Effects of dietary 5-aminolevulinic acid on growth performance and nonspecific immunity of Litopenaeus vannamei, as determined by transcriptomic analysis.

5-aminolevulinic acid (5-ALA) is an endogenous non-protein amino acid that is frequently used in modern agriculture. This study set out to determine how dietary 5-ALA affected the nonspecific immunity and growth performance of Litopenaeus vannamei. The shrimp were supplemented with dietary 5-ALA at 0, 15, 30, 45, and 60 mg/kg for three months. Transcriptome data of the control group and the group supplemented with 45 mg/kg dietary 5-ALA were obtained using transcriptome sequencing. 592 DEGs were identified, of which 426 were up-regulated and 166 were down-regulated. The pathways and genes associated with growth performance and nonspecific immunity were confirmed using qRT-PCR. The highest survival rate, body length growth rate, and weight gain values were observed in shrimp fed diets containing 45 mg/kg 5-ALA. L. vannamei in this group had a significantly higher total hemocyte count, phagocytosis rate and respiratory burst value than those in the control group. High doses of dietary 5-ALA (45 mg/kg, 60 mg/kg) significantly increased the activities of catalase, superoxide dismutase, oxidized glutathione, glutathione-peroxidase, phenoloxidase, lysozyme, acid phosphatase, and alkaline phosphatase. At the transcriptional level, dietary 5-ALA significantly up-regulated the expression levels of antioxidant immune-related genes. The optimal concentration of 5-ALA supplementation was 39.43 mg/kg, as indicated by a broken line regression. Our study suggested that dietary 5-ALA positively impacts the growth and nonspecific immunity of L. vannamei, providing a novel theoretical basis for further research into 5-ALA as a dietary supplement.

Context-dependent T-BOX transcription factor family: from biology to targeted therapy.

T-BOX factors belong to an evolutionarily conserved family of transcription factors. T-BOX factors not only play key roles in growth and development but are also involved in immunity, cancer initiation, and progression. Moreover, the same T-BOX molecule exhibits different or even opposite effects in various developmental processes and tumor microenvironments. Understanding the multiple roles of context-dependent T-BOX factors in malignancies is vital for uncovering the potential of T-BOX-targeted cancer therapy. We summarize the physiological roles of T-BOX factors in different developmental processes and their pathological roles observed when their expression is dysregulated. We also discuss their regulatory roles in tumor immune microenvironment (TIME) and the newly arising questions that remain unresolved. This review will help in systematically and comprehensively understanding the vital role of the T-BOX transcription factor family in tumor physiology, pathology, and immunity. The intention is to provide valuable information to support the development of T-BOX-targeted therapy.

[18F]FAPI adds value to [18F]FDG PET/CT for diagnosing lymph node metastases in stage I-IIIA non-small cell lung cancer: a prospective study.

BACKGROUND: This study investigates the value of fluorine 18 ([18F])-labeled fibroblast activation protein inhibitor (FAPI) for lymph node (LN) metastases in patients with stage I-IIIA non-small cell lung cancer (NSCLC). METHODS: From November 2021 to October 2022, 53 patients with stage I-IIIA NSCLC who underwent radical resection were prospectively included. [18F]-fluorodeoxyglucose (FDG) and [18F]FAPI examinations were performed within one week. LN staging was validated using surgical and pathological findings. [18F]FDG and [18F]FAPI uptake was compared using the Wilcoxon signed-ranks test. Furthermore, the diagnostic value of nodal groups was investigated. RESULTS: In 53 patients (median age, 64 years, range: 31-76 years), the specificity of [18F]FAPI for detecting LN metastasis was significantly higher than that of [18F]FDG (P < 0.001). High LN risk category, greater LN short-axis dimension(≥ 1.0 cm), absence of LN calcification or high-attenuation, and higher LN FDG SUVmax (≥ 10.1) were risk factors for LN metastasis(P < 0.05). The concurrence of these four risk factors accurately predicted LN metastases (Positive Predictive Value [PPV] 100%), whereas the presence of one to three risk factors was unable to accurately discriminate the nature of LNs (PPV 21.7%). Adding [18F]FAPI in this circumstance improved the diagnostic value. LNs with an [18F]FAPI SUVmax<6.2 were diagnosed as benign (Negative Predictive Value 93.8%), and LNs with an [18F]FAPI SUVmax≥6.2 without calcification or high-attenuation were diagnosed as LN metastasis (PPV 87.5%). Ultimately, the integration of [18F]FDG and [18F]FAPI PET/CT resulted in the highest accuracy for N stage (83.0%) and clinical decision revisions for 29 patients. CONCLUSION: In patients with stage I-IIIA NSCLC, [18F]FAPI contributed additional valuable information to reduce LN diagnostic uncertainties after [18F]FDG PET/CT. Integrating [18F]FDG and [18F]FAPI PET/CT resulted in more precise clinical decisions. TRIAL REGISTRATION: The Chinese Clinical Trial Registry: ChiCTR2100044944 (Registered: 1 April 2021, https://www.chictr.org.cn/showprojEN.html?proj=123995 ).

