Effects of arsenic exposure on blood trace element levels in rats and sex differences.

Arsenic (As) is a widespread environmental metalloid and human carcinogen, and its exposure is associated with a wide range of toxic effects, leading to serious health hazards. As poisoning is a complex systemic multi-organ and multi-system damage disease. In this study, a rat model of As poisoning was established to investigate the levels of trace elements in the blood of rats and sex differences in the effect of As on every trace elements in rat blood. Twenty 6-week-old SD (Sprague Dawley) rats were randomly divided into the control group and the As-exposed group. After 3 months, the contents of 19 elements including As in the blood were detected in these two groups by inductively coupled plasma mass spectrometry (ICP-MS). As levels in the blood of As-exposed rats were significantly higher than those in the control group, with increased levels of Rb, Sr, Cs and Ce, and decreased levels of Pd. As showed a significant positive correlation with Rb. There were significant sex differences in blood Se, Pd, Eu, Dy, Ho, and Au levels in the As-exposed group. The results showed that As exposure can lead to an increase of As content in blood and an imbalance of some elements. There were sex differences in the concentration and the correlation between elements of some elements. Elemental imbalances may affect the toxic effects of As and play a synergistic or antagonistic role in As toxicity.

Combined exposure to UV and PM affect skin oxinflammatory responses and it is prevented by antioxidant mix topical application: Evidences from clinical study.

BACKGROUND: Exposure to environmental stressors like particulate matter (PM) and ultraviolet radiation (UV) induces cutaneous oxidative stress and inflammation and leads to skin barrier dysfunction and premature aging. Metals like iron or copper are abundant in PM and are known to contribute to reactive oxygen species (ROS) production. AIMS: Although it has been suggested that topical antioxidant may be able to help in preventing and/or reducing outdoor skin damage, limited clinical evidence under real-life exposure conditions have been reported. The aim of the present study was to evaluate the ability of a topical serum containing 15% ascorbic acid, 0.5% ferulic acid, and 1% tocopherol (CF Mix) to prevent oxinflammatory skin damage and premature aging induced by PM + UV in a human clinical trial. METHODS: A 4-day single-blinded, clinical study was conducted on the back of 15 females (18-40 years old). During the 4 consecutive days, the back test zones were treated daily with or without the CF Mix, followed by with/without 2 h of PM and 5 min of UV daily exposure. RESULTS: Application of the CF Mix prevented PM + UV-induced skin barrier perturbation (Involucrin and Loricrin), lipid peroxidation (4HNE), inflammatory markers (COX2, NLRP1, and AhR), and MMP9 activation. In addition, CF Mix was able to prevent Type I Collagen loss. CONCLUSION: This is the first human study confirming the multipollutants cutaneous damage and suggesting the utility of a daily antioxidant topical application to prevent pollution induced skin damage.

Flat-band Friedrich-Wintgen bound states in the continuum based on borophene metamaterials.

Many applications involve the phenomenon of a material absorbing electromagnetic radiation. By exploiting wave interference, the efficiency of absorption can be significantly enhanced. Here, we propose Friedrich-Wintgen bound states in the continuum (F-W BICs) based on borophene metamaterials to realize coherent perfect absorption with a dual-band absorption peak in commercially important communication bands. Metamaterials consist of borophene gratings and a borophene sheet that can simultaneously support a Fabry-Perot plasmon resonance and a guided plasmon mode. The formation and dynamic modulation of the F-W BIC can be achieved by adjusting the width or carrier density of the borophene grating, while the strong coupling leads to the anti-crossover behavior of the absorption spectrum. Due to the weak angular dispersion originating from the intrinsic flat-band characteristic of the deep sub-wavelength periodic structure, the proposed plasmonic system exhibits almost no change in wavelength and absorption at large incident angles (within 70 degrees). In addition, we employ the temporal coupled-mode theory including near- and far-field coupling to obtain strong critical coupling, successfully achieve coherent perfect absorption, and can realize the absorption switch by changing the phase difference between the two coherent beams. Our findings can offer theoretical support for absorber design and all-optical tuning.

Functional types of long trichoid sensilla responding to sex pheromone components in Plutella xylostella.

