Material-driven immunomodulation and ECM remodeling reverse pulmonary fibrosis by local delivery of stem cell-laden microcapsules.

Recent progress in stem cell therapy has demonstrated the therapeutic potential of intravenous stem cell infusions for treating the life-threatening lung disease of pulmonary fibrosis (PF). However, it is confronted with limitations, such as a lack of control over cellular function and rapid clearance by the host after implantation. In this study, we developed an innovative PF therapy through tracheal administration of microfluidic-templated stem cell-laden microcapsules, which effectively reversed the progression of inflammation and fibrotic injury. Our findings highlight that hydrogel microencapsulation can enhance the persistence of donor mesenchymal stem cells (MSCs) in the host while driving MSCs to substantially augment their therapeutic functions, including immunoregulation and matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) remodeling. We revealed that microencapsulation activates the MAPK signaling pathway in MSCs to increase MMP expression, thereby degrading overexpressed collagen accumulated in fibrotic lungs. Our research demonstrates the potential of hydrogel microcapsules to enhance the therapeutic efficacy of MSCs through cell-material interactions, presenting a promising yet straightforward strategy for designing advanced stem cell therapies for fibrotic diseases.

The role of hepatocyte-derived extracellular vesicles in liver and extrahepatic diseases.

Extracellular vesicles (EVs) are vesicle-like bodies with a double membrane structure that are released from the cell membrane or secreted by cells into the extracellular environment. These include exosomes, microvesicles, and apoptotic bodies. There is growing evidence indicating that the composition of liver cell contents changes following injury. The quantity of EVs and the biologically active substances they carry vary depending on the condition of the liver cells. Hepatocytes utilize EVs to modulate the functions of different liver cells and transfer them to distant organs via the systemic circulation, thereby playing a crucial role in intercellular communication. This review provides a concise overview of the research on the effects and potential mechanisms of hepatocyte-derived EVs (Hep-EVs) on liver diseases and extrahepatic diseases under different physiological and pathological conditions. Common liver diseases discussed include non-alcoholic fatty liver disease (NAFLD), viral hepatitis, alcoholic liver disease, drug-induced liver damage, and liver cancer. Given that NAFLD is the most prevalent chronic liver disease globally, this review particularly highlights the use of hepatocyte-derived EVs in NAFLD for disease progression, diagnosis, and treatment.

Long-term health outcomes of children born by cesarean section: A nationwide population-based retrospective cohort study in Taiwan.

BACKGROUND: Taiwan had high cesarean rate which exceeded the recommended threshold (15%), set by WHO. However, there have not a comprehensive study to discuss the long-term offspring consequences of cesarean section (CS). This study aimed to show whether allergy disorders, obesity and respiratory infection of children are associated with modes of delivery, using the National Health Insurance Research Database (NHIRD) of Taiwan. METHODS: This study used the maternal and child health database of NHIRD. We included the children who birth between 2004 and 2013 and inter-linked the database of the mother and children. The participants were followed until 2018/12/31. We performed a Cox proportional hazards model to identify the association of CS with respiratory tract infection, allergy disorder, and obesity diagnosed in childhood. RESULTS: CS significantly increased the risk of developed childhood asthma (adjusted hazard ratio [aHR] = 1.03; 95% confidence interval [CI]: 1.02-1.03), allergy rhinitis (aHR = 1.04; 95% CI: 1.04-1.05), atopic dermatitis (aHR = 1.05; 95% CI: 1.04-1.06), respiratory tract infection (aHR = 1.07; 95% CI: 1.06-1.07) and overweight (aHR = 1.29; 95% CI: 1.18-1.40) even after adjusting with confounding factor. Development of food allergy (aHR = 1.13; 95% CI: 0.87-1.47) was not associated with cesarean section. CONCLUSION: This study indicated that children delivered by CS more commonly developed respiratory tract infections, asthma, allergic rhinitis, atopic dermatitis, obesity than children delivered vaginally. Among these, obesity have a stronger association with cesarean section.

