A single-atom manganese nanozyme mediated membrane reactor for water decontamination.

Single-atom nanozymes possess high catalytic activity and selectivity, and are emerging as advanced heterogeneous catalysts for environmental applications. Herein, we present the innovative synthesis and characterization of a single-atom manganese-doped carbon nitride (SA-Mn-CN) nanozyme, integrated into a polyvinylidene fluoride (PVDF) membrane for advanced water treatment applications. The SA-Mn-CN nanozyme demonstrates high peroxidase-like activity, efficiently catalyzing the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) and generating reactive oxygen species (ROS) for effective antibacterial action. Notably, the SA-Mn-CN/PVDF membrane showcases enhanced water permeability, superior antifouling properties, and ultra-fast degradation kinetics of organic pollutants. Mechanistic studies reveal that the nanozyme selectively generates Mn(IV)-oxo species via peroxymonosulfate (PMS) activation, crucial for the efficient oxidation processes. Our integrated membrane system effectively removes (within 1 min, > 92 % removal) a variety of organic micropollutants in continuous-flow operations, demonstrating excellent stability and minimal manganese leaching. Compared to conventional advanced oxidation process (AOPs)/membrane system, the SA-Mn-CN/PVDF/PMS system holds the advantages of high catalytic activity and selectivity for generation of reactive species, wide working pH range (pH3-11) and excellent stability and reusability under the backwashing conditions. The developed device-scale AOPs/membrane system was proven to be effective in bacterial inactivation and pollutants degradation, verifying the vast application potential of the SA-Mn-CN/PVDF membrane for practical water decontamination. This work pioneers the development of enzyme-mimicking nanozyme membranes, offering a sustainable and high-performance solution for wastewater treatment, and sets a new benchmark for the design of nanozyme-based catalytic membranes in environmental applications.

Photothermal nano-confinement reactor with bimetallic sites for enhanced peroxymonosulfate activation in antibiotic degradation.

In recent years, photothermal-assisted Fenton-like degradation of organic pollutants has become a prominent green method in environmental pollution control. Nevertheless, the design of suitable catalysts remains a significant challenge for this approach. Herein, zeolite-imidazolate framework-derived CoMn bimetallic nanoparticles embedded in hollow carbon nanofibers (CoMnHCF) have been developed as a photothermal nano-confinement reactor with multiple active sites to enhance reaction performance and promote peroxymonosulfate (PMS) activation. Under light irradiation, the local temperature within the porous spaces of CoMnHCF was significantly higher than the liquid temperature. The confined space concentrated heat, minimized thermal loss, and effectively utilizes this feature to activate PMS for antibiotic degradation. The results demonstrated that this system efficiently degraded various antibiotics, including tetracycline hydrochloride, levofloxacin, sulfamethoxazole, norfloxacin and chlorotetracycline. Photothermal contribution analysis revealed that thermal effects predominate in this system. Further DFT simulations explored the coordination environment of metal elements and the properties of related pollutants, predicting potential structures and reaction sites. A series of water quality experiments and cyclic tests demonstrated the system's significant application potential. This study offered new insights into advancing the integrated use of photothermal conversion and nano-confinement reactor activation of PMS in sewage purification.

In vitro cytotoxicity assessment of carbonaceous gels for bone marrow mesenchymal stem cells.

The current work aimed to elucidate the potential applications of the carbonaceous gels and assess the in vitro cytotoxicity of these gels when suspended in a culture medium and exposed to bone marrow mesenchymal stem cells. Cellular viability, cell cycle distribution, apoptotic cell death, and mitochondrial membrane potential in bone marrow mesenchymal stem cells co-incubated with different concentrations of carbonaceous gels (0.1, 1, 10, 50, and 100 µg/mL) were evaluated. Flow cytometry and immunofluorescence were used to investigate apoptosis and cell cycle distribution. The expression of associated apoptotic proteins was analysed using Western Blot. Although the co-incubation of carbonaceous gels did not significantly affect cell viability, high dosages (100 µg/mL) of these gels led to cellular dysfunction. Specifically, cells exposed to high concentrations of these gels exhibited G2-phase arrest and increased levels of reactive oxygen species. However, the reported impacts did not cause considerable cell death. At the same time, carbonaceous gels did not significantly induce apoptosis. Compared to other carbon nanomaterials, carbonaceous gels' biotoxicity was relatively low, suggesting their potential for various biological applications. Nonetheless, caution should be exercised when considering the concentration of carbonaceous gels for future medical applications.

