High keratin 15 expression reflects favorable prognosis in early cervical cancer patients.

OBJECTIVE: Keratin 15 (KRT15) exhibits inconsistent prognostic roles in different cancers, and its prognostic value in early cervical cancer patients who receive tumor resection remains unknown. This study aimed to assess the relationship of KRT15 expression with prognosis in these patients. METHODS: Totally, 147 early cervical cancer patients who received tumor resection were reviewed in this retrospective study. KRT15 was detected in formalin-fixed paraffin-embedded tumor tissue by immunohistochemistry (IHC). KRT15 IHC scores were computed by multiplying the percentage of positively stained cells (scored as 0-4) and corresponding staining intensity (scored as 0-3), ranging from 0 to 12. RESULTS: Elevated KRT15 IHC score was linked with moderate to well differentiation (P = 0.005), tumor size ≤ 4 cm (P = 0.017), and International Federation of Gynecology and Obstetrics (FIGO) stage Ia/Ib (P < 0.001). KRT15 IHC score was inversely associated with adjuvant radiotherapy (P = 0.025) and adjuvant chemotherapy (P = 0.016). KRT15 IHC score ≥ 1 was linked with increased disease-free survival (DFS) (P = 0.003) and overall survival (OS) (P = 0.049). Meanwhile, KRT15 IHC score ≥ 1 independently predicted increased DFS (hazard ratio = 0.213, P = 0.017), but not OS (P > 0.05). KRT15 IHC score ≥ 3 and KRT15 IHC score ≥ 6 could not predict DFS or OS (all P > 0.05). By subgroup analyses, KRT15 IHC score ≥ 1 forecasted favorable DFS in patients with age > 45 years, human papillomavirus-positive, squamous carcinoma, and tumor size ≤ 4 cm (all P < 0.05). KRT15 IHC score ≥ 1 and KRT15 IHC score ≥ 3 predicted ascended DFS in patients without adjuvant radiotherapy or adjuvant chemotherapy (all P < 0.05). CONCLUSION: High KRT15 expression reflects favorable tumor features and longer survival in early cervical cancer patients who receive tumor resection.

An immunochromatographic strip sensor for rapid and sensitive detection of candesartan, olmesartan medoxomil, and irbesartan in herbal beverages.

Sartans, as a class of antihypertensive drugs, pose a threat to human health when illegally added to herbal beverages. It is crucial to detect sartans in herbal beverages. We have developed a highly sensitive monoclonal antibody against candesartan (CAN), olmesartan medoxomil (OLM), and irbesartan (IRB), with 50% inhibitory concentrations (IC50) that were obtained via indirect enzyme-linked immunosorbent assay (ic-ELISA) as 0.178 ng mL-1, 0.185 ng mL-1, and 0.262 ng mL-1 against CAN, OLM, and IRB, respectively. Based on this monoclonal antibody, we developed a rapid screening method for CAN, OLM, and IRB in herbal beverage samples using an immunochromatographic assay (ICA) strip. Test for 15 minutes after simple and rapid sample pre-treatment and the results of this method can be obtained through naked eye observation. The detection limits (LODs) of the ICA strip for CAN, OLM, and IRB in herbal beverage samples are lower than 0.15 ng mL-1, and the results of the ICA strip and ic-ELISA are consistent in spiked samples and recovery experiments. Therefore, this method can quickly, efficiently, and reliably achieve high-throughput on-site rapid detection of illegally added CAN, OLM, and IRB in herbal beverages.

Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration.

PURPOSE: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown. METHODS: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry. RESULTS: The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8. CONCLUSION: The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.

On-site rapid detection of perfluorooctanoic acid by visual immunochromatographic strip biosensor in domestic water and real human samples.