Depressive symptoms during pregnancy and postpartum: associations with mode of conception and demographic and obstetric factors.

An increasing number of women are conceiving through assisted reproductive technology; however, few studies have investigated their mental health after successful conception. This study investigated the changes in depressive symptoms in women using assisted reproductive technology and the association between the mode of conception and perinatal depressive symptoms. A longitudinal observational study was conducted from 2015 to 2019, 542 pregnant women completed questionnaires on depressive symptoms at eight timepoints during the prepregnancy, pregnancy and first-year postpartum periods. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. A generalized estimating equation regression model was employed for repeated measures. In the assisted reproductive technology group, depressive symptoms were more prevalent during early pregnancy and at 1 month postpartum than before pregnancy, and more prevalent before pregnancy and at 1 month after childbirth than in the spontaneous conception group. No significant association was identified between the mode of conception and depressive symptoms during the antenatal or postnatal period. The lack of full-time employment and prepregnancy depressive symptoms were associated with antenatal depressive symptoms. Primipara status and depressive symptoms during prepregnancy and pregnancy were associated with depressive symptoms during the first-year postpartum. Assisted reproductive technology was not a risk factor for depressive symptoms during the pregnancy and postpartum periods, whereas primipara status, lack of full-time employment and prepregnancy depressive symptoms were negative predictors. Therefore, targeted mental health interventions should address these specific factors to effectively support maternal mental health.

Oral administration of Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 ameliorates DSS-induced colitis in mice.

Ulcerative colitis (UC) belongs to chronic inflammatory disease with a relapsing characterization. Conventional oral drugs of UC are restricted in clinical by premature degradation in the gastrointestinal tract, modest efficacy, and adverse effects. CX5461 can treat autoimmune disease, immunological rejection, and vascular inflammation. However, low solubility, intravenous administration, and non-inflammatory targeting limited its clinical application. Herein, this work aims to develop Sophora Flavescens-derived exosomes-like nanovesicles carrying CX5461 (SFELNVs@CX5461) for efficient CX5461 oral delivery for UC therapy. We identified SFELNVs as nano-diameter (80 nm) with negative zeta potential (-32mV). Cellular uptake has shown that SFELNVs were targeted uptake by macrophages, thus increasing drug concentration. Additionally, oral SFELNVs@CX5461 exhibited good safety and stability, as well as inflammation-targeting ability in the gastrointestinal tract of dextran sodium sulfate (DSS)-induced colitis mice. In vivo, oral administration of SFELNVs and CX5461 could relieve mice colitis. More importantly, combined SFELNVs and CX5461 alleviated mice colitis by inhibiting pro-inflammatory factors (TNF-α, IL-1ß, and IL-6) expression and promoting M2 macrophage polarization. Furthermore, SFELNVs promoted M2 polarization by miR4371c using miRNA sequencing. Our results suggest that SFELNVs@CX5461 represents a novel orally therapeutic drug that can ameliorate colitis, and a promising targeting strategy for safe UC therapy.

Mediating effect of loneliness on the associations of perceived and internalized sexual stigma with suicide in gay and bisexual men.

BACKGROUND/PURPOSE: Loneliness is prevalent among gay and bisexual men (GBM). This study evaluated the mediating effect of loneliness on the associations of perceived sexual stigma (PSS) and internalized sexual stigma (ISS) with suicide in 400 GBM. METHODS: A moderated mediation model was used to test the mediating effects of loneliness between the associations of PSS from family members and ISS with suicide and the moderating effects of sexual orientation, age, and education level on the mediating effects. RESULTS: The results indicated that both PSS and ISS were positively associated with suicide through the full mediation of loneliness. The association of ISS with loneliness was stronger in older GBM. CONCLUSIONS: Intervention programs promoting changes in attitudes toward GBM are warranted to prevent the development of PSS and ISS, loneliness, and suicide in this population.

5-Methoxytryptophan Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting the Intestinal Epithelial Damage and Inflammatory Response.