Soil application of graphitic carbon nitride nanosheets alleviate cadmium toxicity by altering subcellular distribution, chemical forms of cadmium and improving nitrogen availability in soybean (Glycine max L.).

Cadmium (Cd)-contamination impairs biological nitrogen fixation in legumes (BNF), threatening global food security. Innovative strategies to enhance BNF and improve plant resistance to Cd are therefore crucial. This study investigates the effects of graphitic carbon nitride nanosheets (g-C3N4 NSs) on soybean (Glycine max L.) in Cd contaminated soil, focusing on Cd distribution, chemical forms and nitrogen (N) fixation. Soybean plants were treated with 100 mg kg-1 g-C3N4 NSs, with or without 10 mg kg-1 Cd for 4 weeks. Soil addition of g-C3N4 NSs alleviated Cd toxicity and promote soybean growth via scavenging Cd-mediated oxidative stress and improving photosynthesis. Compared to Cd treatment, g-C3N4 NSs increased shoot and root dry weights under Cd toxicity by 49.5% and 63.4%, respectively. g-C3N4 NSs lowered Cd content by 35.7%-54.1%, redistributed Cd subcellularly by increasing its proportion in the cell wall and decreasing it in soluble fractions and organelles, and converted Cd from high-toxicity to low-toxicity forms. Additionally, g-C3N4 NSs improved the soil N cycle, stimulated nodulation, and increased the N-fixing capacity of nodules, thus increasing N content in shoots and roots by 12.4% and 43.2%, respectively. Mechanistic analysis revealed that g-C3N4 NSs mitigated Cd-induced loss of endogenous nitric oxide in nodules, restoring nodule development. This study highlights the potential of g-C3N4 NSs for remediating Cd-contaminated soil, reducing Cd accumulation, and enhancing plant growth and N fixation, offering new insights into the use of carbon nanomaterials for soil improvement and legume productivity under metal(loid)s stress.

Daytime napping and the incidence of Parkinson's disease: a prospective cohort study with Mendelian randomization.

BACKGROUND: The causal relationship between daytime napping and the risk of Parkinson's disease (PD) remains unclear, with prospective studies providing limited evidence. This study investigated the association between daytime napping frequency and duration and PD incidence and explored the causality relationship between this association by conducting Mendelian randomization (MR) analysis. METHODS: This prospective cohort study included 393,302 participants, and accelerometer-measured daytime napping data were available only for 78,141 individuals. Cox proportional hazards regression was used to estimate the association between the daytime napping frequency and duration and the PD risk. The role of the systemic immune-inflammation index (SII) in the association between daytime napping frequency and PD risk was assessed through mediation analyses. Moreover, the causal association between the daytime napping frequency and the PD risk was preliminarily explored by conducting two-sample MR analyses. RESULTS: The median follow-up duration was 12.18 years. The participants who reported napping sometimes or usually exhibited a significantly higher PD risk than those who never/rarely napped during the day [sometimes: hazard ratio (HR), 1.13; 95% confidence interval (CI), 1.03-1.23; usually: HR, 1.33; 95% CI, 1.14-1.55], and SII played a mediating role in this association. However, the MR analyses did not indicate that the daytime napping frequency and PD risk were significantly associated. The participants napping for over 1 h exhibited a significantly elevated PD risk (HR, 1.54; 95% CI, 1.11-2.16). Moreover, no significant interaction was identified between napping frequency or duration and genetic susceptibility to PD (P for interaction > 0.05). CONCLUSIONS: In this study, increased daytime napping frequency and duration were associated with an increased PD risk, but no causal relationship was observed between napping frequency and PD risk in the MR analysis. Larger GWAS-based cohort studies and MR studies are warranted to explore potential causal relationships.

