Effect of electroacupuncture on the intestinal flora-short chain fatty acid metabolism axis in simple obesity rats. / ç”µé’ˆå¯¹å•çº¯æ€§è‚¥èƒ–ç—‡å¤§é¼ è‚ é“èŒç¾¤-çŸ­é“¾è„‚è‚ªé ¸ä»£è°¢è½´çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the intestinal flora-short chain fatty acids (SCFAs) metabolism axis in rats with simple obesity, so as to explore the underlying mechanism of EA in reducing obesity. METHODS: Male SD rats were randomly divided into control group, model group and EA group, with 6 rats in each group. The obesity model was established by feeding the rats with high-fat diet. Rats in the EA group were treated with EA at "Quchi" (LI11) and "Zusanli" (ST36) for 15 min, once daily for 21 consecutive days. The changes of body weight were observed every other day. H.E. staining was used to observe the pathological changes of adipose tissue and liver. The blood lipid content was detected by automatic biochemical analyzer. The diversity of intestinal flora in rat feces was analyzed by 16S rRNA high-throughput sequencing. The content of SCFAs in rat feces was detected by ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS/MS). The correlation between the relative abundance of fecal intestinal flora and the content of SCFAs in rats was analyzed by Pearson method. RESULTS: Compared with the control group, the body weight of rats, the serum total cholesterol (TC) and triglyceride (TG) were significantly increased (P<0.01) in the model group. The results of 16S rRNA sequencing showed that, at the genus level the relative abundance of Bacteroides, Butyrivibrio and Roseburia in were decreased significantly(P<0.05), while that of the Lachnospiraceae_NK4A136_group increased(P<0.05). After the intervention, compared with the model group, the body weight, serum TC and TG contents of rats in the EA group were significantly decreased (P<0.05, P<0.01)；the results of 16S rRNA sequencing showed that, the relative abundance of the Bacteroidota phylum significantly increased (P<0.01) and Firmicutes decreased (P<0.01) at the phylum level, and at the genus level the relative abundances of Bacteroides, Butyrivibrio and Roseburia significantly increased (P<0.01, P<0.05)；the contents of acetic acid and propionic acid in SCFAs significantly increased (P<0.01). H.E. staining showed an increase of the diameter of adipocytes, with obvious lipid droplets and inflammatory infiltration in the model group, which was relatively milder in the EA group. PCoA analysis showed that there were significant differences in the structure of intestinal flora between the control group and the model group, as well as the model group and the EA group. At the phylum level, the relative abundance of Bacteroidota was positively correlated with acetic acid and propionic acid contents, with that of Firmicutes negatively correlated with acetic acid and propionic acid contents (P<0.001). At the genus level, the relative abundances of Bacteroides, Streptococcus and Butyricimonas were positively correlated with acetic acid content (P<0.01, P<0.05), and the relative abundances of Bacteroides, Streptococcus and Roseburia were positively correlated with propionic acid content (P<0.001, (P<0.05). CONCLUSIONS: EA can improve the disorder of lipid metabolism in obese rats by improving the disorder of intestinal flora-SCFAs metabolic axis, thus playing a role in inhibiting obesity.

USP14 inhibition promotes DNA damage repair and represses ovarian granulosa cell senescence in premature ovarian insufficiency.

