Mediastinal and thoracic hematoma following transradial cerebral angiography: a case report.

BACKGROUND: Cerebral angiography through the transradial approach (TRA) is associated with a low risk of complications, but in rare cases, these complications can be life-threatening. CASE PRESENTATION: A 56-year-old female patient was admitted for transradial cerebral angiography due to the complaint of right limb weakness and the diagnosis of cerebral infarction and cerebral artery stenosis. During the procedure, the patient coughed with expectoration and complained of throat discomfort, palpitations, and pains in the right shoulder and back. Emergency CT scan indicated hematoma in the middle mediastinum and the right thoracic cavity, and perforation of a branch of the subclavian artery was highly suspected. Subclavian artery angiography was conducted immediately, which revealed a patchy contrast medium overflow in a branch of the right costocervical trunk. Selective endovascular occlusion therapy was performed successfully with gelfoam particles and placement of 2 microcoils. At 12 days after cerebral angiography, the patient recovered well and was discharged from the hospital. CONCLUSION: Mediastinal and thoracic hematoma may occur due to vessel perforation during TRA cerebral angiography, in which guidewire advancement must be cautious. Early detection and appropriate countermeasures can reduce the severity of vascular perforation and subsequent hematoma.

Discovery of Potent Azetidine-Benzoxazole MerTK Inhibitors with In Vivo Target Engagement.

Inhibition of the receptor tyrosine kinase MerTK by small molecules has the potential to augment the immune response to tumors. Potent, selective inhibitors with high levels of in vivo target engagement are needed to fully evaluate the potential use of MerTK inhibitors as cancer therapeutics. We report the discovery and optimization of a series of pyrazinamide-based type 1.5 MerTK inhibitors bearing an azetidine-benzoxazole substituent. Compound 31 potently engages the target in vivo and demonstrates single agent activity in the immune-driven MC-38 murine syngeneic tumor model.

The mixture of non-persistent endocrine-disrupting chemicals in relation to endometriosis.

Non-persistent endocrine-disrupting chemicals (EDCs) are of significant concern due to their reproductive toxicity. Previous research reported a relationship between a single type of EDCs and endometriosis. Yet, evidence regarding mixed exposure of multiple categories of EDCs is scarce. Between 2014 and 2018, our hospital-based case-control study recruited 238 endometriosis cases diagnosed by laparoscopy and 296 normal controls in China. Seventeen non-persistent EDCs (phthalates and bisphenols) were measured in urine. The association of single EDC with endometriosis was estimated using logistic regression, while the association between EDC mixture and endometriosis was modeled by Bayesian kernel machine regression (BKMR), quantile-based g-computation (q-gcomp), and principal component analysis (PCA). Consistent results were observed in both single and mixture models where phthalates and bisphenols were associated with increased risk of endometriosis (mixture effect: adjusted odds ratio (aOR)=1.44, 1.22-1.70) and the major contributors were bisphenol A (BPA) and the metabolites of di(2-ethylhexyl) phthalate (DEHP). Interaction analysis showed that bisphenols exhibited significant synergistic interactions with phthalates. Our results suggest that non-persistent EDCs are associated with endometriosis but the underlying mechanisms remain to be elucidated. Our finding may have important public health implications in preventing endometriosis.

Associations Between Noise Exposure Level, Noise Kurtosis, and Distortion Product Otoacoustic Emissions in Young Workers With Normal Hearing.

