Characterization and health risks of short- and medium-chain chlorinated paraffins in the gas and size-fractionated particulate phases in ambient air.

Short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs) have garnered significant attention because they have persistence and potential toxicity, and can undergo long-distance transport. Chlorinated paraffins (CPs) inhaled in the size-fractionated particulate phase and gas phase can carry different risks to human health due to their ability to accumulate in different regions of the respiratory tract and exhibit varying deposition efficiencies. In our study, large-volume ambient air samples in both the size-fractionated particulate phase (Dp < 1.0 µm, 1.0-2.5 µm, 2.5-10 µm, and Dp ≥ 10 µm) and gas phase were collected simultaneously in Beijing using an active sampler. The overall levels of SCCPs and MCCPs were relatively high, the ranges being 57-881 and 30-385 ng/m3, respectively. SCCPs tended to be partitioned in the gas phase (on average 75% of the ΣSCCP concentration), while MCCPs tended to be partitioned in the particulate phase (on average 62% of the ΣMCCP concentration). Significant correlations were discovered between the logarithm-transformed gas-particle partition coefficients (KP) and predicted subcooled vapor pressures (PL0) (p < 0.01 for SCCPs and MCCPs) and between the logarithm-transformed KP values and octanol-air partition coefficients (KOA) (p < 0.01 for SCCPs and MCCPs). Thus, the slopes indicated that organic matter absorption was the dominant process involved in gas-particle partitioning. We used the ICRP model to calculate deposition concentrations for particulate-associated CPs in head airways region (15.6-71.4 ng/m³), tracheobronchial region (0.8-4.8 ng/m³), and alveolar region (5.1-21.9 ng/m³), then combined these concentrations with the CP concentrations in the gas phase to calculate estimated daily intakes (EDIs) for inhalation. The EDIs for SCCPs and MCCPs through inhalation of ambient air for the all-ages group were 67.5-184.2 ng/kg/day and 19.7-53.7 ng/kg/day, respectively. The results indicated that SCCPs and MCCPs in ambient air do not currently pose strong risks to human health in the study area.

Innovation and evaluation of vocational pharmaceutical education system under the 1 + X certificate system in China.

BACKGROUND AND OBJECTIVES: The 1 + X certificate system, introduced in China in 2019, integrates academic credentials with vocational skill certificates to meet the heightened demand for skilled talents in the growing economy. This study aims to innovate and evaluate the vocational pharmaceutical education system under the 1 + X certificate framework, specifically addressing the gap between theoretical education and workplace requirements. MATERIALS AND METHODS: A retrospective observational approach analyzed 490 pharmacy students over two academic years. The 2021 cohort underwent 1 + X integrated education, while the 2020 cohort followed conventional education. We collaborated closely with industry partners to identify and compile typical job competencies, formulating work projects aligned with industry demands. Combining the skill level standards and assessment content of "1+X Pharmaceutical Purchasing and Sales" and "1+X Pharmaceutical Preparation", we revised the course standards, incorporating typical work projects into the 2021 pharmacy professional teaching curriculum. This constituted the fundamental content of the 1 + X education reform. Statistical analysis compared course scores and 1 + X certificate examination performance. RESULTS: The 2021 cohort, under the 1 + X educational model, demonstrated higher average scores in pharmacy courses, with significant improvements in pharmacology (1 + X vs. Traditional education: 58.40 ± 14.20 vs. 53.44 ± 14.67), clinical pharmacotherapy (72.74 ± 10.28 vs. 63.15 ± 11.03), and pharmaceutical distribution and marketing (79.34 ± 10.96 vs. 67.50 ± 15.82). 1 + X certificate pass rates and satisfaction with the model were also higher than the 2020 cohort. CONCLUSION: The 1 + X certificate system is useful for developing talent in Chinese vocational education, effectively integrating assessments with industry standards. Future research should aim at evaluating long-term outcomes and improving quantitative skills assessments for enhanced effectiveness.

Establishment and validation of a 5-factor diagnostic model for obstructive and non-obstructive azoospermia based on routine clinical parameters.

