Effects of Long-Term Exposure to Ambient Formaldehyde on Hypertension and Angina Pectoris Symptoms: Evidence From the WHO SAGE Cohort Study.

BACKGROUND: We aimed to investigate the associations of long-term exposure to ambient formaldehyde with hypertension and angina pectoris symptoms in Chinese adults. METHODS AND RESULTS: Participants' information was obtained from the WHO SAGE (World Health Organization Study on Global Aging and Adult Health) study. The Cox proportional hazards regression model was applied to estimate the associations of formaldehyde with hypertension and angina pectoris symptoms. Mediating effect analysis was used to investigate the mediating effect of hypertension between formaldehyde exposure and angina pectoris symptoms. Long-term exposure to formaldehyde was positively associated with the risk of angina pectoris symptoms (hazard ratio [HR], 1.66 [95% CI, 1.29-2.13], per interquartile range [IQR], 3.33, 1015 molecules/cm2) and hypertension (HR, 1.17 [95% CI, 1.02-1.34], per IQR, 3.34, 1015 molecules/cm2). The associations between formaldehyde and angina pectoris symptoms were greater in participants aged ≥65 years (HR, 1.90 [95% CI, 1.29-2.80]) and in rural areas (HR, 2.71 [95% CI, 1.54-4.77]), whereas the associations of formaldehyde with hypertension were stronger in men (HR, 1.27 [95% CI, 1.02-1.58]), rural areas (HR, 1.22 [95% CI, 0.94-1.59]), and in ever smokers (HR, 1.33 [95% CI, 1.02-1.72]). The mediation effect analysis indicated that 18.44% (95% CI, 2.17-37.65) of the association between formaldehyde exposure and angina pectoris symptoms was mediated by hypertension. CONCLUSIONS: Long-term exposure to ambient formaldehyde was positively associated with hypertension and angina pectoris symptoms. The effects of formaldehyde may be modified by age, sex, urbanicity, and smoking status. Hypertension might play a mediating effect in formaldehyde-induced angina pectoris symptoms.

Sodium-iodate injection can replicate retinal and choroid degeneration in pigmented mice: Using multimodal imaging and label-free quantitative proteomics analysis.

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. Sodium iodate (NaIO3), a stable oxidizing agent, has been injected to establish a reproducible model of oxidative stress-induced RPE and photoreceptor death. The aim of our study was to evaluate the morphological and molecular changes of retina and retinal pigment epithelium (RPE)-choroid in NaIO3-treated mouse using multimodal fundus imaging and label-free quantitative proteomics analysis. Here, we found that following NaIO3 injection, retinal degeneration was evident. Fundus photographs showed numerous scattered yellow-white speckled deposits. Optical coherence tomography (OCT) images indicated disruption of the retinal layers, damage of the RPE layer and accumulation of hyper-reflective matter in multiple layers of the outer retina. Widespread foci of a high fundus autofluorescence (FAF) signal were noticed. Fundus fluorescein angiography (FFA) revealed diffuse intense transmitted fluorescence mixed with scattered spot-like blocked fluorescence. Indocyanine green angiography (ICGA) presented punctate hyperfluorescence. Due to the atrophy of the RPE and Bruch's membrane and choroidal capillary complex, the larger choroidal vessels become more prominent in ICGA and optical coherence tomography angiography (OCTA). Transmission electron microscope (TEM) illustrated abnormal material accumulation and damaged mitochondria. Bioinformatics analysis of proteomics revealed that the differentially expressed proteins participated in diverse biological processes, encompassing phototransduction, NOD-like receptor signaling pathway, phagosome, necroptosis, and cell adhesion molecules. In conclusion, by multimodal imaging, we described the phenotype of NaIO3-treated mouse model mimicking oxidative stress-induced RPE and photoreceptor death in detail. In addition, proteomics analysis identified differentially expressed proteins and significant enrichment pathways, providing insights for future research, although the exact mechanism of oxidative stress-induced RPE and photoreceptor death remains incompletely understood.

Role of sphingolipid metabolism signaling in a novel mouse model of renal osteodystrophy based on transcriptomic approach.

BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Male 8-week-old C57BL/6J mice were randomly allocated into three groups: control group (n = 5), adenine and high-phosphate (HP) diet group (n = 20), and the optimized adenine-containing diet group (n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 (Acer1), alkaline ceramidase 2 (Acer2), prosaposin-like 1 (Psapl1), adenosine A1 receptor (Adora1), and sphingosine-1-phosphate receptor 5 (S1pr5) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS: Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.

