Liposomal Nanomaterials: A Rising Star in Glioma Treatment.

Glioma is a primary malignant tumor in the central nervous system. In recent years, the treatment of glioma has developed rapidly, but the overall survival of glioma patients has not significantly improved. Due to the presence of the blood-brain barrier and intracranial tumor barrier, many drugs with good effects to cure glioma in vitro cannot be accurately transported to the corresponding lesions. In order to enable anti-tumor drugs to overcome the barriers and target glioma, nanodrug delivery systems have emerged recently. It is gratifying that liposomes, as a multifunctional nanodrug delivery carrier, which can be compatible with hydrophilic and hydrophobic drugs, easily functionalized by various targeted ligands, biodegradable, and hypoimmunogenic in vivo, has become a quality choice to solve the intractable problem of glioma medication. Therefore, we focused on the liposome nanodrug delivery system, and summarized its current research progress in glioma. Hopefully, this review may provide new ideas for the research and development of liposome-based nanomaterials for the clinical treatment of glioma.

Enhanced Electromagnetic Interference Shielding Properties of CNT/Carbon Composites by Designing a Hierarchical Porous Structure.

With the widespread use of electronic devices, electromagnetic interference (EMI) has become an increasingly severe issue, adversely affecting device performance and human health. Carbon nanotubes (CNTs) are recognized for their electrical conductivity, flexibility, and stability, making them promising candidates for EMI shielding applications. This research developed hierarchical porous-structured CNT/carbon composites for enhancing electromagnetic interference (EMI) shielding properties. Featuring a CNT film with nano-scale pores and an amorphous carbon layer with micro-scale pores, the CNT/carbon composites are strategically arranged to promote the penetration of EM waves into the composite's interior and facilitate multiple reflections, thereby improving the EMI shielding performance. An impressive EMI shielding effectiveness of 61.4 dB was achieved by the CNT/carbon composites, marking a significant improvement over the 36.5 dB measured for the pristine CNT film. Owing to the micro pores in the amorphous carbon layer, a notable reduction in the reflection shielding efficiency (SER) but, concurrently, a substantial increase in the absorption shielding efficiency (SEA) compared with the pristine CNT film was realized in the composites. This study successfully validated the effectiveness of the hierarchical porous structure in enhancing the EMI shielding performance, providing a promising new strategy for the development of lightweight, flexible, and efficient EMI shielding materials.

An Integrated Strategy Based on 10-DAB Extraction and In Situ Whole-Cell Biotransformation of Renewable Taxus Needles to Produce Baccatin III.

Baccatin III is a crucial precursor in the biosynthesis pathway of paclitaxel. Its main sources are extraction from Taxus or chemical synthesis using 10-deacetylbaccatin III (10-DAB) as substrate. However, these preparation approaches exhibit serious limitations, including the low content of baccatin III in Taxus and the complicated steps of chemical synthesis. Heterologous expression of 10-deacetylbaccatin III-10-O-acetyltransferase (TcDBAT) in microbial strains for biotransformation of 10-DAB is a promising alternative strategy for baccatin III production. Here, the promotion effects of glycerol supply and slightly acidic conditions with a low-temperature on the catalysis of recombinant TcDBAT strain were clarified using 10-DAB as substrate. Taxus needles is renewable and the content of 10-DAB is relatively high, it can be used as an effective source of the catalytic substrate 10-DAB. Baccatin III was synthesized by integrating the extraction of 10-DAB from renewable Taxus needles and in situ whole-cell catalysis in this study. 40 g/L needles were converted into 20.66 mg/L baccatin III by optimizing and establishing a whole-cell catalytic bioprocess. The method used in this study can shorten the production process of Taxus extraction for baccatin III synthesis and provide a reliable strategy for the efficient production of baccatin III by recombinant strains and the improvement of resource utilization rate of Taxus needles.

Activation of CD14+ Monocytes via the IFN-γ Signaling Pathway Is Associated with Immune-Related Adverse Events in Hepatocellular Carcinoma Patients Receiving PD-1 Inhibition Combination Therapy.

