Intermittent hypoxia training enhances Aß endocytosis by plaque associated microglia via VPS35-dependent TREM2 recycling in murine Alzheimer's disease.

BACKGROUND: Beta-amyloid (Aß) deposition in the brain parenchyma is a crucial initiating step in the amyloid cascade hypothesis of Alzheimer's disease (AD) pathology. Furthermore, dysfunction of plaque-associated microglia, also known as disease-associated microglia (DAM) has been reported to accelerate Aß deposition and cognitive impairment. Our previous research demonstrated that intermittent hypoxia training (IHT) improved AD pathology by upregulating autophagy in DAM, thereby enhancing oligomeric Aß (oAß) clearance. Considering that oAß internalization is the initial stage of oAß clearance, this study focused on the IHT mechanism involved in upregulating Aß uptake by DAM. METHODS: IHT was administered to 8-month-old APP/PS1 mice or 6-month-old microglial vacuolar protein sorting 35 (VPS35) knockout mice in APP/PS1 background (MG VPS35 KO: APP/PS1) for 28 days. After the IHT, the spatial learning-memory capacity of the mice was assessed. Additionally, AD pathology was determined by estimating the nerve fiber and synapse density, Aß plaque deposition, and Aß load in the brain. A model of Aß-exposed microglia was constructed and treated with IHT to explore the related mechanism. Finally, triggering receptor expressed on myeloid cells 2 (TREM2) intracellular recycling and Aß internalization were measured using a fluorescence tracing technique. RESULTS: Our results showed that IHT ameliorated cognitive function and Aß pathology. In particular, IHT enhanced Aß endocytosis by augmenting the intracellular transport function of microglial TREM2, thereby contributing to Aß clearance. Furthermore, IHT specifically upregulated VPS35 in DAM, the primary cause for the enhanced intracellular recycling of TREM2. IHT lost ameliorative effect on Aß pathology in MG VPS35 KO: APP/PS1 mice brain. Lastly, the IHT mechanism of VPS35 upregulation in DAM was mediated by the transcriptional regulation of VPS35 by transcription factor EB (TFEB). CONCLUSION: IHT enhances Aß endocytosis in DAM by upregulating VPS35-dependent TREM2 recycling, thereby facilitating oAß clearance and mitigation of Aß pathology. Moreover, the transcriptional regulation of VPS35 by TFEB demonstrates a close link between endocytosis and autophagy in microglia. Our study further elucidates the IHT mechanism in improving AD pathology and provides evidence supporting the potential application of IHT as a complementary therapy for AD.

Restoration of functional endometrium in an intrauterine adhesion rat model with endometrial stromal cells transplantation.

BACKGROUND: Intrauterine adhesion (IUA) as a prevalent gynecological disease is developed from infection or trauma. However, therapeutic strategies to repair damaged endometrium are relatively limited. Emerging studies have shed light on the crucial role of endometrial stromal cells (EnSCs) in the process of uterine endometrial regeneration. EnSCs isolated from the uterine endometrium have similar characteristics to mesenchymal stem cells (MSCs). However, it is still unknown whether EnSCs could be used as donor cells to treat IUA. The aim of this study was to evaluate the potential efficacy of EnSCs in treating rat IUA. METHODS: Human EnSCs were isolated from the endometrial tissue of healthy female donors and subjected to extensive expansion and culture in vitro. Immunofluorescence, flow cytometry, cell proliferation assay, trilineage differentiation experiment, and decidualization assay were used to characterize the biological properties of EnSCs. We evaluated the immunoregulatory potential of EnSCs by analyzing their secreted cytokines and conducting bulk RNA sequencing after IFN-γ treatment. After EnSCs were transplanted into the uterine muscle layer in IUA rats, their therapeutic effects and underlying mechanisms were analyzed using histological analysis, Q-PCR, fertility and pregnancy outcome assay, and transcriptome analysis. RESULTS: We successfully isolated EnSCs from the endometrium of human donors and largely expanded in vitro. EnSCs exhibited characteristics of mesenchymal stem cells and retained responsiveness to sex hormones. Following IFN-γ stimulation, EnSCs upregulated the anti-inflammatory cytokines and activated immunosuppressive molecules. Xenogeneic transplantation of EnSCs successfully repaired injured endometrium and significantly restored the pregnancy rate in IUA rats. Mechanistically, the therapeutic effects of EnSCs on IUA endometrium functioned through anti-inflammation, anti-fibrosis and the secretion of regeneration factor. CONCLUSIONS: Due to their large expansion ability, immunoregulatory properties, and great potential in treating IUA, EnSCs, as a valuable source of donor cells, could offer a potential treatment avenue for injury-induced IUA.