Highly potent and broadly neutralizing anti-CD4 trimeric nanobodies inhibit HIV-1 infection by inducing CD4 conformational alteration.

Despite advancements in antiretroviral therapy (ART) suppressing HIV-1 replication, existing antiviral drugs pose limitations, including lifelong medication, frequent administration, side effects and viral resistance, necessitating novel HIV-1 treatment approaches. CD4, pivotal for HIV-1 entry, poses challenges for drug development due to neutralization and cytotoxicity concerns. Nevertheless, Ibalizumab, the sole approved CD4-specific antibody for HIV-1 treatment, reignites interest in exploring alternative anti-HIV targets, emphasizing CD4's potential value for effective drug development. Here, we explore anti-CD4 nanobodies, particularly Nb457 from a CD4-immunized alpaca. Nb457 displays high potency and broad-spectrum activity against HIV-1, surpassing Ibalizumab's efficacy. Strikingly, engineered trimeric Nb457 nanobodies achieve complete inhibition against live HIV-1, outperforming Ibalizumab and parental Nb457. Structural analysis unveils Nb457-induced CD4 conformational changes impeding viral entry. Notably, Nb457 demonstrates therapeutic efficacy in humanized female mouse models. Our findings highlight anti-CD4 nanobodies as promising HIV-1 therapeutics, with potential implications for advancing clinical treatment against this global health challenge.

Structure defining of ultrapotent neutralizing nanobodies against MERS-CoV with novel epitopes on receptor binding domain.

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory disease in humans. High fatality rates and continued infectiousness remain a pressing concern for global health preparedness. Antibodies targeted at the receptor-binding domain (RBD) are major countermeasures against human viral infection. Here, we report four potent nanobodies against MERS-CoV, which are isolated from alpaca, and especially the potency of Nb14 is highest in the pseudotyped virus assay. Structural studies show that Nb14 framework regions (FRs) are mainly involved in interactions targeting a novel epitope, which is entirely distinct from all previously reported antibodies, and disrupt the protein-carbohydrate interaction between residue W535 of RBD and hDPP4 N229-linked carbohydrate moiety (hDPP4-N229-glycan). Different from Nb14, Nb9 targets the cryptic face of RBD, which is distinctive from the hDPP4 binding site and the Nb14 epitope, and it induces the ß5-ß6 loop to inflect towards a shallow groove of the RBD and dampens the accommodation of a short helix of hDPP4. The particularly striking epitopes endow the two Nbs administrate synergistically in the pseudotyped MERS-CoV assays. These results not only character unprecedented epitopes for antibody recognition but also provide promising agents for prophylaxis and therapy of MERS-CoV infection.

Next-Generation Sequencing and Proteomics-Enabled Approach for Rapid and High-Throughput Isolation of Virus-Neutralizing Nanobodies.

Compared with traditional antibodies, nanobodies from camelids have various advantages, including small molecular weight, high affinity, low immunogenicity, convenient production through genetic engineering, etc. Here we combined next-generation sequencing (NGS) with proteomics technology based on affinity purification-mass spectrometry (AP-MS) and bioinformatics analysis to high-throughput screen monoclonal nanobodies from camels immunized with surface glycoprotein (glycoprotein N, Gn) of severe fever with thrombocytopenia syndrome virus and fulfilled production of the screened anti-Gn monoclonal nanobody with high affinity by genetic engineering. The innovative high-throughput technical route developed here could also be expanded to the production of neutralizing nanobodies specific for Rift Valley fever virus.

Optimizing the detection of emerging infections using mobility-based spatial sampling.