Azoospermia is a serious leading male-factor cause of infertility in couples of childbearing age. The two main azoospermia types, obstructive (OA) and non-obstructive (NOA) azoospermia, differ in their treatment approaches. Therefore, their clinical diagnosis is extremely important, requiring an accurate, efficient, and easy-to-use diagnostic model. This retrospective observational study included 707 patients with azoospermia treated between 2017 and 2021, 498 with OA, and 209 with NOA. Hematological and seminal plasma parameters, hormone levels, and testicular volume were used in logistic regression analysis to evaluate and compare their diagnostic performance, results showed that the optimal diagnostic model is constructed by five variables including semen volume, semen pH, seminal plasma neutral α-glucosidase activity, follicle-stimulating hormone in the serum, and testicular volume, compared with follicle-stimulating hormone-based and testicular volume-based models. The 5-factor diagnostic model had an accuracy of 90.4%, sensitivity of 96.4%, positive predictive value of 90.6%, negative predictive value of 89.8%, and area under the curve of 0.931, all higher than in the other two models. However, its specificity (76.1%) was slightly lower than in the other models. Meantime, the internal 5-fold cross-validation results indicated that the 5-factor diagnostic model had a good clinical application value. This study established an accurate, efficient, and relatively accessible 5-factor diagnostic model for OA and NOA, providing a reference for clinical decision-making when selecting an appropriate treatment.

Comparative characteristics of early-onset vs. late-onset advanced colorectal cancer: a nationwide study in China.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC, diagnosed in patients under the age of 50 years) has been increasing around the world. Here, we aimed to systematically identify distinctive features of EOCRC. METHODS: From 2020 to 2021, we conducted a nationwide survey in 19 hospitals, collecting data on advanced CRC patients' demographics, clinical features, disease knowledge, medical experiences, expenditures, and health-related quality of life (HRQOL). We compared these features between EOCRC and late-onset colorectal cancer (LOCRC, ≥ 50 years old) groups and analyzed the association between EOCRC and HRQOL using multivariate linear regression. FINDINGS: In total, 991 patients with EOCRC and 3581 patients with LOCRC were included. Compared to the LOCRC group, the EOCRC group had higher levels of education, were more informed about the risk factors for CRC, were more likely to have widespread metastases throughout the body, were more inclined to undergo gene testing, and were more likely to opt for targeted therapy, radiotherapy, and chemotherapy. However, HRQOL in the EOCRC group was similar to that of the LOCRC group, and no significant association was observed between EOCRC and HRQOL (beta: -0.753, P value: 0.307). INTERPRETATION: In Chinese patients, EOCRC patients had more aggressive features. Despite undergoing more intensified treatments and gene testing, they had similar HRQOL compared with LOCRC. These findings advocate for a more tailored approach to treatment, especially for young CRC patients with advanced TNM stages and metastasis.

Diagnostic value of the creatine kinase-MB/creatine kinase and neutrophil/lymphocyte ratios in acute myocardial infarction.

OBJECTIVE: To investigate the clinical significance of the creatine kinase (CK)-MB/total CK ratio, neutrophil/lymphocyte ratio (NLR) and red blood cell distribution width in acute myocardial infarction (AMI). METHODS: A retrospective analysis was conducted of 196 AMI cases from our hospital's cardiology department; healthy people were selected over the same period as the control. The two groups' test indexes were compared through multivariate logistic regression analysis to screen for AMI risk factors; the receiver operating characteristic (ROC) curve was used to evaluate their AMI predictive values. RESULTS: The serum CK, CK-MB, CK index, neutrophils and NLR values in the AMI group were significantly higher compared with those in the control group (p < 0.05); however, the levels of serum lymphocytes were significantly lower compared with those in the control group (p < 0.05). Multivariate logistic regression analysis showed that elevated CK-MB and NLR levels were risk factors for AMI (p < 0.05). The ROC curve showed that the area under the curve of the NLR and CK levels were 0.917 and 0.594, respectively. CONCLUSION: The CK index and NLR have a clinical predicting value for AMI and could be used as a clinical auxiliary diagnostic index for the assessment of patients with AMI.

Rational Conversion of Imine linkages to Amide Linkages in Covalent Organic Frameworks for Photocatalytic Oxidation with Enhanced Photostability.

Covalent organic frameworks (COFs) and their applications in photocatalysis have been extensively studied, but the instability of imine-linked COFs is an important factor limiting their performance. In this work, two imine-linked COFs were successfully converted to amide-linked COFs through post synthetic modification (PSM). The oxidized COFs presented lower binding energy to O2, exhibited higher photocatalytic activity for oxidation of thioethers and coupling of benzylamines with excellent stability. The present work can serve as a reliable reference for the development of novel highly active and stable COF-based photocatalysts.