Discovery, characterization and mechanism of a Microbacterium esterase for key d-biotin chiral intermediate synthesis.

Esterases are crucial biocatalysts in chiral compound synthesis. Herein, a novel esterase EstSIT01 belonging to family V was identified from Microbacterium chocolatum SIT101 through genome mining and phylogenetic analysis. EstSIT01 demonstrated remarkable efficiency in asymmetrically hydrolyzing meso-dimethyl ester [Dimethyl cis-1,3-Dibenzyl-2-imidazolidine-4,5-dicarboxyate], producing over 99% yield and 99% enantiomeric excess (e.e.) for (4S, 5R)-monomethyl ester, a crucial chiral intermediate during the synthesis of d-biotin. Notably, the recombinant E. coli expressing EstSIT01 exhibited over 40-fold higher activity than that of the wild strain. EstSIT01 displays a preference for short-chain p-NP esters. The optimal temperature and pH were 45 °C and 10.0, with Km and kcat values of 0.147 mmol/L and 5.808 s- 1, respectively. Molecular docking and MD simulations suggest that the high stereoselectivity for meso-diester may attribute to the narrow entrance tunnel and unique binding pocket structure. Collectively, EstSIT01 holds great potential for preparing chiral carboxylic acids and esters.

Osmosensor-mediated control of Ca2+ spiking in pollen germination.

Higher plants survive terrestrial water deficiency and fluctuation by arresting cellular activities (dehydration) and resuscitating processes (rehydration). However, how plants monitor water availability during rehydration is unknown. Although increases in hypo-osmolarity-induced cytosolic Ca2+ concentration (HOSCA) have long been postulated to be the mechanism for sensing hypo-osmolarity in rehydration1,2, the molecular basis remains unknown. Because osmolarity triggers membrane tension and the osmosensing specificity of osmosensing channels can only be determined in vivo3-5, these channels have been classified as a subtype of mechanosensors. Here we identify bona fide cell surface hypo-osmosensors in Arabidopsis and find that pollen Ca2+ spiking is controlled directly by water through these hypo-osmosensors-that is, Ca2+ spiking is the second messenger for water status. We developed a functional expression screen in Escherichia coli for hypo-osmosensitive channels and identified OSCA2.1, a member of the hyperosmolarity-gated calcium-permeable channel (OSCA) family of proteins6. We screened single and high-order OSCA mutants, and observed that the osca2.1/osca2.2 double-knockout mutant was impaired in pollen germination and HOSCA. OSCA2.1 and OSCA2.2 function as hypo-osmosensitive Ca2+-permeable channels in planta and in HEK293 cells. Decreasing osmolarity of the medium enhanced pollen Ca2+ oscillations, which were mediated by OSCA2.1 and OSCA2.2 and required for germination. OSCA2.1 and OSCA2.2 convert extracellular water status into Ca2+ spiking in pollen and may serve as essential hypo-osmosensors for tracking rehydration in plants.

Genome-wide identification of phasiRNAs in Arabidopsis thaliana, and insights into biogenesis, temperature sensitivity, and organ specificity.