Sex pheromones, which consist of multiple components in specific ratios promote intraspecific sexual communications of insects. Plutella xylostella (L.) is a worldwide pest of cruciferous vegetables, the mating behavior of which is highly dependent on its olfactory system. Long trichoid sensilla on male antennae are the main olfactory sensilla that can sense sex pheromones. However, the underlying mechanisms remain unclear. In this study, 3 sex pheromone components from sex pheromone gland secretions of P. xylostella female adults were identified as Z11-16:Ald, Z11-16:Ac, and Z11-16:OH in a ratio of 9.4 : 100 : 17 using gas chromatography - mass spectrometry and gas chromatography with electroantennographic detection. Electrophysiological responses of 581 and 385 long trichoid sensilla of male adults and female adults, respectively, to the 3 components were measured by single sensillum recording. Hierarchical clustering analysis showed that the long trichoid sensilla were of 6 different types. In the male antennae, 52.32%, 5.51%, and 1.89% of the sensilla responded to Z11-16:Ald, Z11-16:Ac, and Z11-16:OH, which are named as A type, B type, and C type sensilla, respectively; 2.93% named as D type sensilla responded to both Z11-16:Ald and Z11-16:Ac, and 0.34% named as E type sensilla were sensitive to both Z11-16:Ald and Z11-16:OH. In the female antennae, only 7.53% of long trichoid sensilla responded to the sex pheromone components, A type sensilla were 3.64%, B type and C type sensilla were both 0.52%, D type sensilla were 1.30%, and 1.56% of the sensilla responded to all 3 components, which were named as F type sensilla. The responding long trichoid sensilla were located from the base to the terminal of the male antennae and from the base to the middle of the female antennae. The pheromone mixture (Z11-16:Ald : Z11-16:Ac : Z11-16:OH = 9.4 : 100 : 17) had a weakly repellent effect on female adults of P. xylostella. Our results lay the foundation for further studies on sex pheromone communications in P. xylostella.

Photoinduced Decarboxylative Difluoroalkylation and Perfluoroalkylation of α-Fluoroacrylic Acids.

Herein, a novel and practical methodology for the photoinduced decarboxylative difluoroalkylation and perfluoroalkylation of α-fluoroacrylic acids is reported. A wide range of α-fluoroacrylic acids can be used as applicable feedstocks, allowing for rapid access to structurally important difluoroalkylated and polyfluoroalkylated monofluoroalkenes with high Z-stereoselectivity under mild conditions. The protocol demonstrates excellent functional group compatibility and provides a platform for modifying complex biologically active molecules.

Temporally Decoupled Ammonia Splitting by a Zn-NH3 Battery with an Ammonia Oxidation/Hydrogen Evolution Bifunctional Electrocatalyst as a Cathode.

Ammonia splitting to hydrogen is a decisive route for hydrogen economy but is seriously limited by the complex device and low efficiency. Here, we design and propose a new rechargeable Zn-NH3 battery based on temporally decoupled ammonia splitting to achieve efficient NH3-to-H2 conversion. In this system, ammonia is oxidized into nitrogen during cathodic charging (2NH3 + 6OH- → N2 + 6H2O + 6e-) with external electrical energy conversion and storage, while during cathodic discharging, water is reduced to hydrogen (2H2O + 2e- → H2 + 2OH-) with electrical energy generation. In this loop, continuous and efficient H2 production without separation and purification is achieved. With the help of the ammonia oxidation reaction (AOR) and hydrogen evolution reaction (HER) bifunctional catalyst of Mo2C/NiCu@C, a rechargeable Zn-NH3 battery is realized that exhibits a high NH3-to-H2 FE of 91.6% with outstanding durability for 900 cycles (300 h) at 20 mA/cm2, enabling efficient and continuous NH3-to-H2 conversion.

An Atlas of Dietary Intakes and Medication Uses on Risk of Bladder Cancer: A Wide-Angle Mendelian Randomization Analysis.