The quality of guidelines on the pancreatic perioperative enhanced recovery after surgery: a systematic quality appraisal using AGREE II instrument.

PURPOSE: To evaluate the quality of guidelines on the pancreatic perioperative enhanced recovery after surgery both domestically and internationally, providing reference and reference for clinical practice. METHODS: Systemically retrieved in the guideline websites, professional association websites and databases, such as up to date, BMJ Best Practice, PubMed, Embase, The Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang Data, China Science and Technology Journal Database(VIP), China Biology Medicine disc (CBMdisc), Medlive, Guidelines International Network(GIN), National Guideline Clearinghouse(NGC), National Institute for Health and Care Excellence(NICE), Registered Nurses Association of Ontario(RNAO), Scottish Intercollegiate Guidelines Network(SIGN), Joanna Briggs Institute Library(JBI), including guidelines and expert consensus on enhanced postsurgical recovery in pancreatic surgery published as of December 20, 2023. The Appraisal of Guidelines for Research and Evaluation II(AGREE II) tool was applied to evaluate the quality of the guidelines by four assessors. RESULTS: This study included seven guidelines, all of which were rated as Grade B in terms of quality, with ICC coefficients ranging from 0.752 to 0.884, indicating a high level of consistency. CONCLUSION: When formulating guidelines in the future, it is recommended to use AGREE II as a reference, emphasizing the standardization of the guideline development process and methods, fully considering patients' values and preferences, focusing on the applicability of the guidelines, and striving to create high-quality evidence-based recommendations.

In vivo staging of colitis, adenoma and carcinoma in CRC progression by combination of H4R/DRD4-targeted fluorescent probes.

Colorectal cancer (CRC) is the third most prevalent malignancy and the second leading cause of cancer-related mortality worldwide. Currently, CRC staging heavily relies on invasive surgical procedures for in vitro pathological analysis, which entails long detection cycles and increases the risk of metastasis. There is an urgent need for specific biomarkers to classify adenomas and cancers, while early in vivo staging detection could potentially reduce mortality and morbidity rates. This study focused on Type IV histamine receptor (H4R), which is highly expressed only in the inflammatory stage, and Dopamine receptor D4 (DRD4), which is highly expressed in colorectal adenoma and carcinoma stages. Fluorescent targeted molecular probes H4R-Cy5 and DRD4-M were constructed respectively. The in vitro cell level proves that H4R-Cy5 only has high specificity for RAW264.7 cells, and DRD4-M only has good affinity for HT29 cells. In inflammation-HT29 subcutaneous tumors, H4R-Cy5 and DRD4-M can target inflammation and tumor lesions respectively. In addition, this study is the first to combine the two probes to explore the feasibility of in vivo non-invasive staging on CRC mouse models. The results show that H4R-Cy5 can distinguish and identify the stages of inflammation in vivo, and the DRD4-M probe can accurately identify the stages of colorectal adenoma and carcinoma in vivo. The combination of these two probes can achieve precise non-invasive staging of colitis, adenoma and carcinoma, which is a major advance in the development of accurate diagnostic methods for colorectal precancerous lesions and has important implications for the selection of treatment strategies.

A new attempt to remove toluene using nickel-iron bimetallic particle electrode reactor.

A new attempt of removing toluene waste gas using a three-dimensional electrode reaction device with nickel-iron bimetallic particle electrode is presented in this paper. The particle electrode was prepared by a simple liquid phase reduction method. Through bimetal modification, the particle electrode mass transfer rate is increased to 1.29 times, and the degradation efficiency of the reactor is increased by nearly 40%, which makes it possible to remove toluene waste gas by other electrochemical methods in addition to plasma method. The removal efficiency of the particle electrode can be stabilized at more than 80% after 5 cycles (50 h). At the same time, the relationship between independent working parameters and dependent variables is analyzed using the central composite design, and the operating parameters are optimized. Based on this study, the removal mechanism and possible degradation pathway of toluene were investigated. This study provides a supplement to the possibility and theoretical basis of new technology application for electrocatalytic oxidation removal of VOCs.