(1) Background: Immune-related adverse events (irAEs) are a series of unique organ-specific inflammatory toxicities observed in patients with hepatocellular carcinoma (HCC) undergoing PD-1 inhibition combination therapy. The specific underlying mechanisms remain unclear. (2) Methods: We recruited 71 patients with HCC undergoing PD-1 inhibition combination therapy. These patients were then divided into two groups based on irAE occurrence: 34 had irAEs and 37 did not. Using Olink proteomics, we analyzed the aberrant inflammation-related proteins (IRPs) in these patient groups. For single-cell RNA sequencing (scRNA-seq) analysis, we collected peripheral blood mononuclear cells (PBMCs) from two representative patients at the pretreatment, irAE occurrence, and resolution stages. (3) Results: Our study revealed distinct plasma protein signatures in HCC patients experiencing irAEs after PD-1 inhibition combination therapy. We clarified the relationship between monocyte activation and irAEs, identified a strongly associated CD14-MC-CCL3 monocyte subset, and explored the role of the IFN-γ signaling pathway in monocyte activation during irAEs. (4) Conclusions: The activation of monocytes induced by the IFN-γ signaling pathway is an important mechanism underlying the occurrence of irAEs in HCC patients receiving PD-1 inhibition combination therapy.

The Global Burden of Disease Attributable to Child and Maternal Malnutrition: 1990-2019.

OBJECTIVE: With this study, we aimed to estimate the disease burden attributable to child and maternal malnutrition (CMM) throughout the world between 1990 and 2019. METHODS: The number, age-standardized rate, population attributable fraction of deaths, disability-adjusted life-years, years of life lost, and years lived with disability associated with CMM were estimated using the Global Burden of Disease Study 2019 by age, sex, year, location, and sociodemographic index at the global level. The slope index of inequality and concentration index were employed to measure socioeconomic-related health inequalities across countries. RESULTS: The number (million) of global deaths, disability-adjusted life-years, and years of life lost related to CMM were 2.9, 294.8, and 250.5 in 2019, showing decreases of 60.8, 57.4, and 60.7% since 1990. However, the number of years lived with CMM-related disability increased from 36.0 in 1990 to 44.3 in 2019. Additionally, the age-standardized rates of these 4 indicators showed varying degrees of decline. The global burden of CMM-related conditions differed with age and sex. The burden was the heaviest in western sub-Saharan Africa, especially in Chad. In terms of diseases, neonatal disorders represented the most significant burden attributed to CMM. Additionally, the CMM burden was more concentrated in regions with low sociodemographic indices, shown by the slope index of inequality and concentration index. CONCLUSIONS: The findings of this study highlight the ongoing global burden of CMM, particularly in terms of years lived with disability. Population-wide actions targeting the effective treatment and relief of CMM may reduce the CMM-related disease burden.

Micro/nanoplastics impair the feeding of goldfish by disrupting the complicated peripheral and central regulation of appetite.

The ubiquitous presence of plastic particles in water bodies poses a potential threat to aquatic species. Although numerous adverse effects of microplastics (MPs) and nanoplastics (NPs) have been documented, their effects on fish feeding, one of the most important behaviors of animals, are far from being fully understood. In this study, the effects of MPs and NPs (at environmentally realistic levels) on fish food consumption and feeding behavior were assessed using goldfish (Carassius auratus) and polystyrene (PS) particles as representatives. In addition, to reveal the potential mechanisms, the effects of MPs and NPs on peripheral and central regulation of appetite were evaluated by examining appetite-regulation related intestinal, serous, and hypothalamic parameters. The results obtained indicated that the 28-day MP- and NP-exposure significantly impaired goldfish feeding by disrupting peripheral and central appetite regulation. Based on differences observed in their effects on the abovementioned behavioral, histological, and physiological parameters, MPs and NPs may interfere with appetite regulation in a size-dependent manner. Blocking the gastrointestinal tract and causing histopathological and functional damage to inner organs may be the main routes through which MPs and NPs disrupt appetite regulation. Our findings suggested that plastic particles exposure may have far-reaching effects on fish species through impaired feeding, which warrants further attention.

Immunoglobulin Superfamily Containing Leucine-Rich Repeat (ISLR) Serves as a Redox Sensor That Modulates Antioxidant Capacity by Suppressing Pyruvate Kinase Isozyme M2 Activity.