The International Agency for Research on Cancer (IARC) classifies PFOA as a Class 1 carcinogen. Here, a new naked-eye PFOA immunochromographic strip was developed to recognize PFOA in domestic water and real human samples within 10 min based on a novel custom designed anti-PFOA monoclonal antibody (mAb) 2A3, which was firstly an immune rapid detection method for PFOA has been proposed. Using computer simulation techniques such as quantum computing to assist in designing the structural formula of PFOA semi antigen, which hapten was firstly proposed. The half maximal inhibitory concentration of PFOA monoclonal antibody (mAb) 2A3 was 2.4 µg/mL. Using mAb 2A3, we developed an immunochromatographic strip (ICS) for detecting PFOA in real samples. The developed method generated results in 10 min, with visual detection limits of 20, 20, and 200 µg/mL and limit of detection of 50, 200, and 500 µg/mL for water, blood and urine samples, respectively. The established ICS and indirect competitive enzyme-linked immunosorbent assay were used to analyze the actual samples, and the results were confirmed by LC-MS/MS. Our study findings showed that the ICS and ic-ELISA can quickly detect PFOA in actual samples.

The tsRNAs (tRFdb-3013a/b) serve as novel biomarkers for colon adenocarcinomas.

The tsRNAs (tRNA-derived small RNAs) are a novel class of small non-coding RNAs derived from transfer-RNAs. Colon adenocarcinoma (COAD) is the most malignant intestinal tumor. This study focused on the identification and characterization of tsRNA biomarkers in colon adenocarcinomas. Data processing and bioinformatic analyses were performed with the packages of R and Python software. The cell proliferation, migration and invasion abilities were determined by CCK-8 and transwell assays. Luciferase reporter assay was used to test the binding of tsRNA with its target genes. With computational methods, we identified the tRNA fragments profiles within COAD datasets, and discriminated forty-two differentially expressed tsRNAs between paired colon adenocarcinomas and non-tumor controls. Among the fragments derived from the 3' end of tRNA-His-GUG (a histidyl-transfer-RNA), tRFdb-3013a and tRFdb-3013b (tRFdb-3013a/b) were notably decreased in colon and rectum adenocarcinomas, especially, tRFdb-3013a/b might tend to be down-regulated in patients with lymphatic or vascular invasion present. The clinical survival of colorectal adenocarcinoma patients with low tRFdb-3013a/b expression was significantly worse than that of high expression patients. In colon adenocarcinoma cells, tRFdb-3013a could have inhibited cell proliferations, and reduced cell migration and invasion abilities. The enrichment analyses showed that most of tRFdb-3013a correlated-genes were enriched in the extracellular matrix associated GO terms, phagosome pathway, and a GSEA molecular signature pathway. Additionally, the 3'UTR of ST3GAL1 mRNA was predicted to contain the binding site of tRFdb-3013a/b, tRFdb-3013a/b might directly target and regulate ST3GAL1 expression in colon adenocarcinomas. These results suggested that tRFdb-3013a/b might serve as novel biomarkers for diagnosis and prognosis of colon adenocarcinomas, and act a key player in the progression of colon adenocarcinomas.

Oct4 activates IL-17A to orchestrate M2 macrophage polarization and cervical cancer metastasis.

BACKGROUND: Cervical cancer is a common malignant tumor in the female. Interleukin (IL)-17A is a proinflammatory factor and exerts a vital function in inflammatory diseases and cancers. M2 macrophage has been confirmed to promote tumor development. Nevertheless, it is not yet known whether IL-17A facilitates cervical cancer development by inducing M2 macrophage polarization. Therefore, this study was conducted to investigate the regulatory effect of IL-17A on M2 macrophage polarization and the underlying mechanism in cervical cancer development. METHODS: RT-qPCR was utilized for testing IL-17A expression in cancer tissues and cells. Flow cytometry was applied to evaluate the M1 or M2 macrophage polarization. Cell proliferative, migratory, and invasive capabilities were measured through colony formation and transwell assays. ChIP and luciferase reporter assays were applied to determine the interaction between IL-17A and octamer-binding transcription factor 4 (OCT4). RESULTS: IL-17A expression and concentration were high in metastatic tissues and cells of cervical cancer. IL-17A was found to facilitate M2 macrophage polarization in cervical cancer. Furthermore, IL-17A facilitated the macrophage-mediated promotion of cervical cancer cell proliferative, migratory, and invasive capabilities. Mechanistic assays manifested that Oct4 binds to and transcriptionally activated IL-17A in cervical cancer cells. Furthermore, Oct4 promoted cervical cancer cell malignant phenotype and M2 macrophage polarization by activating the p38 pathway that, in turn, upregulated IL-17A. Additionally, in vivo experiments confirmed that Oct4 knockdown reduced tumor growth and metastasis. CONCLUSION: Oct4 triggers IL-17A to facilitate the polarization of M2 macrophages, which promotes cervical cancer cell metastasis.

