, we identified crucial factors for OM in GA patients, including LDL, CA724, CEA, AFP, CA125, Hb, CA153, and Ca2+. Additionally, we validated the model's reliability through an analysis of two patient cases and developed a functional online web prediction calculator based on the GBM model. Conclusion: We used the ML method to establish a risk prediction model for GA-related OM and showed that GBM performed best among the six ML models. The model may identify patients with GA-related OM to provide early and timely treatment.

Maternal and Paternal Preconception Serum Concentrations of Per and Polyfluoroalkyl Substances in Relation to Birth Outcomes.

Prenatal per and polyfluoroalkyl substances (PFAS) exposure is associated with adverse birth outcomes. There is an absence of evidence on the relationship between maternal and paternal preconception PFAS exposure and birth outcomes. This study included 312 mothers and 145 fathers with a singleton live birth from a preconception cohort of subfertile couples seeking fertility treatment at a U.S. clinic. PFAS were quantified in serum samples collected before conception. Gestational age (GA) and birthweight (BW) were abstracted from delivery records. We also assessed low birthweight (BW < 2500 g) and preterm birth (GA < 37 completed weeks). We utilized multivariable linear regression, logistic regression, and quantile-based g computation to examine maternal or paternal serum concentrations of individual PFAS and mixture with birth outcomes. Maternal serum concentrations of perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS), and the total PFAS mixture were inversely associated with birthweight. Maternal PFOS concentration was associated with a higher risk of low birthweight. Conversely, paternal PFOS and PFHxS concentrations were imprecisely associated with higher birthweight. No associations were found for gestational age or preterm birth. The findings have important implications for preconception care. Future research with larger sample sizes would assist in validating these findings.

Maternal overweight and obesity modify the association of serum fibroblast growth factor 21 levels with gestational diabetes mellitus: A nested case-control study.

AIMS: To examine the prospective association between fibroblast growth factor 21 (FGF21) and risk of gestational diabetes mellitus (GDM) and the modifying effect of overweight/obesity for this association. METHODS: Serum FGF21 levels were measured at 6-15 weeks of gestation among 332 GDM cases and 664 matched controls. Conditional logistic regression was used to evaluate its association with GDM risk. Interaction analyses on multiplicative and additive scales were conducted to investigate the modifying effect of overweight/obesity. RESULTS: Elevated FGF21 levels were associated with a higher risk of GDM in multivariable models, but the positive association was attenuated after further adjustment for pre-pregnancy body mass index (BMI). A significant multiplicative interaction was noted between FGF21 (both continuous and dichotomous) and pre-pregnancy BMI (p for interaction = 0.049 and 0.03), and the association was only significant in participants with pre-pregnancy BMI ≥24 kg/m2 . When participants were grouped based on pre-pregnancy BMI (≥24 and <24 kg/m2 ) and FGF21 levels (≥median and

Exposure to Trihalomethanes and Bone Mineral Density in US Adolescents: A Cross-Sectional Study (NHANES).

Animal and human studies have suggested that trihalomethane (THM) has toxicity to bone. In this study, we included adolescents from the National Health and Nutrition Examination Survey who had quantified blood and tap water THM concentrations [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and lumbar spine or total body less head (TBLH) bone mineral density (BMD). A 2.7-fold increase in concentrations of blood TCM, DBCM, chlorinated THMs (the sum of TCM, BDCM, and DBCM), and total THMs (the sum of 4 THMs) was associated with lower lumbar spine BMD z-scores by -0.06 [95% confidence interval (CI): -0.12, -0.01], -0.06 (95% CI: -0.11, -0.003), -0.08 (95% CI: -0.14, -0.02), and -0.07 (95% CI: -0.13, -0.003), respectively, in adjusted models. Similarly, a 2.7-fold increase in blood BDCM, DBCM, and chlorinated THM concentrations was associated with lower TBLH BMD z-scores by -0.10 (95% CI: -0.17, -0.02), -0.10 (95% CI: -0.17, -0.03), and -0.11 (95% CI: -0.20, -0.01), respectively. Low-to-moderate predictive power was attained when tap water THM concentrations were used to predict blood THM measurements. Notably, the inverse associations for blood THMs persisted exclusively between water concentrations of DBCM and Br-THMs and the TBLH BMD z-scores. Our findings suggest that exposure to THMs may adversely affect the adolescent BMD.