OBJECTIVES: Growing evidence has suggested that, in addition to noise exposure level, noise temporal structure (i.e., kurtosis) plays an important role in the development of noise-induced hearing loss, while most of the relevant research has been on the results of pure-tone audiometry. This study focuses on the combined effect of noise exposure level and noise kurtosis on distortion product otoacoustic emissions (DPOAEs) in young workers with normal hearing. DESIGN: A cross-sectional study among young workers in manufacturing industries was conducted in Zhejiang Province, China. Individual noise exposure measurements were performed on participants to obtain an A-weighted noise exposure level normalized to 8 hr (LAeq, 8hr), cumulative noise exposure (CNE), kurtosis, and kurtosis-adjusted CNE (CNE-K). The DPOAE test was performed on the participants and DPOAE levels were obtained. The relationships between noise exposure level, kurtosis, and DPOAE levels were explored by univariate analyses. Furthermore, multivariate regression models were conducted to estimate the combined effects of exposure level and kurtosis after adjusting for age, gender, and use of hearing protection devices. RESULTS: The overall DPOAE curves across frequency bands presented a fluctuating downward trend with increasing frequency. Both exposure level and kurtosis were found to be associated with decreases in DPOAE levels. The multivariate regression model including CNE-K as a joint indicator of complex noise showed an increased R2 compared with the model including CNE. After adjustment for age, gender, and the use of hearing protection devices, significant effects of CNE-K on DPOAE levels were observed at 3, 4, and 5 kHz frequencies, with maximum effect presented at 4 kHz. CONCLUSIONS: DPOAE is a sensitive test that can detect cochlear damage in limited areas that cannot be detected by conventional audiometry. The present study provided a more comprehensive understanding of the impact of complex noise on the DPOAE levels. It also suggested that CNE-K was an effective metric in assessing DPOAE levels associated with complex noise.

Biodegradable taro stem cellulose aerogel: A simple approach for adsorbing microplastics and dyestuffs contaminants.

Water pollution and agricultural waste are pressing global issues. Herein, a biomass aerogel derived from waste taro stem microcrystalline cellulose (TS-MCC) was fabricated, in which, the effects of cellulose amount, cross-linker content, pre-freezing protocols on the aerogel's property were studied. The optimized TS-MCC2.0 aerogel exhibited a hierarchical porous structure with good mechanical property (65.04 kPa) and adsorption capacities, with the qm towards microplastics (Polystyrene, PS) and dye (Congo red, CR) being 418.6 mg/g and 951.51 mg/g at 298 K, respectively. Meanwhile, it exhibited good applicability under different pH (3-11) and ionic strength environments, as well as the retained notably simultaneous adsorption ability even under mixed contaminant systems. The mathematical models suggested that the adsorption of PS and CR both fitted pseudo-second-order kinetics, and the adsorption isotherms could be described by the Langmuir and Freundlich models, respectively. Hydrogen bonding, electrostatic attraction, and π-π interactions were inferred as the main adsorption mechanisms towards PS and CR according to Fourier transform infrared spectrometer and X-ray photoelectron spectroscopy analysis. Moreover, the adsorption efficiencies were 92.37 % for PS and 88.34 % for CR after 5 reuse cycles. Therefore, this study provides a green aerogel sorbent for adsorbing microplastics and dyes contaminants.

Blood-derived mitochondrial DNA copy number is associated with Alzheimer disease, Alzheimer-related biomarkers and serum metabolites.