BACKGROUND: Observational studies suggests that diets and medications affect bladder cancer (BC) development, which are subject to confounding and difficult to make causal inference. Here we aimed to investigate whether those observational associations are causal and determining the potential directions and pathways. METHODS: We used 2-sample Mendelian randomization (MR) analysis to assess associations of dietary intakes, medication uses and molecules with BC risk. Genetic summary data were derived from participants of predominantly European ancestry with rigorous instruments selection, where univariable MR, mediation MR and multivariable MR were performed. RESULTS: The results of univariable MR showed 4 dietary intakes and 4 medication uses having a protective effect on BC, while 4 circulating metabolites, 440 circulating proteins and 2 gut microbes were observed to be causally associated with BC risk. Through mediation MR, we found 572 analytes showing consistent mediating effects between dietary intakes or medication uses and BC risk. Furthermore, 9 out of 16 diet-medication pairs showed significant interactions and alterations on BC when consumed jointly. CONCLUSION: In summary, the findings obtained from the current study have important implications for informing prevention strategies that point to potential lifestyle interventions or medication prescriptions to reduce the risk of developing BC.HighlightsThe current study extends observational literature in showing the importance of diets and medications on bladder cancer prevention.The associations of diets and medications on bladder cancer prevention might be through circulating metabolites, circulating proteins and gut microbiotaOur results provide a new understanding of interactions in certain diet-medication pairs which should be taken into account by both physicians and patients during the development of a treatment strategy.

Synergistically optimized electron and phonon transport in high-performance copper sulfides thermoelectric materials via one-pot modulation.

Optimizing thermoelectric conversion efficiency requires the compromise of electrical and thermal properties of materials, which are hard to simultaneously improve due to the strong coupling of carrier and phonon transport. Herein, a one-pot approach realizing simultaneous second phase and Cu vacancies modulation is proposed, which is effective in synergistically optimizing thermoelectric performance in copper sulfides. Multiple lattice defects, including nanoprecipitates, dislocations, and nanopores are produced by adding a refined ratio of Sn and Se. Phonon transport is significantly suppressed by multiple mechanisms. An ultralow lattice thermal conductivity is therefore obtained. Furthermore, extra Se is added in the copper sulfide for optimizing electrical transport properties by inducing generating Cu vacancies. Ultimately, an excellent figure of merit of ~1.6 at 873 K is realized in the Cu1.992SSe0.016(Cu2SnSe4)0.004 bulk sample. The simple strategy of inducing compositional and structural modulation for improving thermoelectric parameters promotes low-cost high-performance copper sulfides as alternatives in thermoelectric applications.

Tumor-targeted delivery of copper-manganese biomineralized oncolytic adenovirus for colorectal cancer immunotherapy.

Oncolytic viral therapy (OVT) is a novel anti-tumor immunotherapy approach, specifically replicating within tumor cells. Currently, oncolytic viruses are mainly administered by intratumoral injection. However, achieving good results for distant metastatic tumors is challenging. In this study, a multifunctional oncolytic adenovirus, OA@CuMnCs, was developed using bimetallic ions copper and manganese. These metal cations form a biomineralized coating on the virus's surface, reducing immune clearance. It is known that viruses upregulate the expression of PD-L1. Copper ions in OA@CuMnCs can decrease the PD-L1 expression of tumor cells, thereby promoting immune cell-related factor release. This process involves antigen presentation and the combination of immature dendritic cells, transforming them into mature dendritic cells. It changes "cold" tumors into "hot" tumors, further inducing immunogenic cell death. While oncolytic virus replication requires oxygen, manganese ions in OA@CuMnCs can react with endogenous hydrogen peroxide. This reaction produces oxygen, enhancing the virus's replication ability and the tumor lysis effect. Thus, this multifunctionally coated OA@CuMnCs demonstrates potent amplification in immunotherapy efficacy, and shows great potential for further clinical OVT. STATEMENT OF SIGNIFICANCE: Oncolytic virus therapy (OVs) is a new anti-tumor immunotherapy method that can specifically replicate in tumor cells. Although the oncolytic virus can achieve a therapeutic effect on some non-metastatic tumors through direct intratumoral injection, there are still three major defects in the treatment of metastatic tumors: immune response, hypoxia effect, and administration route. Various studies have shown that the immune response in vivo can be overcome by modifying or wrapping the surface protein of the oncolytic virus. In this paper, a multifunctional coating of copper and manganese was prepared by combining the advantages of copper and manganese ions. The coating has a simple preparation method and mild conditions, and can effectively enhance tumor immunotherapy.

