Evaluation of the therapeutic efficacy of different doses of LT4 in pregnant women with high-normal TSH levels and TPOAb positivity in the first half of pregnancy.

BACKGROUND: The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. METHODS: Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25 µg levothyroxine intervention group (G25, 69 women), and 50 µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. RESULTS: After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P < 0.05). The rates of abdominal distension and SIBO in the G25 and G50 groups were notably lower in contrast to the G0 group (P = 0.043 and 0.040, respectively). The G50 group had a lower rate of spontaneous abortion and premature membrane rupture than the G0 group (P = 0.01 and 0.015, respectively). Before 11+ 2 weeks of gestation and at thyroid peroxidase antibodies levels ≥ 117 IU/mL, in contrast to the G0 group, the G50 group experienced a decreased rate of spontaneous abortion (P = 0.008). The G50 group had significantly higher newborn weight than the G0 group (P = 0.014), as well as a notably longer newborn length than the G0 and G25 groups (P = 0.005). CONCLUSIONS: For pregnant women with high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positive during the first half of pregnancy, supplementation with 50 µg levothyroxine was more effective in improving their blood lipid status and gastrointestinal symptoms, reducing the incidence of SIBO and premature rupture of membranes, and before 11+2 weeks, TPOAb ≥ 117 IU/mL proved more beneficial in mitigating the risk of spontaneous abortion.

Exploring hospital resilience protective or risk factors: lessons for future disaster response efforts.

Background: Hospital resilience is essential in responding to disasters, but current research focuses mainly on frameworks and models rather than the protection of resilience and analysis of risk factors during public health emergencies. This study aims to examine the development of resilience in Chinese frontline hospitals during the initial COVID-19 outbreak in 2020, providing insights for future disaster response efforts. Objectives: We conducted interviews with 26 hospital staff members who were involved in the initial response to the COVID-19 outbreak in China. We used a semi-structured interview approach and employed purposive sampling and snowball sampling techniques. The interview outline was guided by the 'Action Framework' proposed by the World Health Organization (WHO) for responding to infectious disease emergencies. This framework includes dimensions such as command, surveillance, risk communication, medical response, and public health response. We analyzed the collected data using Colaizzi's seven-step data analysis method and the template analysis method. Results: WHO's 'action framework' effectively highlights the factors that contribute to hospital resilience. While medical response, including the availability of materials and facilities, the use of information technology, and the capacity for infectious disease diagnosis and treatment, remains crucial, other important aspects include awareness and beliefs about infections, treatment experience, interdisciplinary collaboration, and more. Additionally, it is essential to establish an intelligent command system, foster trusting partnerships between teams, improve monitoring capabilities for infectious disease agents, enhance risk communication through information synchronization and transparency, strengthen infection control planning, and improve environmental disinfection capabilities for effective public health emergency response. These contradictions significantly impact the enhancement of hospital resilience in dealing with major infectious disease outbreaks. Conclusion: In responding to sudden major infectious diseases, hospitals play a vital role within the healthcare system. Enhancing hospital resilience involves more than just improving treatment capabilities. It also requires effective command coordination at the hospital level, infection control planning, and the deployment of intelligent equipment. Additionally, planning for effective communication and coordination between hospitals, communities, and the national healthcare system can further enhance hospital resilience.

Urinary Proteomics and Outcomes in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Although several studies have addressed plasma proteomics in heart failure with preserved ejection fraction, limited data are available on the prognostic value of urinary proteomics. The objective of our study was to identify urinary proteins/peptides associated with death and heart failure admission in patients with heart failure with preserved ejection fraction. METHODS AND RESULTS: The study population included participants enrolled in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). The relationship between urine protein levels and the risk of death or heart failure admission was assessed using Cox regression, in both nonadjusted analyses and adjusting for urine creatinine levels, and the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) score. A total of 426 (12.4%) TOPCAT participants had urinary protein data and were included. There were 40 urinary proteins/peptides significantly associated with death or heart failure admission in nonadjusted analyses, 21 of which were also significant adjusted analyses. Top proteins in the adjusted analysis included ANGPTL2 (angiopoietin-like protein 2) (hazard ratio [HR], 0.5731 [95% CI, 0.47-0.7]; P=3.13E-05), AMY2A (α amylase 2A) (HR, 0.5496 [95% CI, 0.44-0.69]; P=0.0001), and DNASE1 (deoxyribonuclease-1) (HR, 0.5704 [95% CI, 0.46-0.71]; P=0.0002). Higher urinary levels of proteins involved in fibrosis (collagen VI α-1, collagen XV α-1), metabolism (pancreatic α-amylase 2A/B, mannosidase α class 1A member 1), and inflammation (heat shock protein family D member 1, inducible T cell costimulatory ligand) were associated with a lower risk of death or heart failure admission. CONCLUSIONS: Our study identifies several novel associations between urinary proteins/peptides and outcomes in heart failure with preserved ejection fraction. Many of these associations are independent of clinical risk scores and may aid in risk stratification in this patient population.