BACKGROUND: Blood-derived mitochondrial DNA copy number (mtDNA-CN) is a proxy measurement of mitochondrial function in the peripheral and central systems. Abnormal mtDNA-CN not only indicates impaired mtDNA replication and transcription machinery but also dysregulated biological processes such as energy and lipid metabolism. However, the relationship between mtDNA-CN and Alzheimer disease (AD) is unclear. METHODS: We performed two-sample Mendelian randomization (MR) using publicly available summary statistics from GWAS for mtDNA-CN and AD to investigate the causal relationship between mtDNA-CN and AD. We estimated mtDNA-CN using whole-genome sequence data from blood and brain samples of 13,799 individuals from the Alzheimer's Disease Sequencing Project. Linear and Cox proportional hazards models adjusting for age, sex, and study phase were used to assess the association of mtDNA-CN with AD. The association of AD biomarkers and serum metabolites with mtDNA-CN in blood was evaluated in Alzheimer's Disease Neuroimaging Initiative using linear regression. We conducted a causal mediation analysis to test the natural indirect effects of mtDNA-CN change on AD risk through the significantly associated biomarkers and metabolites. RESULTS: MR analysis suggested a causal relationship between decreased blood-derived mtDNA-CN and increased risk of AD (OR = 0.68; P = 0.013). Survival analysis showed that decreased mtDNA-CN was significantly associated with higher risk of conversion from mild cognitive impairment to AD (HR = 0.80; P = 0.002). We also identified significant associations of mtDNA-CN with brain FDG-PET (ß = 0.103; P = 0.022), amyloid-PET (ß = 0.117; P = 0.034), CSF amyloid-ß (Aß) 42/40 (ß=-0.124; P = 0.017), CSF t-Tau (ß = 0.128; P = 0.015), p-Tau (ß = 0.140; P = 0.008), and plasma NFL (ß=-0.124; P = 0.004) in females. Several lipid species, amino acids, biogenic amines in serum were also significantly associated with mtDNA-CN. Causal mediation analyses showed that about a third of the effect of mtDNA-CN on AD risk was mediated by plasma NFL (P = 0.009), and this effect was more significant in females (P < 0.005). CONCLUSIONS: Our study indicates that mtDNA-CN measured in blood is predictive of AD and is associated with AD biomarkers including plasma NFL particularly in females. Further, we illustrate that decreased mtDNA-CN possibly increases AD risk through dysregulation of mitochondrial lipid metabolism and inflammation.

N6-methyladenosine modification of SLC38A7 promotes cell migration, invasion, oxidative phosphorylation, and mitochondrial function in gastric cancer.

Solute carrier (SLC) 38 family, responsible for trans-membrane transport of neutral amino acids, plays a role in the proliferation, invasion, and metastasis of cancer cells, but its role in gastric cancer (GC) progression remains unclear. This study aimed to explore the biological effects of SLC38A7 and its regulatory mechanisms in GC. RNA expression data, tumor tissue specimens, and GC cell lines were used for bioinformatics and experimental analyses. Cell Counting Kit-8 assay, wound healing assay, and Transwell invasion assay were used to evaluate cell viability, migration, and invasion, respectively. Oxidative phosphorylation, mitochondrial membrane potential, and expression of the critical proteins in the mitochondrial respiratory chain were assayed using extracellular flux analysis, flow cytometry, and Western blot, respectively. RNA immunoprecipitation assay was used to explore the mechanisms of N6-methyladenosine (m6A) methylation. SLC38A7 was upregulated in GC tissue and cell lines. SLC38A7 silencing suppressed cell viability, migration, invasion, oxidative phosphorylation, and mitochondrial function in cancer cells. SLC38A7 overexpression had the opposite biological effects. Interactions between SLC38A7 and methyltransferase like 3 (METTL3) or insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) were detected. SLC38A7 mRNA stability was maintained by METTL3-IGF2BP2 axis in an m6A-dependent manner. Our results suggest that SLC38A7, stabilized by METTL3 and IGF2BP2-mediated m6A methylation, enhances cell viability, migration, invasion, oxidative phosphorylation, and mitochondrial function in GC, highlighting its role as a potential therapeutic target for GC.

The Relationship between Framingham Stroke Risk Profile on Incident Dementia and Alzheimer's Disease: A 40-Year Follow-Up Study Highlighting Female Vulnerability.