Timely and precise detection of emerging infections is imperative for effective outbreak management and disease control. Human mobility significantly influences the spatial transmission dynamics of infectious diseases. Spatial sampling, integrating the spatial structure of the target, holds promise as an approach for testing allocation in detecting infections, and leveraging information on individuals' movement and contact behavior can enhance targeting precision. This study introduces a spatial sampling framework informed by spatiotemporal analysis of human mobility data, aiming to optimize the allocation of testing resources for detecting emerging infections. Mobility patterns, derived from clustering point-of-interest and travel data, are integrated into four spatial sampling approaches at the community level. We evaluate the proposed mobility-based spatial sampling by analyzing both actual and simulated outbreaks, considering scenarios of transmissibility, intervention timing, and population density in cities. Results indicate that leveraging inter-community movement data and initial case locations, the proposed Case Flow Intensity (CFI) and Case Transmission Intensity (CTI)-informed spatial sampling enhances community-level testing efficiency by reducing the number of individuals screened while maintaining a high accuracy rate in infection identification. Furthermore, the prompt application of CFI and CTI within cities is crucial for effective detection, especially in highly contagious infections within densely populated areas. With the widespread use of human mobility data for infectious disease responses, the proposed theoretical framework extends spatiotemporal data analysis of mobility patterns into spatial sampling, providing a cost-effective solution to optimize testing resource deployment for containing emerging infectious diseases.

Effects of zeolite imidazole frameworks on rice seedlings (Oryza sativa L.): Phytotoxicity, transformation, and bioaccumulation.

Zeolite imidazole frameworks (ZIFs), a class of the metal organic framework, have been extensively studied in environmental applications. However, their environmental fate and potential ecological impact on plants remain unknown. Here, we investigated the phytotoxicity, transformation, and bioaccumulation processes of two typical ZIFs (ZIF-8 and ZIF-67) in rice (Oryza sativa L.) under hydroponic conditions. ZIF-8 and ZIF-67 in the concentration of 50 mg/L decreased root and shoot dry weight maximally by 55.2% and 27.5%, 53.5% and 37.5%, respectively. The scanning electron microscopy (SEM) imaging combined with X-ray diffraction (XRD) patterns revealed that ZIFs on the root surface gradually collapsed and transformed into nanosheets with increasing cultivation time. The fluorescein isothiocyanate (FITC) labeled ZIFs were applied to trace the uptake and translocation of ZIFs in rice. The results demonstrated that the transformed ZIFs were mainly distributed in the intercellular spaces of rice root, while they cannot be transported to culms and leaves. Even so, the Co and Zn contents of rice roots and shoots in the ZIFs treated groups were increased by 1145% and 1259%, 145% and 259%, respectively, compared with the control groups. These findings suggested that the phytotoxicity of ZIFs are primarily attributed to the transformed ZIFs and to a less extent, the metal ions and their ligands, and they were internalized by rice root and increased the Co and Zn contents of shoots. This study reported the transformation of ZIFs and their biological effectiveness in rice, highlighting the potential environmental hazards and risks of ZIFs to crop plants.

Deficiency of leucine-rich repeat kinase 2 aggravates thioacetamide-induced acute liver failure and hepatic encephalopathy in mice.

BACKGROUND: Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). METHODS: TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2G2019S) and LRRK2 knockout (Lrrk2-/-) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. RESULTS: The Lrrk2-/--HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p < 0.05), with no difference found between the WT-HE and Lrrk2G2019S-HE groups. Compared with the other groups, after the TAA injection, the Lrrk2-/- group displayed a significant increase in ammonium and pro-inflammatory cytokines, aggravated hepatic inflammation/necrosis, decreased autophagy, and abnormal phosphorylation of lysosomal Rab10. All three models reported microglial activation, neuronal loss, disordered vesicle transmission, and damaged myelin structure. The Lrrk2-/--HE mice presented no severer neuronal injury than the other genotypes. CONCLUSIONS: LRRK2 deficiency may exacerbate TAA-induced ALF and HE in mice, in which inflammatory response is evident in the brain and aggravated in the liver. These novel findings indicate a need of sufficient clinical awareness of the adverse effects of LRRK2 inhibitors on the liver.

Graphitic carbon nitride alleviates cadmium toxicity to soybeans through nitrogen supply.