Cells defend against oxidative stress by enhancing antioxidant capacity, including stress-activated metabolic alterations, but the underlying intracellular signaling mechanisms remain unclear. This paper reports that immunoglobulin superfamily containing leucine-rich repeat (ISLR) functions as a redox sensor that responds to reactive oxygen species (ROS) stimulation and modulates the antioxidant capacity by suppressing pyruvate kinase isozyme M2 (PKM2) activity. Following oxidative stress, ISLR perceives ROS stimulation through its cysteine residue 19, and rapidly degrades in the autophagy-lysosome pathway. The downregulated ISLR enhances the antioxidant capacity by promoting the tetramerization of PKM2, and then enhancing the pyruvate kinase activity, PKM2-mediated glycolysis is crucial to the ISLR-mediated antioxidant capacity. In addition, our results demonstrated that, in triple-negative breast cancer, cisplatin treatment reduced the level of ISLR, and PKM2 inhibition sensitizes tumors to cisplatin by enhancing ROS production; and argued that PKM2 inhibition can synergize with cisplatin to limit tumor growth. Our results demonstrate a molecular mechanism by which cells respond to oxidative stress and modulate the redox balance.

Spatial distribution and influencing factors of CDC health resources in China: a study based on panel data from 2016-2021.

Background: Measuring the development of Chinese centers for disease control and prevention only by analyzing human resources for health seems incomplete. Moreover, previous studies have focused more on the quantitative changes in healthcare resources and ignored its determinants. Therefore, this study aimed to analyze the allocation of healthcare resources in Chinese centers for disease control and prevention from the perspective of population and spatial distribution, and to further explore the characteristics and influencing factors of the spatial distribution of healthcare resources. Methods: Disease control personnel density, disease control and prevention centers density, and health expenditures density were used to represent human, physical, and financial resources for health, respectively. First, health resources were analyzed descriptively. Then, spatial autocorrelation was used to analyze the spatial distribution characteristics of healthcare resources. Finally, we used spatial econometric modeling to explore the influencing factors of healthcare resources. Results: The global Moran index for disease control and prevention centers density decreased from 1.3164 to 0.2662 (p < 0.01), while the global Moran index for disease control personnel density increased from 0.4782 to 0.5067 (p < 0.01), while the global Moran index for health expenditures density was statistically significant only in 2016 (p < 0.1). All three types of healthcare resources showed spatial aggregation. Population density and urbanization have a negative impact on the disease control and prevention centers density. There are direct and indirect effects of disease control personnel density and health expenditures density. Population density and urbanization had significant negative effects on local disease control personnel density. Urbanization has an indirect effect on health expenditures density. Conclusion: There were obvious differences in the spatial distribution of healthcare resources in Chinese centers for disease control and prevention. Social, economic and policy factors can affect healthcare resources. The government should consider the rational allocation of healthcare resources at the macro level.

Synthesis of Soluble High Molar Mass Poly(Phenylene Methylene)-Based Polymers.

Poly(phenylene methylene) (PPM) is a multifunctional polymer that is also active as an anticorrosion fluorescent coating material. Although this polymer was synthesized already more than 100 years ago, a versatile synthetic route to obtain soluble high molar mass polymers based on PPM has yet to be achieved. In this article, the influence of bifunctional bis-chloromethyl durene (BCMD) as a branching agent in the synthesis of PPM is reported. The progress of the reaction was followed by gel permeation chromatography (GPC) and NMR analysis. PPM-based copolymers with the highest molar mass reported so far for this class of materials (up to Mn of 205,300 g mol-1) were isolated. The versatile approach of using BCMD was confirmed by employing different catalysts. Interestingly, thermal and optical characterization established that the branching process does not affect the thermoplastic behavior and the fluorescence of the material, thus opening up PPM-based compounds with high molar mass for applications.

Prevalence and Determinants of Anxiety and Depression Among Healthcare Workers in Liaoning Province, China.