OBJECTIVE: Sex differences in the association between cardiovascular risk factors and the incident all-cause dementia and the subtype Alzheimer's disease (AD) risk are unclear. METHODS: Framingham Heart Study (FHS) participants (n = 4,171, 54% women, aged 55 to 69 years) were included at baseline and followed up to 40 years. The Framingham Stroke Risk Profile (FSRP) was dichotomized into 2 levels (cutoff: 75th percentile of the FSRP z-scores). Cause-specific hazard models, with death as a competing event, and restricted mean survival time (RMST) model were used to analyze the association between FSRP levels and incident all-cause dementia and AD. Interactions between FSRP and sex were estimated, followed by a sex-stratified analysis to examine the sex modification effect. RESULTS: High FSRP was significantly associated with all-cause dementia (hazard ratio [HR] = 1.25, robust 95% confidence interval [CI] = 1.21 to 1.29, p < 0.001) and AD (HR = 1.58, robust 95% CI = 1.57 to 1.59, p < 0.001) in cause-specific hazard models. High FSRP was significantly associated with incident dementia (HR = 2.81, robust 95% CI = 2.75 to 2.87, p < 0.001) and AD (HR = 2.96, robust 95% CI = 2.36 to 3.71, p < 0.001) in women, but not in men. Results were consistent in the RMST models. Current diabetes and high systolic blood pressure as FSRP components were significantly associated with dementia and AD in women but not in men. INTERPRETATION: High FSRP in mid- to early late life is a critical risk factor for all-cause dementia and AD, particularly in women. Sex-specific interventions and further research to elucidate underlying mechanisms are warranted. ANN NEUROL 2024.

Discovery of A-910, a Highly Potent and Orally Bioavailable Dual MerTK/Axl-Selective Tyrosine Kinase Inhibitor.

TAM receptor tyrosine kinases have emerged as promising therapeutic targets for cancer treatment due to their roles in both tumor intrinsic survival mechanisms and suppression of antitumor immunity within the tumor microenvironment. Inhibiting MerTK and Axl selectively is believed to hinder cancer cell survival, reverse the protumor myeloid phenotype, and suppress efferocytosis, thereby eliciting an antitumor immune response. In this study, we present the discovery of A-910, a highly potent and selective dual MerTK/Axl inhibitor, achieved through a structure-based medicinal chemistry campaign. The lead compound exhibits favorable oral bioavailability, exceptional kinome selectivity, and significantly improved in vivo target engagement. These findings support the use of A-910 as an orally bioavailable in vivo tool compound for investigating the immunotherapy potential of dual MerTK/Axl inhibition.

Baicalein induces apoptosis by targeting ribosomes in Candida auris.

The emergence of the "super fungus" Candida auris poses a significant threat to human health, given its multidrug resistance and high mortality rates. Therefore, developing a new antifungal strategy is necessary. Our previous research showed that Baicalein (BE), a key bioactive compound from the dried root of the perennial herb Scutellaria baicalensis Georgi, has strong fungistatic properties against C. auris. Nevertheless, the antifungal activity of BE against C. auris and its mechanism of action requires further investigation. In this study, we explored how BE affects this fungus using various techniques, including scanning electron microscopy (SEM), Annexin V-FITC apoptosis detection, CaspACE FITC-VAD-FMK In Situ Marker, reactive oxygen species (ROS) assay, singlet oxygen sensor green (SOSG) fluorescent probe, enhanced mitochondrial membrane potential (MMP) assay with JC-1, DAPI staining, TUNEL assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Our findings revealed that BE induced several apoptotic features, including phosphatidylserine (PS) externalization, metacaspase activation, nuclear condensation and DNA fragmentation. BE also increased intracellular ROS levels and altered mitochondrial functions. Additionally, transcriptomic analysis and RT-qPCR validation indicated that BE may induce apoptosis in C. auris by affecting ribosome-related pathways, suggesting that ribosomes could be new targets for antifungal agents, in addition to cell walls, membranes, and DNA. This study emphasizes the antifungal activity and mechanism of BE against C. auris, offering a promising treatment strategy for C. auris infection.

Anti-inflammatory and anti-lung cancer activities of low-molecular-weight and high-sulfate-content sulfated polysaccharides extracted from the edible fungus Poria cocos.