The association between long-term exposure to ambient formaldehyde and respiratory mortality risk: A national study in China.

INTRODUCTION: While ambient formaldehyde (HCHO) concentrations are increasing worldwide, there was limited research on its health effects. OBJECTIVES: To assess the association of long-term exposure to ambient HCHO with the risk of respiratory (RESP) mortality and the associated mortality burden in China. METHODS: Annual and seasonal RESP death and tropospheric HCHO vertical columns data were collected in 466 counties/districts across China during 2013-2016. A difference-in-differences approach combined with a generalized linear mixed-effects regression model was employed to assess the exposure-response association between long-term ambient HCHO exposure and RESP mortality risk. Additionally, we computed the attributable fraction (AF) to gauge the proportion of RESP mortality attributable to HCHO exposure. RESULTS: This analysis encompassed 560,929 RESP deaths. The annual mean ambient HCHO concentration across selected counties/districts was 8.02×1015 ± 2.22×1015 molec.cm-2 during 2013-2016. Each 1.00×1015 molec.cm-2 increase in ambient HCHO was associated with a 1.61 % increase [excess risk (ER), 95 % confidence interval (CI): 1.20 %, 2.03 %] in the RESP mortality risk. The AF of RESP mortality attributable to HCHO was 12.16 % (95 %CI:9.33 %, 14.88 %), resulting in an annual average of 125,422 (95 %CI:96,404, 153,410) attributable deaths in China. Stratified analyses suggested stronger associations in individuals aged ≥65 years old (ER=1.87 %, 95 %CI:1.43 %, 2.32 %), in cold seasons (ER=1.00 %, 95 %CI:0.56 %, 1.44 %), in urban areas (ER=1.65 %, 95 %CI:1.15 %, 2.16 %), and in chronic obstructive pulmonary disease patients (ER=1.95 %, 95 %CI:1.42 %, 2.48 %). CONCLUSIONS: This study suggested that long-term HCHO exposure may significantly increase the risk of RESP mortality, leading to a substantial mortality burden. Targeted measures should be implemented to control ambient HCHO pollution promptly.

Cluster of Differentiation 36 (CD36) Preferentially Mediates Intestinal Absorption of Dietary Z-Astaxanthin and Especially 9-Z-Isomer via Higher Binding Affinity.

Variances in the biological functions of astaxanthin geometric isomers (i.e., all-E, Z) are related to their intestinal absorption, but the mechanism of isomer absorption mediated by transporters remains unclear. Here, models of in vitro cell overexpression, in situ intestinal perfusion, and in vivo mouse inhibition were employed to investigate the impact of cluster of differentiation 36 (CD36) on the absorption of astaxanthin isomers. Cells overexpressing CD36 notably enhanced the uptake of Z-astaxanthin, particularly the 9-Z-isomer (47.76%). The absorption rate and permeability of Z-astaxanthin surpassed that of the all-E-isomer by the in situ model. Furthermore, the addition of the CD36-specific inhibitor sulfo-N-succinimidyl oleate significantly reduced the absorption of Z-astaxanthin in the mouse duodenum and jejunum, especially the 9-Z-isomer (57.66%). Molecular docking and surface plasmon resonance techniques further validated that 9-Z-astaxanthin binds to more amino acids of CD36 with higher affinity and in a fast-binding, fast-dissociating mode, thus favoring transport. Our findings elucidate, for the first time, the mechanism of the CD36-mediated transmembrane transport of astaxanthin geometric isomers.

Association of oxidative balance score with epilepsy and moderate to severe depression: Insights from the NHANES study.

BACKGROUND: Depression is a significant public health issue, closely associated with epilepsy and oxidative stress (OS). This study aims to explore the level of OS in patients with epilepsy and its relationship with moderate to severe depression (MSD). METHODS: This cross-sectional study includes 10,819 participants aged 20-80 from the National Health and Nutrition Examination Survey (NHANES) database (2013-2020 pre-pandemic). Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and epilepsy was diagnosed based on antiepileptic drug use in the past 30 days. The oxidative balance score (OBS) was calculated from dietary recall and lifestyle habits over the previous 24 h. RESULTS: Compared to non-epileptic subjects, epileptic patients have a significantly higher prevalence of depression. Epileptic patients exhibit lower OBS and Dietary Oxidative Balance Scores (DOBS), while there is no significant difference in Lifestyle Oxidative Balance Scores (LOBS). Depressed patients show lower OBS, DOBS, and LOBS. The mediation model indicates that DOBS mediates 3.44 % of epilepsy-related MSD. CONCLUSIONS: Epileptic patients exhibit significantly higher levels of OS and consume more pro-oxidant foods compared to the general population. However, their lifestyle habits do not differ significantly from those of the control group. Additionally, epileptic patients are at a higher risk of developing MSD. Although a pro-oxidant diet may be associated with epilepsy-mediated MSD, its mediating effect is relatively weak.