Volume-based subglottic secretion drainage: a randomized controlled trial.

Background: This study proposed to explore individual management mode for patients with subglottic secretion drainage. Methods: Randomly chosen within the hospital ICU 68 patients from 7 April to 15 June 2023, all the patients randomly assigned to the control group or observation group, and control group adopts the model of intermittent drainage management, observation group based on the volume of subglottic secretion in patients with individualized management, and then analysis the two groups of patients clinical trial results. Results: The clinical trial results showed that there were statistically significant differences (P<0.05) between the control group and the observation group in the incidence of tube blockage events (11 vs. 2), average diurnal pumping frequency (9 vs. 7, 5 vs. 4) between the two groups and the patient satisfaction scores (6 vs. 7), In the partial mucosa injure (22 vs 19) and VAP (5 vs. 1) there were no statistically significant difference (P>0.05). Although there was no statistically significant difference (P>0.05) in the average aspiration volume (12.68±3.41 vs. 12.19±2.68, 8 vs. 8) between the two groups, but the management mode of the observation group indicated that based on patient secretion volume was more consistent with the characteristics of the body's diurnal metabolic differences, because there was a big difference between the average total amount of daytime and nighttime suction between the two groups. Conclusion: Individualized management based on the volume of subglottic secretions produced by patients can further optimize the airway management of patients and reduce the risk of adverse events of subglottic secretions aspiration.

Cancer-associated fibroblasts contributed to hepatocellular carcinoma recurrence and metastasis via CD36-mediated fatty-acid metabolic reprogramming.

Cancer-associated fibroblasts (CAFs) are the main components in the tumor microenvironment. Tumors activate fibroblasts from quiescent state into activated state by secreting cytokines, and activated CAFs may in turn promote tumor progression and metastasis. Therefore, studies targeting CAFs could enrich the therapeutic options for tumor treatment. In this study, we demonstrate that the content of lipid droplets and the expression of autophagosomes were higher in CAFs than in peri-tumor fibroblasts (PTFs), which was inhibited by 5-(tetradecyloxy)-2-furoic acid(TOFA). The expression of CD36 in CAFs was higher than that in PTFs at both mRNA and protein levels. Inhibition of CD36 activity using either the CD36 inhibitor SSO or siRNA had a significant negative impact on the proliferation and migration abilities of CAFs, which was associated with reduced levels of relevant activated genes (α-SMA, FAP, Vimentin) and cytokines (IL-6, TGF-ß and VEGF-α). SSO also inhibited HCC growth and tumorigenesis in nude mice orthotopically implanted with CAFs and HCC cells. Our data further show that CD36+CAFs affected the expression of PD-1 in CTLs leading to CTL exhaustion, and that patients with high CD36 expression in CAFs were correlated with shorter overall survival (OS). Together, our data demonstrate that CAFs were active in lipid metabolism with increased lipid content and lipophagy activity. CD36 may play a key role in the regulation of the biological behaviors of CAFs, which may influence the proliferation and migration of tumor cells by reprograming the lipid metabolism in tumor cells. Thus, CD36 could be an effective therapeutic target for the treatment of HCC.

Nonalcoholic Fatty Liver Disease Development in Male Mice upon Exposure to Flubendiamide.