Retinal microvascular and microstructural alterations in the diagnosis of meibomian gland dysfunction in severely obese population: a new approach.

AIM: To study retinal microvascular and microstructural alterations in meibomian gland dysfunction (MGD) in severely obese population using optical coherence tomography angiography (OCTA). METHODS: Twelve MGD patients with severely obese population (PAT group; 24 eyes) and 12 healthy controls (HC group; 24 eyes) were recruited. OCTA images were segmented into five [superior (S), nasal (N), inferior (I), temporal (T), and central foveal (C)] or nine [inner superior (IS), outer superior (OS), inner nasal (IN), outer nasal (ON), inner inferior (II), outer inferior (OI), inner temporal (IT), outer temporal (OT), and C] subregions. The superficial vessel density (SVD), retinal thickness (RT), foveal avascular zone (FAZ) parameters, and retinal volume were measured. RESULTS: Visual acuity was significantly different between two groups (0.8±0.17 in PAT group vs 0.2±0.06 in HC group). SVD was significantly lower in PATs in N, T, OS, IN, OT, and ON. The area under the receiver operating characteristic curve (AUC) for T was 0.961 [95% confidence interval (CI): 0.908 to 1.000], for OS was 0.962 (95%CI: 0.915 to 1.000). RT was significantly lower in PATs in IS, OS, OI, OT, ON, IT, IN, and II. AUC for OT was 0.935 (95%CI: 0.870 to 0.999), for IS was 0.915 (95% CI: 0.838 to 0.992). Angiography results showed significantly lower area and perimeter of FAZ, SVD of the inner retina and both retinal volume and the average volume thickness in the PAT group. CONCLUSION: Vision may be affected in patients with MGD due to changes in retinal microvessels and microstructures. These changes detected by OCTA may be a potential marker for diagnosing MGD in severe obesity.

Three New Species of Gongronella (Cunninghamellaceae, Mucorales) from Soil in Hainan, China Based on Morphology and Molecular Phylogeny.

The genus Gongronella is important in agriculture and industry by secreting various natural bioactive metabolites such as chitosanases and organic acids. During the most recent 8 years, a total of 14 new species have been described, remarkably enriching the diversity of this genus. In this study, we added three more new species to this valuable genus, based on a combination of morphological traits and phylogenetic information. Six strains of the genus Gongronella were isolated from soil collected in Hainan Province, China. Phylogenetic analyses of ITS and LSU rDNA sequences grouped these strains into three independent clades. According to their unique morphological characteristics, they were classified as G. multiramosa sp. nov., G. qichaensis sp. nov. and G. oleae sp. nov. The G. multiramosa was characterized by multiple branched sporangiophores and was closely related to G. pedratalhadensis. The G. qichaensis was characterized by obscure collars and closely related to G. butleri, G. hydei and G. banzhaoae. The G. oleae was characterized by the presence of oil droplets in the sporangiospores and was closely related to G. chlamydospora and G. multispora. Their descriptions and illustrations were provided, and their differences from morphological allies and phylogenetic-related species are discussed.

Blood Trihalomethane Concentrations and Osteoarthritis among U.S. Population Aged over 50 Years.

Exposure to trihalomethanes (THMs) has been associated with inflammation and oxidative stress, which are implicated in osteoarthritis. However, the association of THM exposure with osteoarthritis is unknown. Therefore, we pooled seven independent National Health and Nutrition Examination Survey cycles (1999-2012) among participants aged over 50 years who had quantified blood concentrations of chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM). Among 4,077 adults aged over 50 years, 781 (21.3%) reported osteoarthritis. Logistic regression models showed increased odds of osteoarthritis across the categories of blood BDCM, DBCM, and brominated THM (Br-THM, which was the sum of BDCM, DBCM, and TBM) concentrations [odds ratios = 1.46 (95% CI 1.09-1.94), 1.53 (95% CI 1.15-2.04), and 1.35 (95% CI 0.97-1.88), respectively], comparing highest versus lowest exposure categories (quartiles or tertiles). Additionally, we found positive dose-response relationships between blood BDCM, DBCM, and Br-THM concentrations and serum markers of oxidative stress (i.e., gamma-glutamyltransferase). In summary, blood Br-THM concentrations were associated with elevated serum levels of gamma-glutamyltransferase as well as an increased risk of osteoarthritis among U.S. adults aged over 50 years. However, more prospective population studies are needed to verify these findings and explore the underlying mechanisms.