The knowledge of biogenesis and target regulation of the phased small interfering RNAs (phasiRNAs) needs continuous update, since the phasiRNA loci are dynamically evolved in plants. Here, hundreds of phasiRNA loci of Arabidopsis thaliana were identified in distinct tissues and under different temperature. In flowers, most of the 24-nt loci are RNA-dependent RNA polymerase 2 (RDR2)-dependent, while the 21-nt loci are RDR6-dependent. Among the RDR-dependent loci, a significant portion is Dicer-like 1-dependent, indicating the involvement of microRNAs in their expression. Besides, two TAS candidates were discovered. Some interesting features of the phasiRNA loci were observed, such as the strong strand bias of phasiRNA generation, and the capacity of one locus for producing phasiRNAs by different increments. Both organ specificity and temperature sensitivity were observed for phasiRNA expression. In leaves, the TAS genes are highly activated under low temperature. Several trans-acting siRNA-target pairs are also temperature-sensitive. In many cases, the phasiRNA expression patterns correlate well with those of the processing signals. Analysis of the rRNA-depleted degradome uncovered several phasiRNA loci to be RNA polymerase II-independent. Our results should advance the understanding on phasiRNA biogenesis and regulation in plants.

Investigating the Bidirectional Association of Rheumatoid Arthritis and Thyroid Function: A Methodologic Assessment of Mendelian Randomization.

OBJECTIVE: Rheumatoid arthritis (RA) and thyroid dysfunction are frequently observed in the same patient. However, whether they co-occur or exhibit a causal relationship remains uncertain. We aimed to systematically investigate the causal relationship between RA and thyroid function using a large sample and advanced methods. METHODS: Bidirectional two-sample Mendelian randomization (MR) analysis was performed based on RA and six thyroid function trait data sets from the European population. The robustness of the results was demonstrated using multiple MR methods and a series of sensitivity analyses. Multivariable MR using Bayesian model averaging (MR-BMA) was performed to adjust for possible competing risk factors. A sensitivity data set, which included data from patients with seropositive RA and controls, was used to repeat the analyses. Furthermore, enrichment analysis was employed to discover the underlying mechanism between RA and thyroid functions. RESULTS: A significantly positive causal effect was identified for RA on autoimmune thyroid disease (AITD) as well as for AITD on RA (P < 0.001). Further sensitivity analyses showed consistent causal estimates from a variety of MR methods. After removing the outliers, MR-BMA results showed that RA and AITD were independent risk factors in their bidirectional causality, even in the presence of other competing risk factors (adjusted P < 0.05). Enrichment analysis showed immune cell activation and immune response play crucial roles in them. CONCLUSION: Our results illustrate the significant bidirectional causal effect of RA and AITD, which holds even in multiple competing risk factors. Clinical screening for thyroid dysfunction in patients with RA deserves further attention, and vice versa.

Functionalized lipid nanoparticles modulate the blood-brain barrier and eliminate α-synuclein to repair dopamine neurons.

The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential disease-modifying efficacy, have difficulty in crossing the blood-brain barrier (BBB) due to their large molecular weight. Herein, we fabricate multi-functionalized lipid nanoparticles (LNP) Lpc-BoSA/CSO with BBB targeting, permeability-increasing and responsive release functions. Borneol is chemically bonded with stearic acid and, as one of the components of Lpc-BoSA/CSO, is used to increase BBB permeability. Immunofluorescence results of brain tissue of 15-month-old C57BL/6 mice show that Lpc-BoSA/CSO disperses across the BBB into brain parenchyma, and the amount is 4.21 times greater than that of conventional LNP. Motor symptoms of mice in Lpc-BoSA/CSO-Exe group are significantly improved, and the content of dopamine is 1.85 times (substantia nigra compacta) and 1.49 times (striatum) that of PD mice. α-Synuclein expression and Lewy bodies deposition are reduced to 51.85% and 44.72% of PD mice, respectively. Immunohistochemical mechanism studies show AKT expression in Lpc-BoSA/CSO-Exe is 4.23 times that of PD mice and GSK-3ß expression is reduced to 18.41%. Lpc-BoSA/CSO-Exe could reduce the production of α-synuclein and Lewy bodies through AKT/GSK-3ß pathway, and effectively prevent the progressive deterioration of Parkinson's disease. In summary, Lpc-BoSA/CSO-Exe increases the entry of exenatide into brain and promotes its clinical application for Parkinson's disease therapy.