BACKGROUND: Premature ovarian insufficiency (POI) is a condition characterized by a substantial decline or loss of ovarian function in women before the age of 40. However, the pathogenesis of POI remains to be further elucidated, and specific targeted drugs which could delay or reverse ovarian reserve decline are urgently needed. Abnormal DNA damage repair (DDR) and cell senescence in granulosa cells are pathogenic mechanisms of POI. Ubiquitin-specific protease 14 (USP14) is a key enzyme that regulates the deubiquitylation of DDR-related proteins, but whether USP14 participates in the pathogenesis of POI remains unclear. METHODS: We measured USP14 mRNA expression in granulosa cells from biochemical POI (bPOI) patients. In KGN cells, we used IU1 and siRNA-USP14 to specifically inhibit USP14 and constructed a cell line stably overexpressing USP14 to examine its effects on DDR function and cellular senescence in granulosa cells. Next, we explored the therapeutic potential of IU1 in POI mouse models induced by D-galactose. RESULTS: USP14 expression in the granulosa cells of bPOI patients was significantly upregulated. In KGN cells, IU1 treatment and siUSP14 transfection decreased etoposide-induced DNA damage levels, promoted DDR function, and inhibited cell senescence. USP14 overexpression increased DNA damage, impaired DDR function, and promoted cell senescence. Moreover, IU1 treatment and siUSP14 transfection increased nonhomologous end joining (NHEJ), upregulated RNF168, Ku70, and DDB1, and increased ubiquitinated DDB1 levels in KGN cells. Conversely, USP14 overexpression had the opposite effects. Intraperitoneal IU1 injection alleviated etoposide-induced DNA damage in granulosa cells, ameliorated the D-galactose-induced POI phenotype, promoted DDR, and inhibited cell senescence in ovarian granulosa cells in vivo. CONCLUSIONS: Upregulated USP14 in ovarian granulosa cells may play a role in POI pathogenesis, and targeting USP14 may be a potential POI treatment strategy. Our study provides new insights into the pathogenesis of POI and a novel POI treatment strategy.

[Chemical components and in vitro anti-aging activity of Yangxue Qingnao Wan based on UPLC-Q-TOF-MS/MS].

The main chemical components of Yangxue Qingnao Wan(YXQNW) were analyzed and identified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS). According to the mass spectrometry information, Mass Hunter 10.0 analysis software was used to compare the collected quasi-molecular ion peaks and secondary fragment ions with literature and reference substances. A total of 131 compounds were identified from YXQNW, including 11 phenylpropanoids, 11 flavonoids, 42 nitrogen-containing compounds, 12 terpenoids, 17 phthalides, 23 quinones, and 15 other compounds. The anti-aging activity of YXQNW and six compounds from YXQNW, including rosmarinic acid, gallic acid, rutin, umbelliferone, hyperoside, and vanillic acid, were evaluated by D-galactose(D-gal)-induced HT22 cell senescence model. The effects of the compounds on HT22 cell damage and individual cell proliferation ability were observed from overall and individual perspectives by the Beyo Click~(TM) EdU-555 cell proliferation kit, and apoptosis was detected by the Annexin V-FITC/PI double staining apoptosis detection kit. Finally, the anti-aging effect of the compounds was tested by a cell senescence ß-galactosidase staining kit. This study provides a more comprehensive analysis of the chemical components of YXQNW and evaluates its anti-aging effect, which will provide a scientific basis for basic research on the efficacy of YXQNW for the treatment of various neurological diseases, such as Alzheimer's disease(AD), headache, and memory loss.

Extraction of antimicrobial peptides from pea protein hydrolysates by sulfonic acid functionalized biochar.

The extraction methods for antimicrobial peptides (AMPs) from plants are varied, but the absence of a standardized and rapid technique remains a challenge. In this study, a functionalized biochar was developed and characterized for the extraction of AMPs from pea protein hydrolysates. The results indicated that the biochar mainly enriched AMPs through electrostatic interaction, hydrogen bonding and pore filling. Then three novel cationic antimicrobial peptides were identified, among which the RDLFK (Arg-Asp-Leu-Phe-Lys) had the greatest inhibitory effect against Staphylococcus aureus and Bacillus subtilis, showcasing IC50 value of 2.372 and 1.000 mg/mL, respectively. Additionally, it was found that RDLFK could damage bacterial cell membranes and penetrate the cells to inhibit DNA synthesis. These results provided that the biochar-based extraction method presents an efficient and promising avenue for isolating AMPs, addressing a critical gap in the current methodologies for their extraction from plant sources.

Enrichment of antioxidant peptide from rice protein hydrolysates via rice husk derived biochar.