Effects of Dietary Melatonin on Antioxidant Capacity, Immune Defense, and Intestinal Microbiota in Red Swamp Crayfish (Procambarus clarkii).

The aim of this study was to investigate the effects of melatonin (MT) feed supplementation on the antioxidant capacity, immune defense, and intestinal flora in Procambarus clarkii (P. clarkii). Six groups of P. clarkii were fed test feeds containing different levels of MT: 0 mg/kg (control), 22.5, 41.2, 82.7, 165.1, and 329.2 mg/kg for a duration of 2 months. The specific growth rate, hepatosomatic index, and condition factor were recorded highest in the test group of shrimp fed an MT concentration of 165.1 mg/kg. Compared to the control group, the rate of apoptosis was lower in hepatopancreas cells of P. clarkii supplemented with high concentrations of MT. Analyses of antioxidant capacity and immune-response-related enzymes in the hepatopancreas indicated that dietary supplementation of MT significantly augmented both the antioxidant system and immune responses. Dietary MT supplementation significantly increased the expression levels of antioxidant-immunity-related genes and decreased the expression levels of genes linked to apoptosis. Dietary MT was associated with an elevation in the abundance of the Firmicutes and a reduction in the abundance of the Proteobacteria in the intestines; besides, resulting in an increase in the abundance of beneficial bacteria, such as Lactobacilli. The broken-line model indicated that the suitable MT concentration was 154.09-157.09 mg/kg. MT supplementation enhanced the growth performance of P. clarkii, exerting a positive influence on the intestinal microbiota, and bolstered both immune response and disease resistance. Thus, this study offered novel perspectives regarding the application of dietary MT supplementation within the aquaculture field.

Dietary lipid supplementation alleviated the impacts of polystyrene nanoplastic exposure in Litopenaeus vannamei.

The widespread occurrence of nanoplastic (NP) pollution in the environment is a growing concern, and its presence poses a potential threat to cultured aquatic animals. Previously, we found that NPs can significantly affect the lipid metabolism of shrimp. However, relevant reports about the effects of increasing dietary lipid levels on NP toxicity are lacking. Therefore, we explored the effects of dietary supplementation with different lipid levels on the growth and lipid metabolism of Pacific white shrimp (Litopenaeus vannamei). We cultured L. vannamei at three dietary lipid levels (3 %, 6 %, and 9 %) and three NP concentrations (0, 1, and 3 mg/L) for 2 months. We evaluated the effects of lipid levels on growth indexes, hepatopancreas morphological structure, lipid metabolism-related enzyme activity, and gene expression of the shrimp. The results showed that as lipid intake increased, the survival rate, body weight growth rate, and hepatosomatic ratio of the shrimp increased while the feed conversion rate decreased. Additionally, the crude protein and crude lipid contents increased, whereas the moisture and ash contents did not change much. We found that the morphological structure of the hepatopancreas was seriously damaged in the 3 mg/L NPs and 3 % dietary lipid group. Finally, lipid metabolism-related enzyme activities and gene expression levels increased with increased dietary lipid levels. Together, these results suggest that increasing dietary lipid content can improve shrimp growth and alleviate lipid metabolism disorders caused by NPs. This study is the first to show that nutrition regulation can alleviate the toxicity of NPs, and it provides a theoretical basis for the green and healthy culture of L. vannamei.

The Combination of Biochar and Bacillus subtilis Biological Agent Reduced the Relative Abundance of Pathogenic Bacteria in the Rhizosphere Soil of Panax notoginseng.