All Roads Lead to Rome: Comparing Nanoparticle- and Small Molecule-Driven Cell Autophagy.

Autophagy, vital for removing cellular waste, is triggered differently by small molecules and nanoparticles. Small molecules, like rapamycin, non-selectively activate autophagy by inhibiting the mTOR pathway, which is essential for cell regulation. This can clear damaged components but may cause cytotoxicity with prolonged use. Nanoparticles, however, induce autophagy, often causing oxidative stress, through broader cellular interactions and can lead to a targeted form known as "xenophagy." Their impact varies with their properties but can be harnessed therapeutically. In this review, the autophagy induced by nanoparticles is explored and small molecules across four dimensions: the mechanisms behind autophagy induction, the outcomes of such induction, the toxicological effects on cellular autophagy, and the therapeutic potential of employing autophagy triggered by nanoparticles or small molecules. Although small molecules and nanoparticles each induce autophagy through different pathways and lead to diverse effects, both represent invaluable tools in cell biology, nanomedicine, and drug discovery, offering unique insights and therapeutic opportunities.

Study on Pyrolysis and Oxidation Characteristics of Coal Gangue Based on TGA-DSC.

Coal gangue spontaneous combustion has caused serious environmental and ecological problems. To investigate the reaction kinetic parameters of the gangue and the exothermic characteristics of the spontaneous combustion of the influence of the law, this study employs the thermogravimetric method to explore the characteristic parameters of the pyrolysis and oxidative combustion process of the gangue from the perspective of thermodynamics, and, at the same time, using the differential scanning calorimetry (DSC) on the exothermic effect of the gangue to explore the gangue to obtain the gangue and the original coal TG/DTG/DSC curves to be compared and from the perspective of thermodynamics. The change rule and potential parameters in the pyrolysis and oxidative combustion process of coal gangue (CG) were analyzed, the oxidation kinetic properties of CG were studied, and the reaction mechanism of oxidative spontaneous combustion of CG was further explained. The results show that the TG/DTG/DSC curves of CG in different gas atmospheres will have significant differences in all stages, and in the process of pyrolysis and oxidative combustion, the thermogravimetric curves of CG and those of the original coal show a consistent trend, except for the large difference in peak amplitude in different stages; in different gas atmospheres, as the rate of warming increases, the TG/DTG/DSC curves of the gangue are tilted toward the high-temperature region, they are inclined to the high-temperature region with the increase of the heating rate, and the phenomenon of "hysteresis" of characteristic temperature occurs. The research results provide a theoretical basis for the construction of a spontaneous combustion early warning system based on the fine division of gangue pyrolysis and oxidation combustion stages.

Single-Cell Nuclear Sequencing Atlas Revealed the Induction of Parkinson's Disease by RELN+ Neuron 3 and the Gene Regulatory Network of MSRA.

AIMS: To determine the cell types that promoted the progression of Parkinson's disease (PD) using the substantia nigra in the brain tissues derived from patients with PD and normal controls. BACKGROUND: PD is an incurable neurodegenerative disease that threatens the physical activity of the aging population, and the complex molecular mechanisms remain be comprehensively elucidated. OBJECTIVE: To describe potential disease-promoting cell types in PD and to provide a theoretical basis. METHODS: Single-cell nuclear sequencing data of nine PD samples and control samples from Gene Expression Omnibus (GEO) were included, and heterogeneous cell subpopulations in the substantia nigra were identified by annotation analysis. Potential pathogenic cell subpopulations of PD were determined based on the expression data of marker genes. Cell differentiation trajectories and communication networks were generated by Pseudotime trajectory analysis and cell communication analysis. Furthermore, single-- cell regulatory network inference and clustering (SCENIC) analysis was conducted to determine the regulatory network of transcription factor-target genes in PD. RESULTS: Among the nine cell subpopulations classified, RELN+neuron 3 showed reduced abundance and dopamine secretion capacity in PD and was therefore considered as a promoter of PD pathogenesis and progression. The regulatory network of MSRA action was involved in the developmental process of cells in the central nervous system, indicating that MSRA and its targets might serve as potential therapeutic targets for PD. RELN+neuron 3 had two directions of differentiation, specifically, branch 1 exhibited a high apoptotic profile and branch 2 exhibited a high cell death profile. In addition, the intensity of EPHA and EPHB signaling was attenuated between RELN+neuron 3 and other cell subpopulations. CONCLUSION: To conclude, this study identified a subpopulation of RELN+neuron 3 cells with markedly reduced abundance in the brain substantia nigra in PD. The MSRA-involved gene regulatory networks was considered as a novel therapeutic network for PD.

