Association between Mixed Heavy Metal Exposure and Arterial Stiffness, with Alkaline Phosphatase Identified as a Mediator.

Elevated arterial stiffness has been associated with exposure to heavy metals such as lead (Pb) and cadmium (Cd). However, the collective impact of multiple metals and the underlying mechanisms are not fully elucidated. The purpose of this study was to assess the combined effects of exposure to nine heavy metals on arterial stiffness and explore whether serum alkaline phosphatase (ALP) acts as a mediator in this relationship. In the retrospective analysis, data from 8,700 participants were retrieved from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. Arterial stiffness was measured by estimated pulse wave velocity (ePWV). The cumulative impact of exposure to multiple metals was examined using adaptive elastic-net, environmental risk score, weighted quantile sum regression, and quantile g-computation. Additionally, mediation analysis was conducted to explore the potential mediating role of serum ALP. We found that combined exposure to multiple metals was consistently associated with elevated ePWV, with Ba, Pb, and Sb exhibiting the greatest contributions. Notably, serum ALP partially mediated the associations between individual (Pb, Sb) and mixed metal exposure with ePWV, with mediation proportions at 10.76% for Pb, 18.22% for Sb, and 11.07% for mixed metal exposure. In conclusion, this study demonstrates a clear association between exposure to heavy metals, either individually or in combination, and heightened arterial stiffness. Furthermore, the findings suggest that serum ALP activity may act as a mediator in these relationships.

Itm2a expression marks periosteal skeletal stem cells that contribute to bone fracture healing.

The periosteum contains skeletal stem/progenitor cells that contribute to bone fracture healing. However, the in vivo identity of periosteal skeletal stem cells (P-SSCs) remains unclear, and membrane protein markers of P-SSCs that facilitate tissue engineering are needed. Here, we identified integral membrane protein 2A (Itm2a) enriched in SSCs using single-cell transcriptomics. Itm2a+ P-SSCs displayed clonal multipotency and self-renewal and sat at the apex of their differentiation hierarchy. Lineage-tracing experiments showed that Itm2a selectively labeled the periosteum and that Itm2a+ cells were preferentially located in the outer fibrous layer of the periosteum. The Itm2a+ cells rarely expressed CD34 or Osx, but expressed periosteal markers such as Ctsk, CD51, PDGFRA, Sca1, and Gli1. Itm2a+ P-SSCs contributed to osteoblasts, chondrocytes, and marrow stromal cells upon injury. Genetic lineage tracing using dual recombinases showed that Itm2a and Prrx1 lineage cells generated spatially separated subsets of chondrocytes and osteoblasts during fracture healing. Bone morphogenetic protein 2 (Bmp2) deficiency or ablation of Itm2a+ P-SSCs resulted in defects in fracture healing. ITM2A+ P-SSCs were also present in the human periosteum. Thus, our study identified a membrane protein marker that labels P-SSCs, providing an attractive target for drug and cellular therapy for skeletal disorders.

Multi-omics analyses reveal aberrant differentiation trajectory with WNT1 loss-of-function in type XV osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a group of severe genetic bone disorders characterized by congenital low bone mass, deformity and frequent fractures. Type XV OI is a moderate to severe form of skeletal dysplasia caused by WNT1 variants. In this cohort study from southern China, we summarized the clinical phenotypes of patients with WNT1 variants and found that the proportion of type XV patients was around 10.3% (25 out of 243) with a diverse spectrum of phenotypes. Functional assays indicated that variants of WNT1 significantly impaired its secretion and effective activity, leading to moderate to severe clinical manifestations, porous bone structure and enhanced osteoclastic activities. Analysis of proteomic data from human skeleton indicated that the expression of SOST was dramatically reduced in type XV patients when comparing to the patients with COL1A1 quantitative variants. Single-cell transcriptome data generated from the human tibia samples of patients diagnosed with type XV OI and leg-length-discrepancy respectively, revealed aberrant differentiation trajectory of skeletal progenitors and impaired maturation of osteocytes with loss of WNT1, resulting in excessive CXCL12+ progenitors, fewer mature osteocytes and existence of abnormal cell populations with adipogenic characteristics. The integration of multi-omics data from human skeleton delineates how WNT1 regulates the differentiation and maturation of skeletal progenitors, which will provide a new direction for the treatment strategy of type XV osteogenesis imperfecta and relative low bone mass diseases such as early onset osteoporosis.