Exploring the clinical value of direct anterior approach THA for short-term hip function improvement: A single-center retrospective analysis of short-term outcomes.

To investigate the outcomes of the direct anterior approach (DAA) in total hip arthroplasty (THA) and its impact on improving hip joint function. This retrospective analysis included 94 patients who underwent THA between December 2017 and December 2020 at Dongguan Hospital, Guangzhou University of Chinese Medicine. The study group comprised 50 patients who received the DAA, while the control group comprised 44 patients who received the postero-lateral approach (PA). The follow-up period was 12 months. A comparison was made between the 2 groups based on perioperative indicators (operation time, intraoperative blood loss, hospitalization time, bed rest time, incision length, pain score), duration of walker use, incidence of postoperative complications, hip joint function (Harris score), quality of life (SF-36), and activities of daily living (ADL). The treatment effectiveness rate was higher in the study group (P < .05). The study group had a longer operation time, lower intraoperative blood loss, shorter hospitalization and bed rest time, smaller incision length, and lower visual analog scale (VAS) score after treatment, with statistically significant differences (P < .05). The study group also had a shorter duration of walker use after surgery (P < .05). The Harris score after treatment was higher in the study group compared to the control group (P < .05). Additionally, the study group had higher SF-36 scores and ADL scores after treatment (P < .05). There was no significant difference in the incidence of postoperative complications between the 2 groups (P > .05). The DAA in THA resulted in reduced pain and intraoperative blood loss, contributing to the promotion of postoperative recovery in patients with good short-term outcomes. This procedure warrants further promotion.

Association of Residential Greenness Exposure with Depression Incidence in Adults 50 Years of Age and Older: Findings from the Cohort Study on Global AGEing and Adult Health (SAGE) in China.

BACKGROUND: Depression is a social and public health problem of great concern globally. Identifying and managing the factors influencing depression are crucial for preventing and decreasing the burden of depression. OBJECTIVES: Our objectives are to explore the association between residential greenness and the incidence of depression in an older Chinese population and to calculate the disease burden of depression prevented by greenness exposure. METHODS: This study was the Chinese part of the World Health Organization Study on Global AGEing and Adult Health (WHO SAGE). We collected the data of 8,481 residents ≥50 years of age in China for the period 2007-2018. Average follow-up duration was 7.00 (±2.51) years. Each participant was matched to the yearly maximum normalized difference vegetation index (NDVI) at their residential address. Incidence of depression was assessed using the Composite International Diagnostic Interview (CIDI), self-reports of depression, and/or taking depression medication. Association between greenness and depression was examined using the time-dependent Cox regression model with stratified analysis by sex, age, urbanicity, annual family income, region, smoking, drinking, and household cooking fuels. Furthermore, the prevented fraction (PF) and attributable number (AN) of depression prevented by exposure to greenness were estimated. RESULTS: Residential greenness was negatively associated with depression. Each interquartile range (IQR) increase in NDVI 500-m buffer was associated with a 40% decrease [hazard ratio (HR)=0.60; 95% confidence interval (CI): 0.37, 0.97] in the risk of depression incidence among the total participants. Subgroup analyses showed negative associations in urban residents (HR=0.32; 95% CI: 0.12, 0.86) vs. rural residents, in high-income residents (HR=0.28; 95% CI: 0.11, 0.71) vs. low-income residents, and in southern China (HR=0.50; 95% CI: 0.26, 0.95) vs. northern China. Over 8.0% (PF=8.69%; 95% CI: 1.38%, 15.40%) and 1,955,199 (95% CI: 310,492; 3,464,909) new cases of depression may be avoided by increasing greenness exposures annually across China. DISCUSSION: The findings suggest protective effects of residential greenness exposure on depression incidence in the older population, particularly among urban residents, high-income residents, and participants living in southern China. The construction of residential greenness should be included in community planning. https://doi.org/10.1289/EHP13947.