Prediction model of ocular metastasis from primary liver cancer: Machine learning-based development and interpretation study.

BACKGROUND: Ocular metastasis (OM) is a rare metastatic site of primary liver cancer (PLC). The purpose of this study was to establish a clinical predictive model of OM in PLC patients based on machine learning (ML). METHODS: We retrospectively collected the clinical data of 1540 PLC patients and divided it into a training set and an internal test set in a 7:3 proportion. PLC patients were divided into OM and non-ocular metastasis (NOM) groups, and univariate logistic regression analysis was performed between the two groups. The variables with univariate logistic analysis p < 0.05 were selected for the ML model. We constructed six ML models, which were internally verified by 10-fold cross-validation. The prediction performance of each ML model was evaluated by receiver operating characteristic curves (ROCs). We also constructed a web calculator based on the optimal performance ML model to personalize the risk probability for OM. RESULTS: Six variables were selected for the ML model. The extreme gradient boost (XGB) ML model achieved the optimal differential diagnosis ability, with an area under the curve (AUC) = 0.993, accuracy = 0.992, sensitivity = 0.998, and specificity = 0.984. Based on these results, an online web calculator was constructed by using the XGB ML model to help clinicians diagnose and treat the risk probability of OM in PLC patients. Finally, the Shapley additive explanations (SHAP) library was used to obtain the six most important risk factors for OM in PLC patients: CA125, ALP, AFP, TG, CA199, and CEA. CONCLUSION: We used the XGB model to establish a risk prediction model of OM in PLC patients. The predictive model can help identify PLC patients with a high risk of OM, provide early and personalized diagnosis and treatment, reduce the poor prognosis of OM patients, and improve the quality of life of PLC patients.

Association of shift work with oxidative stress and alteration of fasting plasma glucose level in Chinese adults.

OBJECTIVE: This study aimed to assess the association of shift work with blood glucose and the mediating role of oxidative stress. METHODS: Fasting plasma glucose (FPG) and urinary concentrations of oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 4-hydroxy-2-nonenal-mercapturic acid, and 8-iso-prostaglandin F2α [8-isoPGF2α ]) were measured among 831 participants. RESULTS: Positive dose-response relationships among shift work duration,  FPG (ptrend < 0.001), and abnormal glucose regulation (AGR; ptrend = 0.035) were found. Compared with participants without shift work, three-shift work was associated with a higher level of FPG (percentage change: 6.49%, 95% CI: 4.21%-8.83%) and a higher prevalence of impaired fasting glucose (odds ratio: 1.886, 95% CI: 1.114-3.192) and AGR (odds ratio: 1.929, 95% CI: 1.197-3.111). A dose-response relationship was found between shift work duration and 8-OHdG (ptrend = 0.002) and 8-isoPGF2α (ptrend = 0.019). Urinary 8-OHdG and 8-isoPGF2α partially mediated the association between shift work duration and FPG levels and the prevalence of impaired fasting glucose and AGR, with mediating proportions ranging from 4.77% to 20.76%. CONCLUSIONS: These findings suggest that shift work is positively associated with blood glucose, and the association is partially mediated by oxidative stress.