Osteogenesis imperfecta is a rare disease characterized by low bone mass, frequent fractures and long bone deformity. Type XV osteogenesis imperfect is an autosomal recessive disorder caused by WNT1 variants, while heterozygous variants of WNT1 result in early onset osteoporosis. In this cohort study, we summarized the clinical features of 25 patients diagnosed with type XV osteogenesis imperfect. The WNT1 variants were confirmed by genetic test. Molecular assays were conducted to reveal the impact of variants on WNT1 protein activity and bone structure. We then compared the protein levels in bone tissues isolated from the type XV patients and patients with mild deformity using proteomic method, and found the expression of SOST, mainly produced by mature osteoblasts and osteocytes, was dramatically reduced in type XV patients. We further compared the global mRNA expression levels in the skeletal cells using single-cell RNA sequencing. Analyses of these data indicated that more immature progenitors were identified and maturation of osteocytes was impaired with WNT1 loss-of-function. Our study helps to understand the underlying pathogenesis of type XV osteogenesis imperfecta.

A critical review of Mnammox coupled with the NDMO for innovative nitrogen removal.

In the context of increasing global nitrogen pollution, traditional biological nitrogen removal technologies like nitrification and denitrification are hindered by high energy consumption. Additionally, the deployment of anaerobic ammonium oxidation (Anammox) technology is constrained due to the slow growth rate of Anammox bacteria and there is a bottleneck in nitrogen removal efficiency. To overcome these technical bottlenecks, researchers have discovered a revolutionary nitrogen removal technology that cleverly combines the redox cycling of manganese with nitrification and denitrification reactions. In this new process, manganese dependent anaerobic ammonium oxidation (Mnammox) bacteria can convert NH4+ to N2 under anaerobic conditions, while nitrate/nitrite dependent manganese oxidation (NDMO) bacteria use NO3-/NO2- as electron acceptors to oxidize Mn2+ to Mn4+. Mn4+ acts as an electron acceptor in Mnammox reaction, thereby realizing the autotrophic nitrogen removal process. This innovative method not only simplifies the steps of biological denitrification, but also significantly reduces the consumption of oxygen and organic carbon, providing a more efficient and environmentally friendly solution to the problem of nitrogen pollution. The article initially provides a concise overview of prevalent nitrogen removal technologies and the application of manganese in these processes, and discusses the role of manganese in biogeochemical cycles, including its discovery, mechanism of action, microbial communities involved, and its impact on these key factors in the process. Subsequently, metabolic principles, benefits, advantages, and environmental considerations of Mnammox coupled with the NDMO process are analyzed in detail. Finally, this article summarizes the shortcomings of current research and looks forward to future research directions. The goal of this article is to provide a valuable reference for researchers to fully understand the application of manganese in nitrogen removal processes.

Association study of brain structure-function coupling and glymphatic system function in patients with mild cognitive impairment due to Alzheimer's disease.

Background: Mild cognitive impairment (MCI) is a critical transitional phase from healthy cognitive aging to dementia, offering a unique opportunity for early intervention. However, few studies focus on the correlation of brain structure and functional activity in patients with MCI due to Alzheimer's disease (AD). Elucidating the complex interactions between structural-functional (SC-FC) brain connectivity and glymphatic system function is crucial for understanding this condition. Method: The aims of this study were to explore the relationship among SC-FC coupling values, glymphatic system function and cognitive function. 23 MCI patients and 18 healthy controls (HC) underwent diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). DTI analysis along the perivascular space (DTI-ALPS) index and SC-FC coupling values were calculated using DTI and fMRI. Correlation analysis was conducted to assess the relationship between Mini-Mental State Examination (MMSE) scores, DTI-ALPS index, and coupling values. Receiver operating characteristic (ROC) curves was conducted on the SC-FC coupling between the whole brain and subnetworks. The correlation of coupling values with MMSE scores was also analyzed. Result: MCI patients (67.74 ± 6.99 years of age) exhibited significantly lower coupling in the whole-brain network and subnetworks, such as the somatomotor network (SMN) and ventral attention network (VAN), than HCs (63.44 ± 6.92 years of age). Whole-brain network coupling was positively correlated with dorsal attention network (DAN), SMN, and visual network (VN) coupling. MMSE scores were significantly positively correlated with whole-brain coupling and SMN coupling. In MCI, whole-brain network demonstrated the highest performance, followed by the SMN and VAN, with the VN, DAN, limbic network (LN), frontoparietal network (FPN), and default mode network (DMN). Compared to HCs, lower DTI-ALPS index was observed in individuals with MCI. Additionally, the left DTI-ALPS index showed a significant positive correlation with MMSE scores and coupling values in the whole-brain network and SMN. Conclusion: These findings reveal the critical role of SC-FC coupling values and the ALPS index in cognitive function of MCI. The positive correlations observed in the left DTI-ALPS and whole-brain and SMN coupling values provide a new insight for investigating the asymmetrical nature of cognitive impairments.