Exploring correlations between immune cell phenotypes and the risk of epilepsy: A bidirectional Mendelian randomization study.

BACKGROUND: Neuroinflammation plays an important pathophysiological role in epilepsy; however, the precise connection between immune cells and epilepsy remains unclear. This study used Mendelian randomization (MR) to analyze the causal relationship between 731 immune cell traits and epilepsy. METHODS: Based on data from a genome-wide association study (GWAS), a bidirectional two-sample MR analysis was conducted to investigate the potential influence of immune cell phenotypes on epilepsy. Five MR methods were used to analyze the results, with the inverse variance weighted (IVW) method as the primary method, and the results were corrected using the false discovery rate (FDR) method. Sensitivity analyses were performed to test for heterogeneity and horizontal pleiotropy. RESULTS: After correction for FDR, four immune traits remained significantly associated with epilepsy risk: CD25 expression on memory (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06,P = 2.55 × 10-4), IgD+CD38dim (OR = 1.05, 95 % CI = 1.02 âˆ¼ 1.08, P = 4.73 × 10-4), CD24+CD27+ (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06, P = 4.82 × 10-4), and IgD-CD38dim (OR = 1.04, 95 % CI = 1.02 âˆ¼ 1.06, P = 1.04 × 10-3) B cells. The risk of generalized epilepsy was significantly associated with two immune cell traits, whereas that of focal epilepsy was significantly associated with seven immune cell traits. Furthermore, immune cell phenotypes are not affected by genetically predicted epilepsy. CONCLUSION: This MR study affirms the causal connection between circulating immune cells and epilepsy, offering guidance for further understanding of the immune mechanisms that underlie epilepsy and the discovery of novel targets for therapy.

Exploration of the causal associations between circulating inflammatory proteins, immune cells, and neuromyelitis optica spectrum disorder: a bidirectional Mendelian randomization study and mediation analysis.

Background: An increasing body of research has demonstrated a robust correlation between circulating inflammatory proteins and neuromyelitis optica spectrum disorders (NMOSD). However, whether this association is causal or whether immune cells act as mediators currently remains unclear. Methods: We employed bidirectional two-sample Mendelian randomization (TSMR) analysis to examine the potential causal association between circulating inflammatory proteins, immune cells, and NMOSD using data from genome-wide association studies (GWAS). Five different methods for Mendelian randomization analyses were applied, with the inverse variance-weighted (IVW) method being the primary approach. Sensitivity analyses were further performed to assess the presence of horizontal pleiotropy and heterogeneity in the results. Finally, a two-step Mendelian randomization (MR) design was employed to examine the potential mediating effects of immune cells. Results: A notable causal relationship was observed between three circulating inflammatory proteins (CSF-1, IL-24, and TNFRSF9) and genetically predicted NMOSD. Furthermore, two immune cell phenotypes, genetically predicted CD8 on naive CD8+ T cells, and Hematopoietic Stem Cell Absolute Count were negatively and positively associated with genetically predicted NMOSD, respectively, although they did not appear to function as mediators. Conclusion: Circulating inflammatory proteins and immune cells are causally associated with NMOSD. Immune cells do not appear to mediate the pathway linking circulating inflammatory proteins to NMOSD.

Construction of gastric cancer prognostic signature based on the E26 transcription factor and the identification of novel oncogene ELK3.

The aim of the present study was to investigate the function of 29 E26 (ETS) transcription factor families in gastric cancer (GC) and determine their association with prognosis. Our analysis of the expression of the ETS family revealed that 28 genes were dysregulated in GC, and that their expression was associated with multiple clinicopathological features (P<0.05). Based on the expression signature of the ETS family, consensus clustering was performed to generate two gastric cancer subtypes. These subtypes exhibited differences in overall survival (OS, P = 0.161), disease-free survival (DFS, P<0.05) and GC grade (P<0.01). Functional enrichment analysis of the target genes associated with the ETS family indicated that these genes primarily contribute to functions that facilitate tumor progression. A systematic statistical analysis was used to construct a prognostic model related to OS and DFS in association with the ETS family. This model demonstrated that the maximum area under the curve (AUC) values for predicting OS and DFS were 0.729 and 0.670, respectively, establishing ETS as an independent prognostic factor for GC Furthermore, a nomogram was created from the prognostic signature, and its predictive accuracy was confirmed by a calibration curve. Finally, the expression and prognostic significance of the six genes comprising the model were also examined. Among these, ELK3 was found to be significantly overexpressed in GC clinical samples. Subsequent in vitro and in vivo studies verified that ELK3 regulates GC proliferation and metastasis, highlighting its potential as a therapeutic target for gastric cancer.