In this study, rice husk biochar was engineered with abundant iron ion sites to enhance the enrichment of antioxidant peptides from rice protein hydrolysates through metal-chelating interactions. The π-π interactions and metal ion chelation were identified as the primary mechanisms for the enrichment process. Through peptide sequencing, four peptides were identified: LKFL (P1: Leu-Lys-Phe-Leu), QLLF (P2: Gln-Leu-Leu-Phe), WLAYG (P3: Trp-Leu-Ala-Tyr-Gly), and HFCGG (P4: His-Phe-Cys-Gly-Gly). The vitro analysis and molecular docking revealed that peptides P1-P4 possessed remarkable scavenging ability against radicals and Fe2+ chelating ability. Notably, peptide P4 showed radical scavenging activity comparable to glutathione (GSH) against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzthiazoline-6-sulphonate (ABTS) radicals. Cellular experiments further confirmed that peptide P4 effectively protected HepG2 cells from oxidative stress-induced damage. The modified rice husk biochar proved to be an effective means for enriching rice antioxidant peptides from protein hydrolysates.

Effects of ground flowering plant traits on the diversity of wild bees in apple orchards during flowering.

Pollination is one of the important ecosystem services related to sustainable development of human society. However, the population diversity and abundance of wild bees, important pollinators, have been significantly reduced by climate change, agricultural intensification, and landscape transformation. Re-establishment of pollinator habitat by planting nectar-producing plants is an important way to maintain pollination service. In this study, we investigated the status of wild bees and the traits of flowering plants in 22 apple orchards during flowering stage in Changping District, Beijing in 2019. We analyzed the response of wild bee diversity to the flowering plant richness, flower color richness, inflorescence type richness, flowering plant coverage, herbaceous layer coverage and different flower color coverage in apple orchards, aiming to provide guidance for the selection of nectar-producing plants to establish the habitat of wild bees. A total of 3517 wild bees were captured during the apple flowering season, representing 49 species, 13 genera, and 5 families. We identified 21 flowering plants species that shared a similar flo-wering period with apple, exhibiting a range of 5 colors and 9 inflorescence types. The Shannon diversity index, evenness index, and social bee richness of wild bee community were positively correlated with flowering plant richness. The total wild bee community richness, social bee richness, underground nesting bee richness were positively correlated with the richness of flowering plant color, but Halictidae bee abundance was negatively correlated with the richness of flowering plant color. The Shannon diversity index and evenness index of wild bee community were positively correlated with the richness of inflorescence types. Megachilidae bee richness was negative correlated with the white flower coverage. Megachilidae bee richness, social bee abundance, and ground nesting bee richness were positively correlated with the purple flower coverage. There was no significant correlation between wild bees and flowering plant richness, flower color richness, inflorescence type richness, flowering plant coverage, herbaceous layer coverage and different flower color coverage in other communities of different families, lifestyles and nesting types. Maintaining diverse ground flowering plants with various traits in orchards is important to improve the diversity of wild bees. In particular, increasing the coverage of purple flower during apple flowering period is helpful to promote the diversity of Megachilidae bee, social bees, and ground nesting bees.

The miRNA and PD-1/PD-L1 signaling axis: an arsenal of immunotherapeutic targets against lung cancer.

Lung cancer is a severe challenge to the health care system with intrinsic resistance to first and second-line chemo/radiotherapies. In view of the sterile environment of lung cancer, several immunotherapeutic drugs including nivolumab, pembrolizumab, atezolizumab, and durvalumab are currently being used in clinics globally with the intention of releasing exhausted T-cells back against refractory tumor cells. Immunotherapies have a limited response rate and may cause immune-related adverse events (irAEs) in some patients. Hence, a deeper understanding of regulating immune checkpoint interactions could significantly enhance lung cancer treatments. In this review, we explore the role of miRNAs in modulating immunogenic responses against tumors. We discuss various aspects of how manipulating these checkpoints can bias the immune system's response against lung cancer. Specifically, we examine how altering the miRNA profile can impact the activity of various immune checkpoint inhibitors, focusing on the PD-1/PD-L1 pathway within the complex landscape of lung cancer. We believe that a clear understanding of the host's miRNA profile can influence the efficacy of checkpoint inhibitors and significantly contribute to existing immunotherapies for lung cancer patients. Additionally, we discuss ongoing clinical trials involving immunotherapeutic drugs, both as standalone treatments and in combination with other therapies, intending to advance the development of immunotherapy for lung cancer.

