Complex interplay of neurodevelopmental disorders (NDDs), fractures, and osteoporosis: a mendelian randomization study.

BACKGROUND: Neurodevelopmental disorders (NDDs), such as Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Tourette Syndrome (TS), have been extensively studied for their multifaceted impacts on social and emotional well-being. Recently, there has been growing interest in their potential relationship with fracture risks in adulthood. This study aims to explore the associations between these disorders and fracture rates, in order to facilitate better prevention and treatment. METHODS: Employing a novel approach, this study utilized Mendelian randomization (MR) analysis to investigate the complex interplay between ADHD, ASD, TS, and fractures. The MR framework, leveraging extensive genomic datasets, facilitated a systematic examination of potential causal relationships and genetic predispositions. RESULTS: The findings unveil intriguing bidirectional causal links between ADHD, ASD, and specific types of fractures. Notably, ADHD is identified as a risk factor for fractures, with pronounced associations in various anatomical regions, including the skull, trunk, and lower limbs. Conversely, individuals with specific fractures, notably those affecting the femur and lumbar spine, exhibit an increased genetic predisposition to ADHD and ASD. In this research, no correlation was found between TS and fractures, or osteoporosis.These results provide a genetic perspective on the complex relationships between NDDs and fractures, emphasizing the importance of early diagnosis, intervention, and a holistic approach to healthcare. CONCLUSION: This research sheds new light on the intricate connections between NDDs and fractures, offering valuable insights into potential risk factors and causal links. The bidirectional causal relationships between ADHD, ASD, and specific fractures highlight the need for comprehensive clinical approaches that consider both NDDs and physical well-being.

Oncological and reproductive outcomes of endometrial atypical hyperplasia and endometrial cancer patients undergoing conservative therapy with hysteroscopic resection: A systematic review and meta-analysis.

INTRODUCTION: Our objective was to conduct a systematic review and meta-analysis of studies evaluating the oncological and reproductive outcomes of patients with endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC) undergoing conservative therapy with hysteroscopic resection (HR). MATERIAL AND METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses. The study strictly followed the methodological framework proposed by the Cochrane Handbook and was retrospectively registered in PROSPERO (CRD42023469986). Searches were conducted in PubMed, Embase, and the Cochrane Library, from inception to October 10, 2023. A checklist based on items of the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary end points for this meta-analysis were complete response (CR), pregnancy, and live birth rates following HR-based therapy in patients with EEC or AH. The secondary end point was the recurrence rate (RR). RESULTS: Twenty-one articles involving 407 patients with clinical stage IA, low or intermediate grade, EEC, and 444 patients with AH managed with HR-based conservative treatment were included for this systematic review. CR to HR-based conservative therapy was achieved in 88.6% of patients with EEC and 97.0% of patients with AH. Of these, 30.6% and 24.2%, respectively, had live births. The overall pooled disease RR was 18.3% and 10.8% in patients with EEC and AH, respectively. Further subset analyses revealed that EEC patients with body mass index (BMI) ≤28 kg/m2 had higher CR rates as well as higher chances of pregnancy and live birth (91.6% CR, 32.9% pregnancy, 31.1% live birth) compared with patients with BMI >28 kg/m2 (86.4% CR, 28.4% pregnancy, 23.0% live birth). The HR followed by oral progestogen subgroup had higher CR rates and higher chances of pregnancy and live birth (91.8% CR, 36.3% pregnancy, 28.2% live birth) than the HR followed by the levonorgestrel intrauterine system subgroup (82.5% CR, 25.3% pregnancy, 16.3% live birth). CONCLUSIONS: Hysteroscopic resection followed by progestins appears to be a promising choice for fertility-sparing treatment in young patients with AH and EEC, with effective and safe responses. The live birth rate remains to be improved by providing medical guidance and encouragement.

Extracellular vesicle-derived TP53BP1, CD34, and PBX1 from human peripheral blood serve as potential biomarkers for the assessment and prediction of vascular aging.