Correlation of internalized stigma with self-esteem, social support and coping styles in patients with rheumatoid arthritis: A cross-sectional study.

AIM: To understand the status of internalized stigma in patients with rheumatoid arthritis (RA) and explore its relationship with self-esteem, social support, and coping style. METHODS: This cross-sectional study selected patients with RA who visited the Rheumatology and Immunology Department of a tertiary hospital from May 2022 to May 2023. The Chinese versions of the Internalized Stigma of Mental Illness Scale-Rheumatoid Arthritis (ISMI-RA), Social Support Rating Scale, Rosenberg Self-Esteem Scale, and Medical Coping Style Questionnaire were administered to assess the internalized stigma, social support, self-esteem, and coping styles, respectively. The Pearson correlation test or Spearman rank correlation was then used to analyze the correlation between these measures. RESULTS: Overall, 69.5% participants reported high level of internalized stigma. The average age of the 174 participants was 52.67 ± 12.24 years, with 87.36 per cent female patients. The mean ISMI-RA score was 54.49 ± 9.62, and the ISMI-RA subscale with the highest average score was alienation. The Pearson's correlations show that internalized stigma was positively associated with the coping styles of avoidance (r = .212, p < .01) and acceptance (r = .560, p < .01), and that internalized stigma was negatively associated with the coping styles of confrontation (r = -.479, p < .01), social support (r = -.570, p < .01), and self-esteem(r = -.512, p < .05). CONCLUSION: The high level of internalized stigma in RA patients suggests that we should develop interventions to improve patients' self-esteem, encourage them to adopt positive coping styles, and gain more social support for them, so as to alleviate their internalized stigma.

Identification of clinical prognosis features and significant DNA methylation regulation in pineoblastoma.

BACKGROUND: Pineoblastoma (PB) represents a great challenge for clinical management due to lack of a specific therapeutic regimen. This study aims to identify relevant prognostic factors and potential treatment targets by mining public databases. METHODS: The clinical characteristics and survival data of PB patients were obtained from the SEER database between 2000 and 2019 for Cox regression analysis and nomogram construction. The PB's DNA methylation data was acquired from two GEO datasets, GSE133801 and GSE215240, for bioinformatics analysis. RESULTS: Of 383 PB patients, Cox univariate analysis unveiled that male gender (p = 0.017), age younger than 3 years at diagnosis (p < 0.001) and absence of radiotherapy (p < 0.001) correlated with poorer overall survival (OS), the subsequent multivariate analysis confirmed sex (p = 0.036), age (p < 0.001) and radiotherapy (p = 0.005) as independent prognostic factors for OS. A nomogram showed robust predictive accuracy as evidenced by AUC values (1-year OS: 0.774, 3-year OS: 0.692, 5-year OS: 0.643). DNA methylation analysis observed tumor hypomethylation, notably in promoter regions. Later, the GO enrichment analysis of aberrantly methylated genes indicated associations with embryonic organ development, cellular membrane composition and DNA-binding transcription, while KEGG analysis revealed enrichment in tumor-associated MAPK, calcium and RAS signaling pathways. CONCLUSIONS: The prognosis of PB is closely associated with sex, age and receipt of radiotherapy, potentially linked to aberrations in the RAS and MAPK signaling pathways. The individual case suggests that dasatinib and trametinib are potential targeted therapies for improving PB prognosis.

Cervical facet joint degeneration, facet joint angle and paraspinal muscle degeneration are correlated with degenerative cervical spondylolisthesis at C4/5: a propensity score-matched study.