In the continuous cropping of Panax notoginseng, the pathogenic fungi in the rhizosphere soil increased and infected the roots of Panax notoginseng, resulting in a decrease in yield. This is an urgent problem that needs to be solved in order to effectively overcome the obstacles associated with the continuous cropping of Panax notoginseng. Previous studies have shown that Bacillus subtilis inhibits pathogenic fungi in the rhizosphere of Panax notoginseng, but the inhibitory effect was not stable. Therefore, we hope to introduce biochar to help Bacillus subtilis colonize in soil. In the experiment, fields planted with Panax notoginseng for 5 years were renovated, and biochar was mixed in at the same time. The applied amount of biochar was set to four levels (B0, 10 kg·hm-2; B1, 80 kg·hm-2; B2, 110 kg·hm-2; B3, 140 kg·hm-2), and Bacillus subtilis biological agent was set to three levels (C1, 10 kg·hm-2; C2, 15 kg·hm-2; C3, 25 kg·hm-2). The full combination experiment and a blank control group (CK) were used. The experimental results show that the overall Ascomycota decreased by 0.86%~65.68% at the phylum level. Basidiomycota increased by -73.81%~138.47%, and Mortierellomycota increased by -51.27%~403.20%. At the genus level, Mortierella increased by -10.29%~855.44%, Fusarium decreased by 35.02%~86.79%, and Ilyonectria increased by -93.60%~680.62%. Fusarium mainly causes acute bacterial wilt root rot, while Ilyonectria mainly causes yellow rot. Under different treatments, the Shannon index increased by -6.77%~62.18%, the Chao1 index increased by -12.07%~95.77%, the Simpson index increased by -7.31%~14.98%, and the ACE index increased by -11.75%~96.12%. The good_coverage indices were all above 0.99. The results of a random forest analysis indicated that Ilyonectria, Pyrenochaeta, and Xenopolyscytalum were the top three most important species in the soil, with MeanDecreaseGini values of 2.70, 2.50, and 2.45, respectively. Fusarium, the primary pathogen of Panax notoginseng, ranked fifth, and its MeanDecreaseGini value was 2.28. The experimental results showed that the B2C2 treatment had the best inhibitory effect on Fusarium, and the relative abundance of Fusarium in Panax notoginseng rhizosphere soil decreased by 86.79% under B2C2 treatment; the B1C2 treatment had the best inhibitory effect on Ilyonectria, and the relative abundance of Ilyonectria in the Panax notoginseng rhizosphere soil decreased by 93.60% under B1C2 treatment. Therefore, if we want to improve the soil with acute Ralstonia solanacearum root rot, we should use the B2C2 treatment to improve the soil environment; if we want to improve the soil with yellow rot disease, we should use the B1C2 treatment to improve the soil environment.

Survival After Out-of-Hospital Cardiac Arrest Before and After Legislation for Bystander CPR.

Importance: The lack of evidence-based implementation strategies is a major contributor to increasing mortality due to out-of-hospital cardiac arrest (OHCA) in developing countries with limited resources. Objective: To evaluate whether the implementation of legislation is associated with increased bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use and improved clinical outcomes for patients experiencing OHCA and to provide policy implications for low-income and middle-income settings. Design, Setting, and Participants: This observational cohort study analyzed a prospective city registry of patients with bystander-witnessed OHCA between January 1, 2010, and December 31, 2022. The Emergency Medical Aid Act was implemented in Shenzhen, China, on October 1, 2018. An interrupted time-series analysis was used to assess changes in outcomes before and after the law. Data analysis was performed from May to October 2023. Exposure: The Emergency Medical Aid Act stipulated the use of AEDs and CPR training for the public and provided clear legal guidance for OHCA rescuing. Main Outcomes and Measures: The primary outcomes were rates of bystander-initiated CPR and use of AEDs. Secondary outcomes were rates of prehospital return of spontaneous circulation (ROSC), survival to arrival at the hospital, and survival at discharge. Results: A total of 13 751 patients with OHCA (median [IQR] age, 59 [43-76] years; 10 011 men [72.83%]) were included, with 7858 OHCAs occurring during the prelegislation period (January 1, 2010, to September 30, 2018) and 5893 OHCAs occurring during the postlegislation period (October 1, 2018, to December 31, 2022). The rates of bystander-initiated CPR (320 patients [4.10%] vs 1103 patients [18.73%]) and AED use (214 patients [4.12%] vs 182 patients [5.29%]) increased significantly after legislation implementation vs rates before the legislation. Rates of prehospital ROSC (72 patients [0.92%] vs 425 patients [7.21%]), survival to arrival at the hospital (68 patients [0.87%] vs 321 patients [5.45%]), and survival at discharge (44 patients [0.56%] vs 165 patients [2.80%]) were significantly increased during the postlegislation period. Interrupted time-series models demonstrated a significant slope change in the rates of all outcomes. Conclusions and Relevance: These findings suggest that implementation of the Emergency Medical Aid Act in China was associated with increased rates of CPR and public AED use and improved survival of patients with OHCA. The use of a systemwide approach to enact resuscitation initiatives and provide legal support may reduce the burden of OHCA in low-income and middle-income settings.

Pollutant removal in an experimental bioretention cell situated in a northern Chinese sponge city.

To assess the viability and effectiveness of bioretention cell in enhancing rainwater resource utilization within sponge cities, this study employs field monitoring, laboratory testing, and statistical analysis to evaluate the water purification capabilities of bioretention cell. Findings indicate a marked purification impact on surface runoff, with removal efficiencies of 59.81% for suspended solids (SS), 39.01% for chemical oxygen demand (COD), 37.53% for ammonia nitrogen (NH3-N), and 30.49% for total phosphorus (TP). The treated water largely complies with rainwater reuse guidelines and tertiary sewage discharge standards. Notably, while previous research in China has emphasized water volume control in sponge city infrastructures, less attention has been given to the qualitative aspects and field-based evaluations. This research not only fills that gap but also offers valuable insights and practical implications for bioretention cell integration into sponge city development. Moreover, the methodology and outcomes of this study serve as a benchmark for future sponge city project assessments, offering guidance to relevant authorities.