Flubendiamide (FLU), a widely used diamide insecticide, has been observed to potentiate adipogenesis in 3T3-L1 preadipocytes in vitro. Whether exposure to FLU disrupts hepatic lipid homeostasis in mammals and induces visceral obesity, however, remains unclear. The aim of this study was to assess the effects of FLU when administered orally to male C57BL/6J mice under normal diet (ND) and high-fat diet (HFD) conditions. FLU accumulated at higher levels in the tissues of the HFD group than those of the ND group, indicating that an HFD contributed to the accumulation of lipophilic pesticides in vivo. Notably, FLU (logP = 4.14) is highly lipophilic and easily accumulates in fat. Exposure to FLU had opposing effects on the lipid metabolism of the liver in the ND and HFD groups. Liver triacylglycerol levels in the ND group were reduced, while those in the HFD group were increased, resulting in more severe hepatic steatosis. More lipid accumulation was also observed in HepG2 cells exposed to FLU. Changes in hepatic lipid deposition in vivo occurred as the enhanced transcriptional regulation of the genes involved in lipid uptake, de novo lipogenesis, and fatty acid ß-oxidation (FAO). Moreover, an excessive increase in FAO caused oxidative stress, which in turn exacerbated the inflammation of the liver. This study revealed the disruptive effect of FLU exposure on hepatic lipid homeostasis, which may facilitate the triggering of nonalcoholic fatty liver disease in HFD-fed mice.

Association between high-density lipoprotein cholesterol and lumbar bone mineral density in Chinese: a large cross-sectional study.

BACKGROUND: The association between lipid and bone metabolism, particularly the role of high-density lipoprotein cholesterol (HDL-C) in regulating bone mineral density (BMD), is of significant interest. Despite numerous studies, findings on this relationship remain inconclusive, especially since evidence from large, sexually diverse Chinese populations is sparse. This study, therefore, investigates the correlation between HDL-C and lumbar BMD in people of different genders using extensive population-based data from physical examinations conducted in China. METHODS: Data from a cross-sectional survey involving 20,351 individuals aged > = 20 years drawn from medical records of health check-ups at the Health Management Centre of the Henan Provincial People's Hospital formed the basis of this study. The primary objective was to determine the correlation between HDL-C levels and lumbar BMD across genders. The analysis methodology included demographic data analysis, one-way ANOVA, subgroup analyses, multifactorial regression equations, smoothed curve fitting, and threshold and saturation effect analyses. RESULTS: Multifactorial regression analysis revealed a significant inverse relationship between HDL-C levels and lumbar BMD in both sexes, controlling for potential confounders (Male: ß = -8.77, 95% CI -11.65 to -5.88, P < 0.001; Female: ß = -4.77, 95% CI -8.63 to -0.90, P = 0.015). Subgroup and threshold saturation effect analyses indicated a stronger association in males, showing that increased HDL-C correlates with reduced lumbar BMD irrespective of age and body mass index (BMI). The most significant effect was observed in males with BMI > 28 kg/m2 and HDL-C > 1.45 mmol/L and in females with a BMI between 24 and 28 kg/m2. CONCLUSION: Elevated HDL-C is associated with decreased bone mass, particularly in obese males. These findings indicate that individuals with high HDL-C levels should receive careful clinical monitoring to mitigate osteoporosis risk. TRIAL REGISTRATION: The research protocol received ethics approval from the Ethics Committee at Beijing Jishuitan Hospital, in conformity with the Declaration of Helsinki guidelines (No. 2015-12-02). These data are a contribution of the China Health Quantitative CT Big Data Research team, registered at clinicaltrials.gov (code: NCT03699228).

Curative Effect Analysis of Endoscopic Submucosal Dissection in Giant Laterally Spreading Rectal Tumors.

GOAL: The objective of this study was to investigate the clinical efficacy of endoscopic submucosal dissection (ESD) in the treatment of giant lateral developing rectal-type tumors (laterally spreading tumors, LSTs). BACKGROUND: There are no specialized studies on the efficacy of ESD in the treatment of LSTs measuring >5 cm in diameter, surgery was often used in the past, but it has the disadvantages of large trauma, many complications, and high cost. METHODS: The data of 185 patients with rectal LSTs who had undergone ESD in the digestive endoscopy center of our hospital from January 2012 to June 2020 were retrospectively analyzed. Based on the size of the lesions, the patients were divided into 2 groups: diameter ≤5 cm (110 cases) and diameter >5 cm (75 cases), and we summarized and analyzed the en bloc resection rate, curative resection rate, procedure time, muscle injury, bleeding, perforation, postoperative stricture, and recurrence. RESULTS: There was no difference in the en bloc resection rate and R0 resection rate between the 2 groups ( P =0.531). Moreover, there was no difference in the incidence of delayed perforation, postoperative stenosis, and recurrence, but the incidence of delayed bleeding was significantly higher in the giant LST group than the small LST group ( P =0.001). Moreover, for giant rectal LSTs, the growth pattern of the lesion, JNET classification, and the extent of postoperative mucosal defect do not significantly affect the efficacy of ESD. It is worth mentioning that the operation time was longer in the group with a diameter >5 cm, in which perforation was more frequent and the muscle layer was more likely to be injured during ESD ( P <0.001). The muscle injury during ESD was mainly related to the diameter of the lesion, the crossing the rectal pouch, and the operation time. CONCLUSIONS: The use of ESD to treat giant rectal LSTs (>5 cm) is relatively difficult and can easily lead to intraoperative muscle injury, perforation, and late postoperative bleeding. However, if active intervention is performed, patients can still achieve good efficacy and prognosis, which can be applied in hospitals with certain conditions.