[Type â £ Hiatal Hernia With Severe Anemia as the Main Clinical Manifestation:Report of One Case].

Type Ⅳ hiatal hernia with a high risk usually presents sudden or suddenly worsening epigastric pain,vomiting,and dysphagia.It is not conducive to early diagnosis and treatment when symptoms are atypical.Type Ⅳ hiatal hernia with severe anemia is rare.This article reports an atypical case of type Ⅳ hiatal hernia with melena and severe anemia as the main manifestations,aiming to improve clinicians' identification of the atypical clinical presentations of type Ⅳ hiatal hernia.

Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy.

Autism spectrum disorder (ASD) has become a common neurodevelopmental disorder. The heterogeneity of ASD poses great challenges for its research and clinical translation. On the basis of reviewing the heterogeneity of ASD, this review systematically summarized the current status and progress of pathogenesis, diagnostic markers, and interventions for ASD. We provided an overview of the ASD molecular mechanisms identified by multi-omics studies and convergent mechanism in different genetic backgrounds. The comorbidities, mechanisms associated with important physiological and metabolic abnormalities (i.e., inflammation, immunity, oxidative stress, and mitochondrial dysfunction), and gut microbial disorder in ASD were reviewed. The non-targeted omics and targeting studies of diagnostic markers for ASD were also reviewed. Moreover, we summarized the progress and methods of behavioral and educational interventions, intervention methods related to technological devices, and research on medical interventions and potential drug targets. This review highlighted the application of high-throughput omics methods in ASD research and emphasized the importance of seeking homogeneity from heterogeneity and exploring the convergence of disease mechanisms, biomarkers, and intervention approaches, and proposes that taking into account individuality and commonality may be the key to achieve accurate diagnosis and treatment of ASD.

Immune Regulatory Networks and Therapy of γδ T Cells in Liver Cancer: Recent Trends and Advancements.

The roles of γδ T cells in liver cancer, especially in the potential function of immunotherapy due to their direct cytotoxic effects on tumor cells and secretion of important cytokines and chemokines, have aroused research interest. This review briefly describes the basic characteristics of γδ T cells, focusing on their diverse effects on liver cancer. In particular, different subtypes of γδ T cells have diverse or even opposite effects on liver cancer. We provide a detailed description of the immune regulatory network of γδ T cells in liver cancer from two aspects: immune components and nonimmune components. The interactions between various components in this immune regulatory network are dynamic and pluralistic, ultimately determining the biological effects of γδ T cells in liver cancer. We also integrate the current knowledge of γδ T-cell immunotherapy for liver cancer treatment, emphasizing the potential of these cells in liver cancer immunotherapy.

[Molecular mechanism of residual lumbago and leg pain after transforaminal endoscopic treatment of lumbar disc herniation].

