Plin4 exacerbates cadmium-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Strong evidence indicates that environmental stressors are the risk factors for male testosterone deficiency (TD). However, the mechanisms of environmental stress-induced TD remain unclear. Based on our all-cause male reproductive cohort, we found that serum ferrous iron (Fe2⁺) levels were elevated in TD donors. Then, we explored the role and mechanism of ferroptosis in environmental stress-reduced testosterone levels through in vivo and in vitro models. Data demonstrated that ferroptosis and lipid droplet deposition were observed in environmental stress-exposed testicular Leydig cells. Pretreatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, markedly mitigated environmental stress-reduced testosterone levels. Through screening of core genes involved in lipid droplets formation, it was found that environmental stress significantly increased the levels of perilipins 4 (PLIN4) protein and mRNA in testicular Leydig cells. Further experiments showed that Plin4 siRNA reversed environmental stress-induced lipid droplet deposition and ferroptosis in Leydig cells. Additionally, environmental stress increased the levels of METTL3, METTL14, and total RNA m6A in testicular Leydig cells. Mechanistically, S-adenosylhomocysteine, an inhibitor of METTL3 and METTL14 heterodimer activity, restored the abnormal levels of Plin4, Fe2⁺ and testosterone in environmental stress-treated Leydig cells. Collectively, these results suggest that Plin4 exacerbates environmental stress-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

Mycoplasma genitalium Membrane Lipoprotein Induces GAPDH Malonylation in Urethral Epithelial Cells to Regulate Cytokine Response.

Membrane lipoproteins serve as primary pro-inflammatory virulence factors in Mycoplasma genitalium. Membrane lipoproteins primarily induce inflammatory responses by activating Toll-like Receptor 2 (TLR2); however, the role of the metabolic status of urethral epithelial cells in inflammatory response remains unclear. In this study, we found that treatment of uroepithelial cell lines with M. genitalium membrane lipoprotein induced metabolic reprogramming, characterized by increased aerobic glycolysis, decreased oxidative phosphorylation, and increased production of the metabolic intermediates acetyl-CoA and malonyl-CoA. The metabolic shift induced by membrane lipoproteins is reversible upon blocking MyD88 and TRAM. Malonyl-CoA induces malonylation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and malonylated GAPDH could dissociate from the 3' untranslated region of TNF-α and IFN-γ mRNA. This dissociation greatly reduces the inhibitory effect on the translation of TNF-α and IFN-γ mRNA, thus achieving fine-tuning control over cytokine secretion. These findings suggest that GAPDH malonylation following M. genitalium infection is an important inflammatory signal that plays a crucial role in urogenital inflammatory diseases.

National age-specific mortality trends for cervical and breast cancers in urban-rural areas of China from 2009 to 2021: a population-based analysis.

BACKGROUND: Cervical and breast cancers are among the top 4 leading causes of cancer-related mortality in women. This study aimed to examine age-specific temporal trends in mortality for cervical and breast cancers in urban and rural areas of China from 2009 to 2021. METHODS: Age-specific mortality data for cervical and breast cancers among Chinese women aged 20-84 years were obtained from China's National Disease Surveillance Points system spanning the years 2009 to 2021. Negative binomial regression models were utilized to assess urban-rural differences in mortality rate ratios, while Joinpoint models with estimated average annual percent changes (AAPC) and slopes were employed to compare temporal trends and the acceleration of mortality rates within different age groups. RESULTS: From 2009 to 2021, there was a relative increase in age-specific mortality associated with the two cancers observed in rural areas compared with urban areas. A rising trend in the screening age of 35-64 [AAPC: 4.0%, 95% confidence interval (CI) 0.5-7.6%, P = 0.026] for cervical cancer was noted in rural areas, while a stable trend (AAPC: - 0.7%, 95% CI - 5.8 to 4.6%, P = 0.78) was observed in urban areas. As for breast cancer, a stable trend (AAPC: 0.3%, 95% CI - 0.3 to 0.9%, P = 0.28) was observed in rural areas compared to a decreasing trend (AAPC: - 2.7%, 95% CI - 4.6 to - 0.7%, P = 0.007) in urban areas. Urban-rural differences in mortality rates increased over time for cervical cancer but decreased for breast cancer. Mortality trends for both cervical and breast cancers showed an increase with age across 4 segments, with the most significant surge in mortality observed among the 35-54 age group across urban and rural areas, periods, and regions in China. CONCLUSIONS: Special attention should be given to women aged 35-54 years due to mortality trends and rural-urban disparities. Focusing on vulnerable age groups and addressing rural-urban differences in the delivery of cancer control programs can enhance resource efficiency and promote health equity.