Defect Engineering of Ultrasmall TiO2 Nanoparticles Enables Highly Efficient Photocatalysts for Solar H2 Production from Woody Biomass.

The conversion of woody biomass to H2 through photocatalysis provides a sustainable strategy to generate renewable hydrogen fuel but was limited by the slow decomposition rate of woody biomass. Here, we fabricate ultrasmall TiO2 nanoparticles with tunable concentration of oxygen vacancy defects (VO-TiO2) as highly efficient photocatalysts for photocatalytic conversion of woody biomass to H2. Owing to the positive role of oxygen vacancy in reducing energy barrier for the generation of •OH which was the critical species to oxidize woody biomass, the obtained VO-TiO2 achieves rapid photocatalytic conversion of α-cellulose and poplar wood chip to H2 in the presence of Pt nanoclusters as the cocatalyst. As expected, the highest H2 generation rate in α-cellulose and poplar wood chip system respectively achieve 1146 and 59 µmol h-1 g-1, and an apparent quantum yield of 4.89% at 380 nm was obtained in α-cellulose aqueous solution.

Health Risk Assessment of Employees Exposed to Chlorination By-products of Recreational Water in Large Amusement Parks in Shanghai.

Objective: Chlorination is often used to disinfect recreational water in large amusement parks; however, the health hazards of chlorination disinfection by-products (DBPs) to occupational populations are unknown. This study aimed to assess the exposure status of chlorinated DBPs in recreational water and the health risks to employees of large amusement parks. Methods: Exposure parameters of employees of three large amusement parks in Shanghai were investigated using a questionnaire. Seven typical chlorinated DBPs in recreational water and spray samples were quantified by gas chromatography, and the health risks to amusement park employees exposed to chlorinated DBPs were evaluated according to the WHO's risk assessment framework. Results: Trichloroacetic acid, dibromochloromethane, bromodichloromethane, and dichloroacetic acid were detected predominantly in recreational water. The carcinogenic and non-carcinogenic risks of the five DBPs did not exceed the risk thresholds. In addition, the carcinogenic and non-carcinogenic risks of mixed exposure to DBPs were within the acceptable risk limits. Conclusion: Typical DBPs were widely detected in recreational water collected from three large amusement parks in Shanghai; however, the health risks of DBPs and their mixtures were within acceptable limits.

Enhanced Osteogenesis in 2D and 3D Culture Systems Using RGD Peptide and α-TCP Phase Transition within Alginate-Based Hydrogel.

Cell-laden hydrogels have been extensively investigated in various tissue engineering fields by their potential capacity to deposit numerous types of cells in a specific area. They are largely used in soft-tissue engineering applications because of their low mechanical strength. In addition, sodium alginate is well-known for its encapsulation, loading capacity and for being easily controllable; however, it lacks cell-binding ligands and hence the ability to adhere cells. In this study, it is aimed to enhance osteogenesis in cells encapsulated in alginate and improve its mechanical properties by introducing a synthetic peptide and calcium phosphate phase transition. To increase cell-hydrogel interactions and increasing cell viability, an RGD peptide is added to a photocrosslinkable methacrylate-modified alginate, and alpha-tricalcium phosphate (α-TCP) is added to the hydrogel to increase its mechanical strength via phase transition. Cell proliferation, growth, and differentiation are assessed in both 2D and 3D cell cultures. The addition of α-TCP significantly improved the mechanical properties of the hydrogel. Moreover, the RGD peptide and α-TCP showed a synergistic effect with significantly improved cell adhesion and osteogenesis in both 2D and 3D cell cultures. Therefore, the functional hydrogel developed in this study can potentially be used for bone tissue regeneration.