Investigation of altered retinal microvasculature in female patients with rheumatoid arthritis: optical coherence tomography angiography detection.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder that primarily causes symmetrical polyarthritis and bone deformity. In RA patients, sight-threatening inflammatory eye complications would be expected. OBJECTIVE: The objective of the study is to ascertain the macular retinal vessel density changes in RA patients and controls using optical coherence tomography angiography (OCTA), and to investigate the association between disease and microvascular density alterations. METHODS: A total of 12 RA patients (24 eyes) and 12 age- and gender-matched control participants (24 eyes) were recruited to the study. We used the Early Treatment Diabetic Retinopathy Study partitioning, hemispheric quadrants and annular partitioning to segment each image into different subregions. The vascular density of superficial retina layer, deep retina layer and conjunctival capillary plexus was quantitatively measured by OCTA and compared with the control group. Correlation analysis was used to explore the relationship between STMI and conjunctival capillaries densities. RESULTS: In the superficial retinal layer, the vascular density of S, I, L, SL, SR, IL and C1-C5 were significantly decreased in the RA group compared with the control group (P<0.05). For the deep retinal layer, the vascular density of S, SL, SR, IL, C1, C2 and C4 also decreased in RA group. A significant positive correlation was indicated between conjunctival vascular and STMI densities (r = 0.713, P<0.05). CONCLUSION: OCTA results suggest that RA patients present with a reduced macular retinal vascular density. These subtle alterations of ocular microcirculation may precede severe eye involvements and may be a potential biomarker for early distinguishing abnormal eyes from healthy eyes.

Amplitude of Low-Frequency Fluctuation to Determine Disturbed Spontaneous Brain-Activity Pattern in Patients with Diabetic Optic Neuropathy.

Purpose: This study aimed to explore the spontaneous brain activity in patients with diabetic optic neuropathy (DON) by using the amplitude of low-frequency fluctuation (ALFF) technique. Methods: Sixteen DON patients and 16 age- and sex-matched healthy controls (HCs) were recruited. ALFF along with functional MRI method was used to detect the intrinsic brain activity alterations. The mean values of ALFF in DON patients and HCs were analyzed by receiver operating characteristic (ROC) curves. Pearson's correlation analysis was used to determine the correlation between Hospital Anxiety and Depression Scale (HADS) and ALFF values of DONs. Results: The DON group showed significantly increased ALFF values in the fusiform gyrus, and decreased ALFF values in the medial frontal gyrus/left frontal superior orbit/right frontal medial orbit, and left frontal inferior triangle. ROC curve analysis indicated that the accuracy of AUC was good. The anxiety scale and depression scale of the DON group were negatively correlated with the ALFF values of the medial frontal gyrus. Conclusion: DON is a neurodegenerative disease involving multiple brain regions. The abnormal activity of neurons in these brain regions helps to reveal the underlying neural mechanisms of brain activity related to DON.

Association of Gestational Diabetes With Subsequent Long-Term Risk of Mortality.

Importance: Gestational diabetes has been associated with numerous chronic diseases. However, few studies have examined the association of gestational diabetes with long-term mortality risk. Objective: To investigate the associations between gestational diabetes and long-term risks of total and cause-specific mortality. Design, Setting, and Participants: This cohort study analyzed participants of the Nurses' Health Study II who were followed for 30 years (1989-2019). Participants included US female nurses aged 25 to 42 years who reported at least 1 pregnancy (≥6 months) at 18 years or older across their reproductive life span. Data were analyzed from May 1, 2022, to May 25, 2023. Exposure: Gestational diabetes across the reproductive life span. Main Outcomes and Measures: Hazard ratios (HRs with 95% CIs) for total and cause-specific mortality were estimated by Cox proportional hazards regression models. Results: A total of 91 426 parous participants were included, with a mean (SD) age of 34.9 (4.7) years and a body mass index of 24.1 (4.7) at baseline. During a follow-up period of 2 609 753 person-years, 3937 deaths were documented, including 255 deaths from cardiovascular disease and 1397 from cancer. Participants with a history of gestational diabetes had a higher crude mortality rate than those without a history of gestational diabetes (1.74 vs 1.49 per 1000 person-years; absolute difference = 0.25 per 1000 person-years). The corresponding HR for total mortality was 1.28 (95% CI, 1.13-1.44), which did not materially change after additional adjustment for potential confounders and lifestyle factors during the reproductive life span (HR, 1.25; 95% CI, 1.11-1.41). The association persisted regardless of the subsequent development of type 2 diabetes and was more robust among participants who adopted less healthy lifestyles; experienced gestational diabetes in 2 or more pregnancies (HR, 1.48; 95% CI, 0.99-2.19); had gestational diabetes both in the initial and subsequent pregnancies (HR, 1.71; 95% CI, 1.11-2.63); and concurrently reported hypertensive disorders in pregnancy (HR, 1.80; 95% CI, 1.21-2.67), preterm birth (HR, 2.46; 95% CI, 1.66-3.64), or low birth weight (HR, 2.11; 95% CI, 1.21-3.68). Cause-specific mortality analyses revealed that gestational diabetes was directly associated with the risk of mortality due to cardiovascular disease (HR, 1.59; 95% CI, 1.03-2.47). Additionally, gestational diabetes was inversely associated with cancer mortality (HR, 0.76; 95% CI, 0.59-0.98); however, it was only evident among participants who later developed type 2 diabetes. Conclusions and Relevance: Results of this cohort study suggest that participants who reported a history of gestational diabetes exhibited a small but elevated risk of subsequent mortality over 30 years. The findings emphasize the importance of considering gestational diabetes as a critical factor in later-life mortality risk.