BACKGROUND CONTEXT: Prior studies have hypothesized that degenerative cervical spondylolisthesis (DCS) may be influenced by loss of stability due to disc, facet joint or cervical alignment. Meanwhile, it is commonly believed that the facet joints and paraspinal muscles participate in maintaining cervical spine stability. However, the impact of paraspinal muscle morphology and detailed facet joint features on DCS requires further investigation. PURPOSE: To compare facet joint characteristics, disc degeneration and muscle morphology between patients with DCS and those without DCS. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: Consecutive surgical patients with degenerative cervical spondylosis from June 2016 to August 2023 were recruited. OUTCOME MEASURES: DCS was assessed on X-ray based on the translation distance. Cervical facet joint degeneration (CFD), the facet joint angle on the axial plane (FA-A) and the facet joint angle on the sagittal plane (FA-S), and facet joint tropism (FT) were measured on computerized tomography (CT). Paraspinal muscle degeneration was assessed on magnetic resonance imaging (MRI) including by the adjusted cross-sectional area (aCSA), the functional aCSA, the fat infiltration ratio (FI%). The Pfirrmann grade of the cervical disc was also evaluated. METHODS: Demographic and clinical data were compared in matched and unmatched cohorts. Disc degeneration, muscle degeneration and facet joint characteristics, including FA, FT and CFD, were compared between patients with and without DCS. Furthermore, the degree of CFD was compared with that of adjacent segments in both groups. Additionally, logistic regression was performed to determine independent risk factors for DCS. Finally, the receiver operating characteristic (ROC) curve, area under the curve (AUC) and cutoff value for the risk factors were calculated. RESULTS: A total of 431 surgical patients were propensity score matched for age, sex and BMI, and 146 patients were included in the final analysis, with 73 patients in the DCS group and 73 patients in the non-DCS group. DCS patients exhibited more severe CFD at C4/5 (segment with spondylolisthesis). Additionally, DCS was generally associated with more severe CFD, a more horizontal FA-S, more FT and worse paraspinal muscle health but similar disc degeneration. In addition, anterior spondylolisthesis was related to more severe CFD and decreased functional aCSA of the flexors and extensors. Finally, more severe CFD, a more horizontal FA-S and a higher FI% on deep extensor were revealed to be risk factors for DCS, with cutoff values of 1.5, 44.5̊, and 37.1%, respectively. CONCLUSIONS: This study demonstrated that CFD, the FA and FT and parasipnal muscle degeneration were associated with DCS. And may provide novel insight into the pathogenesis and nature history of DCS and suggest the evolution of degeneration in the cervical spine.

LiNbO3 and LiTaO3 Coating Effects on the Interface of the LiCoO2 Cathode: A DFT Study of Li-Ion Transport.

In solid-state batteries, the interface between cathodes and solid electrolytes is crucial and coating layers play a vital role. LiNbO3 has been known as a promising coating material, whereas recent studies showed its degradation via releasing oxygen and lithium during cycling. This computational study addresses the elucidation of essential characteristics of the coating materials by examining LiNbO3 and its counterpart LiTaO3 interfaces to a representative layered cathode, LiCoO2. Employing the interface CALYPSO method, we constructed explicit models of both coatings on LiCoO2. Our findings indicate that LiTaO3 offers easier Li+ migration at the interface due to the smaller difference in Li adiabatic potential at the interface, whereas LiNbO3 more effectively suppresses oxygen activity at high delithiation states via lowering the O 2p states. This comparative analysis provides essential insights into optimizing coating materials for improved battery performance.

IL-32 aggravates metabolic disturbance in human nucleus pulposus cells by activating FAT4-mediated Hippo/YAP signaling.