Fluorescent solid-state strips based on SiO2 shell-stabilized perovskite nanocrystals applying for magnetic aptasensing detection of aflatoxin B1 toxin in food.

In this work, the perovskite fluorescent nanocrystals (CsPbBr3) were successfully synthesized and wrapped with SiO2 shell, utilized for the assembly of solid-state detection strip capable of conveniently and specifically detection of aflatoxin B1 (AFB1). The SiO2 coating aimed to enhance the stability of CsPbBr3 nanocrystals. The resulting CsPbBr3@SiO2 material exhibited remarkable fluorescence properties, and further self-assembled onto solid-state plate, generating AFB1-specific quenched fluorescence at a specific wavelength of 515 nm. When combined with the capture of AFB1 by magnetic nanoparticles conjugated with aptamers (MNPs-Apt), it was achieved the good separation and specific detection of AFB1 toxin in food matrices. The constructed fluorescent solid-state detection strip based on CsPbBr3@SiO2 exhibited good response to AFB1 toxin within a linear range of 0.1-100 ng mL-1 and an impressive detection limit as low as 0.053 ng mL-1. This presents a new strategy for the rapid screening and convenient detection of highly toxic AFB1.

Preparation of Hydrophilic Hyper-Cross-Linked Polystyrene Nanospheres with Antibacterial for Improved Water Lubrication Performance.

The present study utilizes styrene as a raw material to prepare hyper-cross-linked polystyrene nanospheres (HPSs) through the Friedel-Crafts reaction, establishing stable covalent bond structures within the polymer chains. The hydrophilic polystyrene nanospheres─TMA@SHPSs were successfully synthesized via sulfonation and ion exchange reactions, demonstrating exceptional properties in reducing friction and wear. Compared with pure water, the addition of 4.0 wt % TMA@SHPSs results in a 62.2% reduction in the friction coefficient, accompanied by a significant decrease to 1.17 × 105 µm3 in wear volume. The results demonstrate that TMA@SHPSs, as water-based lubrication additives, generate composite protective films (tribo-chemical protective films and physical protective films) during the friction process, which effectively prevents direct contact between the friction pairs and achieves remarkable antifriction and antiwear effects. The results of the antimicrobial activity test indicate that TMA@SHPSs demonstrate exceptional antibacterial efficacy due to the bacteriostatic effect induced by hydration and the bactericidal properties of quaternary ammonium cations.

Comparative Transcriptomics Analysis Reveals the Differences in Transcription between Resistant and Susceptible Pepper (Capsicum annuum L.) Varieties in Response to Anthracnose.

Pepper (Capsicum annuum L.) is a herbaceous plant species in the family Solanaceae. Capsicum anthracnose is caused by the genus Colletotrichum. spp., which decreases pepper production by about 50% each year due to anthracnose. In this study, we evaluated the resistance of red ripe fruits from 17 pepper varieties against anthracnose fungus Colletotrichum capsici. We assessed the size of the lesion diameter and conducted significance analysis to identify the resistant variety of B158 and susceptible variety of B161. We selected a resistant cultivar B158 and a susceptible cultivar B161 of pepper and used a transcription to investigate the molecular mechanisms underlying the plant's resistance to C. capsici, of which little is known. The inoculated fruit from these two varieties were used for the comparative transcription analysis, which revealed the anthracnose-induced differential transcription in the resistant and susceptible pepper samples. In the environment of an anthrax infection, we found that there were more differentially expressed genes in resistant varieties compared to susceptible varieties. Moreover, the response to stimulus and stress ability was stronger in the KANG. The transcription analysis revealed the activation of plant hormone signaling pathways, phenylpropanoid synthesis, and metabolic processes in the defense response of peppers against anthracnose. In addition, ARR-B, AP2-EREBP, bHLH, WRKY, and NAC are associated with disease resistance to anthracnose. Notably, WRKY and NAC were found to have a potentially positive regulatory role in the defense response against anthracnose. These findings contribute to a more comprehensive understanding of the resistance mechanisms of red pepper fruit to anthracnose infection, providing valuable molecular insights for further research on the resistance mechanisms and genetic regulations during this developmental stage of pepper.