Graphitic carbon nitride (g-C3N4) is a promising candidate for heavy metal remediation, primarily composed of carbon (C) and nitrogen (N). It has been demonstrated that g-C3N4 adjusts rhizosphere physicochemical conditions, especially N conditions, alleviating the absorption and accumulation of Cadmium (Cd) by soybeans. However, the mechanisms by which g-C3N4 induces N alterations to mitigates plant uptake of Cd remain unclear. This study investigated the impact of g-C3N4-mediated changes in N conditions on the accumulation of Cd by soybeans using pot experiments. It also explored the microbiological mechanisms underlying alterations in soybean rhizospheric N cycling induced by g-C3N4. It was found that g-C3N4 significantly increased N content in the soybean rhizosphere (p < 0.05), particularly in terms of available nitrogen (AN) of nitrate and ammonium. Plants absorbed more ammonium nitrogen (NH4⁺-N), the content of which in the roots showed a significant negative correlation with Cd concentration in plant (p < 0.05). Additionally, g-C3N4 significantly affected rhizospheric functional genes associated with N cycling (p < 0.05) by increasing the ratio of the N-fixation functional gene nifH and decreasing the ratios of functional genes amoA and nxrA involved in nitrification. This enhances soybean's N-fixing potential and suppresses denitrification potential in the rhizosphere, preserving NH4⁺-N. Niastella, Flavisolibacter, Opitutus and Pirellula may play a crucial role in the N fixation and preservation process. In summary, the utilization of g-C3N4 offers a novel approach to ensure safe crop production in Cd-contaminated soils. The results of this study provide valuable data and a theoretical foundation for the remediation of Cd polluted soils.

Early-life tobacco smoke exposure and stroke risk: a prospective study of 341,783 and 352,737 UK Biobank participants.

INTRODUCTION: Stroke is a life-threatening condition that causes a major medical burden globally. The currently used methods for the prevention or prediction of stroke have certain limitations. Exposure to tobacco in early life, including smoking during adolescence and maternal smoking during pregnancy, can affect adolescent development and lead to several negative outcomes. However, the association between early-life tobacco exposure and stroke is not known. METHODS: In this prospective cohort study, for the analyses involving exposure to maternal smoking during pregnancy and age of smoking initiation, we included 304,984 and 342,893 participants, respectively., respectively from the UK Biobank. Cox proportional hazard regression model and subgroup analyses were performed to investigate the association between early-life tobacco exposure and stroke. Mediation analyses were performed to identify the mediating role of biological aging in the association between early tobacco exposure and stroke. RESULTS: Compared with participants whose mothers did not smoke during pregnancy, participants whose mothers smoked during pregnancy showed an 11% increased risk of stroke (HR: 1.11, 95% CI: 1.05-1.18, P < 0.001). Compared with participants who never smoked, participants who smoked during adulthood, adolescence and childhood showed a 22%, 24%, and 38% increased risk of stroke during their adulthood, respectively. Mediation analysis indicated that early-life tobacco exposure can cause stroke by increasing biological aging. CONCLUSION: This study reveals that exposure to tobacco during early life is associated with an increased risk of experiencing a stroke, and increased biological aging can be the underlying mechanism.

P-tau217 correlates with neurodegeneration in Alzheimer's disease, and targeting p-tau217 with immunotherapy ameliorates murine tauopathy.

Neuronal loss is the central issue in Alzheimer's disease (AD), yet no treatment developed so far can halt AD-associated neurodegeneration. Here, we developed a monoclonal antibody (mAb2A7) against 217 site-phosphorylated human tau (p-tau217) and observed that p-tau217 levels positively correlated with brain atrophy and cognitive impairment in AD patients. Intranasal administration efficiently delivered mAb2A7 into male PS19 tauopathic mouse brain with target engagement and reduced tau pathology/aggregation with little effect on total soluble tau. Further, mAb2A7 treatment blocked apoptosis-associated neuronal loss and brain atrophy, reversed cognitive deficits, and improved motor function in male tauopathic mice. Proteomic analysis revealed that mAb2A7 treatment reversed alterations mainly in proteins associated with synaptic functions observed in murine tauopathy and AD brain. An antibody (13G4) targeting total tau also attenuated tau-associated pathology and neurodegeneration but impaired the motor function of male tauopathic mice. These results implicate p-tau217 as a potential therapeutic target for AD-associated neurodegeneration.

Accelerated biological aging as potential mediator mediates the relationship between pro-inflammatory diets and the risk of depression and anxiety: A prospective analysis from the UK biobank.