Molecular mechanism of thiram-induced abnormal chondrocyte proliferation via lncRNA MSTRG.74.1-BNIP3 axis.

Thiram, a widely used organic pesticide in agriculture, exhibits both bactericidal and insecticidal effects. However, prolonged exposure to thiram has been linked to bone deformities and cartilage damage, contributing to the development of tibial dyschondroplasia (TD) in broilers and posing a significant threat to global agricultural production. TD, a prevalent nutritional metabolic disease, manifests as clinical symptoms like unstable standing, claudication, and sluggish movement in affected broilers. In recent years, there has been growing recognition of the regulatory role of long non-coding RNA (lncRNA) in tibial cartilage formation among broilers through diverse signaling pathways. This study employs in vitro experimental models, growth performance analysis, and clinical observation to assess broilers' susceptibility to thiram pollution. Transcriptome sequencing analysis revealed a significant elevation in the expression of lncRNA MSTRG.74.1 in both the con group and the thiram-induced in vitro group. The results showed that lncRNA MSTRG.74.1 plays a pivotal role in influencing the proliferation and abnormal differentiation of chondrocytes. This regulation occurs through the negative modulation of apoptotic genes, including Bax, Cytc, Bcl2, Apaf1, and Caspase3, along with genes Atg5, Beclin1, LC3b, and protein p62. Moreover, the overexpression of lncRNA MSTRG.74.1 was found to regulate broiler chondrocyte development by upregulating BNIP3. In summary, this research sheds light on thiram-induced abnormal chondrocyte proliferation in TD broilers, emphasizing the significant regulatory role of the lncRNA MSTRG.74.1-BNIP3 axis, which will contribute to our understanding of the molecular mechanisms underlying TD development in broilers exposed to thiram.

Glutenin-chitosan 3D porous scaffolds with tunable stiffness and systematized microstructure for cultured meat model.

A glutenin (G)-chitosan (CS) complex (G-CS) was cross-linked by water annealing with aim to prepare structured 3D porous cultured meat scaffolds (CMS) here. The CMS has pore diameters ranging from 18 to 67 µm and compressive moduli from 16.09 to 60.35 kPa, along with the mixing ratio of G/CS. SEM showed the porous organized structure of CMS. FTIR and CD showed the increscent content of α-helix and ß-sheet of G and strengthened hydrogen-bondings among G-CS molecules, which strengthened the stiffness of G-CS. Raman spectra exhibited an increase of G concentration resulted in higher crosslinking of disulfide-bonds in G-CS, which aggrandized the bridging effect of G-CS and maintained its three-dimensional network. Cell viability assay and immuno-fluorescence staining showed that G-CS effectively facilitated the growth and myogenic differentiation of porcine skeletal muscle satellite cells (PSCs). CLSM displayed that cells first occupied the angular space of hexagon and then ring-growth circle of PSCs were orderly formed on G-CS. The texture and color of CMS which loaded proliferated PSCs were fresh-meat like. These results showed that physical cross-linked G-CS scaffolds are the biocompatible and stable adaptable extracellular matrix with appropriate architectural cues and natural micro-environment for structured CM models.

Molecular mechanism of miR-203a targeting Runx2 to regulate thiram induced-chondrocyte development.

Thiram is a kind of organic compound, which is commonly used for sterilization, insecticidal and deodorization in daily life. Its toxicology has been broadly studied. Recently, more and more microRNAs have been shown to participate in the regulation of cartilage development. However, the potential mechanism by which microRNA regulates chondrocyte growth is still unclear. Our experiments have demonstrated that thiram can hamper chondrocytes development and cause a significant increase in miR-203a content in vitro and in vivo trials. miR-203a mimic significantly decrease in mRNA and protein expression of Wnt4, Runx2, COL2A1, ß-catenin and ALP, and significantly enhance the mRNA and protein levels of GSK-3ß. It has been observed that overexpression of miR-203a hindered chondrocytes development. In addition, Runx2 was confirmed to be a direct target of miR-203a by dual luciferase report gene assay. Transfection of si-Runx2 into chondrocytes reveals that significant downregulation of genes is associated with cartilage development. Overall, these results suggest that overexpression of miR-203a inhibits the expression of Runx2. These findings are conducive to elucidate the mechanism of chondrocytes dysplasia induced by thiram and provide new research ideas for the toxicology of thiram.