Study on chemical characterization and sleep-improvement function of Prunella vulgaris L. based on the functional components.

Prunella vulgaris L. (P. vulgaris) has great application value and development prospects in improving sleep. In this study, we continued to evaluate the sleep-improvement function and mechanism of P. vulgaris from both chemical characterization and function based on sleep-improvement functional ingredients, rosmarinic acid and salviaflaside, screened out in the previous stage as the index components. The chemical constituents of P. vulgaris and its phenolic acid fraction were characterized by the UPLC-MSn technology. The quality of the sleep-improvement phenolic acid fraction of P. vulgaris was scientifically evaluated by fingerprints combined with quantitative analysis of rosmarinic acid and salviaflaside. The function of phenolic acid parts of P. vulgaris in improving sleep was verified by different insomnia models including the PCPA-induced insomnia model and surface platform sleep deprivation model. HE staining was used to observe the effect of P. vulgaris on the morphology of nerve cells in different brain regions. In vivo experiments and molecular docking explored the sedative-hypnotic effects of functional ingredients of P. vulgaris. All these results investigated the material basis and mechanism of P. vulgaris to improve sleep from multiple perspectives, which contribute to providing a basis for the development of functional food to improve sleep.

Metabolic profiling of idiopathic pulmonary fibrosis in a mouse model: implications for pathogenesis and biomarker discovery.

Background: Alterations in metabolites and metabolic pathways are thought to be important triggers of idiopathic pulmonary fibrosis (IPF), but our lack of a comprehensive understanding of this process has hampered the development of IPF-targeted drugs. Methods: To fully understand the metabolic profile of IPF, C57BL/6 J male mice were injected intratracheally with bleomycin so that it could be used to construct a mouse model of IPF, and lung tissues from 28-day and control IPF mice were analyzed by pathology and immunohistochemistry. In addition, serum metabolites from IPF mice were examined using LC-ESI-MS/MS, and the differential metabolites were analyzed for KEGG metabolic pathways and screened for biomarkers using machine learning algorithms. Results: In total, the levels of 1465 metabolites were detected, of which 104 metabolites were significantly altered after IPF formation. In IPF mouse serum, 52% of metabolite expression was downregulated, with lipids (e.g., GP, FA) and organic acids and their derivatives together accounting for more than 70% of the downregulated differentially expressed metabolites. In contrast, FA and oxidised lipids together accounted for 60% of the up-regulated differentially expressed metabolites. KEGG pathway enrichment analyses of differential metabolites were mainly enriched in the biosynthesis of unsaturated fatty acids, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism. Seven metabolites were screened by machine learning LASSO models and evaluated as ideal diagnostic tools by receiver operating characteristic curves (ROCs). Discussion: In conclusion, the serum metabolic disorders found to be associated with pulmonary fibrosis formation will help to deepen our understanding of the pathogenesis of pulmonary fibrosis.

Synthesis of C-Alkyl Glycosides from Alkyl Bromides and Glycosyl Carboxylic Acids via Ni/Photoredox Dual Catalysis.

C-Alkyl glycosides, an important class of C-glycosides, are widely found in various drugs and natural products. The synthesis of C-alkyl glycosides has attracted considerable attention. Herein, we developed a Ni/photoredox catalyzed decarboxylative C(sp3)-C(sp3) coupling reaction of stable glycosylcarboxylic acids with simple aliphatic bromides to generate C-alkyl glycosides. The method successfully linked several functional molecular fragments (natural products or drugs) to a sugar moiety, showing the extensive application prospects of this transformation. Controlled experiments and DFT calculations demonstrated that the reaction pathway contains a free radical process, and a possible mechanism is proposed.