Mutual Associations of Exposure to Ambient Air Pollutants in the First 1000 Days of Life With Asthma/Wheezing in Children: Prospective Cohort Study in Guangzhou, China.

BACKGROUND: The first 1000 days of life, encompassing pregnancy and the first 2 years after birth, represent a critical period for human health development. Despite this significance, there has been limited research into the associations between mixed exposure to air pollutants during this period and the development of asthma/wheezing in children. Furthermore, the finer sensitivity window of exposure during this crucial developmental phase remains unclear. OBJECTIVE: This study aims to assess the relationships between prenatal and postnatal exposures to various ambient air pollutants (particulate matter 2.5 [PM2.5], carbon monoxide [CO], sulfur dioxide [SO2], nitrogen dioxide [NO2], and ozone [O3]) and the incidence of childhood asthma/wheezing. In addition, we aimed to pinpoint the potential sensitivity window during which air pollution exerts its effects. METHODS: We conducted a prospective birth cohort study wherein pregnant women were recruited during early pregnancy and followed up along with their children. Information regarding maternal and child characteristics was collected through questionnaires during each round of investigation. Diagnosis of asthma/wheezing was obtained from children's medical records. In addition, maternal and child exposures to air pollutants (PM2.5 CO, SO2, NO2, and O3) were evaluated using a spatiotemporal land use regression model. To estimate the mutual associations of exposure to mixed air pollutants with the risk of asthma/wheezing in children, we used the quantile g-computation model. RESULTS: In our study cohort of 3725 children, 392 (10.52%) were diagnosed with asthma/wheezing. After the follow-up period, the mean age of the children was 3.2 (SD 0.8) years, and a total of 14,982 person-years were successfully followed up for all study participants. We found that each quartile increase in exposure to mixed air pollutants (PM2.5, CO, SO2, NO2, and O3) during the second trimester of pregnancy was associated with an adjusted hazard ratio (HR) of 1.24 (95% CI 1.04-1.47). Notably, CO made the largest positive contribution (64.28%) to the mutual effect. After categorizing the exposure according to the embryonic respiratory development stages, we observed that each additional quartile of mixed exposure to air pollutants during the pseudoglandular and canalicular stages was associated with HRs of 1.24 (95% CI 1.03-1.51) and 1.23 (95% CI 1.01-1.51), respectively. Moreover, for the first year and first 2 years after birth, each quartile increment of exposure to mixed air pollutants was associated with HRs of 1.65 (95% CI 1.30-2.10) and 2.53 (95% CI 2.16-2.97), respectively. Notably, SO2 made the largest positive contribution in both phases, accounting for 50.30% and 74.70% of the association, respectively. CONCLUSIONS: Exposure to elevated levels of mixed air pollutants during the first 1000 days of life appears to elevate the risk of childhood asthma/wheezing. Specifically, the second trimester, especially during the pseudoglandular and canalicular stages, and the initial 2 years after birth emerge as crucial susceptibility windows. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-ROC-17013496; https://tinyurl.com/2ctufw8n.

Effects of long-term exposure to ambient fine particulate matter and its specific components on blood pressure and hypertension incidence.

BACKGROUND: Epidemiological evidence on the association of PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 µm) and its specific components with hypertension and blood pressure is limited. METHODS: We applied information of participants from the World Health Organization's (WHO) Study on Global Ageing and Adult Health (SAGE) to estimate the associations of long-term PM2.5 mass and its chemical components exposure with blood pressure (BP) and hypertension incidence in Chinese adults ≥ 50 years during 2007-2018. Generalized linear mixed model and Cox proportional hazard model were applied to investigate the effects of PM2.5 mass and its chemical components on the incidence of hypertension and BP, respectively. RESULTS: Each interquartile range (IQR = 16.80 µg/m3) increase in the one-year average of PM2.5 mass concentration was associated with a 17 % increase in the risk of hypertension (HR = 1.17, 95 % CI: 1.10, 1.24), and the population attributable fraction (PAF) was 23.44 % (95 % CI: 14.69 %, 31.55 %). Each IQR µg/m3 increase in PM2.5 exposure was also related to increases of systolic blood pressure (SBP) by 2.54 mmHg (95 % CI:1.99, 3.10), and of diastolic blood pressure (DBP) by 1.36 mmHg (95 % CI: 1.04, 1.68). Additionally, the chemical components of SO42-, NO3-, NH4+, OM, and BC were also positively associated with an increased risk of hypertension incidence and elevated blood pressure. CONCLUSIONS: These results indicate that long-term exposure to PM2.5 mass and its specific components may be major drivers of escalation in hypertension diseases.