Background: Colitis is a refractory intestinal inflammatory disease significantly affecting the quality of a patient's life and increasing the risk of exacerbation. The primary factors leading to colitis encompass infections, insufficient blood flow, and the buildup of collagen as well as white blood cells. Among various available therapeutics, 5-methoxytryptophan (5-MTP) has emerged as one of the protectants by inhibiting inflammatory damage. Nonetheless, there is no report on the role of 5-MTP in the treatment of colitis. Materials and Methods: To verify the anti-inflammatory effect of 5-MTP in vivo, we first constructed mouse model with dextran sulfate sodium-induced colitis. Furthermore, the macrophage infiltration and release of inflammatory factors through western blot (WB) and hematoxylin-eosin staining analyses were examined. Intestinal epithelial cell tight junction damage and apoptosis were investigated by WB analysis, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Finally, we examined the generation of cellular inflammation and analyzed the influence of 5-MTP on M1 polarization at the cellular level. Results: This study initially confirmed that 5-MTP possessed an excellent therapeutic effect on colitis. 5-MTP inhibits macrophage infiltration and the generation of inflammatory factors. In addition to its effects on immune cells, 5-MTP significantly inhibits intestinal epithelial cell tight junction damage and apoptosis in vivo. Moreover, it inhibits inflammation and M1 polarization response in vitro. Conclusion: 5-MTP counteracts excessive inflammation, thereby preventing intestinal epithelial tight junction damage. In addition, inhibition of apoptosis suggests that 5-MTP may be a potential therapeutic agent for colitis.

Influence of parental attitudes and coping styles on mental health during online teaching in the COVID-19 pandemic.

During the COVID-19 pandemic, the online delivery model became the primary mode of education. With multiple pressures on society and families, mental health issues for parents have become particularly pronounced. Most of the current research has focused on the psychological state of education practitioners and children, with little attention to parents' mental health issues. Therefore, this study explored the attitudes and coping styles of parents who experienced the process of their children being taught online over a long period and the factors influencing their mental health. This cross-sectional study was conducted between November 2021 and January 2022, using an anonymous online questionnaire to survey 1500 parents with children aged 6-13 years. The Chinese versions of the Patient Health Questionnaire Depression Scale (PHQ-9), the Parenting Stress Scale (PSS), the General Mental Health Questionnaire (GHQ-12), and the Brief Coping Style Scale (SCSQ), and a related factors questionnaire were used to survey the subjects. The normal distribution of the data was examined using the Shapiro-Wilk method. A multivariate regression analysis was conducted to identify factors significantly associated with parental mental health during the COVID-19 pandemic. Only 30.24% of parents agreed with online classes during the pandemic, and 52.28% used positive coping methods during stressful situations. Multivariate regression models identified significant factors associated with parental mental health: parent's gender, child's grade level, perceived stress about online classes, whether the child has ADHD, positive or negative coping styles, and subjective attitudes of support for online classes or not. The results of the study suggest that as online classes become more socially acceptable, it is necessary to be concerned about the risk of mental illness for parents and develop policies and interventions, especially for parents who adopt negative coping styles and endorse online classes. The focus should be on the stress of online classes on parents, improving the acceptance of online classes and psychological well-being, regulating the way parents deal with their children, and targeting subgroups of children with ADHD symptoms during the COVID-19 pandemic.

A pan-cancer analysis of Wnt family member 7B in human cancers.

Background: Previous studies have highlighted the crucial role of Wnt7B in the development of various cancers, including breast, pancreatic, and gastric cancers. However, research into the involvement of Wnt7B is often confined to specific tumor types, with a noticeable lack of comprehensive studies spanning multiple cancer forms. The potential of Wnt7B as a diagnostic or prognostic cancer biomarker has not been fully explored. Methods: In this study, we combined bioinformatics and immunohistochemistry analyses to examine the expression patterns and functions of Wnt7B in cancerous and adjacent noncancerous tissues across a range of tumors. Results: Our data indicate that Wnt7B may serve as a novel prognostic biomarker and therapeutic target in certain cancers. Conclusion: We found significant upregulation of Wnt7B expression levels in the majority of cancer cases examined. Furthermore, Wnt7B can influence cancer prognosis by modulating the tumor microenvironment, immune cell infiltration, and tumor stemness, among other factors. Additionally, we examined the associations between anticancer drug sensitivity and Wnt7B expression, which could aid in the development of more precise clinical therapies.