[Retracted] SFRP2 modulates non­small cell lung cancer A549 cell apoptosis and metastasis by regulating mitochondrial fission via Wnt pathways.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the JC1­stained cellular images shown in Fig. 2C on p. 1928 were strikingly similar to data that had already been published in different form in another article written by different authors at different research institutes [Yao S and Yan W: Overexpression of Mst1 reduces gastric cancer cell viability by repressing the AMPK­Sirt3 pathway and activating mitochondrial fission. Onco Targets Ther 11: 8465­8479, 2019]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 20: 1925­1932, 2019; DOI: 10.3892/mmr.2019.10393].

Deciphering the role of HLF in idiopathic orbital inflammation: integrative analysis via bioinformatics and machine learning techniques.

Idiopathic orbital inflammation, formerly known as NSOI (nonspecific orbital inflammation), is characterized as a spectrum disorder distinguished by the polymorphic infiltration of lymphoid tissue, presenting a complex and poorly understood etiology. Recent advancements have shed light on the HLF (Human lactoferrin), proposing its critical involvement in the regulation of hematopoiesis and the maintenance of innate mucosal immunity. This revelation has generated significant interest in exploring HLF's utility as a biomarker for NSOI, despite the existing gaps in our understanding of its biosynthetic pathways and operational mechanisms. Intersecting multi-omic datasets-specifically, common differentially expressed genes between GSE58331 and GSE105149 from the Gene Expression Omnibus and immune-related gene compendiums from the ImmPort database-we employed sophisticated analytical methodologies, including Lasso regression and support vector machine-recursive feature elimination, to identify HLF. Gene set enrichment analysis and gene set variation analysis disclosed significant immune pathway enrichment within gene sets linked to HLF. The intricate relationship between HLF expression and immunological processes was further dissected through the utilization of CIBERSORT and ESTIMATE algorithms, which assess characteristics of the immune microenvironment, highlighting a noteworthy association between increased HLF expression and enhanced immune cell infiltration. The expression levels of HLF were corroborated using data from the GSE58331 dataset, reinforcing the validity of our findings. Analysis of 218 HLF-related differentially expressed genes revealed statistically significant discrepancies. Fifteen hub genes were distilled using LASSO and SVM-RFE algorithms. Biological functions connected with HLF, such as leukocyte migration, ossification, and the negative regulation of immune processes, were illuminated. Immune cell analysis depicted a positive correlation between HLF and various cells, including resting mast cells, activated NK cells, plasma cells, and CD8 T cells. Conversely, a negative association was observed with gamma delta T cells, naive B cells, M0 and M1 macrophages, and activated mast cells. Diagnostic assessments of HLF in distinguishing NSOI showed promising accuracy. Our investigation delineates HLF as intricately associated with NSOI, casting light on novel biomarkers for diagnosis and progression monitoring of this perplexing condition.

Cholecystopleural fistula: A case report and literature review.

INTRODUCTION: Gallstone with acute cholecystitis is one of the most common diseases in the clinic. If the disease is serious, gallbladder gangrene, perforation, and sepsis may be caused. Gallbladder diseases rarely cause thoracic-related complications, especially pleural fistula, which is very rare in clinical practice. PATIENT CONCERNS: A 52-year-old male patient was admitted to the emergency department for 1 month with recurrent right middle and upper abdominal pain. DIAGNOSIS: Computed tomography diagnosis: cholecystitis and peri-inflammation, small abscess around the base of the gallbladder, local peritonitis, and bilateral pleural effusion. INTERVENTIONS: After admission, conservative treatment was given. On the 4th day of admission, the symptoms worsened, and an emergency catheter drainage was performed on the right thoracic cavity to extract 900 mL of dark yellow effusion. After the operation, a large amount of bili-like fluid was continuously drained from the thoracic drainage tube. After the iatrogenic biliary fistula caused by thoracic puncture was excluded, cholecystopleural fistula was considered to be cholecystopleural fistula. On the 6th day of admission, endoscopic retrograde cholangiopancreatography (ERCP) + cholecystography + Oddi sphincterotomy + laminating biliary stent was performed in the emergency department, and cholecystopleural fistula was confirmed during the operation. OUTCOMES: The patient recovered well after surgery, computed tomography examination on the 20th day after surgery indicated that pleural effusion was significantly reduced, and the patient was cured and discharged. The patient returned to the hospital 8 months after the ERCP operation to pull out the bile duct-covered stent. The patient did not complain of any discomfort after the postoperative follow-up for 3 years, and no recurrence of stones, empyema, and other conditions was found. CONCLUSION: Cholecystopleural fistula is one of the serious complications of acute cholecystitis, which is easy to misdiagnose clinically. If the gallbladder inflammation is severe, accompanied by pleural effusion, the pleural effusion is bili-like liquid, or the content of bilirubin is abnormally elevated, the existence of the disease should be considered. Once the diagnosis is clear, active surgical intervention is needed to reduce the occurrence of complications. Endoscopic therapy (ERCP) can be used as both a diagnostic method and an important minimally invasive treatment.