Sulfated polysaccharides (SPSs) have excellent physicochemical properties, attracting research interest in the pharmaceutical industry. A previous study extracted SPS (named Suc40) from the edible fungus, Poria cocos and demonstrated that it exhibited anti-inflammatory and anticancer activities. In this study, three fractions of Suc40, Suc40 F1, Suc40 F2, and Suc40 F3, with different molecular weights and sulfate contents were prepared through gel-filtration column chromatography. The molecular weights of F1, F2, and F3 were approximately 616.23, 82.57, and 6.21 kDa, respectively, and their sulfate content were 0.23, 1.65, and 1.90 mmol/g, respectively. The fractions' anti-inflammatory activities were determined by assessing their ability to suppress inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Suc40 F2 and Suc40 F3 suppressed interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production by 60 % and 35 %, respectively. Suc40 F2 and Suc40 F3 suppressed protein kinase B (AKT)/p38 and p38 signaling, which resulted in anti-inflammatory effects. The fractions' anti-lung cancer activity was evaluated by assessing their H1975 cell proliferation inhibition. Suc40 F3 at a concentration of 800 µg/ml exhibited maximal cell proliferation inhibition. The low molecular weight and high sulfate content of Suc40 F3 were associated with its enhanced anti-inflammatory and anti-lung cancer activities.

Insulin-like growth factor-binding protein 7 exacerbates inflammatory response and lipid metabolism imbalance in alcohol-associated liver disease.

Alcohol-associated liver disease(ALD), caused by excessive alcohol consumption, are often associated with inflammatory outbreaks and lipid deposition in the liver. The role of Insulin-like growth factor-binding protein 7 (IGFBP7), an important metabolic regulator, in ALD, its underlying regulatory mechanism, and its potential implication in anti-ALD therapies remain unknown. We investigated the effects of IGFBP7 on hepatic inflammation and lipid metabolism disruption in a mouse model of ALD. Mice were fed by chronic ethanol feeding plus a single binge of ethanol feeding(chronic-plus-single-binge model). In addition, ethanol exposure modeling studies were performed on cultured hepatocytes to verify molecular correlations. The results showed that IGFBP7 expression was significantly elevated in the livers of mice and hepatocytes after chronic ethanol exposure. Subsequently, the results of a study by specific knockout of IGFBP7(IGFBP7-cKO) in mouse hepatocytes and lentiviral silencing of IGFBP7 in vivo suggested that IGFBP7 deletion could improve liver function levels in alcohol-fed mice; It also attenuated the outbreak of hepatitis factor and the disorder of lipid metabolism in mice.Using RNA-seq sequencing of mouse liver tissue, we found that IGFBP7 affects several downstream metabolic signaling pathways, including PPAR, MAPK, FoxO, etc. Then, we used the PPARα plasmid in hepatocytes and discovered that overexpressing PPARα reversed the impact of IGFBP7 on lipid metabolism disorders in hepatocytes. In conclusion, IGFBP7 deficiency in alcohol-associated liver disease alleviates the decline in liver function and the imbalance of lipid metabolism in mice, attenuates the inflammatory outbreak, and affects a variety of downstream lipid metabolism factors by regulating PPARα. Hence, IGFBP7 may be an effective therapeutic target in the treatment of ALD.

The influences of ApoE isoforms on endothelial adherens junctions and actin cytoskeleton responding to mCRP.

Apolipoprotein E4 (ApoE4) plays an important role responding to monomeric C-reactive protein (mCRP) via binding to CD31 leading to cerebrovascular damage and Alzheimer's disease (AD). Using phosphor-proteomic profiling, we found altered cytoskeleton proteins in the microvasculature of AD brains, including increased levels of hyperphosphorylated tau (pTau) and the actin-related protein, LIMA1. To address the hypothesis that cytoskeletal changes serve as early pathological signatures linked with CD31 in brain endothelia in ApoE4 carriers, ApoE4 knock-in mice intraperitoneal injected with mCRP revealed that mCRP increased the expressions of phosphorylated CD31 (pCD31) and LIMA1, and facilitate the binding of pCD31 to LIMA1. mCRP combined with recombinant APOE4 protein decreased interaction of CD31 and VE-Cadherin at adherens junctions (AJs), along with altered the expression of various actin cytoskeleton proteins, causing microvasculature damage. Notably, the APOE2 protein attenuated these changes. Overall, our study demonstrates that ApoE4 responds to mCRP to disrupt the endothelial AJs which link with the actin cytoskeleton and this pathway could play a key role in the barrier dysfunction leading to AD risk.