Recent Progress in the Synthesis of 3D Complex Plasmonic Intragap Nanostructures and Their Applications in Surface-Enhanced Raman Scattering.

Plasmonic intragap nanostructures (PINs) have garnered intensive attention in Raman-related analysis due to their exceptional ability to enhance light-matter interactions. Although diverse synthetic strategies have been employed to create these nanostructures, the emphasis has largely been on PINs with simple configurations, which often fall short in achieving effective near-field focusing. Three-dimensional (3D) complex PINs, distinguished by their intricate networks of internal gaps and voids, are emerging as superior structures for effective light trapping. These structures facilitate the generation of hot spots and hot zones that are essential for enhanced near-field focusing. Nevertheless, the synthesis techniques for these complex structures and their specific impacts on near-field focusing are not well-documented. This review discusses the recent advancements in the synthesis of 3D complex PINs and their applications in surface-enhanced Raman scattering (SERS). We begin by describing the foundational methods for fabricating simple PINs, followed by a discussion on the rational design strategies aimed at developing 3D complex PINs with superior near-field focusing capabilities. We also evaluate the SERS performance of various 3D complex PINs, emphasizing their advanced sensing capabilities. Lastly, we explore the future perspective of 3D complex PINs in SERS applications.

Neurodevelopmental disorders in children born to mothers involved in maternal motor vehicle crashes.

BACKGROUND: To evaluate the association between maternal MVCs during pregnancy and neurodevelopmental disorders (NDDs, including intellectual disability, ADHD, ASD, and infantile cerebral palsy) in children. METHODS: This population-based cohort of live births in Taiwan was analyzed, comparing children born to mothers involved in MVCs during pregnancy with those without such exposure. Children were linked to the insurance database to identify the possible diagnosis of NDDs. The Cox proportional hazards regression model was used to estimate the relative hazards. RESULTS: A total of 19,277 children with maternal MVCs and 76,015 children without exposure were included. Children exposed to maternal MVCs during the first two trimesters or whose mothers sustained mild to severe injuries showed a higher risk of intellectual disability. Severe maternal injuries also increased the risk of infantile cerebral palsy (aHR = 3.86; 1.27-11.78). MVCs in the third trimester, or mild maternal injuries, were associated with a higher risk of ASD (third trimester: aHR = 1.40; 1.04-1.87; mild injuries: aHR = 1.38; 1.09-1.74). CONCLUSION: Children exposed to maternal MVCs with severe injuries had a higher risk of intellectual disability and cerebral palsy. Third-trimester exposure may increase the risk of ASD. However, these findings should be interpreted cautiously as genetic factors may contribute to the observed association. IMPACT: There is some evidence linking maternal MVCs during pregnancy to the development of neurodevelopmental disorders in children. Children of mothers with severely injured were more likely to suffer from infantile cerebral palsy and intellectual disability. The risk of autism spectrum disorder is higher in children whose mothers are involved in MVCs during the late stage of pregnancy, and there is also an increased risk of intellectual disability during the first two trimesters.

Reversible Photochromic Phenomenon of Plasmonic Metal/Semiconductor Heterostructures via Photoinduced Electron Storage.