Suppressed testicular macrophage M1 polarization by HDAC5 enforces insensitivity to LPS-elicited blood-testis barrier damage.

Infertility caused by lipopolysaccharide (LPS) exposure due to infection is endangering male fertility worldwide, but the mechanism remains unclear. The blood-testis barrier (BTB) is essential for maintaining spermatogenesis and male fertility. In the present study, we showed that LPS (5.0 mg/kg) treatment markedly down-regulated the expression of BTB-related proteins, expanded the biotin penetration distance and caused histopathological injury in seminiferous tubules in mouse testes. Notably, testicular macrophage M1 polarization induced by LPS seems to be related to BTB damage, which was well confirmed by co-culture of RAW264.7 and TM4 cells in vitro. Interestingly, a low-dose LPS (0.1 mg/kg) pretreatment attenuated down-regulation of BTB-related proteins expression and histopathological injury and shorten biotin penetration distance in seminiferous tubules caused by LPS. Correspondingly, a low-dose LPS pretreatment suppresses testicular macrophage M1 polarization induced by LPS in mouse testes. Further experiments revealed that histone deacetylase 5 (HDAC5) was markedly down-regulated at 2 h and slightly down-regulated at 8 h, but up-regulated at 24 h in mouse testes after LPS treatment. Additionally, low-dose LPS pretreatment against the down-regulation of HDAC5 protein caused by LPS treatment. Notably, the suppressed testicular macrophage M1 polarization by low-dose LPS pretreatment was broken by BRD4354, a specific inhibitor of HDAC5 in vitro. These results suggest suppressed testicular macrophage M1 polarization by HDAC5 enforces insensitivity to LPS-elicited BTB damage.

Endoplasmic Reticulum Membrane Protein Complex Regulates Cancer Stem Cells and is Associated with Sorafenib Resistance in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need for novel therapeutic targets. This study aimed to elucidate the role of endoplasmic reticulum membrane protein complex subunit 1 (EMC1) in HCC progression and its therapeutic potential. Methods: Publicly available sequencing data and biopsy specimens were analyzed to assess EMC's clinical value and functions in HCC. In vitro experiments validated EMC functions, and multiplex immunofluorescence analysis examined EMC-associated sorafenib resistance mechanisms. EMC1 expression was knocked down in HCC cell lines, followed by cell viability, wound healing, and transwell migration assays. Tumor growth and response to sorafenib treatment were evaluated in mouse models. Metabolomic analysis assessed changes in the TCA cycle. Results: EMC genes were aberrantly expressed in HCC, and high EMC1 expression correlated with poorer survival rates. EMC1 disruption enhanced HCC cells' sensitivity to sorafenib, reducing cell viability, increasing apoptosis, and decreasing tumor size and weight. EMC1 maintained cancer cell stemness and promoted M2 macrophage infiltration. Metabolomic analysis revealed significant changes in the TCA cycle, indicating EMC1's role in HCC metabolic reprogramming. Importantly, EMC1 is highly associated with sorafenib resistance, potentially linked to CTNNB1 mutation or activation. Conclusion: EMC1 plays a critical role in regulating the sorafenib resistance in HCC. Targeting EMC1 may improve HCC treatment efficacy.

Pectic polysaccharides from Tartary buckwheat sprouts: Effects of ultrasound-assisted Fenton treatment and mild alkali treatment on their physicochemical characteristics and biological functions.