OBJECTIVE: To observe the residual of lumbago and leg pain with contained type （CT） and non-contained type （NCT） lumbar disc herniation （LDH） after transforaminal endoscopic treatment, and to explore the role of hypoxia-inducible factor-1α（HIF-1α） and transient receptor potential vanillate 1（TRPV1） pathway. METHODS: A total of 68 single-segment LDH patients were selected from July 2021 to October 2022, including 44 males and 24 females；aged 26 to 67 years old with an average of（43.63±11.94） years old；course of disease was 4 to 36 （18.91±10.34） months；body mass index was （24.45±4.00） kg·m-2；there were 7 cases of L3,4 segments, 32 cases of L4,5 segments, and 29 cases of L5S1 segments. All of them were performed with percutaneous intervertebral endoscopic extraction of nucleus pulposus and were divided into contained group（CT group） and non-contained group （NCT group） with 34 cases respectively according to the integrity of outer layer of fibrous annulus observed during operation. A total of 17 patients who underwent open surgery for scoliosis or vertebral fracture were selected as control group, including 12 males and 5 females；aged 21 to 65 years old with an average of （39.41±12.80） years old；body mass index was （24.86±4.11） kg·m-2. The relative mRNA expression quantity of HIF-1α, TRPV1 in nucleus pulposus were measured by quantitative real-time PCR. The contents of neurokinin 1 receptor （NK1R）, nerve growth factor （NGF）, vascular endothelial growth factor （VEGF） in nucleus pulposus and the serum substance P （SP） and calcitonin gene-related peptide （CGRP） were detected by enzyme linked immunosorbent assay （ELISA）. The threshold of lumbar tenderness was detected by a pressure pain meter. The degree of lumbago and lumbar function were evaluated by visual analog scale （VAS） and Oswestry disability index （ODI） separately. The residual rate of postoperative lumbago and leg pain was assessed. RESULTS: The mRNA relative expression quantity of HIF-1α and TRPV1, and the contents of NK1R, NGF and VEGF in nucleus pulposus, and the levels of serum SP and CGRP before surgery in the NCT group were higher than those in the CT group（P<0.05）, and those in the CT group were higher than the control group（P<0.05）. At day 7 after surgery, the serum SP and CGRP levels, lumbago and leg pain VAS scores and lumbar ODI index in two LDH groups were lower than before surgery （P<0.05）, and those in the NCT group were higher than the CT group（P<0.05）, and the threshold of lumbar tenderness in the NCT group was lower than the CT group（P<0.05）. The differences of lumbago and leg pain VAS scores, lumbar ODI index and lumbar tenderness threshold between preoperative and postoperative 7 days in the NCT group were lower than those in the CT group（P<0.05）. The residual rate of lumbago and leg pain at 7 days after surgery in the NCT group was higher than that in the CT group（P<0.05）. CONCLUSION: HIF-1α and TRPV1 pathway promoted the excessive production of NGF, VEGF, NK1R in nucleus pulposus and serum neuropeptides SP and CGRP, which may lead to the higher residual rate of lumbago and leg pain with non-contained lumbar disc herniation postoperative.

Salidroside promotes pro-angiogenesis and repair of blood brain barrier via Notch/ITGB1 signal path in CSVD Model.

INTRODUCTION: Salidroside (SAL), extracted from Rhodiola rosea, has been widely used in coronary heart disease and myocardial ischemia for decades. Previous studies have demonstrated that SAL could reduce arteriosclerosis, and thus combat ischemic brain damage. However, the in-depth function of the salidroside in Cerebral Small Vascular Disease (CSVD) has not been discovered, and related molecular mechanism is still unclear. OBJECTIVES: The present study aims to explore the effects of salidroside in angiogenesis as well as repair of blood brain barrier (BBB) and its possible mechanisms. METHODS: We established a rat model of SHR via 2-vessel gradual occlusion (SHR-2VGO) to mimic the CSVD. Subsequently, the MRI, pathomorphism, as well as Morriss water maze test were conducted to determine CSVD-related indicators. 8 weeks post-surgery, animals were randomly administered SAL, DAPT, ATN161 or saline.The aim was to explore the protective effects of SAL in CSVD as well as its possible mechanism. RESULTS: Here we found that SAL could attenuate cerebral hypoperfusion-induced BBB disruption, promote the pro-angiogenesis through enhancing the cell budding. Further investigations demonstrated that SAL could significantly increase the expression of Notch1, Hes1, Hes5, and ITGB1. In addition, we confirmed that SAL could activate Notch signal path, and then up-regulate ITGB1 to promote pro-angiogenesis and thus protect BBB from disruption. CONCLUSION: The aforementioned findings demonstrated that SAL could protect BBB integrity through Notch-ITGB1 signaling path in CSVD, which indicated that SAL could be a potential medicine candidate for CSVD treatment.

Coupling Electron Transfer and Redox Site in Boranil Covalent Organic Framework Toward Boosting Photocatalytic Water Oxidation.

The efficient polymeric semiconducting photocatalyst for solar-driven sluggish kinetics with multielectron transfer oxygen evolution has spurred scientific interest. However, existing photocatalysts limited by π-conjugations, visible-light harvest, and charge transfer often compromise the O2 production rate. Herein, we introduced an alternative strategy involving a boranil functionalized-based fully π-conjugated ordered donor and acceptor (D-A) covalent organic frameworks (Ni-TAPP-COF-BF2 ) photocatalyst. The co-catalyst-free Ni-TAPP-COF-BF2 exhibits an excellent ~11-fold photocatalytic water oxidation rate, reaching 1404 µmol g-1 h-1 under visible light irradiation compared to pristine Ni-TAPP-COF (123 µmol g-1 h-1 ) alone and surpasses to reported organic frameworks counterpart. Both experimental and theoretical results demonstrate that the push/pull mechanism (metalloporphyrin/BF2 ) is responsible for the appropriate light-harvesting properties and extending π-conjugation through chelating BF2 moieties. This strategy benefits in narrowing band structure, improving photo-induced charge separation, and prolonged charge recombination. Further, the lower spin magnetic moment of M-TAPP-COF-BF2 and the closer d-band center of metal sites toward the Fermi level lead to a lower energy barrier for *O intermediate. Reveal the potential of the functionalization strategy and opens up an alternative approach for engineering future photocatalysts in energy conversion applications.