A comprehensive framework for the delimitation of species within the Bemisia tabaci cryptic complex, a global pest-species group.

Identifying cryptic species poses a substantial challenge to both biologists and naturalists due to morphological similarities. Bemisia tabaci is a cryptic species complex containing more than 44 putative species; several of which are currently among the world's most destructive crop pests. Interpreting and delimiting the evolution of this species complex has proved problematic. To develop a comprehensive framework for species delimitation and identification, we evaluated the performance of distinct data sources both individually and in combination among numerous samples of the B. tabaci species complex acquired worldwide. Distinct datasets include full mitogenomes, single-copy nuclear genes, restriction site-associated DNA sequencing, geographic range, host speciation, and reproductive compatibility datasets. Phylogenetically, our well-supported topologies generated from three dense molecular markers highlighted the evolutionary divergence of species of the B. tabaci complex and suggested that the nuclear markers serve as a more accurate representation of B. tabaci species diversity. Reproductive compatibility datasets facilitated the identification of at least 17 different cryptic species within our samples. Native geographic range information provides a complementary assessment of species recognition, while the host range datasets provide low rate of delimiting resolution. We further summarized different data performances in species classification when compared with reproductive compatibility, indicating that combination of mtCOI divergence, nuclear markers, geographic range provide a complementary assessment of species recognition. Finally, we represent a model for understanding and untangling the cryptic species complexes based on the evidence from this study and previously published articles.

Global trends and spatial drivers of diabetes mellitus mortality, 1990-2019: a systematic geographical analysis.

Objective: Diabetes mellitus is the leading cause of death worldwide, and multiple risk factors associated with diabetes mortality. Methods: Employing spatial statistics, we characterized the spatial distribution and patterns of diabetes mortality, and revealed the spatial relationship between diabetes mortality and 11 socioeconomic and environmental risk factors at the country level, from 1990 to 2019. Results: Globally, significantly high rates of diabetes mortality were primarily clustered in countries with limited land areas or located on islands, such as Fiji, Kiribati, Eswatini, and Trinidad and Tobago. Countries with weaker economic independence are more likely to have higher diabetes mortality rates. In addition, the impact of socioeconomic and environmental factors was significant at the country level, involving health expenditure, number of physicians, household and ambient air pollution, smoking, and alcohol consumption. Notably, the spatial relationship between diabetes mortality and ambient air pollution, as well as alcohol consumption, showed negative correlations. Countries with high diabetes mortality rates generally had lower levels of ambient air pollution and alcohol consumption. Conclusion: The study highlights the spatial clustering of diabetes mortality and its substantial variation. While many risk factors can influence diabetes mortality, it's also essential to consider the level of these factors at the country level. Tailoring appropriate interventions based on specific national circumstances holds the potential to more effectively mitigate the burden of diabetes mortality.

Predictive Value of 5-Methoxytryptophan on Long-Term Clinical Outcome after PCI in Patients with Acute Myocardial Infarction-a Prospective Cohort Study.

BACKGROUND: In recent years, 5-Methoxytryptophan (5-MTP) has been identified as an endothelial factor with vaso-protective and anti-inflammatory properties. METHODS: In this prospective cohort study, a total of 407 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) successfully were enrolled. A 1-year follow-up Kaplan-Meier survival analysis was used for evaluating the correlation between 5-MTP and major adverse cardiovascular event (MACE) while Cox proportional-hazards regression was used to identify predictive values of 5-MTP on MACE after AMI. RESULTS: Increased 5-MTP level led to a significant downtrend in the incidence of MACE (All Log-rank p < 0.05). Thus, a high baseline 5-MTP could reduce the 1-year incidence of MACE (HR = 0.33, 95%Cl 0.17-0.64, p = 0.001) and heart failure (HF) (HR = 0.28, 95% Cl 0.13-0.62, p = 0.002). Subgroup analysis indicated the predictive value of 5-MTP was more significant in patients aged ≤ 65 years and those with higher baseline NT-proBNP, T2DM, STEMI, and baseline HF with preserved LVEF (HFpEF) characteristics. CONCLUSIONS: Plasma 5-MTP is an independent and protective early biomarker for 1-year MACE and HF events in patients with AMI, especially in younger patients and those with T2DM, STEMI, and baseline HFpEF characteristics.