Association between polycyclic aromatic hydrocarbons and infertility in U.S. women: National Health and Nutrition Examination Survey 2013-2016.

Although there is a body of research indicating the potential impact of polycyclic aromatic hydrocarbons (PAHs) exposure on male infertility, the understanding of how PAH might affect female infertility is still limited. This study aimed to evaluate associations of PAHs, both individually and as a mixture, with female infertility using multiple logistic regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (QGC) models based on data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016. The study included 729 female participants. Multiple logistic regression results indicated that there was a significant association between the third tertile of 2-hydroxy fluorene (2-OHFLU) and female infertility, and the OR was 2.84 (95% CI: 1.24-6.53, P value = 0.015) compared with the first tertile after adjusting for the potential covariates. The BKMR model revealed a positive overall trend between mixed PAH exposure and female infertility, particularly when the mixture was at or above the 55th percentile, where 2-hydroxynaphthalene (2-OHNAP) and 1-hydroxypyrene (1-OHPYR) were the primary influences of the mixture. The univariate exposure-response function indicated positive associations between individual PAH exposure, specifically 2-OHNAP, 2-OHFLU, and 1-OHPYR, and female infertility. The QGC model also indicated a positive trend between exposure to a mixture of PAHs and female infertility, although it did not reach statistical significance (OR = 1.33, 95%CI: 0.86-2.07), with 1-OHPYR having the greatest positive effect on the outcome. This study suggested that exposure to PAHs may be associated with female infertility and further research is needed to consolidate and confirm these findings.

Environmental health hazards of untreated livestock wastewater: potential risks and future perspectives.

Due to technological and economic limitations, waste products such as sewage and manure generated in livestock farming lack comprehensive scientific and centralized treatment. This leads to the exposure of various contaminants in livestock wastewater, posing potential risks to both the ecological environment and human health. This review evaluates the environmental and physical health risks posed by common pollutants in livestock wastewater and outlines future treatment methods to mitigate these risks. Residual wastes in livestock wastewater, including pathogenic bacteria and parasites surviving after epidemics or diseases on various farms, along with antibiotics, organic wastes, and heavy metals from farming activities, contribute to environmental damage and pose risks to human health. As the livestock industry's development increasingly impacts society's future negatively, addressing the issue of residual wastes in livestock wastewater discharge becomes imperative. Ongoing advancements in wastewater treatment systems are consistently updating and refining practices to effectively minimize waste exposure at the discharge source, mitigating risks to environmental ecology and human health. This review not only summarizes the "potential risks of livestock wastewater" but also explores "the prospects for the development of wastewater treatment technologies" based on current reports. It offers valuable insights to support the long-term and healthy development of the livestock industry and contribute to the sustainable development of the ecological environment.

AhR Activation Ameliorates Intestinal Barrier Damage in Immunostressed Piglets by Regulating Intestinal Flora and Its Metabolism.

The primary factor leading to elevated rates of diarrhea and decreased performance in piglets is immunological stress. The regulation of immune stress through the intestinal flora is a crucial mechanism to consider. In total, 30 weaned piglets were randomly allocated to five groups: the basal diet group (Control), basal diet + lipopolysaccharides group (LPS), basal diet + 250 µg/kg 6-Formylindolo [3,2-b] carbazole + LPS group (FICZ), basal diet + 3mg/kg Cardamonin + LPS group (LCDN), and basal diet + 6mg/kg Cardamonin + LPS group (HCDN/CDN). The results showed that compared with those of the LPS group, the expression of tight junction proteins (occludin; claudin-1) in the FICZ group was significantly increased, and the mRNA levels of IL-1ß and TNF-α were significantly reduced (p < 0.05). HCDN treatment had a better effect on LPS-induced intestinal barrier damage in this group than it did in the LCDN group. HCDN treatment leads to a higher villus height (VH), a higher ratio of villi height to crypt depth (V/C), higher tight junction proteins (ZO-1; occludin), and higher short-chain fatty acids (SCFAs). In addition, correlation analyses showed that Succinivibrio was positively correlated with several SCFAs and negatively correlated with prostaglandin-related derivatives in the FICZ group and CDN group (p < 0.05). In summary, Cardamonin alleviates intestinal mucosal barrier damage and inflammatory responses by regulating the intestinal microbiota and its metabolism.