BACKGROUND: Vascular aging is an important pathophysiological basis for the senescence of various organs and systems in the human body, and it is a common pathogenetic trigger for many chronic diseases in the elderly. METHODS: The extracellular vesicles (EVs) from young and aged umbilical vein endothelial cells were isolated and identified by qPCR the differential expression levels of 47 mRNAs of genes closely related to aging in the two groups. RESULTS: There were significant differences in the expression levels of 18 genes (we noted upregulation in PLA2G12A, TP53BP1, CD144, PDE11A, FPGT, SERPINB4, POLD1, and PPFIBP2 and downregulation in ATP2C2, ROBO2, RRM2, GUCY1B1, NAT1-14, VEGFR2, WTAPP1, CD146, DMC1, and GRIK2). Subsequent qPCR identification of the above-mentioned genes in PBMCs and plasma-EVs from the various age groups revealed that the trend in expression levels in peripheral blood plasma-EVs of the different age groups was approximately the same as that in PBMCs. Of these mRNAs, the expression of four genes-PLA2G12A, TP53BP1, OPRL1, and KIAA0895-was commensurate with increasing age. In contradistinction, the expression trend of four genes (CREG1, PBX1, CD34, and SLIT2) was inversely proportional to the increase in age. Finally, by taking their intersection, we determined that the expression of TP53BP1 was upregulated with increasing human age and that CD34 and PBX1 were downregulated with increasing age. CONCLUSION: Our study indicates that human peripheral blood plasma-EV-derived TP53BP1, CD34, and PBX1 potentially comprise a noninvasive biomarker for assessing and predicting vascular aging.

Acute IL-6 exposure triggers canonical IL6Ra signaling in hiPSC microglia, but not neural progenitor cells.

BACKGROUND: Prenatal exposure to elevated interleukin (IL)-6 levels is associated with increased risk for psychiatric disorders with a putative neurodevelopmental origin, such as schizophrenia (SZ), autism spectrum condition (ASC) and bipolar disorder (BD). Although rodent models provide causal evidence for this association, we lack a detailed understanding of the cellular and molecular mechanisms in human model systems. To close this gap, we characterized the response of human induced pluripotent stem cell (hiPSC-)derived microglia-like cells (MGL) and neural progenitor cells (NPCs) to IL-6 in monoculture. RESULTS: We observed that human forebrain NPCs did not respond to acute IL-6 exposure in monoculture at both protein and transcript levels due to the absence of IL6R expression and soluble (s)IL6Ra secretion. By contrast, acute IL-6 exposure resulted in STAT3 phosphorylation and increased IL6, JMJD3 and IL10 expression in MGL, confirming activation of canonical IL6Ra signaling. Bulk RNAseq identified 156 up-regulated genes (FDR < 0.05) in MGL following acute IL-6 exposure, including IRF8, REL, HSPA1A/B and OXTR, which significantly overlapped with an up-regulated gene set from human post-mortem brain tissue from individuals with schizophrenia. Acute IL-6 stimulation significantly increased MGL motility, consistent with gene ontology pathways highlighted from the RNAseq data and replicating rodent model indications that IRF8 regulates microglial motility. Finally, IL-6 induces MGLs to secrete CCL1, CXCL1, MIP-1α/ß, IL-8, IL-13, IL-16, IL-18, MIF and Serpin-E1 after 3 h and 24 h. CONCLUSION: Our data provide evidence for cell specific effects of acute IL-6 exposure in a human model system, ultimately suggesting that microglia-NPC co-culture models are required to study how IL-6 influences human cortical neural progenitor cell development in vitro.

Design and Multiple Applications of Mixed-Ligand Metal-Organic Frameworks with Dual Emission.