Systematic Druggable Genome-Wide Mendelian Randomization Identifies Therapeutic Targets for Functional Outcome After Ischemic Stroke.

BACKGROUND: Stroke is a leading cause of death worldwide, with a lack of effective treatments for improving the prognosis. The aim of the present study was to identify novel therapeutic targets for functional outcome after ischemic stroke . METHODS AND RESULTS: Cis-expression quantitative trait loci data for druggable genes were used as instrumental variables. The primary outcome was the modified Rankin Scale score at 3 months after ischemic stroke, evaluated as a dichotomous variable (3-6 versus 0-2) and also as an ordinal variable. Drug target Mendelian randomization, Steiger filtering analysis, and colocalization analysis were performed. Additionally, phenome-wide Mendelian randomization analysis was performed to identify the safety of the drug target genes at the genetic level. Among >2600 druggable genes, genetically predicted expression of 16 genes (ABCC2, ATRAID, BLK, CD93, CHST13, NR1H3, NRBP1, PI3, RIPK4, SEMG1, SLC22A4, SLC22A5, SLCO3A1, TEK, TLR4, and WNT10B) demonstrated the causal associations with ordinal modified Rankin Scale (P<1.892×10-5) or poor functional outcome (modified Rankin Scale 3-6 versus 0-2, P<1.893×10-5). Steiger filtering analysis suggested potential directional stability (P<0.05). Colocalization analysis provided further support for the associations between genetically predicted expression of ABCC2, NRBP1, PI3, and SEMG1 with functional outcome after ischemic stroke. Furthermore, phenome-wide Mendelian randomization revealed additional beneficial indications and few potential safety concerns of therapeutics targeting ABCC2, NRBP1, PI3, and SEMG1, but the robustness of these results was limited by low power. CONCLUSIONS: The present study revealed 4 candidate therapeutic targets for improving functional outcome after ischemic stroke, while the underlying mechanisms need further investigation.

Bruton's tyrosine kinase inhibition ameliorated neuroinflammation during chronic white matter ischemia.

Chronic cerebral hypoperfusion (CCH), a disease afflicting numerous individuals worldwide, is a primary cause of cognitive deficits, the pathogenesis of which remains poorly understood. Bruton's tyrosine kinase inhibition (BTKi) is considered a promising strategy to regulate inflammatory responses within the brain, a crucial process that is assumed to drive ischemic demyelination progression. However, the potential role of BTKi in CCH has not been investigated so far. In the present study, we elucidated potential therapeutic roles of BTK in both in vitro hypoxia and in vivo ischemic demyelination model. We found that cerebral hypoperfusion induced white matter injury, cognitive impairments, microglial BTK activation, along with a series of microglia responses associated with inflammation, oxidative stress, mitochondrial dysfunction, and ferroptosis. Tolebrutinib treatment suppressed both the activation of microglia and microglial BTK expression. Meanwhile, microglia-related inflammation and ferroptosis processes were attenuated evidently, contributing to lower levels of disease severity. Taken together, BTKi ameliorated white matter injury and cognitive impairments induced by CCH, possibly via skewing microglia polarization towards anti-inflammatory and homeostatic phenotypes, as well as decreasing microglial oxidative stress damage and ferroptosis, which exhibits promising therapeutic potential in chronic cerebral hypoperfusion-induced demyelination.

Corrigendum: Prescription pattern and effectiveness of antihypertensive drugs in patients with aortic dissection who underwent surgery.

[This corrects the article DOI: 10.3389/fphar.2023.1291900.].

Composition control of additively manufactured color-graded temporary veneer.