Extracellular matrix (ECM) metabolism disorders in the inflammatory microenvironment play a key role in the pathogenesis of intervertebral disc degeneration (IDD). Interleukin-32 (IL-32) has been reported to be involved in the progression of various inflammatory diseases; however, it remains unclear whether it participates in the matrix metabolism of nucleus pulposus (NP) cells. Therefore, this study aimed to investigate the mechanism of IL-32 on regulating the ECM metabolism in the inflammatory microenvironment. RNA-seq was used to identify aberrantly expressed genes in NP cells in the inflammatory microenvironment. Western blotting, real-time quantitative PCR, immunohistochemistry and immunofluorescence analysis were performed to measure the expression of IL-32 and metabolic markers in human NP tissues or NP cells treated with or without tumor necrosis factor-α (TNF-α). In vivo, an adeno-associated virus overexpressing IL-32 was injected into the caudal intervertebral discs of rats to assess its effect on IDD. Proteins interacting with IL-32 were identified via immunoprecipitation and mass spectrometry. Lentivirus overexpressing IL-32 or knocking down Fat atypical cadherin 4 (FAT4), yes-associated protein (YAP) inhibitor-Verteporfin (VP) were used to treat human NP cells, to explore the pathogenesis of IL-32. Hippo/YAP signaling activity was verified in human NP tissues. IL-32 expression was significantly upregulated in degenerative NP tissues, as indicated in the clinical samples. Furthermore, IL-32 was remarkably overexpressed in TNF-α-induced degenerative NP cells. IL-32 overexpression induced IDD progression in the rat model. Mechanistically, the elevation of IL-32 in the inflammatory microenvironment enhanced its interactions with FAT4 and mammalian sterile 20-like kinase1/2 (MST1/2) proteins, prompting MST1/2 phosphorylation, and activating the Hippo/YAP signaling pathway, causing matrix metabolism disorder in NP cells. Our results suggest that IL-32 mediates matrix metabolism disorders in NP cells in the inflammatory micro-environment via the FAT4/MST/YAP axis, providing a theoretical basis for the precise treatment of IDD.

[Research progress on striatal D2-MSNs plasticity mediated improvement of motor dysfunction by exercises in Parkinson's disease].

Parkinson's disease (PD), a prevalent neurodegenerative condition, manifests predominantly through the degeneration of nigrostriatal dopaminergic (DA) pathways, culminating in a notable depletion of striatal dopamine. This pathophysiological process critically impairs the DA-mediated regulation of motor behaviors within the basal ganglia circuitry, particularly impacting various subtypes of striatal medium spiny neurons. Recent advancements in neuroscientific research have illuminated the pivotal role of D2-dopamine receptor expressing medium spiny neurons (D2-MSNs) plasticity in coordinating motor control in PD. Intriguingly, aerobic exercise emerges as a potent therapeutic intervention, capable of preventing or improving motor impairments. This ameliorative effect is mediated through the modulation of DA receptor activity and the consequent activation of downstream extracellular signal-regulated kinase (Erk) signaling pathway. This article meticulously reviewed the intricate regulatory mechanisms governing the structural and functional plasticity of striatal D2-MSNs in the context of PD. It particularly emphasized the transformative impact of aerobic exercise on motor deficits in PD, attributing this effect to the modulation of striatal D2-MSNs.

The impact of metabolic syndrome on the cerebral cortex: a Mendelian randomization study.

Metabolic syndrome exhibits associations with diverse neurological disorders, and its potential influence on the cerebral cortex may be one of the many potential factors contributing to these adverse outcomes. In this study, we aimed to investigate the causal relationship between metabolic syndrome and changes in cerebral cortex structure using Mendelian randomization analysis. Genome-wide association study data for the 5 components of metabolic syndrome were obtained from individuals of European descent in the UK Biobank. Genome-wide association study data for 34 known cortical functional regions were sourced from the ENIGMA Consortium. Data on Alzheimer's disease, major depression, and anxiety disorder were obtained from the IEU Open genome-wide association study database. The causal links between metabolic syndrome elements and cerebral cortex architecture were evaluated using inverse variance weighting, Mendelian randomization-Egger, and weighted median techniques, with inverse variance weighting as the primary method. Inverse variance weighting, Mendelian randomization Egger, weighted median, simple mode, and weighted mode methods were employed to assess the relationships between metabolic syndrome and neurological diseases (Alzheimer's disease, major depression, and anxiety disorder). Outliers, heterogeneity, and pleiotropy were assessed using Cochran's Q test, MR-PRESSO, leave-one-out analysis, and funnel plots. Globally, no causal link was found between metabolic syndrome and overall cortical thickness or surface area. However, regionally, metabolic syndrome may influence the surface area of specific regions, including the caudal anterior cingulate, postcentral, posterior cingulate, rostral anterior cingulate, isthmus cingulate, superior parietal, rostral middle frontal, middle temporal, insula, pars opercularis, cuneus, and inferior temporal. It may also affect the thickness of the medial orbitofrontal, caudal middle frontal, paracentral, superior frontal, superior parietal, and supramarginal regions. These findings were nominally significant and withstood sensitivity analyses, showing no substantial heterogeneity or pleiotropy. Furthermore, we found an association between metabolic syndrome and the risk of Alzheimer's disease, major depression, and anxiety disorder. This study suggests a potential association between metabolic syndrome and changes in cerebral cortex structure, which may underlie certain neurological disorders. Furthermore, we found an association between metabolic syndrome and the risk of Alzheimer's disease, major depression, and anxiety disorder. Early diagnosis of metabolic syndrome holds significance in preventing these neurological disorders.