The transfer and migration process of the photogenerated charge carriers in plasmonic metal/semiconductor heterostructures not only affects their photocatalytic performance but also triggers some captivating phenomena. Here, a reversible photochromic behavior is observed on the Au/CdS heterostructures when they are investigated as photocatalysts for hydrogen production. The photochromism takes place upon excitation of the CdS component, in which the photogenerated holes are rapidly consumed by ethanol, while the electrons are transferred and stored on the Au cores, resulting in the blue shift of their localized surface plasmon resonance. The colloidal solution can restore its initial color after pumping with air, and the photochromic behavior can be cycled five times without obvious degradation. The finding represents great progress toward the photochromic mechanism of metal/semiconductor heterostructures and also reveals the importance of understanding the dynamic process of the photogenerated charge carriers in these heterostructures.

Synergistic immunotherapy with a calcium-based nanoinducer: evoking pyroptosis and remodeling tumor-associated macrophages for enhanced antitumor immune response.

The challenges posed by low immunogenicity and the immunosuppressive tumor microenvironment (TME) significantly hinder the efficacy of cancer immunotherapy. Pyroptosis, characterized as a pro-inflammatory cell death pathway, emerges as a promising approach to augment immunotherapy by promoting immunogenic cell death (ICD). The predominance of M2 phenotype tumor-associated macrophages (TAMs) in the TME underscores the critical need for TAM reprogramming to mitigate this immunosuppression. Herein, we introduce a calcium-based, intelligent-responsive nanoinducer (CaZCH NPs), designed to concurrently initiate pyroptosis and remodel TAMs, thereby amplifying antitumor immunotherapy effects. Modified with hyaluronic acid, CaZCH NPs can target tumor cells. Once internalized, CaZCH NPs respond to the acidic environment, releasing Ca2+, curcumin and H2O2 to induce mitochondrial Ca2+ overload and oxidation stress, leading to caspase-3/GSDME-mediated cell pyroptosis. Concurrently, O2 produced by CaZCH and pro-inflammatory cytokines from pyroptotic cells work together to shift TAM polarization towards the M1 phenotype, effectively countering TME's immunosuppressive effect. Notably, the synergistic effect of Ca2+-mediated pyroptosis and TAM remodeling demonstrates superior antitumor efficiency in colorectal cancer models. The induced ICD, coupled with M1-type TAMs, effectively enhances immunogenicity and mitigates immunosuppression, promoting dendritic cell maturation and activating CD8+ T cell-dependent systemic antitumor immunity. Our study presents a promising synergistic strategy for achieving highly efficient immunotherapy using a simple calcium-based nanoinducer.

Risks of Hyperopia, Myopia, Astigmatism, and Strabismus in Children With Autism Spectrum Disorder: A Nationwide, Population-Based Cohort Study.

OBJECTIVE: In this population-based cohort study, we compared the risks of incident hyperopia, myopia, astigmatism, and strabismus between children with autism spectrum disorder (ASD) and children without ASD. METHODS: This study included children who were born in Taiwan at any time between 2004 and 2017. Data were collected from the Taiwan Maternal and Child Health Database. We included 20,688 children with ASD and 2,062,120 matched controls to estimate the risks of incident hyperopia, myopia, astigmatism, and strabismus. Cox proportional hazards regression models were constructed for risk assessment. The models were adjusted for sex, calendar year of birth, and gestational age at birth. Statistical significance was determined by calculating adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: Children with ASD had higher risks of incident hyperopia (aHR: 1.78; 95% CI: 1.70-1.86), myopia (aHR: 1.27; 95% CI: 1.24-1.30), astigmatism (aHR: 1.51; 95% CI: 1.46-1.56), and strabismus (aHR: 2.18; 95% CI: 2.05-2.32) than did those without it. CONCLUSION: Clinicians should screen children with ASD for potential ophthalmic conditions. Further studies are required to elucidate the mechanisms underlying the associations between ASD and ophthalmic diseases. The roles of types and severities of ASD symptoms in detecting ophthalmic disease also requires further study.

Clinical significance and potential mechanism of AEBP1 in glioblastoma.