An exploratory framework for mapping, mechanism, and management of urban soundscape quality: From quietness to naturalness.

BACKGROUND: Despite growing attention from researchers and governments, challenges persist in comprehensively assessing urban sound quality by integrating both quietness and naturalness aspects. GOALS: This study aimed to develop an innovative soundscape quality index that concurrently evaluates quietness and naturalness in urban soundscapes. Our objectives included conducting urban soundscape quality mapping, analyzing influential mechanisms, and identifying priority zones for sound environment management. APPROACHES: We collected sound pressure level (SPL) and raw audio data, from which we computed a normalized difference soundscape index (NDSI). With a dataset comprising 28 explanatory variables encompassing land use, built environment, vegetation characteristics, and temporal factors, we employed the random forest (RF) model to predict 10 indicators, including eight SPL-related indices, NDSI, and the QNS (quietness and naturalness soundscape) index. Crucially, we utilized SHAP (SHapley Additive exPlanations) values to interpret the RF model. FINDINGS: Spatial variations in quietness and naturalness were evident, closely associated with road networks and vegetation, respectively, with discernible temporal variations. The top three variables influencing QNS were distance to major roads, normalized difference vegetation index (NDVI), and proportion of tree coverage. Moreover, interaction effects highlighted dual negative or synergistic promoting effects on QNS from factors such as road width, human disturbance, vegetation configurations, and land cover. Notably, these mechanisms were successfully applied to six typical tourist attractions in Xiamen city, where five types of management zones were mapped based on priority considerations of population density and soundscape quality. Interestingly, natural soundscape reserves were highly correlated with city parks, high-risk zones predominantly overlapped with road networks, and potential zones comprised inner communities between streets. SIGNIFICANCE: The framework demonstrated effectiveness in mapping, exploring mechanisms, and guiding management strategies for the urban sound environment.

Analysis of 78 trace liquid crystal monomers in air by gas chromatography coupled with triple quadrupole mass spectrometry.

Liquid crystal monomers (LCMs) comprise a class of organic pollutants that have garnered considerable attention because of their dioxin-like toxicity (i.e., modulation of genes) and presence in various environments. However, limited information about the identities, occurrence, and distribution of LCMs has highlighted an urgent need for a high-throughput and sensitive analytical method. In this study, we developed and validated a rapid, simple, sensitive method that involves minimal solvent consumption. The method was applied for the simultaneous detection and identification of 78 LCMs in atmospheric total suspended particulate samples (dae < 100 µm) using gas chromatography coupled with triple quadrupole mass spectrometry. The results showed high degrees of linearity with correlation coefficients >0.995 in the concentration range of 5.0-500 ng/mL. The instrumental detection limits ranged from 0.7 to 5.3 pg, and the method detection limits ranged from 0.1 to 0.9 pg/m3. The accuracy of the method was between 70 % and 130 % for most analytes, and the relative standard deviations of six replicates were <15 % at three levels of spiking (10, 50, and 200 ng/mL). The developed analytical method was applied to analyze real air particulate samples from Beijing, China. Overall, 45 LCMs ranged from 65.5 to 145.7 pg/m3, with a mean concentration of 92.5 pg/m3. Among them, (trans,trans)-4-propyl-4'-ethenyl-1,1'-bicyclohexane (PVB) was the most abundant, with an average concentration of 33.6 pg/m3. The total estimated daily intakes of LCMs for adults and children were 15.6 and 46.6 pg/kg bw/day, respectively. Accordingly, the method described herein is suitable for quantifying LCMs in atmospheric particulate samples. This study will be valuable for investigating LCM environmental occurrence, behaviors, and risk assessments.

Viscoelastic hydrogels regulate adipose-derived mesenchymal stem cells for nucleus pulposus regeneration.