A lipidomic study on the lens epithelial cells of patients with age related cataracts.

Age related cataracts (ARC) represent the main reason for blindness globally. The lens epithelial cells (LECs) participate not only in the metabolism of many substances in the lens but also in maintaining lens transparency. This study used lipidomics to investigate the metabolic differences in LECs of ARC patients with different severity, aiming at identifying potential metabolic biomarkers of ARC. Patients diagnosed with ARC and underwent cataract surgery at Shanghai Tongren Hospital were selected to participate in this study, which were classified as mild ARC group and severe ARC group. During their cataract surgery, anterior lens capsules(LCs) containing LECs were obtained. The lipidomics of LECs were analyzed using the liquid chromatography­mass spectrometry (LC-MS). Potential pathways of lipids were searched for using databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst platform. In LEC lipids, 26 lipids have been identified as potential biomarkers between mild ARC and severe ARC, with AUC values of 0.67-0.94. The pathway analysis results revealed that the Glycerophospholipid (GPL) metabolism was significantly influenced, indicating that these metabolic markers contribute significantly to regulating this pathway. The LEC metabolic spectrum demonstrates a proficient ability to differentiate between patients with varying levels of cataracts. Herein, we have successfully identified potential metabolic biomarkers and pathways that have proven to be valuable in enhancing our understanding of ARC pathogenesis. The finding has translational value for developing new cataract treatment methods in the future.

Developing a Framework for Industrial Noise Risk Management Based on Noise Kurtosis and Its Adjustment.

OBJECTIVES: Noise risk control or management based on noise level has been documented, but noise risk management based on a combination of noise level and noise's temporal structure is rarely reported. This study aimed to develop a framework for industrial noise risk management based on noise kurtosis (reflecting noise's temporal structure) and its adjustment for the noise level. DESIGN: A total of 2805 Chinese manufacturing workers were investigated using a cross-sectional survey. The noise exposure data of each subject included LEX,8h, cumulative noise exposure (CNE), kurtosis, and kurtosis-adjusted LEX,8h (LEX,8h-K). Noise-induced permanent threshold shifts were estimated at 3, 4, and 6 kHz frequencies (NIPTS346) and 1, 2, 3, and 4 kHz frequencies (NIPTS1234). The prevalence of high-frequency noise-induced hearing loss prevalence (HFNIHL%) and noise-induced hearing impairment (NIHI%) were determined. Risk346 or Risk1234 was predicted using the ISO 1999 or NIOSH 1998 model. A noise risk management framework based on kurtosis and its adjustment was developed. RESULTS: Kurtosis could identify the noise type; Kurtosis combining noise levels could identify the homogeneous noise exposure group (HNEG) among workers. Noise kurtosis was a risk factor of HFNIHL or NIHI with an adjusted odds ratio of 1.57 or 1.52 (p < 0.01). At a similar CNE level, the NIPTS346, HFNIHL%, NIPTS1234, or NIHI% increased with increasing kurtosis. A nonlinear regression equation (expressed by logistic function) could rebuild a reliable dose-effect relationship between LEX,8h-K and NIPTS346 at the 70 to 95 dB(A) noise level range. After the kurtosis adjustment, the median LEX,8h was increased by 5.45 dB(A); the predicted Risk346 and Risk1234 were increased by 11.2 and 9.5%, respectively; NIPTS346-K of complex noise at exposure level <80, 80 to 85, and 85 to 90 dB(A), determined from the nonlinear regression equation, was almost the same as the Gaussian noise. Risk management measures could be recommended based on the exposure risk rating or the kurtosis-adjusted action levels (e.g., the lower and upper action levels were 80 and 85 dB(A), respectively). CONCLUSIONS: The kurtosis and its adjustment for noise levels can be used to develop an occupational health risk management framework for industrial noise. More human studies are needed to verify the risk management framework.