Herein, we revealed the factors that affect the emission in mixed-ligand metal-organic frameworks (MOFs) with the combination of terephthalic acid (BDC), 2-aminoterephthalic acid (BDC-NH2), and 2,5-dihydroxylterephthalic acid [BDC-(OH)2] as models. The -NH2 and -(OH)2 groups change the π-conjugation and luminescence behaviors than BDC, so the ligands show different optical behaviors. The Zn2+ ion with a 3d10 full electronic structure shows little effect on the emission of the ligand and is selected as the metal node. We found that the emission of BDC is weak and incompatible to that of BDC-NH2, so only the emission of BDC-NH2 was observed in the BDC/BDC-NH2-MOF. Crosstalk occurs between the emissions from BDC and BDC-(OH)2 for the single emission from BDC/BDC-(OH)2-MOFs, even different ratios are selected. The MOFs prepared with BDC-NH2 and BDC-(OH)2 show dual emission at 450 and 550 nm, while the relative intensity was easily tuned with the ligand ratio and excitation wavelength. Thus, abundant optical behaviors and extensive applications were realized, including but not limited to (1) dual emission from single MOFs, (2) tunable color from blue to yellow with the excitation from 290 to 370 nm for information encryption and decryption, (3) white emission obtained under an excitation of 330 nm, and (4) response of -NH2 groups to HCHO and Fe3+ ions for ratiometric fluorescence sensing and visual detection. This work revealed the factors that affect the emission in mixed-ligand MOFs, studied their optical behaviors, and realized different applications with single MOFs.

Effects of Weak Bedding Plane, Fault, and Extreme Rainfall on the Landslide Event of a High Cut-Slope.

High cut-slopes are widespread in engineering constructions and often converted into landslides. Some extreme circumstances facilitate the landslide process, such as the weak bedding plane, rainfall, and faults. Therefore, this paper intends to offer insights into the influence of the weak bedding plane, extreme rainfall as well as faults on the landslide process of the high cut-slope. In this paper, the Anling landslide in Anhui Province, China, is selected as an example. Geological surveys, displacement monitoring, data analysis, as well as numerical simulation are carried out. The entire excavation construction and landslide deformation process are simulated to reveal the formation mechanism of the landslide using the finite difference code, FLAC3D. The effects of the fault on the landslide and the effectiveness of adjusting protection measures by adding piles are investigated on the basis of the finite difference analysis. According to monitoring data and numerical simulation, the weak bedding plane and extreme rainfall are considered the main factors leading to the Anling landslide. Field investigation and numerical experiments indicate that the fault shall facilitate and accelerate the landslide process. The construction of piles in a suitable position for the landslide is a reasonable and economical measure to stabilize the landslide.

Self-synthesized TiO2 nanoparticles-pH-mediated dispersive solid phase extraction coupled with high performance liquid chromatography for the determination of quinolones in biological matrices.

A simple and efficient pH-mediated dispersive solid phase extraction (dSPE) based on terbium doped titanium dioxide nanoparticles (TiO2-Tb NPs) combined with high performance liquid chromatography (HPLC) has been firstly developed for the determination of quinolones (QNs) in various biological samples. The adsorption kinetics and isotherms were investigated to indicate that the kinetic and equilibrium adsorption were well-described by pseudo-second order kinetic and Henry, Langmuir isotherm model, respectively. The parameters influencing the extraction performance were systematically investigated. The QNs are transferred into TiO2-Tb NPs in the first step at pH = 6.0 and eluted into acidic aqueous phase at pH = 2.5 in the second step. Under the optimum extraction and determination conditions, a linearity range with the coefficient of determination (R2) from 0.9977 to 0.9991 were obtained in a range of 10-10,000 ng mL-1. The limits of detection (LODs) based on a signal-to-noise ratio of 3 were 3.3 ng mL-1. The recoveries of the three QNs in human urine, rabbit plasma and serum samples ranged from 69.3% to 117.6%, with standard deviations ranging from 2.4% to 9.9%. Therefore, this pH-mediated dSPE-HPLC method exhibited the advantages of remarkable sensitivity, ease of operation, rapidity, low cost and environmental friendliness.