Investigating metabolic dysregulation in serum of triple transgenic Alzheimer's disease male mice: implications for pathogenesis and potential biomarkers.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease that lacks convenient and accessible peripheral blood diagnostic markers and effective drugs. Metabolic dysfunction is one of AD risk factors, which leaded to alterations of various metabolites in the body. Pathological changes of the brain can be reflected in blood metabolites that are expected to explain the disease mechanisms or be candidate biomarkers. The aim of this study was to investigate the changes of targeted metabolites within peripheral blood of AD mouse model, with the purpose of exploring the disease mechanism and potential biomarkers. Targeted metabolomics was used to quantify 256 metabolites in serum of triple transgenic AD (3 × Tg-AD) male mice. Compared with controls, 49 differential metabolites represented dysregulation in purine, pyrimidine, tryptophan, cysteine and methionine and glycerophospholipid metabolism. Among them, adenosine, serotonin, N-acetyl-5-hydroxytryptamine, and acetylcholine play a key role in regulating neural transmitter network. The alteration of S-adenosine-L-homocysteine, S-adenosine-L-methionine, and trimethylamine-N-oxide in AD mice serum can served as indicator of AD risk. The results revealed the changes of metabolites in serum, suggesting that metabolic dysregulation in periphery in AD mice may be related to the disturbances in neuroinhibition, the serotonergic system, sleep function, the cholinergic system, and the gut microbiota. This study provides novel insights into the dysregulation of several key metabolites and metabolic pathways in AD, presenting potential avenues for future research and the development of peripheral biomarkers.

Local and Remote Chemogenetic Suppression of Hippocampal Seizures in Rats.

BACKGROUND: Innovative treatments of refractory epilepsy are widely desired, for which chemogenetic technology can provide region- and cell-type-specific modulation with relative noninvasiveness. OBJECTIVES: We aimed to explore the specific applications of chemogenetics for locally and remotely networks controlling hippocampal seizures. METHODS: A virus coding for a modified human Gi-coupled M4 muscarinic receptor (hM4Di) on pyramidal cells was injected into either the right hippocampal CA3 or the bilateral anterior nucleus of the thalamus (ANT) in rats. After one month, seizures were induced by 4-aminopyridine (4-AP) injection into the right CA3. Simultaneously, clozapine-N-oxide (CNO) (2.5 mg/kg) or clozapine (0.1 mg/kg), the specific ligands acting on hM4Di, were injected intraperitoneally. We also set up hM4Di control and clozapine control groups to eliminate the influence of viral transfection and the ligand alone on the experimental results. RESULTS: For both local and remote controls, the mean seizure duration was significantly reduced upon ligand application in the experimental groups. Seizure frequency, on the other hand, only showed a significant decrease in local control, with a lower frequency in the clozapine group than in the CNO group. Both the effects of CNO and clozapine were time-dependent, and clozapine was faster than CNO in local seizure control. CONCLUSION: This study shows the potency of chemogenetics to attenuate hippocampal seizures locally or remotely by activating the transfected hM4Di receptor with CNO or clozapine. ANT is suggested as a potentially safe chemogenetic application target in the epileptic network for focal hippocampal seizures.

Study on the mechanism of arsenic-induced renal injury based on SWATH proteomics technology.