Subtle structural alteration in indisulam switches the molecular mechanisms for the inhibitory effect on the migration of gastric cancer cells.

Gastric cancer is a highly metastatic malignant tumor with high morbidity and mortality globally. Recent studies reported that sulfonamide derivatives such as indisulam exhibited inhibitory effects on the viability and migration of cancer cells. However, multiple clinical trials revealed that indisulam did not significantly prevent cancer progression due to metastasis and drug resistance. Therefore, it is necessary to discover new potent derivatives to explore alternative therapeutic strategies. Here, we synthesize multiple indisulam derivatives and examine their inhibitory effects on the viability and migration of gastric cancer cells. Among them, compounds SR-3-65 and WXM-1-170 exhibit better inhibitory effects on the migration of gastric cancer cells than indisulam. Mechanistically, we discover that they could attenuate the PI3K/AKT/GSK-3ß/ß-catenin signaling pathway and lead to the suppression of epithelial-to-mesenchymal transition (EMT)-related transcription factors. The influence of SR-3-65 on the migration of gastric cancer cells is blocked by the PI3K inhibitor LY294002 while SR-3-65 and WXM-1-170 reverse the effect of PI3K activator 740 Y-P on the migration of gastric cancer cells. Molecular docking and molecular dynamics simulation further confirm that PI3K is the target of SR-3-65. Our study unveils a novel mechanism by which SR-3-65 and WXM-1-170 inhibit the migration of gastric cancer cells. Together with the previous discovery, we reveal that subtle structural change in indisulam results in a striking switch on the molecular targets and their associated signaling pathways for the inhibition of the migration of gastric cancer cells. These findings might provide informative insights for the development of targeted therapy for gastric cancer.

Metagenomic next-generation sequencing for diagnosis of fatal Balamuthia amoebic encephalitis.

INTRODUCTION: Balamuthia amoebic encephalitis (BAE), caused by Balamuthia mandrillaris, is a rare and life-threatening infectious disease with no specific and effective treatments available. The diagnosis of BAE at an early stage is difficult because of the non-specific clinical manifestations and neuroimaging. CASE DESCRIPTION: A 52-year-old male patient, who had no previous history of skin lesions, presented to the emergency department with an acute headache, walking difficulties, and disturbance of consciousness. The patient underwent a series of examinations, including regular cerebrospinal fluid (CSF) studies and magnetic resonance imaging, and tuberculous meningoencephalitis was suspected. Despite being treated with anti-TB drugs, no clinical improvement was observed in the patient. Following corticosteroid therapy, the patient developed a rapid deterioration in consciousness with dilated pupils. Metagenomic next-generation sequencing (mNGS) revealed an unexpected central nervous system (CNS) amoebic infection, and the patient died soon after the confirmed diagnosis. CONCLUSION: This study highlights the application of mNGS for the diagnosis of patients with suspected encephalitis or meningitis, especially those caused by rare opportunistic infections.

Association between Psoriasis and Renal Functions: An Integration Study of Observational Study and Mendelian Randomization.