Astragaloside IV Alleviates Depression in Rats by Modulating Intestinal Microbiota, T-Immune Balance, and Metabolome.

This study aims to explore the effects of Astragaloside IV (AS-IV) on abnormal behaviors, intestinal microbiota, intestinal T-immune balance, and fecal metabolism of a model of depression in rats. Herein, we integrally applied 16S rRNA sequencing, molecular biological techniques, and 1H NMR-based fecal metabolomics to demonstrate the antidepression activity of AS-IV. The results suggested that AS-IV regulated the depression-like behaviors of rats, which are presented by an increase of body weight, upregulation of sucrose preference rates, and a decrease of immobility time. Additionally, AS-IV increased the abundances of beneficial bacteria (Lactobacillus and Oscillospira) in a model of depression in rats. Moreover, AS-IV regulated significantly the imbalance of Th17/Treg cells, and the abnormal contents of both anti-inflammatory factors and pro-inflammatory factors. Besides, fecal metabolomics showed that AS-IV improved the abnormal levels of short-chain fatty acids and amino acids. Collectively, our research supplemented new data, supporting the potential of AS-IV as an effective diet or diet composition to improve depression-like behaviors, dysfunctions of microbiota, imbalance of T immune, and the abnormality of fecal metabolome. However, the causality of the other actions was not proven because of the experimental design and the methodology used. The current findings suggest that AS-IV could function as a promising diet or diet composition to alleviate depressed symptoms.

VEPH1 suppresses the progression of gastric cancer by regulating the Hippo-YAP signalling pathway.

BACKGROUND: Ventricular zone-expressed PH domain-containing protein homologue 1 (VEPH1) is a recently discovered intracellular adaptor protein that plays an important role in human development. It has been reported that VEPH1 is closely related to the process of cellular malignancy, but its role in gastric cancer has not been elucidated. This study investigated the expression and function of VEPH1 in human gastric cancer (GC). METHODS: We performed qRT‒PCR, Western blotting, and immunostaining assays in GC tissue samples to evaluate VEPH1 expression. Functional experiments were used to measure the malignancy of GC cells. A subcutaneous tumorigenesis model and peritoneal graft tumour model were established in BALB/c mice to determine tumour growth and metastasis in vivo. RESULTS: VEPH1 expression is decreased in GC and correlates with the overall survival rates of GC patients. VEPH1 inhibits GC cell proliferation, migration, and invasion in vitro and suppresses tumour growth and metastasis in vivo. VEPH1 regulates the function of GC cells by inhibiting the Hippo-YAP signalling pathway, and YAP/TAZ inhibitor-1 treatment reverses the VEPH1 knockdown-mediated increase in the proliferation, migration and invasion of GC cells in vitro. Loss of VEPH1 is associated with increased YAP activity and accelerated epithelial-mesenchymal transition (EMT) in GC. CONCLUSION: VEPH1 inhibited GC cell proliferation, migration, and invasion in vitro and in vivo and exerted its antitumour effects by inhibiting the Hippo-YAP signalling pathway and EMT process in GC.

MiR-5590-3p inhibits the proliferation and invasion of ovarian cancer cells through mediating the Wnt/ß-catenin signaling pathway by targeting TNIK.