Low back pain is a leading cause of disability worldwide, often attributed to intervertebral disc (IVD) degeneration with loss of the functional nucleus pulposus (NP). Regenerative strategies utilizing biomaterials and stem cells are promising for NP repair. Human NP tissue is highly viscoelastic, relaxing stress rapidly under deformation. However, the impact of tissue-specific viscoelasticity on the activities of adipose-derived stem cells (ASC) remains largely unexplored. Here, we investigated the role of matrix viscoelasticity in regulating ASC differentiation for IVD regeneration. Viscoelastic alginate hydrogels with stress relaxation time scales ranging from 100 s to 1000s were developed and used to culture human ASCs for 21 days. Our results demonstrated that the fast-relaxing hydrogel significantly enhanced ASCs long-term cell survival and NP-like extracellular matrix secretion of aggrecan and type-II collagen. Moreover, gene expression analysis revealed a substantial upregulation of the mechanosensitive ion channel marker TRPV4 and NP-specific markers such as SOX9, HIF-1α, KRT18, CDH2 and CD24 in ASCs cultured within the fast-relaxing hydrogel, compared to slower-relaxing hydrogels. These findings highlight the critical role of matrix viscoelasticity in regulating ASC behavior and suggest that viscoelasticity is a key parameter for novel biomaterials design to improve the efficacy of stem cell therapy for IVD regeneration. STATEMENT OF SIGNIFICANCE: Systematically characterized the influence of tissue-mimetic viscoelasticity on ASC. NP-mimetic hydrogels with tunable viscoelasticity and tissue-matched stiffness. Long-term survival and metabolic activity of ASCs are substantially improved in the fast-relaxing hydrogel. The fast-relaxing hydrogel allows higher rate of cell protrusions formation and matrix remodeling. ASC differentiation towards an NP-like cell phenotype is promoted in the fast-relaxing hydrogel, with more CD24 positive expression indicating NP committed cell fate. The expression of TRPV4, a molecular sensor of matrix viscoelasticity, is significantly enhanced in the fast-relaxing hydrogel, indicating ASC sensing matrix viscoelasticity during cell development. The NP-specific ECM secretion of ASC is considerably influenced by matrix viscoelasticity, where the deposition of aggrecan and type-II collagen are significantly enhanced in the fast-relaxing hydrogel.

Persistent ∆FosB expression limits recurrent seizure activity and provides neuroprotection in the dentate gyrus of APP mice.

Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer's disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity. However, the suppression of calbindin in conditions of neuronal hyperexcitability has been demonstrated to provide neuroprotection to dentate granule cells, indicating that ∆FosB may act over long timescales to coordinate neuroprotective pathways. To test this hypothesis, we used viral-mediated expression of ∆JunD to interfere with ∆FosB signaling over the course of several months in transgenic mice expressing mutant human amyloid precursor protein (APP), which exhibit spontaneous seizures and develop AD-related neuropathology and cognitive deficits. Our results demonstrate that persistent ∆FosB activity acts through discrete modes of hippocampal target gene regulation to modulate neuronal excitability, limit recurrent seizure activity, and provide neuroprotection to hippocampal dentate granule cells in APP mice.

Objectively measured daytime sleepiness predicts weight change among adults: Findings from the Wisconsin Sleep Cohort Study.

OBJECTIVE: Body mass index (BMI) trajectories are associated with night-time sleep, but it is not clear how they relate to daytime sleepiness in population data. This study aimed to examine longitudinal associations between levels and changes in daytime sleepiness and BMI trajectories among men and women. METHODS: We estimated growth curve models among 827 participants in the Wisconsin Sleep Cohort Study (mean [sd] age = 55.2 [8.0] years at baseline). The outcome variable was BMI (kg/m2) and the key predictor was daytime sleepiness measured by Multiple Sleep Latency Test (MSLT) scores. Covariates included demographics, health behaviors, retirement status, stimulant use, and depressive symptoms. In sensitivity analyses, we evaluated the potential effects of cardiovascular disease, shift work status, and sleep apnea on the robustness of sleepiness and BMI associations. RESULTS: At the between-person level, men who were sleepier had higher BMI levels. At the within-person level, age moderated the positive association between sleepiness and BMI among women. Specifically, young women who became sleepier over time gained more BMI than older women with comparable increases in sleepiness. Furthermore, while BMI tended to increase with age among women, BMI trajectories were steeper among sleepy women than among well-rested women, who experienced less increase in BMI over time. CONCLUSION: The study suggested that levels and changes in daytime sleepiness as objectively measured by MSLT scores are associated with body mass among adults.