Dual-Ligand Lanthanide Metal-Organic Framework for Sensitive Ratiometric Fluorescence Detection of Hypochlorous Acid.

Sensitivity, selectivity, visible detection, and rapid response are the main concerns for an analytical method. Herein, we reported a metal-organic framework (MOF)-based ratiometric fluorescence detection strategy for hypochlorous acid (HClO). The MOF was prepared with dual ligands, 2-aminoterephthalic acid (BDC-NH2) and dipicolinic acid (DPA) and Eu3+ ions as a metal node, denoted as Eu-BDC-NH2/DPA. The dual-ligand strategy realized the dual emission for ratiometric sensing and visual detection, adjusted the size and morphology of MOFs to obtain a good dispersion for a rapid response, and provided an amino group for the special recognition of HClO. Thus, the MOF exhibited a dual emission derived from BDC-NH2 and Eu3+ ions at 433 and 621 nm, respectively, under a single excitation at 270 nm. A hydrogen bond forms between an -NH2 group and HClO to weaken the blue fluorescence at 433 nm, while the antenna effect emission from Eu3+ ions kept stable, so ratiometric sensing was realized with an easy-to-differentiate color change for visible detection. The ratiometric sensing showed a self-calibration effect and reduced the background. Thus, the high sensitivity, visual detection, low detection limit (37 nM), and short response time (within 20 s) for the detection of HClO were realized with the MOF as a probe. The analysis of real samples demonstrated the practical application of the MOF for HClO. The introduction of mixed ligands is an effective strategy to regulate the emission behaviors of MOFs for the improved analytical performance.

Construction of NaYF4 Library for Morphology-Controlled Multimodality Applications.

Morphology and size of the nanoparticles are highly related to the properties; establishing a library to summarize the relationship between the morphology/size and property is very helpful for associated applications. However, the NaYF4 library and thus the correlation between the morphology and property are still absent. Here NaYF4 library is presented and their morphologies and structures are illustrated at atomic scale for the first time. How about the crystal formation affects the morphology is further used to guide the property. Through rational doping, upconversion luminescence, magnetic resonance (MR) and computed tomography are investigated with the nanoprisms, nanoflowers, and nanoplates as models to reveal the effect of the size and morphology. The difference of the properties provides strong evidence on the importance of the library. In particular, the "imperfect structure" of nanoflower is observed on atomic scale and enhances the MR response. The different upconversion intensity ratio for the emissions at 475 and 693 nm is observed from doped NaYF4 with different morphology. Thus, controllable fabrication of NaYF4 with desired morphology is indispensable to achieve the optimal properties as the guidance on how to choose matrix from the library to meet the specific applications.

Active Sites Intercalated Ultrathin Carbon Sheath on Nanowire Arrays as Integrated Core-Shell Architecture: Highly Efficient and Durable Electrocatalysts for Overall Water Splitting.

The development of active bifunctional electrocatalysts with low cost and earth-abundance toward oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) remains a great challenge for overall water splitting. Herein, metallic Ni4 Mo nanoalloys are firstly implanted on the surface of NiMoOx nanowires array (NiMo/NiMoOx ) as metal/metal oxides hybrid. Inspired by the superiority of carbon conductivity, an ultrathin nitrogen-doped carbon sheath intercalated NiMo/NiMoOx (NC/NiMo/NiMoOx ) nanowires as integrated core-shell architecture are constructed. The integrated NC/NiMo/NiMoOx array exhibits an overpotential of 29 mV at 10 mA cm-2 and a low Tafel slope of 46 mV dec-1 for HER due to the abundant active sites, fast electron transport, low charge-transfer resistance, unique architectural structure and synergistic effect of carbon sheath, nanoalloys, and oxides. Moreover, as OER catalysts, the NC/NiMo/NiMoOx hybrids require an overpotential of 284 mV at 10 mA cm-2 . More importantly, the NC/NiMo/NiMoOx array as a highly active and stable electrocatalyst approaches ≈10 mA cm-2 at a voltage of 1.57 V, opening an avenue to the rational design and fabrication of the promising electrode materials with architecture structures toward the electrochemical energy storage and conversion.