Correlation between serum tryptophan metabolism and treatment efficacy of dapoxetine in patients with premature ejaculation: A pilot study.

INTRODUCTION: Primary premature ejaculation (PPE) is a common male neurobiological disorder. Currently, there is consensus that the impairment in central serotonin (5-HT) neurotransmission constitutes a key pathogenic factor in PPE. Selective serotonin reuptake inhibitors (SSRIs) serve as the primary pharmacological intervention; however, a comprehensive elucidation of their mechanism of action remains incomplete. Owing to significant individual variability in efficacy, SSRIs exhibit a high discontinuation rate. Hence, there is an urgent need to address the selection of SSRIs for PPE treatment. OBJECTIVE: This study aims to investigate the characteristics of tryptophan (TRP) metabolism in patients with PPE and to assess its influence on the efficacy of SSRIs. METHODS: The exploratory study included a total of 16 patients with PPE and 16 control subjects who were healthy men without any sexual dysfunction. Upon enrollment in the study, all participants underwent a thorough medical history review and physical examination. Subsequently, their serum levels of TRP, its metabolites, large neutral amino acids (LNAAs), and metabolite ratios were assessed using a liquid chromatography-mass spectrometry (LC-MS) assay. After a period of 4 weeks of dapoxetine treatment, all patients with PPE underwent reassessment using the Premature Ejaculation Diagnostic Tool (PEDT) score and intravaginal ejaculatory latency time (IELT) test. RESULTS: The ratio of serum TRP to other LNAAs (TRP/LNAAs) in patients with PPE was found to be significantly lower compared to the control group (P < 0.05). Conversely, the ratio of kynurenine to TRP (KYN/TRP) was observed to be significantly higher in the PPE patients compared to the control group (P < 0.05). Including the serum TRP/LNAAs ratio and KYN/TRP ratio in the prediction model yielded the highest prediction efficiency for PPE. There was a significant negative correlation between the ratio of TRP/LNAAs before the treatment and the IELT after 4 weeks of the treatment. Additionally, there was a significant positive correlation observed between the ratio of TRP/LNAAs before the treatment and the PEDT score after 4 weeks of the treatment. CONCLUSIONS: This study demonstrates that the reduction in the TRP/LNAAs ratio and the elevation of the KYN/TRP ratio are significant characteristics associated with PPE. These findings suggest that diminished tryptophan availability in the brain and the activation of the kynurenine (KYN) pathway may play a role in the pathogenesis of PPE. The TRP/LNAAs ratio has potential as a reliable indicator of central serotonin (5-HT) levels. Considering the TRP/LNAAs ratio when selecting SSRIs for the treatment of PPE may enhance the response rate of this medication.

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.

The multimodality cell segmentation challenge: toward universal solutions.

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyper-parameters in different experimental settings. Here, we present a multimodality cell segmentation benchmark, comprising more than 1,500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.

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.

Nanodrug-bacteria conjugates-mediated oncogenic collagen depletion enhances immune checkpoint blockade therapy against pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) cancer cells specifically produce abnormal oncogenic collagen to bind with integrin α3ß1 receptor and activate the downstream focal adhesion kinase (FAK), protein kinase B (AKT), and mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, this promotes immunosuppression and tumor proliferation and restricts the response rate of clinical cancer immunotherapies. METHODS: Here, by leveraging the hypoxia tropism and excellent motility of the probiotic Escherichia coli strain Nissle 1917 (ECN), we developed nanodrug-bacteria conjugates to penetrate the extracellular matrix (ECM) and shuttle the surface-conjugated protein cages composed of collagenases and anti-programmed death-ligand 1 (PD-L1) antibodies to PDAC tumor parenchyma. FINDINGS: We found the oncogenic collagen expression in human pancreatic cancer patients and demonstrated its interaction with integrin α3ß1. We proved that reactive oxygen species (ROS) in the microenvironment of PDAC triggered collagenase release to degrade oncogenic collagen and block integrin α3ß1-FAK signaling pathway, thus overcoming the immunosuppression and synergizing with anti-PD-L1 immunotherapy. CONCLUSIONS: Collectively, our study highlights the significance of oncogenic collagen in PDAC immunotherapy, and consequently, we developed a therapeutic strategy that can deplete oncogenic collagen to synergize with immune checkpoint blockade for enhanced PDAC treatment efficacy. FUNDING: This work was supported by the University of Wisconsin Carbone Cancer Center Research Collaborative and Pancreas Cancer Research Task Force, UWCCC Transdisciplinary Cancer Immunology-Immunotherapy Pilot Project, and the start-up package from the University of Wisconsin-Madison (to Q.H.).