Ozone exposure associates with sperm quality indicators: Sperm telomere length as a potential mediating factor.

Evidence linking O3 exposure and human semen quality is limited and conflicting and the mechanism underlying the association remains unclear. Therefore, we investigated the associations between ambient O3 exposure and sperm quality parameters and explored the mediating role of sperm mitochondrial DNA copy number (mtDNAcn) and sperm telomere length (STL) among 1068 potential sperm donors who provided 5002 repeated semen samples over approximately 90 days. We found that every 10 µg/m3 increase in O3 exposure was associated with a decrease in STL, sperm concentration, total count, total motile sperm number, and semen volume. However, O3 exposure was associated with increased total motility and progressive motility. The association for sperm quality parameters was stronger when exposure was measured at spermatogenesis stages I and II. For STL, the strongest association was observed when exposure was measured at spermatogenesis stage II. Additionally, we found that approximately 9% and 8% of the association between O3 exposure and sperm concentration and count was mediated by STL, respectively. In summary, our findings suggest that O3 pollution may affect sperm telomere length, eventually leading to reduced semen quality.

Hypertensive disorders of pregnancy and risk of asthma and chronic obstructive pulmonary disease: a prospective cohort study.

Background: Hypertensive disorders of pregnancy (HDPs) have been associated with respiratory dysfunction during pregnancy and postpartum. In this study, we explored the associations between HDPs (gestational hypertension and preeclampsia) and the risk of incident asthma and chronic obstructive pulmonary disease (COPD) during adulthood and the potential mediating role of chronic hypertension. Methods: We included parous nurses in the Nurses' Health Study II reporting a pregnancy lasting no less than 6 months. The associations between HDPs and asthma and COPD were estimated using Cox proportional hazards models with adjustment for confounders. Findings: We included 73,807 nurses [92.5% (68,246 of 73,807) White] in asthma analyses and 79,843 [92.4% (73,746 of 79,843) White] in COPD analyses, whose mean (SD, range) age, at baseline, were both 34.8 (4.7, 25.0-44.0) years. During 24 years of follow-up, we identified 2663 incident cases of asthma and 537 COPD. Compared with nurses without HDPs, nurses reporting HDPs had an increased HR for incident asthma and COPD of 1.22 (95% CI 1.10-1.36) and 1.39 (95% CI 1.11-1.74), respectively. The risk of asthma was similar when gestational hypertension and preeclampsia were assessed separately [HR = 1.25 (95% CI 1.08-1.43) and 1.24 (95% CI 1.11-1.38), respectively]. However, only nurses with preeclampsia had a higher risk of COPD (HR = 1.41, 95% CI 1.11-1.78). Mediation analyses estimated that chronic hypertension explained 18.6% (95% CI 8.9-35.0%) and 10.7% (95% CI 2.9-32.4%) of the associations between HDPs and asthma and COPD, respectively. Interpretation: HDPs may serve as useful markers of increased susceptibility to chronic respiratory diseases during adulthood. Funding: The National Institutes of Health grants.