Psoriasis is an autoimmune-mediated disease with several comorbidities in addition to typical skin lesions. Increasing evidence shows the relationships between psoriasis and renal functions, but the relationship and causality remain unclear. We aimed to investigate the associations and causality between psoriasis and four renal functions, including the estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), urine albumin to creatinine ratio (UACR), and chronic kidney disease (CKD). For the population-based study, we analyzed the National Health and Nutrition Examination Survey (NHANES) data from five cycles (2003-2006 and 2009-2014) on psoriasis and renal functions. Subgroup analyses were conducted among different categories of participants. Meanwhile, a bidirectional two-sample Mendelian randomization (TSMR) study in European populations was also performed using summary-level genetic datasets. Causal effects were derived by conducting an inverse-variance weighted (MR-IVW) method. A series of pleiotropy-robust MR methods was employed to validate the robustness. Multivariable MR (MVMR) was conducted to complement the result when five competing risk factors were considered. A total of 20,244 participants were enrolled in the cross-sectional study, where 2.6% of them had psoriasis. In the fully adjusted model, participants with psoriasis had significantly lower eGFR (p = 0.025) compared with the healthy group. Individuals who are nonoverweight are more likely to be affected by psoriasis, leading to an elevation of BUN (Pint = 0.018). In the same line, TSMR showed a negative association between psoriasis and eGFR (p = 0.016), and sensitive analysis also consolidated the finding. No causality was identified between psoriasis and other renal functions, as well as the inverse causality (p > 0.05). The MVMR method further provided quite consistent results when adjusting five confounders (p = 0.042). We detected a significant negative effect of psoriasis on eGFR, with marginal association between BUN, UACR, and CKD. The adverse of psoriasis on the renal should merit further attention in clinical cares.

JUJUNCAO-Stem-Based Interfacial Solar-Driven Evaporator with Natural Two-Phase Composite Structures of Functional Partition and Inherent Ultralow Vaporization Enthalpy of Water for Stable and Efficient Steam Production.

The interfacial solar-driven evaporation has been deemed as an environmentally friendly approach for freshwater generation. Nevertheless, there is still a challenge to obtain solar evaporators with efficient vapor production from low-cost and renewable biomass through a simple preparation process. Herein, the JUJUNCAO stem was selected as the substrate material, and a kind of interfacial solar-driven evaporator with natural two-phase composite structures and inherent ultralow water vaporization enthalpy was constructed by a dip-coating process. The natural two-phase composite structures were utilized as independent functional partition: the low-tortuosity and hydrophilic vascular bundles served as hierarchical channels for rapid water transportation and continuous steam escape, and the honeycomb-like parenchyma cells were considered natural heat insulators for effective thermal management. Furthermore, the JUJUNCAO stem exhibited inherent ultralow water vaporization enthalpy which was only 1.15 kJ g-1. Benefiting from the natural two-phase composite structures of functional partition and inherent ultralow water vaporization enthalpy, the C-Js evaporator could achieve an evaporation rate of 2.77 kg m-2 h-1 with an efficiency of 85.6% under 1 sun illumination. Meanwhile, the C-Js exhibited a stable and ideal evaporation performance and metal ion rejection behavior in the actual brine desalination process. Owing to the cost-effective and simple pretreatment process, the C-Js evaporator has the potential for freshwater generation in undeveloped areas.

The effect and mechanism of low-molecular-weight heparin on the decidualization of stromal cells in early pregnancy.