Claudin-7 is essential for the maintenance of colonic stem cell homoeostasis via the modulation of Wnt/Notch signalling.

Intestinal stem cells (ISCs) play a crucial role in the continuous self-renewal and recovery of the intestinal epithelium. In previous studies, we have revealed that the specific absence of Claudin-7 (Cldn-7) in intestinal epithelial cells (IECs) can lead to the development of spontaneous colitis. However, the mechanisms by which Cldn-7 maintains homeostasis in the colonic epithelium remain unclear. Therefore, in the present study, we used IEC- and ISC-specific Cldn-7 knockout mice to investigate the regulatory effects of Cldn-7 on colonic Lgr5+ stem cells in the mediation of colonic epithelial injury and repair under physiological and inflammatory conditions. Notably, our findings reveal that Cldn-7 deletion disrupts the self-renewal and differentiation of colonic stem cells alongside the formation of colonic organoids in vitro. Additionally, these Cldn-7 knockout models exhibited heightened susceptibility to experimental colitis, limited epithelial repair and regeneration, and increased differentiation toward the secretory lineage. Mechanistically, we also established that Cldn-7 facilitates the proliferation, differentiation, and organoid formation of Lgr5+ stem cells through the maintenance of Wnt and Notch signalling pathways in the colonic epithelium. Overall, our study provides new insights into the maintenance of ISC function and colonic epithelial homoeostasis.

Single-Cell Transcriptome Analysis of Small Cell Neuroendocrine Carcinoma of the Endometrium Reveals ISL1 as a Potential Biomarker for Diagnosis and Treatment.

BACKGROUND: As a dedifferentiated tumor, small cell endometrial neuroendocrine tumors (NETs) are rare and frequently diagnosed at an advanced stage with a poor prognosis. Current treatment recommendations are often extrapolated from histologically similar tumors in other sites or based on retrospective studies. The exploration for diagnostic and therapeutic markers in small cell NETs is of great significance. METHODS: In this study, we conducted single-cell RNA sequencing on a specimen obtained from a patient diagnosed with small cell endometrial neuroendocrine carcinoma (SCNEC) based on pathology. We revealed the cell map and intratumoral heterogeneity of the cancer cells through data analysis. Further, we validated the function of ISL LIM Homeobox 1 (ISL1) in vitro in an established neuroendocrine cell line. Finally, we examined the association between ISL1 and tumor staging in small cell lung cancer (SCLC) patient samples. RESULTS: We observed the significant upregulation of ISL1 expression in tumor cells that showed high expression of the neuroepithelial markers. Additionally, in vitro cell function experiments demonstrated that the high ISL1 expression group exhibited markedly higher cell proliferation and migration abilities compared to the low expression group. Finally, we showed that the expression level of ISL1 was correlated with SCLC stages. CONCLUSIONS: ISL1 protein in NETs shows promise as a potential biomarker for diagnosis and treatment.

Pyroptosis in myocardial ischemia/reperfusion and its therapeutic implications.

Ischemic heart disease, a prevalent cardiovascular disease with global significance, is associated with substantial morbidity. Timely and successful reperfusion is crucial for reducing infarct size and enhancing clinical outcomes. However, reperfusion may induce additional myocardium injury, manifesting as myocardial ischemia/reperfusion (MI/R) injury. Pyroptosis is a regulated cell death pathway, the signaling pathway of which is activated during MI/R injury. In this process, the inflammasomes are triggered, initiating the cleavage of gasdermin proteins and pro-interleukins, which results in the formation of membrane pores and the maturation and secretion of inflammatory cytokines. Numerous preclinical evidence underscores the pivotal role of pyroptosis in MI/R injury. Inhibiting pyroptosis is cardioprotective against MI/R injury. Although certain agents exhibiting promise in preclinical studies for attenuating MI/R injury through inhibiting pyroptosis have been identified, the suitability of these compounds for clinical trials remains untested. This review comprehensively summarizes the recent developments in this field, with a specific emphasis on the impact of pyroptosis on MI/R injury. Deciphering these findings not only sheds light on new disease mechanisms but also paves the way for innovative treatments. And then the exploration of the latest advances in compounds that inhibit pyroptosis in MI/R is discussed, which aims to provide insights into potential therapeutic strategies and identify avenues for future research in the pursuit of effective clinical interventions.