Buckwheat sprouts are rich in pectic polysaccharides, which possess numerous health-improving benefits. However, the precise structure-activity relationship of pectic polysaccharides from Tartary buckwheat sprouts (TP) is still scant, which ultimately restricts their applications in the food industry. Hence, both ultrasound-assisted Fenton treatment (UAFT) and mild alkali treatment (MATT) were utilized for the modification of TP, and then the effects of physicochemical characteristics of original and modified TPs on their bioactivities were assessed. Our findings reveled that the UAFT treatment could precisely reduce TP's molecular weight, with the levels decreased from 8.191 × 104 Da to 0.957 × 104 Da. Meanwhile, the MATT treatment could precisely reduce TP's esterification degree, with the values decreased from 28.04 % to 4.72 %. Nevertheless, both UAFT and MATT treatments had limited effects on the backbone and branched chain of TP. Moreover, our findings unveiled that the UAFT treatment could notably promote TP's antioxidant, antiglycation, and immunostimulatory effects, while remarkedly reduce TP's anti-hyperlipidemic effect, which were probably owing to that the UAFT treatment obviously reduced TP's molecular weight. Additionally, the MATT treatment could also promote TP's immunostimulatory effect, which was probably attributed to that the MATT treatment significantly decreased TP's esterification degree. Interestingly, the MATT treatment could regulate TP's antioxidant and antiglycation effects, which was probably attributed to that the MATT treatment simultaneously reduced its esterification degree and bound phenolics. Our findings are conducive to understanding TP's structure-activity relationship, and can afford a scientific theoretical basis for the development of functional or healthy products based on TPs. Besides, the UAFT treatment can be a promising approach for the modification of TP to improve its biological functions.

Spatial proteomic profiling elucidates immune determinants of neoadjuvant chemo-immunotherapy in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) presents significant clinical and therapeutic challenges due to its aggressive nature and generally poor prognosis. We initiated a Phase II clinical trial (ChiCTR1900027160) to assess the efficacy of a pioneering neoadjuvant chemo-immunotherapy regimen comprising programmed death-1 (PD-1) blockade (Toripalimab), nanoparticle albumin-bound paclitaxel (nab-paclitaxel), and the oral fluoropyrimidine derivative S-1, in patients with locally advanced ESCC. This study uniquely integrates clinical outcomes with advanced spatial proteomic profiling using Imaging Mass Cytometry (IMC) to elucidate the dynamics within the tumor microenvironment (TME), focusing on the mechanistic interplay of resistance and response. Sixty patients participated, receiving the combination therapy prior to surgical resection. Our findings demonstrated a major pathological response (MPR) in 62% of patients and a pathological complete response (pCR) in 29%. The IMC analysis provided a detailed regional assessment, revealing that the spatial arrangement of immune cells, particularly CD8+ T cells and B cells within tertiary lymphoid structures (TLS), and S100A9+ inflammatory macrophages in fibrotic regions are predictive of therapeutic outcomes. Employing machine learning approaches, such as support vector machine (SVM) and random forest (RF) analysis, we identified critical spatial features linked to drug resistance and developed predictive models for drug response, achieving an area under the curve (AUC) of 97%. These insights underscore the vital role of integrating spatial proteomics into clinical trials to dissect TME dynamics thoroughly, paving the way for personalized and precise cancer treatment strategies in ESCC. This holistic approach not only enhances our understanding of the mechanistic basis behind drug resistance but also sets a robust foundation for optimizing therapeutic interventions in ESCC.

Efficacy and safety of KRAS G12C inhibitor IBI351 monotherapy in patients with advanced non-small cell lung cancer: results from a phase 2 pivotal study.