Purpose: To assess the anxiety and depression and their predictors among healthcare workers in Liaoning Province, China. Methods: In order to explore the influencing factors and prevalence of anxiety and depression among healthcare workers, a cross-sectional research design was used to survey 500 healthcare workers using the 14-item Hospital Anxiety Depression Scale (HADS), the Rosenberg Self-Esteem Scale (RSES), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Survey of Perceived Organizational Support (SPOS). Results: About 47.12% of the healthcare workers suffered from anxiety and 71.63% suffered from depression. In our study, we found that the health status (OR: 0.540, 95% CI: 0.298-0.976), self-esteem (OR: 0.395, 95% CI: 0.251-0.619), PSS (OR: 0.621, 95% CI: 0.388-0.994), organizational support (OR: 0.533, 95% CI. 0.333-0.854) were protective factors for healthcare workers suffering from anxiety, and resistance to COVID-19 (OR: 1.703, 95% CI: 1.082-2.681) was a risk factor for healthcare workers suffering from anxiety, while good quality of life (OR: 0.385, 95% CI: 0.206-0.719) self-esteem (OR: 0.187, 95% CI: 0.110-0.317), and PSS (OR: 0.475, 95% CI: 0.267-0.847) were protective factors for healthcare workers suffering from depression, and at the age of 35-40 years (OR: 2.475, 95% CI: 1.140-5.369) and resistance to COVID-19 (OR: 2.219, 95% CI: 1.313-3.751) were risk factors for healthcare workers suffering from depression. Conclusion: The anxiety and depression status of healthcare workers in China is poor, and hospital administrators should take positive measures to support healthcare workers and give positive expectations to alleviate negative emotions such as anxiety and depression.

Enrofloxacin exposure undermines gut health and disrupts neurotransmitters along the microbiota-gut-brain axis in zebrafish.

The environmental prevalence of antibiotic residues poses a potential threat to gut health and may thereby disrupt brain function through the microbiota-gut-brain axis. However, little is currently known about the impacts of antibiotics on gut health and neurotransmitters along the microbiota-gut-brain axis in fish species. Taking enrofloxacin (ENR) as a representative, the impacts of antibiotic exposure on the gut structural integrity, intestinal microenvironment, and neurotransmitters along the microbiota-gut-brain axis were evaluated in zebrafish in this study. Data obtained demonstrated that exposure of zebrafish to 28-day environmentally realistic levels of ENR (6 and 60 µg/L) generally resulted in marked elevation of two intestinal integrity biomarkers (diamine oxidase (DAO) and malondialdehyde (MDA), upregulation of genes that encode inter-epithelial tight junction proteins, and histological alterations in gut as well as increase of lipopolysaccharide (LPS) in plasma, indicating an evident impairment of the structural integrity of gut. Moreover, in addition to significantly altered neurotransmitters, markedly higher levels of LPS while less amount of two short-chain fatty acids (SCFAs), namely acetic acid and valeric acid, were detected in the gut of ENR-exposed zebrafish, suggesting a disruption of gut microenvironment upon ENR exposure. Along with corresponding changes detected in gut, significant disruption of neurotransmitters in brain indicated by marked alterations in the contents of neurotransmitters, the activity of acetylcholin esterase (AChE), and the expression of neurotransmitter-related genes were also observed. These findings suggest exposure to environmental antibiotic residues may impair gut health and disrupt neurotransmitters along the microbiota-gut-brain axis in zebrafish. Considering the prevalence of antibiotic residues in environments and the high homology of zebrafish to other vertebrates including human, the risk of antibiotic exposure to the health of wild animals as well as human deserves more attention.

Associations between digital literacy, health literacy, and digital health behaviors among rural residents: evidence from Zhejiang, China.