Metabolic Nanoregulator Remodels Gut Microenvironment for Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is strongly related to the occurrence of accumulation of toxic reactive oxygen species (ROS), inflammation of the mucosa, and an imbalance of intestinal microbes. However, current treatments largely focus on a single factor, yielding unsatisfactory clinical outcomes. Herein, we report a biocompatible and IBD-targeted metabolic nanoregulator (TMNR) that synergistically regulates cellular and bacterial metabolism. The TMNR comprises a melanin-gallium complex (MNR) encapsulated within a thermosensitive and colitis-targeting hydrogel, all composed of natural and FDA-approved components. The TMNR confers superior broad-spectrum antioxidant properties, effectively scavenging reactive oxygen species (ROS) and blocking inflammatory signaling pathways. The presence of Ga3+ in TMNR selectively disrupts iron metabolism in pathogenic microorganisms due to its structural resemblance to the iron atom. Additionally, incorporating a thermosensitive injectable hydrogel enables targeted delivery of TMNR to inflammatory regions, prolonging their retention time and providing a physical barrier function for optimizing IBD treatment efficacy. Collectively, TMNR effectively modulates the redox balance of inflamed colonic epithelial tissue and disrupts iron metabolism in pathogenic microorganisms, thereby eliminating inflammation and restoring intestinal homeostasis against IBD. Hence, this work presents a comprehensive approach for precise spatiotemporal regulation of the intestinal microenvironmental metabolism for IBD treatment.

Concentration-Driven Evolution of Adaptive Artificial Ion Channels or Nanopores with Specific Anticancer Activities.

In nature, ceramides are a class of sphingolipids possessing a unique ability to self-assemble into protein-permeable channels with intriguing concentration-dependent adaptive channel cavities. However, within the realm of artificial ion channels, this interesting phenomenon is scarcely represented. Herein, we report on a novel class of adaptive artificial channels, Pn-TPPs, based on PEGylated cholic acids bearing triphenylphosphonium (TPP) groups as anion binding motifs. Interestingly, the molecules self-assemble into chloride ion channels at low concentrations while transforming into small molecule-permeable nanopores at high concentrations. Moreover, the TPP groups endow the molecules with mitochondria-targeting properties, enabling them to selectively drill holes on the mitochondrial membrane of cancer cells and subsequently trigger the caspase 9 apoptotic pathway. The anticancer efficacies of Pn-TPPs correlate with their abilities to form nanopores. Significantly, the most active ensembles formed by P5-TPP exhibits impressive anticancer activity against human liver cancer cells, with an IC50 value of 3.8 µM. While demonstrating similar anticancer performance to doxorubicin, P5-TPP exhibits a selectivity index surpassing that of doxorubicin by a factor of 16.8.

Ambient PM2.5 and cardiopulmonary mortality in the oldest-old people in China: A national time-stratified case-crossover study.

BACKGROUND: Evidence on the associations of fine particulate matter (PM2.5) with cardiopulmonary mortality in the oldest-old (aged 80+ years) people remains limited. METHODS: We conducted a time-stratified case-crossover study of 1,475,459 deaths from cardiopulmonary diseases in China to estimate the associations between short-term exposure to ambient PM2.5 and cardiopulmonary mortality among the oldest-old people. FINDINGS: Each 10 µg/m3 increase in PM2.5 concentration (6-day moving average [lag05]) was associated with higher mortality from cardiopulmonary diseases (excess risks [ERs] = 1.69%, 95% confidence interval [CI]: 1.54%, 1.84%), cardiovascular diseases (ER = 1.72%, 95% CI: 1.54%, 1.90%), and respiratory diseases (ER = 1.62%, 95% CI: 1.33%, 1.91%). Compared to the other groups, females (ER = 1.94%, 95% CI: 1.73%, 2.15%) (p for difference test = 0.043) and those aged 95-99 years (ER = 2.31%, 95% CI: 1.61%, 3.02%) (aged 80-85 years old was the reference, p for difference test = 0.770) presented greater mortality risks. We found 14 specific cardiopulmonary causes associated with PM2.5, out of which emphysema (ER = 3.20%, 95% CI: 1.57%, 4.86%) had the largest association. Out of the total deaths, 6.27% (attributable fraction [AF], 95% CI: 5.72%, 6.82%) were ascribed to short-term PM2.5 exposure. CONCLUSIONS: This study provides evidence of PM2.5-induced cardiopulmonary mortality and calls for targeted prevention actions for the oldest-old people. FUNDING: This work was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Foreign Expert Program of the Ministry of Science and Technology, the Natural Science Foundation of Guangdong, China, and the Science and Technology Program of Guangzhou.