Inorganic Colloidal Perovskite Quantum Dots for Robust Solar CO2 Reduction.

Inorganic perovskite quantum dots as optoelectronic materials have attracted enormous attention in light-harvesting and emitting devices. However, photocatalytic conversion based on inorganic perovskite halides has not been reported. Here, we have synthesized colloidal quantum dots (QDs, 3-12 nm) of cesium lead halide perovskites (CsPbBr3 ) as a new type of photocatalytic material. The band gap energies and photoluminescence (PL) spectra are tunable over the visible spectral region according to quantum size effects on an atomic scale. The increased carrier lifetime revealed by time-resolved PL spectra, indicates the efficient electron-hole separation and transfer. As expected, the CsPbBr3 QDs with high selectivity of greater than 99 % achieve an efficient yield of 20.9 µmol g-1 towards solar CO2 reduction. This work has opened a new avenue for inorganic colloidal perovskite materials as efficient photocatalysts to convert CO2 into valuable fuels.

Dynamic response of a simply supported liquid-crystal elastomer beam under moving illumination.

Optically responsive liquid crystal elastomer (LCE) devices have thriving potential to flourish in soft robots and microdrives, owing to their advantages of remote controllability, structural simplicity, and no power supply. In terms of illumination-driven modes, most research has focused on the dynamic response of LCE devices under continuous and periodic illumination, while the theoretical study of the dynamic response under moving illumination is limited. In this paper, based on the coupling of LCE and mechanical deformation under moving illumination, the dynamic model of a LCE simply supported beam is built to investigate its dynamic response under moving illumination. The analytical solution of the dynamic response of the LCE beam under moving illumination is derived through the modal superposition method and the Duhamel integration, and the solution is programed and analyzed with matlab software. By numerical calculations, the influence of the internal and driving parameters of the structure on the dynamic response of the LCE simply supported beam can be analyzed. The results show that when the moving speed of illumination reaches the first-order critical frequency, the maximum amplitude of the dynamic response at the beam mid-span will reach a peak. Meanwhile, the dynamic response of beam can be improved by increasing the illumination width, increasing the light intensity, increasing the shrinkage coefficient, and reducing the damping coefficient. This work provides theoretical guidance for applying the dynamic response of LCE devices under moving illumination in soft robots, microactuators, energy harvesters, sensors, etc.

"Three-in-One" Nanozyme Composite for Augmented Cascade Catalytic Tumor Therapy.

Cascade catalytic reaction exhibits simple procedure and high efficiency, such as that from the orderly assembly of different enzymes in biological systems. Mimicking of the natural cascade procedure becomes critical, but the orderly assembly of different enzymes is still challenging. Herein, single Au-Pt nanozyme is reported with "three-in-one" functions to initiate cascade conversions for O2 supply as mimic catalase, H2 O2 production with its glucose oxidase-like property, and • OH generation as mimic peroxidase for chemodynamic therapy (CDT). Thus, the complex assembly and cross-talk among the different enzymes are avoided. To this end, metastable Cu2 O NPs, as scaffolds, are used to anchor ultrasmall Au-Pt nanozyme, while metal-organic framework (MOF) is used to encapsulate the nanozyme for tumor microenvironment response and shielding protein adsorption. Pluronic F127 is then modified on the surface to improve hydrophilicity and biocompatibility of the composite. The endogenous acidity and glutathione in tumor degrade MOF to expose nanozyme for cascade catalytic CDT. The high photothermal conversion ability also enhances the CDT, while Cu2+ ions consume GSH to further improve CDT efficiency as augmented cascade catalytic tumor therapy. Thus, a new paradigm is provided with drug-free single nanozyme for improving tumor therapeutic efficacy and minimizing side effects.