OBJECTIVE: Within the digital society, the limited proficiency in digital health behaviors among rural residents has emerged as a significant factor intensifying health disparities between urban and rural areas. Addressing this issue, enhancing the digital literacy and health literacy of rural residents stands out as a crucial strategy. This study aims to investigate the relationship between digital literacy, health literacy, and the digital health behaviors of rural residents. METHODS: Initially, we developed measurement instruments aimed at assessing the levels of digital literacy and health literacy among rural residents. Subsequently, leveraging micro survey data, we conducted assessments on the digital literacy and health literacy of 968 residents in five administrative villages in Zhejiang Province, China. Building upon this foundation, we employed Probit and Poisson models to empirically scrutinize the influence of digital literacy, health literacy, and their interaction on the manifestation of digital health behaviors within the rural population. This analysis was conducted from a dual perspective, evaluating the participation of digital health behaviors among rural residents and the diversity to which they participate in such behaviors. RESULTS: Digital literacy exhibited a notably positive influence on both the participation and diversity of digital health behaviors among rural residents. While health literacy did not emerge as a predictor for the occurrence of digital health behavior, it exerted a substantial positive impact on the diversity of digital health behaviors in the rural population. There were significant interaction effects between digital literacy and health literacy concerning the participation and diversity of digital health behaviors among rural residents. These findings remained robust even after implementing the instrumental variable method to address endogeneity issues. Furthermore, the outcomes of robust analysis and heterogeneity analysis further fortify the steadfastness of the aforementioned conclusions. CONCLUSION: The findings suggest that policymakers should implement targeted measures aimed at enhancing digital literacy and health literacy among rural residents. This approach is crucial for improving rural residents' access to digital health services, thereby mitigating urban-rural health inequality.

Exposure to microplastics renders immunity of the thick-shell mussel more vulnerable to diarrhetic shellfish toxin-producing harmful algae.

Despite both microplastics (MPs) and harmful algae blooms (HABs) may pose a severe threat to the immunity of marine bivalves, the toxification mechanism underlying is far from being fully understood. In addition, owing to the prevalence and sudden occurrence characteristics of MPs and HABs, respectively, bivalves with MP-exposure experience may face acute challenge of harmful algae under realistic scenarios. However, little is known about the impacts and underlying mechanisms of MP-exposure experience on the susceptibility of immunity to HABs in bivalve mollusks. Taking polystyrene MPs and diarrhetic shellfish toxin-producing Prorocentrum lima as representatives, the impacts of MP-exposure on immunity vulnerability to HABs were investigated in the thick-shell mussel, Mytilus coruscus. Our results revealed evident immunotoxicity of MPs and P. lima to the mussel, as evidenced by significantly impaired total count, phagocytic activity, and cell viability of haemocytes, which may result from the induction of oxidative stress, aggravation of haemocyte apoptosis, and shortage in cellular energy supply. Moreover, marked disruptions of immunity, antioxidant system, apoptosis regulation, and metabolism upon MPs and P. lima exposure were illustrated by gene expression and comparative metabolomic analyses. Furthermore, the mussels that experienced MP-exposure were shown to be more vulnerable to P. lima, indicated by greater degree of deleterious effects on abovementioned parameters detected. In general, our findings emphasize the threat of MPs and HABs to bivalve species, which deserves close attention and more investigation.

Psychometric Characteristics of the Chinese Version of the Tuberculosis Related-Stigma Scale in a Population of Medical Students and Its Correlation with Selected Demographic Characteristics.

Background: As future health workers, medical students' attitudes towards tuberculosis (TB) patients can impact TB control. However, in China, there is a lack of well-quantified assessment regarding the stigma among medical students towards TB patients. Therefore, this study aimed to validate the Chinese version of the Tuberculosis related-Stigma Scale (TSS) in medical students and to apply the scale to measure stigma and its determinants. Methods: A total of 1035 eligible medical students participated in the cross-sectional questionnaire. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were first conducted to test Chinese version of the TSS construct validity, and then internal consistency was assessed using Cronbach's α. Finally, multiple linear regression analyses were conducted to identify predictors of stigma. Results: EFA extracted two factors ("Social distance" and "Exclusionary sentiments"). The CFA further confirmed the two-factor construct. The internal consistency, convergent and divergent validity of the adapted Chinese version of the TSS was acceptable. Furthermore, Whether one has received TB health education and whether know a person with TB are associated with all dimensions of TB stigma, while differences in sex and place of residence play different roles in influencing the different dimensions of stigma. Conclusion: The adapted Chinese version of the TSS can be used to assess the level of stigma among medical students in China towards tuberculosis patients. When implementing future interventions to reduce stigma associated with TB, special attention should be given to medical students from urban areas, of male gender, who have not received TB health education, and no know a person with TB. However, these two dimensions ("Social distance" and "Exclusionary sentiments") are impacted by different determinants and should therefore be addressed separately when designing, implementing, and evaluating measures to reduce stigma.