OBJECTIVE: The aim of this study was to design and assess composite resin composition for patient-specific esthetic color-graded temporary veneer. METHODS: Various compositions of composite structures (assorted by Ba2SiO4 filler, TiO2 pigment, and photoinitiator) were prepared via additive manufacturing with 3 s UV exposure (405 nm, 10 W/cm2) per 50 µm thick layer followed by 20 min post-curing treatment after fabrication. The effect of each component on the generated color shades was observed and compared to the commonly used VITA shade guide. The coloration was explored by staining aging treatment under dry, wet, artificial saliva environments, coffee, and cola. The mechanical properties were also evaluated. Color measurement and comparison were done using a colorimeter (lightness (L*), green-red color (a*), and blue-yellow color (b*)), and the changes were calculated by CIEDE2000 (ΔE00), translucency parameter (TP) and whiteness index (WID). The composition color analysis results were then applied to produce a color-graded temporary veneer for mimicking a natural look. RESULT: Mechanically, all composition result in adequate bending strength with maximum achievable strength of 111.64 MPa. At the same time, the composite color was affected by each constituent differently. The L* value, which indicates the color lightness of the composite, was considerably tuned by the TiO2 pigment, whereas Ba2SiO4 filler only triggered minor changes. Photoinitiator concentration significantly affected the yellowness, indicated by the increased b* value. Similar tendency also observed toward the calculated TP and WID as well. Based on these evaluations, color-graded temporary veneer successfully generated, matching the VITA A3, A2, and B1 shades gradation. However, the stability of the composite color decreased at high amounts of Ba2SiO4 and photoinitiator. SIGNIFICANCE: The study presents a composition guide for fabricating temporary patient-specific color-graded veneer. It provides insights on the effect of the constituent material on dental esthetics.

The Worries of Out-of-Home Activities in Patients With Inflammatory Bowel Disease: A Survey Study During the COVID-19 Pandemic.

Background: Patients with inflammatory bowel disease (IBD) often experience worries related to travel due to frequent bowel movements. However, there is currently limited research focusing on the travel worries of patients with IBD. The aim of this study was to assess the level of worry regarding out-of-home activities in patients with IBD and identify factors associated with worry. Methods: This study included patients with IBD who visited the outpatient clinics between September 2020 and March 2022, during the COVID-19 pandemic. Participants completed a self-designed questionnaire, providing general clinical data and indicating their level of worry for out-of-home activities. Results: A total of 529 patients with IBD completed the questionnaire. Patients with Crohn's disease (CD) had a higher proportion of individuals under 40 years old and males compared to patients with ulcerative colitis (UC). Regarding out-of-home activities, patients with UC expressed greater worry about going out and taking buses than patients with CD. However, there were no significant differences observed between the two groups in terms of travel worries and worries about finding public washrooms. A significant majority (85.4%) of patients with clinically active IBD expressed worries about not finding public washrooms when going out, while 46.7% of patients in clinical remission had similar worries. Moreover, the worry about finding public washrooms was higher in patients with UC compared to those with CD, both during the clinical activity and remission. Conclusion: This survey conducted during the COVID-19 pandemic reported worries among patients with IBD about out-of-home activities. The patients with clinically active IBD, especially UC, expressed worries about not finding public washrooms when going out. We highlight the actual psychological and quality of life challenges faced by patients with IBD.

Enhancing storage stability of pea peptides through encapsulation in maltodextrin and gum tragacanth via monitoring scavenge ability to free radicals.

Pea peptides can lead to degradation through oxidation, deamidation, hydrolysis, or cyclization during production, processing, and storage, which in turn limit their broader application. To stabilize pea peptides, this study employed spray drying technology to create a pea peptide micro-encapsule using maltodextrin, gum tragacanth, and pea peptides. Four key factors, including polysaccharide ratio, glycopeptide ratio, solid-liquid ratio, and inlet temperature, were optimized to enhance the antioxidant properties of the pea peptide micro-encapsule. The results indicated that the utilization of maltodextrin and gum tragacanth significantly improves the storage stability and antioxidant activity of pea peptides. Moreover, optimal storage stability for pea peptides was achieved with a polysaccharide ratio of 9:1, a glycopeptide ratio of 10:1, a solid-liquid ratio of 4:40, and an inlet temperature of 180 °C. After 60 days of storage, the encapsulated pea peptides maintained 70.22 %, 25.19 %, and 40.32 % for scavenging abilities to hydroxyl radical, superoxide anion, and ABTS radical, respectively. In contrast, the unencapsulated pea peptides showed a decline to 47.02 %, 0 %, and 24.46 % in the same antioxidant activities after storage. These findings underscore the potential of spray drying technology to enhance the functional properties of pea peptides for various applications.