BACKGROUND: The relationship between inflammatory dietary patterns and the risk of depression/anxiety has not been clearly established due to differences in study populations, geographic regions, sex, and methods of calculating the inflammatory index. METHODS: We drew upon a prospective cohort in the UK Biobank and calculated the energy-adjusted dietary inflammatory index (E-DII). The follow-up time was defined from the date of completing the last dietary survey questionnaire to the date of diagnosis of depression, anxiety, phobic anxiety, other types of anxiety, death, loss to follow-up, or the respective censoring dates for England (September 30, 2021), Scotland (July 31, 2021), and Wales (February 28, 2018). The final follow-up times end on September 30, 2021, July 31, 2021, and February 28, 2018, for England, Scotland, and Wales, respectively. During the follow-up process, if a participant develops the condition, dies, or is lost to follow-up, the follow-up is terminated. We used Cox regression to evaluate the connection between E-DII and depression/anxiety. We employed restricted cubic spline curves for nonlinear relationships. We also conducted mediation analyses to explore whether biological age mediated the relationship between E-DII and depression. Additionally, we investigated whether genetic susceptibility modified the relationship between E-DII and depression through interaction modeling. RESULTS: In the final analysis, we included a total of 151,295, 159,695, 165,649, and 160,097 participants for the analysis of depression, all types of anxiety, specific phobia anxiety, and other types of anxiety, respectively. For every one-unit increase in E-DII, the risk of experiencing depression and anxiety increased by 5 % and 4 %, respectively. We identified a "J"-shaped nonlinear relationship (P for nonlinear = 0.003) for both depression and anxiety. A significant association with an elevated risk of depression was observed when E-DII exceeded 0.440, and an increased risk of anxiety was noted when E-DII was more than -0.196. Mediation analysis demonstrated that PhenoAge age acceleration (AA) (For depression, proportion of mediation = 9.6 %; For anxiety, proportion of mediation = 10.1 %) and Klemera-Doubal method Biological Age (KDM AA) (For depression, proportion of mediation = 2.9 %; For anxiety, proportion of mediation = 5.1 %) acted as mediators between E-DII and the development of depression and anxiety (P < 0.05). CONCLUSIONS: Diets with pro-inflammatory characteristics are associated with a heightened risk of depression and anxiety. Furthermore, the association of pro-inflammatory diets and depression is mediated by biological age.

Association between serum uric acid and cardiovascular fitness among US adults: A cross-sectional study.

Background: While serum uric acid (SUA) is known as a cardiovascular disease risk factor and is associated with increased cardiovascular mortality, the relationship between SUA and cardiovascular adaptability under exercise stress remains unclear. Aims: This study aims to elucidate the relationship between SUA levels and cardiovascular fitness, particularly as manifested during cardiopulmonary exercise testing. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, this study included 5765 participants aged 12-49 years. Heart rate recovery (HRR) during cardiopulmonary exercise testing was measured as an indicator of cardiovascular fitness. Multivariate linear regression analysis was used to explore the association between SUA levels and heart rate recovery at 1 min (HRR1) and 2 min (HRR2) post-exercise. Results: After adjusting for potential confounders, an inverse relationship was found between SUA levels and both HRR1 and HRR2. Multivariate adjusted smoothing spline plots demonstrated a decrease in HRR1 and HRR2 with increasing SUA levels. This negative correlation was observed across nearly all subgroups. Conclusions: Elevated SUA levels are indicative of poorer cardiovascular adaptability in the adult US population.

Inhibition of SFTSV replication in humanized mice by a subcutaneously administered anti-PD1 nanobody.

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening disease caused by a novel bunyavirus (SFTSV), mainly transmitted by ticks. With no effective therapies or vaccines available, understanding the disease's mechanisms is crucial. Recent studies found increased expression of programmed cell death-1 (PD-1) on dysfunctional T cells in SFTS patients. However, the role of the PD-1/programmed cell death-ligand 1 (PD-L1) pathway in SFTS progression remains unclear. We investigated PD-1 blockade as a potential therapeutic strategy against SFTSV replication. Our study analyzed clinical samples and performed in vitro experiments, revealing elevated PD-1/PD-L1 expression in various immune cells following SFTSV infection. An anti-PD-1 nanobody, NbP45, effectively inhibited SFTSV infection in peripheral blood mononuclear cells (PBMCs), potentially achieved through the mitigation of apoptosis and the augmentation of T lymphocyte proliferation. Intriguingly, subcutaneous administration of NbP45 showed superior efficacy compared to a licensed anti-PD-1 antibody in an SFTSV-infected humanized mouse model. These findings highlight the involvement of the PD-1/PD-L1 pathway during acute SFTSV infection and suggest its potential as a host target for immunotherapy interventions against SFTSV infection.