BACKGROUND: Arsenic (As) poisoning is a worldwide endemic disease affecting thousands of people. As is excreted mainly through the renal system, and arsenic has toxic effects on the kidneys, but the mechanism has not been elucidated. In this study, the molecular basis of arsenic's nephrotoxicity was studied by using a high-throughput proteomics technique. METHODS: Eight SD (Sprague-Dawley) rats, half male and half female, were fed an As diet containing 50 mg/kg NaAsO2. Age- and sex-matched rats fed with regular chow were used as controls. At the end of the experiment (90 days), kidney tissue samples were collected and assessed for pathological changes using hematoxylin-eosin staining. Proteomic methods were used to identify alterations in protein expression levels in kidney tissues, and bioinformatic analyses of differentially expressed proteins between arsenic-treated and control groups were performed. The expression of some representative proteins was validated by Western blot analysis. RESULTS: NaAsO2 could induce renal injury. Compared with the control group, 112 proteins were up-regulated, and 46 proteins were down-regulated in the arsenic-treated group. These proteins were associated with the electron transport chain, oxidative phosphorylation, mitochondrial membrane, apoptosis, and proximal tubules, suggesting that the mechanisms associated with them were related to arsenic-induced kidney injury and nephrotoxicity. The expressions of Atp6v1f, Cycs and Ndufs1 were verified, consistent with the results of omics. CONCLUSION: These results provide important evidence for arsenic-induced kidney injury and provide new insights into the molecular mechanism of arsenic-induced kidney injury.

Discovery from Hypericum elatoides and synthesis of hyperelanitriles as α-aminopropionitrile-containing polycyclic polyprenylated acylphloroglucinols.

The search for lead compounds with anti-neuroinflammatory activity from structurally 'optimized' natural products is a crucial and promising strategy in the quest to discover safe and efficacious agents for treating neurodegenerative diseases. A phytochemical investigation on the aerial portions of Hypericum elatoides led to the isolation of five nitrogenous polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperelanitriles A-D (1-4) and hyperelamine A (5). Their structures were determined by spectroscopic analysis, ECD and NMR calculations, and X-ray crystallography. To the best of our knowledge, compounds 1-4 represent the first examples of acylphloroglucinols featuring an α-aminonitrile moiety, while 5 is a rare enamine-containing PPAP. Further, the synthesis of these naturally occurring PPAP-based nitriles or amines was accomplished. Compound 5 exhibited inhibitory activity against LPS-activated NO production in BV-2 cells, potentially through the suppression of TLR-4/NF-κB signaling. Here we show the isolation, structural elucidation, synthesis, and bioactive evaluation of compounds 1-5.

U-shaped relationship between ozone exposure and preterm birth risk associated with preconception telomere length.

There are conflicting findings regarding the association of ozone (O3) exposure with preterm birth (PTB) occurrence. In the present study, two cohorts were combined to explore the relationship between maternal O3 exposure during pregnancy and PTB risk, and analyze the underlying mechanisms of this relationship in terms of alterations in the preconception telomere length. Cohort 1 included mothers who participated in the National Free Preconception Health Examination Project in Henan Province from 2014 to 2018 along with their newborns (n = 1,066,696). Cohort 2 comprised mothers who conceived between 2016 and 2018 and their newborns (n = 1871) from six areas in Henan Province. The telomere length was assessed in the peripheral blood of mothers at the preconception stage. Data on air pollutant concentrations were collected from environmental monitoring stations and individual exposures were assessed using an inverse distance-weighted model. O3 concentrations (100.60 ± 14.13 µg/m3) were lower in Cohort 1 than in Cohort 2 (114.09 ± 15.17 µg/m3). Linear analyses showed that PTB risk decreased with increasing O3 exposure concentrations in Cohort 1 but increased with increasing O3 exposure concentrations in Cohort 2. Nonlinear analyses revealed that PTB risk tended to decrease and then increase with increasing O3 exposure concentrations in both cohorts. Besides, PTB risk was reduced by 88% for each-unit increase in telomere length in those exposed to moderate O3 concentrations (92.4-123.7 µg/m3, P < 0.05). While no significant association was observed between telomere length and PTB at extreme O3 concentration exposure during entire pregnancy (<92.4 or >123.7 µg/m3, P > 0.05) in Cohort 2. These findings reveal a nonlinear (U-shaped) relationship between O3 exposure and PTB risk. Furthermore, telomere with elevated length was associated with decreased risk of PTB only when exposed to moderate concentrations of O3, but not when exposed to extreme concentrations of O3 during pregnancy.