MicroRNAs (miRNAs) are crucial regulatory molecules involved in diverse biological processes and human diseases, including ovarian cancer (OC). miR-5590-3p has been involved in multiple malignant solid tumors, but its exact role in the progression of OC is largely unknown. This study mainly focuses on how miR-5590-3p works in OC and illuminating the underlying mechanism. We found that miR-5590-3p was significantly downregulated in human OC cell lines and patient tissues. Cell counting 8 (CCK-8) and Transwell assays proved that overexpression or inhibition of miR-5590-3p suppressed or promoted cell proliferation and cell invasion. Subsequently, TNIK was identified as a target of miR-5590-3p. Silence of TNIK by small interfering RNA (siRNA) reversed the increasing effect of miR-5590-3p inhibition on cell proliferation and invasion in OC cell lines. Furthermore, our results showed that the Wnt/ß-catenin pathway was inhibited by its specific inhibitor XAV-939, but miR-5590-3p inhibitor and adenoviral TNIK overexpression vector (Ad-TNIK) reactivated the activation of Wnt/ß-catenin signaling and increased cell malignancy. Lastly, tumorigenicity assay demonstrated that inhibition of miR-5590-3p increased tumor volume and weight in vivo. In conclusion, miR-5590-3p may function as a cancer suppressor gene in OC progression through the Wnt/ß-catenin signaling by transcriptionally suppressing TNIK expression, which provides a potential therapeutic approach for ovarian cancer treatment.

Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous and lethal hepatobiliary tumor with few therapeutic strategies. The metabolic reprogramming of tumor cells plays an essential role in the development of tumors, while the metabolic molecular classification of iCCA is largely unknown. Here, we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients, hoping to provide a novel perspective to understand and treat iCCA. METHODS: We performed integrated multiomics analysis in 116 iCCA samples, including whole-exome sequencing, bulk RNA-sequencing and proteome analysis. Based on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models, the metabolic subtype of iCCA was determined. Survival and prognostic gene analyses were used to compare overall survival (OS) differences between metabolic subtypes. Cell proliferation analysis, 5-ethynyl-2'-deoxyuridine (EdU) assay, colony formation assay, RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinase α (DGKA) in iCCA cells. RESULTS: Three metabolic subtypes (S1-S3) with subtype-specific biomarkers of iCCA were identified. These metabolic subtypes presented with distinct prognoses, metabolic features, immune microenvironments, and genetic alterations. The S2 subtype with the worst survival showed the activation of some special metabolic processes, immune-suppressed microenvironment and Kirsten rat sarcoma viral oncogene homolog (KRAS)/AT-rich interactive domain 1A (ARID1A) mutations. Among the S2 subtype-specific upregulated proteins, DGKA was further identified as a potential drug target for iCCA, which promoted cell proliferation by enhancing phosphatidic acid (PA) metabolism and activating mitogen-activated protein kinase (MAPK) signaling. CONCLUSION: Via multiomics analyses, we identified three metabolic subtypes of iCCA, revealing that the S2 subtype exhibited the poorest survival outcomes. We further identified DGKA as a potential target for the S2 subtype.

Thorough Optimization for Intrinsically Stretchable Organic Photovoltaics.

The development of intrinsically stretchable organic photovoltaics (is-OPVs) with a high efficiency is of significance for practical application. However, their efficiencies lag far behind those of rigid or even flexible counterparts. To address this issue, an advanced top-illuminated OPV is designed and fabricated, which is intrinsically stretchable and has a high performance, through systematic optimizations from material to device. First, the stretchability of the active layer is largely increased by adding a low-elastic-modulus elastomer of styrene-ethylene-propylene-styrene tri-block copolymer (SEPS). Second, the stretchability and conductivity of the opaque electrode are enhanced by a conductive polymer/metal (denoted as M-PH1000@Ag) composite electrode strategy. Third, the optical and electrical properties of a sliver nanowire transparent electrode are improved by a solvent vapor annealing strategy. High-performance is-OPVs are successfully fabricated with a top-illuminated structure, which provides a record-high efficiency of 16.23%. Additionally, by incorporating 5-10% elastomer, a balance between the efficiency and stretchability of the is-OPVs is achieved. This study provides valuable insights into material and device optimizations for high-efficiency is-OPVs, with a low-cost production and excellent stretchability, which indicates a high potential for future applications of OPVs.