OBJECTIVE: This study aimed to analyze the effect of low-molecular-weight heparin (LMWH) on the decidualization of stromal cells in early pregnancy and explore the effect of LMWH on pregnancy outcomes. METHODS: Recurrent spontaneous abortion (RSA) mouse model (CBA/J × DBA/2) and normal pregnant mouse model (CBA/J × BALB/c) were established. The female mice were checked for a mucus plug twice daily to identify a potential pregnancy. When a mucus plug was found, conception was considered to have occurred 12 h previously. The pregnant mice were divided randomly into a normal pregnancy control group, an RSA model group, and an RSA + LMWH experimental group (n = 10 mice in each group). Halfway through the 12th day of pregnancy, the embryonic loss of the mice was observed; a real-time quantitative polymerase chain reaction was used to detect the messenger ribonucleic acid (mRNA) expressions of prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) in the decidua of the mice. Additionally, the decidual tissues of patients with RSA and those of normal women in early pregnancy who required artificial abortion were collected and divided into an RSA group and a control group. Decidual stromal cells were isolated and cultured to compare cell proliferation between the two groups, and cellular migration and invasion were detected by membrane stromal cells. Western blotting was used to detect the protein expressions of proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metalloproteinase- (MMP) 2, and MMP-7 in stromal cells treated with LMWH. RESULTS: Compared with the RSA group, LMWH significantly reduced the pregnancy loss rate in the RSA mice (p < 0.05). Compared with the RSA group, the LMWH + RSA group had significantly higher expression levels of PRL and IGFBP1 mRNA (p < 0.01). LMWH promoted the proliferation, migration, and invasion of human decidual stromal cells; compared with the control group, the expression levels of MMP-2, MMP-7, cyclin D1, and PCNA proteins in the decidual stromal cells of the LMWH group increased (p < 0.05). CONCLUSIONS: The use of LMWH can improve pregnancy outcomes by enhancing the proliferation and migration of stromal cells in early pregnancy and the decidualization of stromal cells.

A system review of central nervous system tumors on children in China: epidemiology and clinical characteristics.

BACKGROUND: Central nervous system (CNS) tumors are the most common solid tumors in children and the leading cause of cancer-related death in the latter. Currently, the incidence rate exceeds that of leukemia and ranks first in the incidence of malignant tumors in children. METHODS: The epidemiological data on childhood CNS tumors were collected from the Chinese Cancer Registry Annual Report. The annual percent change (APC) of incidence and mortality-rate changes were estimated via Joinpoint regression. Due to a lack of pertinent data, we performed a system review on the clinical-pathological characteristics in Chinese publications. RESULTS: There was no significant increase in the incidence rate (APC: -0.1, 95% CI: -1.5 to 1.3), but there was a significant increase in the mortality rate (APC: 1.8, 95% CI: 0.3 to 3.4) for childhood CNS tumors. In the subgroup analysis, there were significant increases in both the incidence and mortality rates in rural areas (APC in the incidence: 6.2, 95% CI: 2.4 to 10.2; APC in mortality: 4.4, 95% CI: 0.4 to 8.4). The most common location and type of childhood CNS were, respectively, the cerebral hemisphere (25.5%, 95% CI: 21.7% to 29.4%) and astrocytomas (26.8%, 95% CI: 23.9% to 29.6%). CONCLUSIONS: The epidemiological trends, and the relevant prediction, highlighted the need to pay continual attention to childhood CNS tumors, and the clinicopathology evinced its own distinctive characteristics. Timely detection and effective treatment must be further promoted regarding childhood CNS tumors with a view to decreasing the disease burden, especially in rural areas.

Mechanism Exploration of Environmental Pollutants on Premature Ovarian Insufficiency: a Systematic Review and Meta-analysis.

As a public health problem, premature ovarian insufficiency leads to infertility or sub-fertility. In addition to premature ovarian insufficiency (POI) increases the lifetime risk of bone fragility, cardiovascular disease, and cognitive impairment. To investigate the effects of environmental pollutants on the occurrence of POI and explore its mechanism, we conducted a computer search for articles published in electronic databases by December 13, 2022. Three reviewers independently examined all included studies and scored the qualities of included studies using the Newcastle-Ottawa Scale criteria. In this meta-analysis, eight clinical studies as well as ten preclinical findings showed a pooled OR of 2.331 and 95% CI of 1.968-2.760. This confirms that environmental pollutants, including POPs, heavy metals, PAEs, PAHs, cosmetic and pharmaceutical products, and cigarette smoke, are indeed significant risk factors for POI. In addition, it is demonstrated from the results of this study that signaling pathway of calcium and PI3K Akt and Xpnpep2, Col1, Col3, Col4, Cx43, Egr3, Tff1, and Ptgs2 genes may all be involved in the process. Environmental pollutants, including POPs, heavy metals, PAEs, PAHs, cosmetic and pharmaceutical products, and cigarette smoke, are indeed significant risk factors for POI.