Sigmoid colon cancer presenting as a large abdominal mass accompanied by abscess and rupture: a case report and literature review.

Introduction and Importance: Colon cancer presenting as a large abdominal mass accompanied by abscess and rupture is rare and prone to be misdiagnosed and delayed. In addition, the treatment plan is not clear when combined with abdominal wall metastasis. Case Presentation: A 79-year-old woman presented with a large abdominal mass accompanied by abscess and rupture. It was misdiagnosed as a soft tissue infection in a local hospital, and after a comprehensive examination, it was diagnosed as sigmoid colon cancer with abdominal wall metastasis and abscess formation. The patient underwent a one-stage surgery, including en bloc resection of the tumor and invaded abdominal wall, as well as autologous tissue abdominal wall reconstruction, with a good clinical prognosis. Clinical Discussion: For the diagnosis of large abdominal masses, abdominal CT, and pus culture are more valuable than ultrasound. For colon cancer with abdominal wall metastasis, one-stage surgery to completely remove the tumor and full-thickness of the abdominal wall, and the use of autologous tissue abdominal wall reconstruction technology to repair defects is feasible. Conclusion: This case highlights the importance of using colon cancer as one of the differential diagnoses for the diagnosis for large abdominal mass accompanied by abscess and rupture in elderly patients, as well as the possibility of one-stage surgical resection of the tumor and invasion of the abdominal wall and reconstruction of the abdominal wall with autologous tissue when there is abdominal wall metastasis.

Progress and recommendations of developing occupational exposure limits for noise-A systematic review.

Objective: Noise exposure limit is one of the critical measures to prevent noise-induced hearing loss (NIHL). This review aimed to review the progress and recommendations for developing occupational exposure limits (OELs) for workplace noise. Methods: A systematic review was used. Thirty-eight national or international organizations' noise exposure standards (including OEL) and laws, regulations, and guidelines for noise exposure control were analyzed. Articles on recommendations for revising noise OEL standards between 2000 and 2023 were selected. Results: The definition of different noise types (especially for non-steady and impulsive noise) varied worldwide, and the used 8-h OEL varied from 80 to 90 dB(A). Maximum sound pressure level (Lmax) and noise dose for industrial noise and peak sound pressure level (Lpeak) for impulsive noise have been incorporated into the OELs. Countries developed noise risk management measures based on OELs, action levels (ALs), and exposure risk ratio or classification. The risk of co-exposure to noise and ototoxic organic substances and the effects of noise on susceptible populations were concerns in EU country standards. Scholars suggested revising the existing noise exposure standards based on noise's temporal structure (expressed by kurtosis), effective noise level, impulsive noise OEL, action level, and key factors of risk assessment. Conclusions: Indicators such as Lmax, noise dose, Lpeak, and action level can be incorporated into noise OELs. Developing noise OEL standards should consider the co-exposure of noise and ototoxic substances, HPD's noise attenuation, susceptible groups, and noise's temporal structure.

Astrocyte-derived clusterin disrupts glial physiology to obstruct remyelination in mouse models of demyelinating diseases.

Multiple sclerosis (MS) is a debilitating demyelinating disease characterized by remyelination failure attributed to inadequate oligodendrocyte precursor cells (OPCs) differentiation and aberrant astrogliosis. A comprehensive cell atlas reanalysis of clinical specimens brings to light heightened clusterin (CLU) expression in a specific astrocyte subtype links to active lesions in MS patients. Our investigation reveals elevated astrocytic CLU levels in both active lesions of patient tissues and female murine MS models. CLU administration stimulates primary astrocyte proliferation while concurrently impeding astrocyte-mediated clearance of myelin debris. Intriguingly, CLU overload directly impedes OPC differentiation and induces OPCs and OLs apoptosis. Mechanistically, CLU suppresses PI3K-AKT signaling in primary OPCs via very low-density lipoprotein receptor. Pharmacological activation of AKT rescues the damage inflicted by excess CLU on OPCs and ameliorates demyelination in the corpus callosum. Furthermore, conditional knockout of CLU emerges as a promising intervention, showcasing improved remyelination processes and reduced severity in murine MS models.