DANCE: a deep learning library and benchmark platform for single-cell analysis.

DANCE is the first standard, generic, and extensible benchmark platform for accessing and evaluating computational methods across the spectrum of benchmark datasets for numerous single-cell analysis tasks. Currently, DANCE supports 3 modules and 8 popular tasks with 32 state-of-art methods on 21 benchmark datasets. People can easily reproduce the results of supported algorithms across major benchmark datasets via minimal efforts, such as using only one command line. In addition, DANCE provides an ecosystem of deep learning architectures and tools for researchers to facilitate their own model development. DANCE is an open-source Python package that welcomes all kinds of contributions.

Hydrogels Containing Chitosan-Modified Gold Nanoparticles Show Significant Efficacy in Healing Diabetic Wounds Infected with Antibiotic-Resistant Bacteria.

Purpose: Persistent Infections and inflammation are associated with impaired wound healing in diabetic patients. There is a pressing demand for innovative antimicrobial strategies to address infections arising from antibiotic-resistant bacteria. Polymer-modified gold nanoparticles (AuNPs) show broad-spectrum antibacterial properties and significant biocompatibility. This study investigated the antibacterial and wound healing efficacy of hydrogel dressings conjugated with chitosan-AuNPs in diabetic model rats. Methods: Chitosan (CS)-functionalized gold nanoparticles (CS-AuNPs) were incorporated into hydrogel dressings (Gel/CS-AuNPs), which were formulated through the chemical cross-linking of gelatin with sodium alginate (SA). The basic characteristics of Gel/CS-AuNPs were analyzed by TEM, SEM, XRD, and UV-visible spectra. Rheological, swelling, degradation, and adhesive properties of Gel/CS-AuNPs were also determined. In vitro anti-bactericidal effects of the Gel/CS-AuNPs were analyzed with E. coli, S. aureus, and MRSA. In vitro biocompatibility of the Gel/CS-AuNPs was evaluated using NIH3T3 cells. The in vivo antibacterial and wound healing efficacy of the Gel/CS-AuNPs was analyzed in the diabetic wound model rats. Histological and immunofluorescence staining were performed to determine the status of angiogenesis, epithelization, inflammation response, and collagen deposition. Results: Gel/CS-AuNPs demonstrated significant high biodegradability, water absorption bactericidal, and biocompatibility, and slight adhesiveness. Gel/CS-AuNPs exhibited pronounced antibacterial efficacy against gram-negative, gram-positive, and MRSA in a CS-AuNPs-dose-dependent manner. In the diabetic wound model rats, Gel/CS-AuNPs effectively killed MRSA, reduced inflammation, and promoted angiogenesis and collagen deposition and remodeling at the wound site. As a result, Gel/CS-AuNPs expedited the recovery process for infected diabetic wounds. Among the hydrogels with different CS-AuNPs concentrations, Gel/CS-Au25 with 25% CS-AuNPs showed the best bactericidal and wound healing performance. Conclusion: Gel/CS-AuNPs significantly improve the healing of MRSA-infected diabetic wounds in the rat model. Therefore, Gel/CS-AuNPs show great promise for the treatment of diabetic infection wound healing.

Skin-derived precursor conditioned medium alleviated photoaging via early activation of TGF-ß/Smad signaling pathway by thrombospondin1: In vitro and in vivo studies.