Combined impact of sleep and obesity on female infertility in the NHANES 2017-2020.

BACKGROUND: Sleep health and obesity may affect the risk of female infertility. However, few studies focused on the interaction of obesity and sleep health on the female infertility risk. This study aimed to evaluate the combined impact of trouble sleeping / sleep duration and overweight/obesity/ abdominal obesity on the risk of female infertility. METHODS: The data for this cross-sectional study was obtained from National Health and Nutritional Examination Survey, which provided information on trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and confounding factors. Adopted weighted univariate and multivariate logistic regression models to explore the relationship between trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and the risk of infertility, respectively, and the combined effect of trouble sleeping and overweight/obesity, trouble sleeping and abdominal obesity, sleep duration and overweight/obesity, sleep duration and abdominal obesity, on the female infertility risk. RESULTS: This study included a total of 1,577 women, and 191 were diagnosed with infertility. Women with infertility had a higher proportion of people with overweight/obesity, abdominal obesity, sleep duration ≤ 7 h and trouble sleeping than those with non-infertility. The result indicated that trouble sleeping [odds ratio (OR) = 2.25, 95% confidence intervals (CI): 1.49-3.39], sleep duration ≤ 7 h (OR = 1.59, 95% CI: 1.03-2.48), and the combined impact of abdominal obesity and trouble sleeping (OR = 2.18, 95% CI: 1.28-3.72), abdominal obesity and sleep duration ≤ 7 h (OR = 2.00, 95% CI: 1.17-3.40), overweight/obesity and trouble sleeping (OR = 2.29, 95% CI: 1.24-4.26), and overweight/obesity and sleep duration ≤ 7 h (OR = 1.88, 95% CI: 1.01-3.49) were associated with increased odds of infertility, respectively. CONCLUSION: There was combined effects of trouble sleeping/sleep duration ≤ 7 h and overweight/obesity/ abdominal obesity on increased odds of female infertility.

Mapping the immune cell landscape of severe atopic dermatitis by single-cell RNA-seq.

BACKGROUND: Efforts to profile atopic dermatitis (AD) tissues have intensified, yet comprehensive analysis of systemic immune landscapes in severe AD remains crucial. METHODS: Employing single-cell RNA sequencing, we analyzed over 300,000 peripheral blood mononuclear cells from 12 severe AD patients (Eczema area and severity index (EASI) > 21) and six healthy controls. RESULTS: Results revealed significant immune cell shifts in AD patients, including increased Th2 cell abundance, reduced NK cell clusters with compromised cytotoxicity, and correlated Type 2 innate lymphoid cell proportions with disease severity. Moreover, unique monocyte clusters reflecting activated innate immunity emerged in very severe AD (EASI > 30). While overall dendritic cells (DCs) counts decreased, a distinct Th2-priming subset termed "Th2_DC" correlated strongly with disease severity, validated across skin tissue data, and flow cytometry with additional independent severe AD samples. Beyond the recognized role of Th2 adaptive immunity, our findings highlight significant innate immune cell alterations in severe AD, implicating their roles in disease pathogenesis and therapeutic potentials. CONCLUSION: Apart from the widely recognized role of Th2 adaptive immunity in AD pathogenesis, alterations in innate immune cells and impaired cytotoxic cells have also been observed in severe AD. The impact of these alterations on disease pathogenesis and the effectiveness of potential therapeutic targets requires further investigation.