INTRODUCTION: KRAS G12C mutation is a well-recognized and increasingly promising therapeutic target with significant unmet clinical needs in NSCLC patients. IBI351 is a potent covalent and irreversible inhibitor of KRAS G12C. Here, we present the efficacy and safety of IBI351 from an open-label, single-arm, phase 2 pivotal study. METHODS: Eligible NSCLC patients with KRAS G12C who failed standard therapy were enrolled. IBI351 was orally administered at a dose of 600 mg twice daily. Primary endpoint was confirmed objective response rate (ORR) assessed by independent radiological review committee (IRRC) as per RECIST v1.1. Other endpoints were safety, IRRC-confirmed disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS). RESULTS: As of December 13, 2023, 116 pts were enrolled (ECOG PS 1: 91.4%; brain metastasis: 30.2%; prior treatments with both anti-PD-1/PD-L1 inhibitors and platinum-based chemotherapy: 84.5%). As per IRRC assessment, confirmed ORR was 49.1% (95% CI: 39.7-58.6), and DCR was 90.5% (95% CI: 83.7-95.2). The median DoR was not reached while disease progression or death events occurred in 22 (38.6%) pts, and the median PFS was 9.7 months (95% CI: 5.6-11.0). OS data was immature. Treatment-related adverse events (TRAEs) occurred in 107 (92.2%) pts while 48 (41.4%) pts had grade≥3 TRAEs. Common TRAEs were anemia (44.8%), alanine aminotransferase increased (28.4%), aspartate aminotransferase increased (27.6%), asthenia (26.7%) and protein urine present (25.0%). TRAEs leading to treatment discontinuation occurred in 9 (7.8%) pts. In biomarker evaluable pts (n=95), all pts had positive KRAS G12C in tissue while 72 pts were blood positive and 23 pts were blood negative for KRAS G12C. Pts with KRAS G12C in both blood and tissue had higher tumor burden at baseline (p <0.05) and worse PFS (p <0.05). Tumor mutation profiling identified TP53 (45.3%), STK11 (30.5%) and KEAP1 (21.1%) as the most common genes co-mutated with KRAS G12C. Among 13 genes with mutation frequency ≥5%, mutations of 6 genes (STK11, KEAP1, PIK3CG, POLE, SMAD4, and BRINP3) were significantly associated with worse PFS (p <0.05). Mutation in STK11 also showed significant association with higher tumor burden at baseline and lower response rate (p <0.05). CONCLUSIONS: IBI351 monotherapy demonstrated promising and sustained efficacy with manageable safety, supporting its potential as a new treatment option for KRAS G12C-mutant NSCLC.

Chicken Meal as a Fishmeal Substitute: Effects on Growth, Antioxidants, and Digestive Enzymes in Lithobates catesbeianus.

In pursuit of sustainable aquaculture, this study was performed to evaluate chicken meal as a substitute for fishmeal in bullfrog diets. Three experimental groups were established: a control group (FM) with 20% fishmeal, a CM50 group with 50% replacement (10% fishmeal), and a CM100 group with 100% replacement (0 fishmeal). Bullfrogs were fed for 56 days. The CM50 group exhibited significant increases in total weight gain and survival rate and a notable decrease in feed coefficient (p < 0.05). However, the CM100 group showed contrary effects. Increasing chicken meal substitution correlated with decreased amino acid content in muscle. Notably, the CM50 group demonstrated enhanced activities of antioxidant enzymes (CAT, T-AOC) and elevated gene expression levels (cat, sod, gst, etc.) in muscle and the intestine (p < 0.05), improved intestinal morphology, enhanced digestive enzyme activities (amylase, lipase), and reduced expression of inflammatory factors (il-1ß, il-8, il-17, etc.). Conversely, the CM100 group's indicators regressed to levels similar to or worse than those of the FM group. Therefore, a 50% substitution of fishmeal with chicken meal effectively promoted bullfrog survival, protected the intestines, and enhanced antioxidant capacity, supporting its potential as a fishmeal alternative. However, the adverse outcomes of the CM100 strategy, including growth retardation and reduced amino acid content in muscle, indicate that complete replacement is unsuitable.

The negative association between the docosapentaenoic acid intake and the incidence of AMD based on NHANES 2005-2008.