Glioblastomas (GBM), the most common primary brain tumor, lack accurate prognostic markers and have a poor prognosis. Our study was designed to identify effective biomarkers for GBM prognosis analysis and development of precise treatments. Differentially expressed genes (DEGs) between GBM patients and controls were analyzed from the Xena database and GEPIA. Based on the screened DEGs, univariate COX and LASSO regression analysis were performed to identify the most relevant genes associated with GBM prognosis. Genes highly expressed in GBM patients were selected to construct receiver operating characteristic analysis and enrichment analysis was constructed on groups of high and low expression of adipocyte enhancer-binding protein 1 (AEBP1). CIBERSORT, ssGSEA and ESTIMATE were used to perform immune infiltration analysis. About 3297 DEGs were identified using data from Xena database; 8 prognostic genes were identified. AEBP1, which plays a role in neuronal differentiation and development, was positively correlated in GBMs with immune infiltration; its high expression in cancer patients is associated with short overall survival and advanced tumor staging. This study suggests that AEBP1 could serve as a prognostic marker for GBMs and that patients with high expression may have a better response to immunotherapy.

Evaluation of Factors Influencing Postoperative Cognitive Dysfunction in Patients After Cranial Tumor Surgery.

BACKGROUND: The authors retrospectively analyzed the perioperative data of 81 patients who underwent cranial tumor surgery to explore the factors influencing POCD in patients after the surgery. METHODS: The authors evaluated preoperative cognitive dysfunction using the Mini-Mental State Examination (MMSE) score measured. For patients whose cognitive function was normal, the authors retrieved the MMSE score on the seventh day after surgery and compared it to determine whether the patients had POCD. The authors used a univariate logistic regression analysis to analyze the perioperative factors in patients, namely, age, gender, history of underlying diseases, tumor size, peritumoral edema, duration of surgery, blood loss, intraoperative fluid infusion, and type of anesthetic drugs. The authors then performed a multivariate logistic regression analysis for the statistically significant factors. RESULTS: The authors found that 23 of 81 patients (28.4%) developed POCD. Univariate logistic analysis showed that a history of diabetes mellitus, peritumoral edema, intraoperative blood loss, and anesthetic drugs were the risk factors for patients developing POCD after cranial tumor surgery. Multivariate logistic regression analysis showed that a history of diabetes mellitus, peritumoral edema, and use of ciprofol as the anesthetic drug were independent risk factors for POCD after cranial tumor surgery. CONCLUSIONS: A history of diabetes mellitus, the degree of brain tumor edema, and the choice of anesthetic drugs significantly influence the occurrence of POCD in patients after cranial tumor surgery.

Plasma MiR-190 is a potential clinical biomarker for acute respiratory distress syndrome in children and its regulatory role in ARDS cell models by targeting KLF15.

BACKGROUND: The present research aimed to investigate the clinical value of plasma miR-190 in children with acute respiratory distress syndrome (ARDS) and the impact of miR-190 on LPS-induced ARDS cell models. METHODS: The plasma miR-190 levels were measured using real-time quantitative reverse transcription PCR (RT-qPCR). LPS-treated human pulmonary microvascular endothelial cells (HPMECs) were established and then transfected with miR-190 mimic, inhibitor, or miR-negative controls. The levels of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). The effects of miR-190 on HPMEC proliferation and apoptosis were evaluated by CCK-8 assay and flow cytometry. The regulation of KLF15 by miR-190 was detected by luciferase report assay. RESULTS: The plasma miR-190 expression was increased in ARDS children and it was positively related to the severity and 28 day-survival. Plasma miR-190 could distinguish ARDS children from healthy children. Inhibition of miR-190 increased LPS-induced HPMEC cell proliferation and decreased cell apoptosis and inflammatory cytokines IL-6, IL-1ß, and TNF-α. KLF15 was a direct target of miR-190. CONCLUSION: Increased plasma miR-190 may be a clinical diagnostic and prognostic predictor for ARDS children. Inhibition of miR-190 may improve LPS-induced ARDS by increasing cell proliferation, inhibiting cell apoptosis and inflammatory response by targeting KLF15.