Inflammatory protein associations with brain MRI measures: Framingham Offspring Cohort.

INTRODUCTION: Brain magnetic resonance imaging (MRI) and inflammatory biomarkers are crucial for investigating preclinical neurocognitive disorders. Current investigations focus on a few inflammatory markers. The study aims to investigate the associations between inflammatory biomarkers and MRI measures and to examine sex differences among the associations in the Framingham Heart Study. METHODS: Dementia and stroke-free participants underwent OLINK Proteomics profiling and MRI measurements within 5 years. Pairwise cross-sectional analysis assessed 68 biomarkers with 13 brain MRI volumes, adjusting for covariates and familial correlations. RESULTS: Elevated CDCP1, IL6, OPG, and 4E.BP1 were related to smaller total cerebral brain volume (TCBV), whereas higher HGF, IL8, and MMP10 were associated with smaller TCBV, total and frontal white matter volumes. Higher SCF and TWEAK were associated with larger TCBV. In sex-stratified analyses, associations were observed exclusively among males. DISCUSSION: We report several associations between inflammatory biomarkers and brain volumes, highlighting different associations within sex subgroups. HIGHLIGHTS: Higher CDCP1, IL6, OPG, and 4E.BP1 levels were associated with smaller TCBV. Higher levels of HGF, IL8 and MMP10 were associated with smaller TCBV, CWV and FWV. Higher levels of SCF and TWEAK, were associated with larger TCBV. Significance diminished in models adjusting for CVD risk factors. Associations were observed exclusively in males.

UFMylation is involved in serum inflammatory cytokines generation and splenic T cell activation induced by lipopolysaccharide.

UFMylation, a novel ubiquitin-like protein modification system, has been recently found to be activated in inflammation. However, the effects of UFMylation activation on inflammation in vivo remains unclear. In the present study, we generated a UFMylation activated mice using transgenic (TG) techniques. Lipopolysaccharide (LPS) was used to induce systemic inflammation in both TG and non-transgenic (NTG) mice. Serum cytokines were detected using a Mouse Cytokine Array, and the proportions of splenic NK, B and T cells were determined by using flow cytometry. We found that TG mice showed increased serum G-CSF, TNF RII and decreased serum TCA-3, CD30L, bFGF, IL-15 and MIG compared with NTG mice at baseline. Furthermore, serum cytokines in TG mice exhibited different responses to LPS compared to NTG mice. LPS up-regulated serum TNF RII, G-CSF, MCP-5, RANTES, KC, BLC, MIG and down-regulated IL-1b, IL-2, IL-3, IL-4, IL-5, IL-7, IL-10, IL-12p40, IL-15, IL-17, IFN-γ, TCA-3, Eotaxin-2, LIX, MCP-1, TNFα, GM-CSF in NTG mice, whereas LPS up-regulated G-CSF, MCP-5, RANTES, KC, BLC, MIG, ICAM-1, PF4, Eotaxin, CD30L, MIP-1a, TNFRI and down-regulated IL-1b, IL-3, LIX, MCP-1, TNFα, GM-CSF in TG mice. Data from flow cytometry indicated that LPS significantly reduced the percentages of NK and NKT cells in NTG mice, whereas UFMylation activation inhibited LPS-induced NKT cell decrease. The proportions of B cells, total CD4+ and total CD8+ T cells were comparable between TG and NTG mice in response to LPS treatment, whereas the percentages of CD4+CD69+ and CD8+CD69+T cells were lower in TG mice. These findings suggest that UFMylation may alter LPS-induced serum cytokine profile and participate in splenic T cell activation in vivo.