PUD@HA/PEEK Scaffold Induces Subchondral Bone Regeneration to Repair Osteochondral Defect in Rabbits.

Osteochondral defects (OCDs) pose a significant challenge in clinical practice, and recent advancements in their repair indicate that satisfying subchondral bone repair may be critical for this. Herein, a series of hydroxyapatite/poly(ether ether ketone) (HA/PEEK) scaffolds were fabricated with varying mass percentages (0, 20, 30, and 40%) to induce subchondral bone regeneration. Subsequently, an optimal scaffold with 40% HA/PEEK was selected to establish osteochondral scaffolds with poly(ether urethane) urea-Danshensu (PUD) for repairing the OCD. The material characteristics of HA/PEEK and PUD were investigated using scanning electron microscopy, tensile, swelling, and fatigue tests, and cytological experiments. The effects of serial HA/PEEK scaffolds on subchondral bone repair were then assessed by using microcomputed tomography, hard tissue slicing, and histological staining. Furthermore, the optimal 40% HA/PEEK scaffold was used to develop osteochondral scaffolds with PUD to observe the effect on the OCD repair. HA/PEEK materials exhibited an even HA distribution in PEEK. However, when composited with HA, PEEK exhibited inferior mechanical strength. 40%HA/PEEK scaffolds showed an optimum effect on in vivo subchondral bone repair. Cartilage regeneration on 40%HA/PEEK scaffolds was pronounced. After PUD was introduced onto the HA/PEEK, the PUD@40%HA/PEEK scaffold produced the expected effect on the repair of the OCD in rabbits. Therefore, achieving satisfactory subchondral bone repair can benefit surficial cartilage repair. The PUD@40%HA/PEEK scaffold could induce subchondral bone regeneration to repair the OCD in rabbits and could provide a novel approach for the repair of the OCD in clinical practice.

A comprehensive analysis and experimental validation of TK1 in uterine corpus endometrial carcinoma.

Uterine corpus endometrial carcinoma (UCEC) is becoming a main malignant cancer that threaten to women's health. Thymidine kinase 1 (TK1) is considering to be associated with tumorigenesis and development. Nevertheless, the function of TK1 in UCEC is still unclear. Herein, we analyzed the TK1 expression level in pan-cancer and found that TK1 was upregulated in a variety of cancers including UCEC. Patients of UCEC with high expression of TK1 were related to poor outcome. TK1 was also related to clinical stage, histologic grade and lymph node metastasis. Abnormal expression of TK1 in UCEC was related to promoter methylation while gene mutation was not frequent. TK1 and its associated genes appeared to be prominent in cell cycle and DNA replication, according to GO and KEGG analysis. Analysis of immune infiltration revealed a negative correlation between TK1 and CD8 + T cells, macrophages, and dendritic cells. In vitro experiments, TK1 knockdown resulted in the inhibition of proliferation, migration, invasion and EMT in UCEC cell lines.

[Mechanism of intestinal injury induced by acute diquat poisoning in rats].