Photoaging is one major exogenous factor of skin aging. Efficacy and safety of current anti-photoaging therapies remained to be improved. Our previous studies indicated that skin-derived precursors (SKPs) alleviated photodamage by early activation of TGF-ß/Smad signaling pathway via thrombospondin1 (TSP1). However, the research concerning SKP conditioned medium (SKP-CM) has never been reported. In the current study, we aimed to explore the anti-photoaging effects of SKP-CM both in vitro and in vivo, and to elucidate the possible mechanisms. Mouse SKP-CM (mSKP-CM) collection was optimized by a comparative method. The concentration of protein and growth factors in mSKP-CM was detected using BCA protein assay kit and growth factor protein chip. The anti-photoaging effects of mSKP-CM and its regulation of key factors in the TGF-ß/Smad signaling pathway were explored using UVA + UVB photoaged mouse fibroblasts (mFBs) and nude mice dorsal skin. The research revealed that mSKP-CM contained significantly higher-concentration of protein and growth factors than mouse mesenchymal stem cell conditioned medium (mDMSC-CM). mSKP-CM alleviated mFBs photoaging by restoring cell viability and relieving senescence and death. ELISA, qRT-PCR, and western blot results implied the potential mechanisms were associated with the early activation of TGF-ß/Smad signaling pathway by TSP1. In vivo experiments demonstrated that compared with the topical intradermal mDMSC-CM injection and retinoic acid cream application, the photodamaged mice dorsal skin intradermally injected with mSKP-CM showed significantly better improvement. Consistent with the in vitro results, both western blot and immunohistochemistry results confirmed that protein expression of TSP1, smad2/3, p-smad2/3, TGF-ß1, and collagen I increased, and matrix metalloproteinases decreased. In summary, both in vitro and in vivo experiments demonstrated that mSKP-CM alleviated photoaging through an early activation of TGF-ß/Smad signaling pathway via TSP1. SKP-CM may serve as a novel and promising cell-free therapeutical approach for anti-photoaging treatment and regenerative medicine.

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.

Molecular-Level Interfacial Chemistry Regulation of MXene Enables Energy Storage beyond Theoretical Limit.

Ti3C2Tx MXene often suffers from poor lithium storage behaviors due to its electrochemically unfavorable OH terminations. Herein, we propose molecular-level interfacial chemistry regulation of Ti3C2Tx MXene with phytic acid (PA) to directly activate its OH terminations. Through constructing hydrogen bonds (H-bonds) between oxygen atoms of PA and OH terminations on Ti3C2Tx surface, interfacial charge distribution of Ti3C2Tx has been effectively regulated, thereby enabling sufficient ion-storage sites and expediting ion transport kinetics for high-performance energy storage. The results show that Li ions preferably bind to H-bond acceptors (oxygen atoms from PA), and the flexibility of H-bonds therefore renders their interactions with adsorbed Li ions chemically "tunable", thus alleviating undesirable localized geometric changes of the OH terminations. Meanwhile the H-bond-induced microscopic dipoles can act as directional Li-ion pumps to expedite ion diffusion kinetics with lower energy barrier. As a result, the as-designed Ti3C2Tx/PA achieves a 2.4-fold capacity enhancement compared with pristine Ti3C2Tx (even beyond theoretical capacity), superior long-term cyclability (220.0 mAh g-1 after 2000 cycles at 2.0 A g-1), and broad temperature adaptability (-20 to 50 °C). This work offers a promising interface engineering strategy to regulate microenvironments of inherent terminations for breaking through the energy storage performance of MXenes.

Modulation of the emission spectrum of rare-earth ions using inverse-designed photonic crystals cavities.

Rare-earth elements play an indispensable role in the optical communication and laser industries, due to their superior luminescent properties. Nevertheless, the selective enhancement and suppression of different emission bands during energy level transitions for multi-band emitting rare-earth ions presents a significant research challenge, which we aim to address. This study explores the potential of leveraging an inverse-designed dual-cavity photonic crystals structure to manipulate the emission spectrum, thereby facilitating the augmentation or suppression of distinct emission bands. We utilized a convolutional neural network model to establish the relationship between geometric parameters and the local density of states, forecasting the optimal cavity geometry parameters for achieving the desired modulation outcomes. This paper delineates the neural network's generalization capabilities, along with the modulation efficacy of the dual-cavity configuration, both confirmed through numerical validation. Our findings highlight the modulatory capacity of Dy3+ ions, which exhibit three emission spectrum in the visible range, to achieve pure color light emission within the devised cavity structure. Notably, our approach yielded enhancements of up to 2.79-fold and 2.81-fold in pure yellow and red light emissions respectively, compared to free space emissions. The single-sided emission enhancement reaches 16.28-fold for yellow light and 30.79-fold for red light. This emphasizes the transformative potential of this methodology in crafting rare-earth-based luminescent materials with meticulously engineered emission attributes.

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.