Occurrence of p-phenylenediamine antioxidants in human urine.

General populations are widely exposed to various p-phenylenediamine antioxidants (PPDs). N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), a typical p-phenylenediamine antioxidant, has been detected in human urine samples. However, the occurrence of other widely used PPDs in human urine is still unclear. This study comprehensively characterized the occurrence of 9 PPDs in human urine from 151 Chinese adults. Our results showed that all target PPDs were detected in human urine samples, with the total concentrations of PPDs ranging from 0.41 to 38 ng/mL. PPDs in human urine was dominated by 6PPD (mean 1.2 ng/mL, range < LOD - 3.8 ng/mL), followed by N-phenyl-N'-cyclohexyl-p-phenylenediamine (CPPD; 0.85 ng/mL,

Distribution of parabens and 4-HB in human blood.

Human blood has been commonly and routinely analyzed to determine internal human exposure to parabens. However, data on the occurrence of parabens and their common metabolite, p-hydroxybenzoic acid (4-HB), in different human blood matrixes is still limited. In this study, 139 pairs of serum and whole blood samples were collected from Chinese adults, and then analyzed them for 5 parabens and 4-HB. Methylparaben (MeP) and propylparaben (PrP) were consistently the predominant parabens in human serum (mean 2.3 and 2.1 ng/mL, respectively) and whole blood (1.9 and 1.3 ng/mL, respectively). Mean concentrations of 4-HB in human serum and whole blood were 7.7 and 12 ng/mL, respectively. Concentrations of parabens, except benzylparaben (BzP), and 4-HB in human serum were significantly (p < 0.01) correlated with that in whole blood. Distribution pattern of parabens and 4-HB in human blood was evaluated, for the first time, based on their partitioning between human serum and whole blood (Kp). Mean Kp values of parabens, except BzP, increased with the alkyl chain length from 0.83 to 1.6. BzP (mean 1.4) had a comparable mean Kp value to PrP (mean 1.4). Among target analytes, 4-HB had the lowest mean Kp value (0.75). These data are important to select appropriate blood matrixes for conducting human exposure assessment and epidemiological studies on parabens.

Association between ethylene oxide levels and depressive symptoms: A cross-sectional study based on NHANES 2013-2018 database.

BACKGROUND AND AIM: Ethylene oxide (EO) is a commonly used compound with known health risks. However, the specific association between EO exposure and the development of depressive symptoms has not been well established. Therefore, this study aimed to examine the potential association between EO exposure, as indicated by hemoglobin adduct of ethylene oxide (HbEO) levels, and the occurrence of depressive symptoms. METHODS: We employed logistic regression, restricted cubic spline, and subgroup analysis to investigate the association between EO exposure and the occurrence of depressive symptoms. Additionally, we conducted a mediating effect analysis to explore the potential factors influencing the association between EO exposure and depressive symptoms. RESULTS: Elevated HbEO levels were associated with the development of depressive symptoms. After adjusting for potential confounders, the highest quartile of HbEO levels showed an odds ratio (OR) of 3.37 [95 % confidence interval (CI): 1.87-6.10, P = 0.002] compared with the lowest quartile. Additionally, a linear association was observed between HbEO levels and the risk of depressive symptoms. We also revealed that the levels of several inflammatory factors and triglycerides mediated the association between EO exposure and the occurrence of depressive symptoms. CONCLUSIONS: Higher levels of EO exposure were related to an increased risk of developing depressive symptoms. The analysis also suggested that the inflammatory response might play a mediating role in the pathway from EO exposure to depressive symptoms.