Novel insights into Feammox coupled with the NDFO: A critical review.

Ammonium oxidation coupled with Fe(III) reduction, known as Feammox, and nitrate-dependent ferrous oxidation (NDFO) are two processes that can be synergistically achieved through the Fe(III)/Fe(II) cycle. This integrated approach enables the simultaneous removal of ammonia nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) from wastewater, representing a novel method for complete nitrogen removal. This study presents a systematic and exhaustive examination of the Feammox-NDFO coupled process. An initial thorough exploration of the underlying mechanisms behind the coupling process is conducted, highlighting how the Fe(III)/Fe(II) cycle enables the concurrent occurrence of these reactions. Further, the functional microorganisms associated with and playing a crucial role in the Feammox-NDFO process are summarized. Next, the key influencing factors that govern the efficiency of the Feammox-NDFO process are explored. These include parameters such as pH, temperature, carbon source, iron source, nitrogen source, and various electron shuttles that may mediate electron transfer. Understanding the impact of these factors is essential for optimizing the process. The most recent trends and endeavors on the Feammox-NDFO coupling technology in wastewater treatment applications are also examined. This includes examining both laboratory-scale studies and field trials, highlighting their successes and challenges. Finally, an outlook is presented regarding the future advancement of the Feammox-NDFO technology. Areas of improvement and novel strategies that could further enhance the efficiency of simultaneous nitrogen removal from the iron cycle are discussed. In summary, this study aspires to offer a thorough comprehension of the Feammox-NDFO coupled process, with a focus on its mechanisms, influencing factors, applications, and prospects. It is anticipated to yield invaluable insights for the advancement of process optimization, thus sparking fresh ideas and strategies aimed at accomplishing the thorough elimination of nitrogen from wastewater via the iron cycle.

The Prognostic Value of Preoperative Inflammatory Markers for Pathological Grading of Glioma Patients.

Introduction: The independent diagnostic value of inflammatory markers neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) and the diagnostic efficacy of NLR, derived neutrophil to lymphocyte ratio (dNLR), PLR, and lymphocyte-to-monocyte ratio (LMR) in glioma cases remain unclear. We investigated the correlation of preoperative peripheral blood inflammatory markers with pathological grade, Ki-67 Proliferation Index, and IDH-1 gene phenotype in patients with glioma, focusing on tumor grade and prognosis. Methods: We retrospectively analyzed the clinical, pathological, and laboratory data of 334 patients with glioma with varying grades and 345 with World Health Organization (WHO I) meningioma who underwent initial surgery at the Affiliated Hospital of Jining Medical University from December 2019 to December 2021. The diagnostic value of peripheral blood inflammatory markers for glioma was investigated. Results: The proportion of men smoking and drinking was significantly higher in the glioma group than in the meningioma group (P < .05); in contrast, the age and body mass index (Kg/m2) were significantly lower in the glioma group (P = .01). Significant differences were noted in the pathological grade (WHO II, III, and IV), Ki-67 Proliferation Index, and peripheral blood inflammatory markers such as lymphocyte median, NLR, dNLR, and PLR between the groups (P < .05). No significant correlation existed between peripheral blood inflammatory factors and IDH-1 gene mutation status or tumor location in patients with glioma (P > .05). LMR, NLR, dNLR, and PLR, varied significantly among different glioma types (P < .05). White blood cell (WBC) count, neutrophil, NLR, and dNLR correlated positively with glioma risk. Further, WBC, neutrophil, NLR, dNLR, and LMR had a high diagnostic efficiency. Conclusion: Peripheral blood inflammatory markers, serving as noninvasive biomarkers, offer high sensitivity and specificity for diagnosing glioma, differentiating it from meningioma, diagnosing GBM, and distinguishing GBM from low-grade glioma. These markers may be implemented as routine screening tools.

Association of baseline serum sodium with long-term outcomes in newly diagnosed coronary heart disease patients without heart failure: a prospective cohort study.