Recent developments in the fabrication of food microparticles and nanoparticles using microfluidic systems.

Microfluidics is revolutionizing the production of microparticles and nanoparticles, offering precise control over dimensions and internal structure. This technology facilitates the creation of colloidal delivery systems capable of encapsulating and releasing nutraceuticals. Nutraceuticals, often derived from food-grade ingredients, can be used for developing functional foods. This review focuses on the principles and applications of microfluidic systems in crafting colloidal delivery systems for nutraceuticals. It explores the foundational principles behind the development of microfluidic devices for nutraceutical encapsulation and delivery. Additionally, it examines the prospects and challenges with using microfluidics for functional food development. Microfluidic systems can be employed to form emulsions, liposomes, microgels and microspheres, by manipulating minute volumes of fluids flowing within microchannels. This versatility can enhance the dispersibility, stability, and bioavailability of nutraceuticals. However, challenges as scaling up production, fabrication complexity, and microchannel clogging hinder the widespread application of microfluidic technologies. In conclusion, this review highlights the potential role of microfluidics in design and fabrication of nutraceutical delivery systems. At present, this technology is most suitable for exploring the role of specific delivery system features (such as particle size, composition and morphology) on the stability and bioavailability of nutraceuticals, rather than for large-scale production of nutraceutical delivery systems.

Determination of Tumor Marker Screening for Lung Cancer Using ROC Curves.

Introduction: Lung cancer ranks first among malignant tumors worldwide and is a leading cause of cancer-related mortality in both men and women. Combining tumor marker testing is a strategy to screen individuals at high risk of pulmonary cancer and minimize pulmonary cancer mortality. Therefore, tumor marker screening is crucial. In this study, we analyzed combinations of tumor markers for lung cancer screening using receiver operating characteristic (ROC) curve analysis. Methods: A retrospective descriptive study was conducted on patients diagnosed with lung cancer, as well as healthy and benign lung diseases, using data from the China Huludao Central Hospital database between January 2016 and July 2022. The t-test and ROC curve were utilized to assess the effectiveness of individual tumor marker and the combination of multiple tumor markers. Tumor markers are molecular products metabolized and secreted by tumor tissues, characterized by cells or body fluids. They serve as indicators of tumor stage and grading, monitor treatment response, and predict recurrence. Results: In this study, 267 healthy participants, 385 patients with benign lesions, and 296 patients with lung cancer underwent tumor marker screening. The sensitivity of five tumor markers-CEA, CYFRA21-1, NSE, pro-GRP, and CA125-was found to be <55%. This study revealed that a single tumor marker had limited value in lung cancer screening. However, combining two or more markers yielded varying area under the curves (AUC), with no significant impact on screening accuracy. The combination of CEA + CA125 demonstrated the highest accuracy for lung cancer screening in healthy participants. At a cutoff of 0.447 for CEA + CA125, the combination showed a sensitivity of 0.676 and specificity of 0.846 for lung cancer screening. Conversely, for patients with benign lung lesions, the optimal combination was CEA + NSE, with a cutoff of 0.393, yielding a sensitivity of 0.645 and specificity of 0.766 for lung cancer screening. Conclusion: The five tumor markers-CEA, CA125, CY211, NSE, GRP-show promising results in screening healthy individuals and patients with lung cancer. However, only CEA, NSE, and GRP effectively differentiate patients with benign lung lesions from those with lung cancer. A single tumor marker has limited utility in detecting and screening for lung cancer and should be combined with other tumor markers. CEA + CA125 emerges as a superior tumor marker for distinguishing healthy individuals from those with lung cancer, whereas the CEA + NSE combination is more effective in identifying tumor markers in patients with benign lung lesions and lung cancer.

Reciprocal communication between FAPs and muscle cells via distinct extracellular vesicle miRNAs in muscle regeneration.