Introduction: Age-related macular degeneration (AMD) is an ophthalmic disease that causes visual impairment and is one of the leading causes of blindness in the elderly. Fatty acids are essential nutrients required by the body and play a cornerstone role in the life activities of the body. Many studies have reported that fatty acids are involved in the development of AMD. To confirm this association, we conducted the present study. Methods: We analyzed the association between all fatty acid intake and AMD using National Health and Nutrition Examination Survey (NHANES) data from 2005-2008. Quantile regression was performed to assess the effect of fatty acids on AMD at different intake levels. Results: After adjusting for covariates, only saturated fatty acids showed no significant difference between AMD patients and non-AMD patients (23.64 g vs. 26.03 g, p = 0.052). Total fat (70.88 g vs. 78.86 g, p = 0.024), monounsaturated fatty acids (25.87 g vs. 28.95 g, p = 0.019), polyunsaturated fatty acids (15.10 g vs. 17.07 g, p = 0.017) showed significant differences between the two groups. When AMD was considered as an outcome, the association between AMD and docosaentaenoic acid (DPA) was negative in the multivariate logic model (model 1: OR = <0.001, 95% CI = <0.001 ~ 0.734; model 2: OR = <0.001, 95% CI = <0.001 ~ 0.002; model 3: OR = <0.001, 95% CI = <0.001 ~ 0.002). In the quantile regression, DPA was shown to be negatively associated with the presence of AMD only in the fourth quartile in model 2 and model 3 (model 2: OR = <0.001, 95% CI = <0.001 ~ 0.927; model 3: OR = <0.001, 95% CI = <0.001 ~ 0.775). Discussion: Therefore, based on above results, we concluded that DPA intake could prevent the development of AMD.

Exploring the recycled water acceptance based on the technological perspective of UTAUT2: a hybrid analytical approach.

Introduction: The development of advanced sewage technologies empowers the industry to produce high-quality recycled water, which greatly influences human's life and health. Thus, this study investigates the mechanism of individuals' adoption of recycled water from the technology adoption perspective. Methods: Employing the mixed method of structural equation modeling and artificial neural network analysis, we examined a research model developed from the extended Unified Theory of Acceptance and Use of Technology (UTAUT2) framework. To examine the research model, this study employs a leading web-survey company (Sojump) to collect 308 valid samples from the residents in mainland China. Results: The structural equation modeling results verified the associations between the six predictors (performance expectancy, effort expectancy, social influence, facilitating conditions, environmental motivation, and price value), individuals' cognitive and emotional attitudes, and acceptance intention. The artificial neural network analysis validates and complements the structural equation modeling results by unveiling the importance rank of the significant determinants of the acceptance decisions. Discussion: The study provides theoretical implications for recycled water research and useful insights for practitioners and policymakers to reduce the environmental hazards of water scarcity.

α-Ketoglutarate plays an inflammatory inhibitory role by regulating scavenger receptor class a expression through N6-methyladenine methylation during sepsis.

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

Systematic pan-cancer analysis identified RASSF1 as an immunological and prognostic biomarker and validated in lung cancer.

Background: Ras association domain family member 1 (RASSF1) encodes the RASSF1A protein, serving as a scaffold protein situated at the intersection of a complex signalling network. Aims: To evaluate the immunological and prognostic significance of RASSF1 expression in various types of human cancers, with a specific focus on lung cancer. Methods: Differential expression analysis of RASSF1 was conducted based on data from The Cancer Genome Atlas, Genotype-Tissue Expression, and Cancer Cell Line Encyclopaedia databases. Prognostic analysis was performed using the Cox regression test and Kaplan-Meier test. Spearman's test was utilized for correlation analysis. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) gene sets were employed to enrich the associated signaling pathways. Immunohistochemical staining and quantitative real-time PCR were employed to detect protein and mRNA expression levels, respectively. Results: RASSF1 expression was significantly lower in tumour tissues than in normal tissues in most cancers, and Cox regression analysis demonstrated a significant correlation between RASSF1 expression and the prognosis of over 12 types of cancer. Specifically, high RASSF1 expression was associated with poor OS in nine cancer types, including GBMLGG (HR = 4.98, P = 1.2e-31), LGG (HR = 3.72, P = 2.5e-10), and LAML (HR = 1.48, P = 2.4e-3). Further analysis showed that RASSF1 expression was significantly correlated with immune checkpoint- and immune-related genes. Moreover, RASSF1 expression is involved in tumour microenvironment (TME), RNA modification, genomic heterogeneity, and tumour stemness. GO and KEGG analyses showed that RASSF1 was closely related to tumour immune-related pathways. Finally, RASSF1A was moderately correlated with PD-L1 (R = 0.556), and RASSF1A overexpression significantly affected the expression of several genes involved in the Th17 cell differentiation signalling pathway in lung cancer. Conclusions: RASSF1 was differentially expressed in 29 human cancers and played a critical role in tumour immunity. Thus, RASSF1 has the potential to be used as a prognostic marker and reference for achieving more precise immunotherapy, particularly in lung cancer.