Sodium is crucial for maintaining cardiovascular health, especially in relation to heart failure. The impact of baseline serum sodium concentrations on the outcomes of newly diagnosed coronary heart disease (CHD) without heart failure remains unclear. This prospective cohort study included 681 patients who were newly diagnosed with CHD. Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to assess the relationship between serum sodium concentrations and major adverse cardiovascular events. The improvement in traditional prediction models by the addition of serum sodium concentrations was assessed using changes in the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During a median follow-up of 51.04 months (IQR: 40.88-53.80 months), 131 events were recorded. Multivariate Cox proportional hazards models showed that the L2 group (136-138.9 mmol/L) had the highest MACE risk. Compared to L2, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the L1 (130-135.9 mmol/L), L3 (139-140.9 mmol/L), L4 (141-142.9 mmol/L), and L5 (143-147.0 mmol/L) groups were 0.31 (0.14-0.70, P = 0.005), 0.48 (030-0.78, P = 0.003), 0.56 (0.34-0.92, P = 0.022), and 0.37 (0.22-0.64, P < 0.001), respectively. Including serum sodium concentrations in the prediction model significantly improved the C-statistic from 0.647 to 0.679 (P = 0.022), with an NRI of 0.338 (P < 0.001) and an IDI of 0.026 (P < 0.001). RCS analysis showed a nonlinear relationship: within the 130-138 mmol/L sodium range, MACE risk gradually increased with higher sodium levels (HR 1.39, 95% CI 1.09-1.76, P = 0.008); whereas within the 138-147 mmol/L range, the risk gradually decreased (HR 0.88, 95% CI 0.80-0.98, P = 0.014). Baseline serum sodium concentrations are significantly associated with long-term cardiovascular risk in newly diagnosed CHD patients, showing an inverted U-shaped relationship, whereas low serum sodium may be specifically linked to higher risks of death and nonfatal myocardial infarction. Further research is needed to explore the impact of long-term changes in serum sodium concentrations on disease prognosis.

Evidence for Regulation of Cordycepin Biosynthesis by Transcription Factors Krüppel-Like Factor 4 and Retinoid X Receptor Alpha in Caterpillar Medicinal Mushroom Cordyceps militaris (Ascomycetes).

Cordyceps militaris, Chinese traditional medicinal fungus, has many bioactive properties. Cordycepin (3'-deoxyadenosine) is a major bioactive component of C. militaris. Various methods can significantly elevate cordycepin production, which suggests a diverse set of metabolic regulatory mechanisms. Thus, we aimed to identify transcription factors that regulate cordycepin biosynthesis pathways. Transcriptome analysis of wild-type C. militaris, C. militaris GYS60, a cordycepin high-producing strain, and C. militaris GYS80, a low-producing strain, were used to measure expression and function of genes related to cordycepin biosynthesis. The transcriptome expression data were confirmed by quantitative real-time polymerase chain reaction. We identified 155 relevant transcription factors in 19 families that included Fork head/winged helix factors, other C4 zinc finger-type factors, C2H2 zinc finger factors, tryptophan cluster factors, nuclear receptors with C4 zinc fingers, homeodomain factors, and Rel homology region factors. Energy generation and amino acid conversion pathways were activated in GYS60 so that abundance of cordycepin precursors was increased. Genes and transcription factors for rate-limiting enzymes in these pathways were identified. Overexpression of two key transcription factors, Kruppel-like factor 4 (Klf4) and Retinoid X receptor alpha (Rxra), promoted high cordycepin production in GYS60. In GYS60, Klf4 and Rxra were responsible for upregulation of genes in cordycepin biosynthesis, namely an oxidoreductase, 3',5'-cyclic AMP phosphodiesterase, a transferase, and adenylate cyclase. Upregulation of these genes increased 3'-AMP content, thereby elevating cordycepin synthesis.

Long-term exposure to dimefluthrin inhibits the growth of Acrossocheilus fasciatus.