Non-Covalently Stapled H+ /Cl- Ion Channels Activatable by Visible Light for Targeted Anticancer Therapy.

The development of stimuli-responsive artificial H+ /Cl- ion channels, capable of specifically disturbing the intracellular ion homeostasis of cancer cells, presents an intriguing opportunity for achieving high selectivity in cancer therapy. Herein, we describe a novel family of non-covalently stapled self-assembled artificial channels activatable by biocompatible visible light at 442 nm, which enables the co-transport of H+ /Cl- across the membrane with H+ /Cl- transport selectivity of 6.0. Upon photoirradiation of the caged C4F-L for 10 min, 90 % of ion transport efficiency can be restored, giving rise to a 10.5-fold enhancement in cytotoxicity against human colorectal cancer cells (IC50 =8.5 µM). The mechanism underlying cancer cell death mediated by the H+ /Cl- channels involves the activation of the caspase 9 apoptosis pathway as well as the scarcely reported disruption of the autophagic processes. In the absence of photoirradiation, C4F-L exhibits minimal toxicity towards normal intestine cells, even at a concentration of 200 µM.

Astaxanthin Isomers: A Comprehensive Review of Isomerization Methods and Analytic Techniques.

The presence of multiple conjugated double bonds and chiral carbon atoms endows astaxanthin with geometric and optical isomers, and these isomers widely exist in biological sources, food processing, and in vivo absorption. However, there remains no systematic summary of astaxanthin isomers regarding isomerization methods and analytic techniques. To address this need, this Review focuses on a comprehensive analysis of Z-isomerization methods of astaxanthin, including solvent system, catalyst, and heat treatment. Comparatively, high-efficiency and health-friendly methods are more conducive to put into practical use, such as food-grade solvents and food-component catalysts. In addition, we outline the recent advances in analysis techniques of astaxanthin isomers, as well as the structural characteristics reflected by various methods (e.g., HPLC, NMR, FTIR, and RS). Furthermore, we summarized the related research on the safety evaluation of astaxanthin isomers. Finally, future trends and barriers in Z-transformation and analysis of astaxanthin isomers are also discussed.

Cluster-determinant 36 (CD36) mediates intestinal absorption of dietary astaxanthin and affects its secretion.

The functional activity of dietary astaxanthin is closely related to its absorption, and the absorption of dietary carotenoids mainly mediated by transmembrane transport protein (TTP) has become the mainstream research direction in recent years. However, the main TTP mediating astaxanthin absorption and its potential mechanisms are still unclear. Hence, based on the preliminary screening results, this study aims to elucidate the role of cluster-determinant 36 (CD36) mediating astaxanthin absorption from the perspective of expression levels through in vitro cell model, in situ single-pass intestinal perfusion model and in vivo mice model. The results showed that astaxanthin uptake was significantly increased by 45.13% in CD36 overexpressing cells and decreased by 20.92% in the case of sulfo-N-succinimidyl oleate (SSO) inhibition. A similar trend also appeared in the duodenum and jejunum by in situ model. Moreover, astaxanthin uptake in the small intestine of CD36 knockout mice was significantly reduced by 88.22%. Furthermore, the inhibition or knockout of CD36 suppressed the expression of other transporters (SR-BI and NPC1L1). Interestingly, CD36 was also involved in the downstream secretion pathway, which is manifested by interfering with the expression of related proteins (ERK1/2, MTP, ApoB48, and ApoAI). Therefore, these results indicate the important role of CD36 in astaxanthin transmembrane transport for the first time, providing vital exploration way for the absorption of dietary fat-soluble substances.