Muscle regeneration is a complex process relying on precise teamwork between multiple cell types, including muscle stem cells (MuSCs) and fibroadipogenic progenitors (FAPs). FAPs are also the main source of intramuscular adipose tissue (IMAT). Muscles without FAPs exhibit decreased IMAT infiltration but also deficient muscle regeneration, indicating the importance of FAPs in the repair process. Here, we demonstrate the presence of bidirectional crosstalk between FAPs and MuSCs via their secretion of extracellular vesicles (EVs) containing distinct clusters of miRNAs that is crucial for normal muscle regeneration. Thus, after acute muscle injury, there is activation of FAPs leading to a transient rise in IMAT. These FAPs also release EVs enriched with a selected group of miRNAs, a number of which come from an imprinted region on chromosome 12. The most abundant of these is miR-127-3p, which targets the sphingosine-1-phosphate receptor S1pr3 and activates myogenesis. Indeed, intramuscular injection of EVs from immortalized FAPs speeds regeneration of injured muscle. In late stages of muscle repair, in a feedback loop, MuSCs and their derived myoblasts/myotubes secrete EVs enriched in miR-206-3p and miR-27a/b-3p. The miRNAs repress FAP adipogenesis, allowing full muscle regeneration. Together, the reciprocal communication between FAPs and muscle cells via miRNAs in their secreted EVs plays a critical role in limiting IMAT infiltration while stimulating muscle regeneration, hence providing an important mechanism for skeletal muscle repair and homeostasis.

Juglone induces ferroptosis in glioblastoma cells by inhibiting the Nrf2-GPX4 axis through the phosphorylation of p38MAPK.

BACKGROUND: Ferroptosis, a non-apoptotic form of cell death induced by accumulation of free iron ions and lipid peroxidation, its importance for cancer treatment is gradually being recognized. Research on the anti-cancer mechanism of juglone is accumulating. However, the specific mechanism by which it directs glioblastoma (GBM) to death is unknown. METHODS: We used in vitro and in vivo experiments to explore the anti-GBM effect generated by juglone through the ferroptosis pathway. RESULTS: Juglone mainly causes cell death by inducing ferroptosis. Mechanistically, juglone can significantly activate the phosphorylation of p38MAPK. According to transcriptome sequencing and protein interaction analysis, the Nrf2-GPX4 signaling pathway is identified as the primary pathway through which juglone mediates ferroptosis. In vitro and in vivo experiments further verified that juglone induces the ferroptosis of GBM by activating the phosphorylation of p38MAPK and negatively regulating the Nrf2-GPX4 signaling pathway. CONCLUSION: Juglone induces ferroptosis and inhibits the growth of GBM by targeting the Nrf2/Gpx4 signaling pathway and thus holds promise as a novel ferroptosis inducer or anti-GBM drug.

Association between Perfluoroalkyl Substances in Follicular Fluid and Polycystic Ovary Syndrome in Infertile Women.

In recent years, perfluoroalkyl substances (PFASs), a family of fluorinated organic com pounds, have garnered much attention due to their reproductive and developmental toxicity in humans. Polycystic ovary syndrome (PCOS) is a prevalent endocrine disease that affects women of reproductive age and is a significant contributor to female infertility. A previous study suggested that PFASs play a possible role in PCOS. We conducted a clinical study investigating the relationship between PCOS and PFAS in follicular fluid. A total of 73 infertile patients with PCOS and 218 controls were recruited from the International Peace Maternity and Child Health Hospital, affiliated with the Shanghai Jiao Tong University School of Medicine. The concentrations of 12 PFASs in follicular fluid samples and sex hormones in serum were measured. Correlation analysis and multiple linear regression revealed a positive relationship between perfluorooctanoic acid (PFOA) and testosterone (T) concentrations. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each PFAS were estimated using multivariable logistic regression and quantile-based g-computation (QGC). The PFOA concentrations in follicular fluid were correlated with increased odds of PCOS (second vs. first quartile: OR = 3.65, 95% CI: 1.47-9.05, p = 0.005; third vs. first quartile: OR = 2.91, 95% CI: 1.17-7.26, p = 0.022; fourth vs. first quartile: OR = 3.13, 95% CI: 1.21-8.09, p = 0.019; P for trend = 0.032). This association was confirmed with QGC. Mediation analysis suggested that the mediation effect of T in association with PFOA and PCOS was not statistically significant. Our study suggests that PFOA may be a risk factor for PCOS.