Iron-incorporated metal-organic frameworks for oxidative cleavage of trans-anethole to p-anisaldehyde.

An iron-incorporated Zn-MOF catalyst Zn-bpydc·Fe was fabricated for the oxidative cleavage of trans-anethole to p-anisaldehyde under facile conditions, under 1 atm of O2. The Fe coordinated bipyridine serves as the catalytically active center inside the structural skeleton of Zn-MOFs. This work affords a new avenue for the mild oxidation of olefins.

Short-Term Exposure to Nitrogen Dioxide Modifies Genetic Predisposition in Blood Lipid and Fasting Plasma Glucose: A Pedigree-Based Study.

(1) Background: Previous studies suggest that exposure to nitrogen dioxide (NO2) has a negative impact on health. But few studies have explored the association between NO2 and blood lipids or fasting plasma glucose (FPG), as well as gene-air pollution interactions. This study aims to fill this knowledge gap based on a pedigree cohort in southern China. (2) Methods: Employing a pedigree-based design, 1563 individuals from 452 families participated in this study. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and FPG were measured. We investigated the associations between short-term NO2 exposure and lipid profiles or FPG using linear mixed regression models. The genotype-environment interaction (GenoXE) for each trait was estimated using variance component models. (3) Results: NO2 was inversely associated with HDLC but directly associated with TG and FPG. The results showed that each 1 µg/m3 increase in NO2 on day lag0 corresponded to a 1.926% (95%CI: 1.428-2.421%) decrease in HDLC and a 1.400% (95%CI: 0.341-2.470%) increase in FPG. Moreover, we observed a significant genotype-NO2 interaction with HDLC and FPG. (4) Conclusion: This study highlighted the association between NO2 exposure and blood lipid profiles or FPG. Additionally, our investigation suggested the presence of genotype-NO2 interactions in HDLC and FPG, indicating potential loci-specific interaction effects. These findings have the potential to inform and enhance the interpretation of studies that are focused on specific gene-environment interactions.

TRAF6 triggers Mycobacterium-infected host autophagy through Rab7 ubiquitination.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an E3 ubiquitin ligase that is extensively involved in the autophagy process by interacting with diverse autophagy initiation and autophagosome maturation molecules. However, whether TRAF6 interacts with lysosomal proteins to regulate Mycobacterium-induced autophagy has not been completely characterized. Herein, the present study showed that TRAF6 interacted with lysosomal key proteins Rab7 through RING domain which caused Rab7 ubiquitination and subsequently ubiquitinated Rab7 binds to STX17 (syntaxin 17, a SNARE protein that is essential for mature autophagosome), and thus promoted the fusion of autophagosomes and lysosomes. Furthermore, TRAF6 enhanced the initiation and formation of autophagosomes in Mycobacterium-induced autophagy in both BMDMs and RAW264.7 cells, as evidenced by autophagic flux, colocalization of LC3 and BCG, autophagy rates, and autophagy-associated protein expression. Noteworthy to mention, TRAF6 deficiency exacerbated lung injury and promoted BCG survival. Taken together, these results identify novel molecular and cellular mechanisms by which TRAF6 positively regulates Mycobacterium-induced autophagy.

In Situ Encapsulation of Cytochrome c within Covalent Organic Frames Using Deep Eutectic Solvents under Ambient Conditions.

In situ integration of enzymes with covalent organic frameworks (COFs) to form hybrid biocatalysts is both significant and challenging. In this study, we present an innovative strategy employing deep eutectic solvents (DESs) to synergistically synthesize COFs and shield cytochrome c (Cyt c). By utilizing DESs as reaction solvents in combination with water, we successfully achieved rapid and in situ encapsulation of Cyt c within COFs (specifically COF-TAPT-TFB) under ambient conditions. The resulting Cyt c@COF-TAPT-TFB composite demonstrates a remarkable preservation of enzymatic activity. This encapsulation strategy also imparts exceptional resistance to organic solvents and exhibits impressive recycling stability. Additionally, the enhanced catalytic efficiency of Cyt c@COF-TAPT-TFB in a photoenzymatic cascade reaction is also showcased.