OBJECTIVE: To investigate the effects of diquat (DQ) on the expression of intestinal pyroptosis-related proteins and tight junction proteins in rats,and to analyze the role of pyroptosis in the intestinal injury of rats with acute DQ poisoning. METHODS: A total of 36 Wistar male rats were randomly divided into control group, and 3 hours, 12 hours, 36 hours and 3 days exposure groups, with 6 rats in each group. Each exposure group was given 1/2 median lethal dose (LD50) of 115.5 mg/kg DQ by one-time gavage. The control group was given the same amount of normal saline by gavage. The control group was anesthetized at 3 hours after DQ gavage to take jejunal tissues; each exposure group was anesthetized at 3 hours, 12 hours, 36 hours, and 3 days after DQ gavage to take jejunal tissues, respectively. The general conditions of the rats were recorded. The pathological changes of jejunum tissue were observed by hematoxylin-eosin (HE) staining. The expression of intestinal pyroptosis-related proteins [NOD-like receptor protein 3 (NLRP3), cysteine aspartate-specific protease 1 (caspase-1), Gasdemin D (GSDMD)] in the intestinal tissues was observed by immunohistochemical staining. Western blotting was used to detect the expression of intestinal pyroptosis-related proteins and intestinal tight junction proteins (Occludin and Claudin-1). RESULTS: Light microscopy showed that pathological changes occurred in jejunum tissue at the early stage of exposure (3 hours), and the injury was the most serious in the 12 hours exposure group, with a large number of inflammatory cells infiltrating in the tissue, and the damage was significantly reduced after 3 days exposure. Immunohistochemical results showed that NLRP3, caspase-1 and GSDMD were expressed in the jejunal mucosa of the control group and the exposure groups, and the positive cells in the control group were less expressed with light staining. The expression of the above proteins in the exposed group was increased significantly and the staining was deep. Western blotting results showed that compared with the control group, the expression of NLRP3 protein in jejunum tissues of all groups was increased, with the most significant increase in the 36 hours group (NLRP3/ß-actin: 1.47±0.06 vs. 0.43±0.14, P < 0.01). Compared with the control group, the expression of GSDMD protein in the 3 hours, 12 hours and 36 hours exposure groups increased, and the expression of GSDMD protein in the 3 hours and 12 hours exposure groups increased significantly (GSDMD/ß-actin: 1.04±0.40, 1.25±0.15 vs. 0.65±0.25, both P < 0.05). The expression of caspase-1 protein was increased in 36 hours exposure group compared with the control group (caspase-1/ß-actin: 1.44±0.34 vs. 0.98±0.19, P > 0.05). Compared with the control group, the expression of Occludin and Claudin-1 proteins in each exposure group decreased, and the expression of Occludin proteins was significantly decreased in the 3 hours, 12 hours, and 36 hours exposure groups decreased significantly (Occludin/ß-actin: 0.74±0.17, 0.91±0.20, 0.79±0.23 vs. 1.41±0.08, all P < 0.05). Although the protein expression of Claudin-1 decreased in each exposure group, the difference was not statistically significant. CONCLUSIONS: The intestinal injury caused by acute DQ poisoning may be related to the activation of pyroptosis pathway of small intestinal cells and the reduction of the density of intercellular junctions.

Association of long-term ozone air pollution and age-related macular degeneration in older Chinese population.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of legal blindness. It remains unclear whether and to what extent the ambient ozone pollution could increase the risk of AMD. METHODS: A nationwide cross-sectional survey was conducted in 129 major cities in 27 of 31 provincial regions across China from 2018 to 2021. Data in relation to demographics, residential address, and medical histories were collected. The exposure-response relationship between ozone exposure and AMD was explored using the restricted cubic splines. A piecewise logistic regression model was used to examine the magnitudes of the association, after adjusting demographic, social-economic and co-pollutants. Residential ozone exposures were estimated using a satellite-based model. RESULTS: A total of 624,167 middle-aged and older participants were included in the final analyses, the overall prevalence of AMD was 16.76 %. The risk of AMD was consistently increasing with higher warm-season ozone concentration, and the risk became much larger after the cut-off of 110 µg/m3 (approximately 50 ppb). Every 10 µg/m3 increment in warm-season ozone concentration, the adjusted odds ratio (OR) for AMD were 1.15 (1.13, 1.16) and 1.66 (1.63, 1.69) when the warm-season ozone concentration was below or above 110 µg/m3, respectively. CONCLUSION: This large-scale nationwide study provides the first epidemiological evidence demonstrating significant associations between long-term residential ozone exposure and AMD prevalence. Based on our findings, in conjunction with WHO global air quality guidelines, we suggest that a warm-season ozone of 110 µg/m3 should be adopted for middle-aged and older populations to reduce the risk of AMD. Ongoing efforts to reduce ozone exposure in communities through improved air quality regulations and public education are essential for the improvement of public health.

TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.

Ovarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.

Prognostic value of plasma diquat concentration in patients with acute oral diquat poisoning: a retrospective study.

Objectives: Diquat poisoning is an important public health and social security agency. This study aimed to develop a prognostic model and evaluate the prognostic value of plasma diquat concentration in patients with acute oral diquat poisoning, focusing on how its impact changes over time after poisoning. Methods: This was a retrospective cohort study using electronic healthcare reports from the Second Hospital of Hebei Medical University. The study sample included 80 patients with acute oral Diquat poisoning who were admitted to the hospital between January 2019 and May 2022. Time-to-event analyses were performed to assess the risk of all-cause mortality (30 days and 90 days), controlling for demographics, comorbidities, vital signs, and other laboratory measurements. The prognostic value of plasma DQ concentration on admission was assessed by computing the area under a time-dependent receiver operating characteristic curve (ROC). Results: Among the 80 patients, 29 (36.25%) patients died, and 51 (63.75%) patients survived in the hospital. Non-survivors had a median survival time (IQR) of 1.3(1.0) days and the longest survival time of 4.5 days after DQ poisoning. Compared with non-survivors, survivors had significantly lower amounts of ingestion, plasma DQ concentration on admission, lungs injury within 24 h after admission, liver injury within 24 h after admission, kidney injury within 24 h after admission, and CNS injury within 36 h after admission, higher APACHE II score and PSS within 24 h after admission (all p < 0.05). Plasma Diquat concentration at admission (HR = Exp (0.032-0.059 × ln (t))) and PSS within 24 h after admission (HR: 4.470, 95%CI: 1.604 ~ 12.452, p = 0.004) were independent prognostic factors in the time-dependent Cox regression model. Conclusion: Plasma DQ concentration at admission and PSS within 24 h after admission are independent prognostic factors for the in-hospital case fatality rate in patients with acute oral DQ poisoning. The prognostic value of plasma DQ concentration decreased with time.

Associations between fine particulate air pollution with small-airway inflammation: A nationwide analysis in 122 Chinese cities.

Alveolar nitric oxide is a non-invasive indicator of small-airway inflammation, a key pathophysiologic mechanism underlying lower respiratory diseases. However, no epidemiological studies have investigated the impact of fine particulate matter (PM2.5) exposure on the concentration of alveolar nitric oxide (CANO). To explore the associations between PM2.5 exposure in multiple periods and CANO, we conducted a nationwide cross-sectional study in 122 Chinese cities between 2019 and 2021. Utilizing a satellite-based model with a spatial resolution of 1 × 1 km, we matched long-term, mid-term, and short-term PM2.5 exposure for 28,399 individuals based on their home addresses. Multivariable linear regression models were applied to estimate the associations between PM2.5 at multiple exposure windows and CANO. Stratified analyses were also performed to identify potentially vulnerable subgroups. We found that per interquartile range (IQR) unit higher in 1-year average, 1-month average, and 7-day average PM2.5 concentration was significantly associated with increments of 17.78% [95% confidence interval (95%CI): 12.54%, 23.26%], 8.76% (95%CI: 7.35%, 10.19%), and 4.00% (95%CI: 2.81%, 5.20%) increment in CANO, respectively. The exposure-response relationship curves consistently increased with the slope becoming statistically significant beyond 20 µg/m3. Males, children, smokers, individuals with respiratory symptoms or using inhaled corticosteroids, and those living in Southern China were more vulnerable to PM2.5 exposure. In conclusion, our study provided novel evidence that PM2.5 exposure in long-term, mid-term, and short-term periods could significantly elevate small-airway inflammation represented by CANO. Our results highlight the significance of CANO measurement as a non-invasive tool for early screening in the management of PM2.5-related inflammatory respiratory diseases.