Dimefluthrin (DIM) is a synthetic pyrethroid insecticide commonly used for the control of pests, particularly for mosquitoes and other flying insects. However, the effects of DIM on non-target aquatic organisms are not known. In this study, we evaluated the long-term effects of DIM on juvenile Acrossocheilus fasciatus (a species of teleost fish) by exposing them to two different concentrations (0.8 µg/L and 4 µg/L) for 60 days. After 60 d of exposure, DIM induced a significant decrease in body weight and irregular, diffused villi in the intestines of A. fasciatus, accompanied by alterations in the expression of immune-related genes. Furthermore, Gene Ontology (GO) enrichment analysis revealed that among the differentially expressed genes (DEGs), all downregulated genes were enriched in processes such as small molecule/cellular amino acid metabolism, generation of precursor metabolites and energy, and phosphatase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the downregulated genes were associated with processes such as cytokine-cytokine receptor interaction, chemokine signaling pathway, JAK-STAT signaling pathway, intestinal immune network for IgA production, natural killer cell-mediated cytotoxicity, and antigen processing and presentation. In contrast, upregulated DEGs were linked to processes such as necroptosis, phototransduction, and Hippo signaling pathway. These results demonstrate the potential toxicity of DIM to non-target aquatic organisms, indicating the broader ecological implications of its use.

ß-Cyclodextrin/dialdehyde glucan-coated keratin nanoparticles for oral delivery of insulin.

Successful oral insulin administration can considerably enhance the quality of life (QOL) of diabetes patients who must frequently take insulin injections. However, Oral insulin administration is seriously hampered by gastrointestinal enzymes, wide pH range, mucus and mucosal layers, which limit insulin oral bioavailability to ≤2 %. Herein, we developed a simple, inexpensive and safe dual ß-cyclodextrin/dialdehyde glucan-coated keratin nanoparticle (ß-CD-K-IN-DG). The resulted ß-CD-K-IN-DG not only gave the ultra-high insulin loading (encapsulation efficiency (98.52 %)), but also protected insulin from acid and enzymatic degradation. This ß-CD-K-IN-DG had a notable hypoglycemic effect, there was almost 80 % insulin release after 4 h of incubation under hyperglycemic conditions. Ex vivo results confirmed that ß-CD-K-IN-DG possessed high mucus-penetration ability. Transepithelial transport and uptake mechanism studies revealed that bypass transport pathway and endocytosis promoted ß-CD-K-IN-DG entered intestinal epithelial cells, thus increased the bioavailability of insulin (12.27 %). The improved stability of insulin during in vivo transport implied that ß-CD-K-IN-DG might be a potential tool for the effective oral insulin administration.

Correction of Thin Cirrus Absorption Effects in Landsat 8 Thermal Infrared Sensor Images Using the Operational Land Imager Cirrus Band on the Same Satellite Platform.

Data from the Operational Land Imager (OLI) and the Thermal Infrared Sensor (TIRS) instruments onboard the Landsat 8 and Landsat 9 satellite platforms are subject to contamination by cloud cover, with cirrus contributions being the most difficult to detect and mask. To help address this issue, a cirrus detection channel (Band 9) centered within the 1.375-µm water vapor absorption region was implemented on OLI, with a spatial resolution of 30 m. However, this band has not yet been fully utilized in the Collection 2 Landsat 8/9 Level 2 surface temperature data products that are publicly released by U.S. Geological Survey (USGS). The temperature products are generated with a single-channel algorithm. During the surface temperature retrievals, the effects of absorption of infrared radiation originating from the warmer earth's surfaces by ice clouds, typically located in the upper portion of the troposphere and re-emitting at much lower temperatures (approximately 220 K), are not taken into consideration. Through an analysis of sample Level 1 TOA and Level 2 surface data products, we have found that thin cirrus cloud features present in the Level 1 1.375-µm band images are directly propagated down to the Level 2 surface data products. The surface temperature errors resulting from thin cirrus contamination can be 10 K or larger. Previously, we reported an empirical and effective technique for removing thin cirrus scattering effects in OLI images, making use of the correlations between the 1.375-µm band image and images of any other OLI bands located in the 0.4-2.5 µm solar spectral region. In this article, we describe a variation of this technique that can be applied to the thermal bands, using the correlations between the Level 1 1.375-µm band image and the 11-µm BT image for the effective removal of thin cirrus absorption effects. Our results from three data sets acquired over spatially uniform water surfaces and over non-uniform land/water boundary areas suggest that if the cirrus-removed TOA 11-µm band BT images are used for the retrieval of the Level 2 surface temperature (ST) data products, the errors resulting from thin cirrus contaminations in the products can be reduced to about 1 K for spatially diffused cirrus scenes.