The role of miR-222-2p in exosomes secreted by hexavalent chromium-induced premature senescent hepatocytes as a SASP component.

With the development of world industrialization, the environmental pollution of hexavalent chromium [Cr(VI)] is becoming an increasingly serious problem. In particular, the mechanisms by which long-term and low-dose exposure to Cr(VI) leading the development of related cancers are not well understood. As senescent cells gradually lose their ability to proliferate and divide, they will not be malignantly transformed. However, Senescence-associated secretory phenotype (SASP) released by senescent cells into the cellular microenvironment can act on neighboring cells. Since SASP has a bidirectional regulatory role in the malignant transformation of cells. Hence, It is very necessary to identified the composition and function of SASP which secreted by Cr(VI) induced senescent L02 hepatocytes (S-L02). Exosomes, a vesicle-like substances released extracellularly after the fusion of intracellular multivesicular bodies with cell membrane, are important components of SASP and contain a large number of microRNAs (miRNAs). By establishing Cr(VI)-induced S-L02 model, we collected the exosomes from the supernatants of S-L02 and L02 culture medium respectively, and screened out the highly expressed miRNAs in the exosomes of S-L02, namely the new SASP components. Among them, the increase of miR-222-5p was the most significant. It was validated that as SASP, miR-222-5p can inhibit the proliferation of L02 and S-L02 hepatocytes and at the same time accelerate the proliferation and migration ability of HCC cells. Further mechanistic studies revealed that miR-222-5p attenuated the regulatory effect of protein phosphatase 2A subunit B isoform R2-α (PPP2R2A) on Akt via repressing its target gene PPP2R2A, causing reduced expressions of forkhead box O3 (FOXO3a), p27 and p21, and finally increasing the proliferation of HCC cells after diminishing the negative regulation of on cell cycle. This study certainly provides valuable laboratory evidence as well as potential therapeutic targets for the prevention and further personalized treatment of Cr(VI)-associated cancers.

Ubiquitylation of RUNX3 by RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, but the early diagnosis rate is low. The RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in several cancers but its mechanism of action in LUAD is unclear. In this study, the biological activity of MEX3C was assessed in LUAD. MEX3C and RUNX3 mRNA levels in the tissues of LUAD patients were determined using reverse transcription­quantitative PCR. The involvement of MEX3C in the growth and metastasis of LUAD cells was measured by EdU assay, CCK-8, colony formation, Transwell assay, TUNEL, and flow cytometry. Expression of apoptosis and epithelial-mesenchymal transition related proteins were determined using western blotting analysis. LUAD cells transfected with si-MEX3C were administered to mice subcutaneously to monitor tumor progression and metastasis. We found that MEX3C is strongly upregulated in LUAD tissue sections, and involved in proliferation and migration. A549 and H1299 cells had significantly higher levels of MEX3C expression compared to control HBE cells. Knockdown of MEX3C dramatically decreased cell proliferation, migration, and invasion, and accelerated apoptosis. Mechanistically, we demonstrate MEX3C induces ubiquitylation and degradation of tumor suppressor RUNX3. Moreover, RUNX3 transcriptionally represses Suv39H1, as revealed by RNA pull-down and chromatin immunoprecipitation assays. The in vivo mice model demonstrated that knockdown of MEX3C reduced LUAD growth and metastasis significantly. Collectively, we reveal a novel MEX3C-RUNX3-Suv39H1 signaling axis driving LUAD pathogenesis. Targeting MEX3C may represent a promising therapeutic strategy against LUAD.

Transcription factor BACH1 in cancer: roles, mechanisms, and prospects for targeted therapy.

Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status of BACH1 in malignant tumor behaviors, and summarize its role in immune regulation in cancer. Moreover, this review focuses on the potential of BACH1 as a novel therapeutic target and prognostic biomarker. Notably, the mechanisms underlying the roles of BACH1 in ferroptosis, oxidative stress and tumor microenvironment remain to be explored. BACH1 has a dual impact on cancer, which affects the accuracy and efficiency of targeted drug delivery. Finally, the promising directions of future BACH1 research are prospected. A systematical and clear understanding of BACH1 would undoubtedly take us one step closer to facilitating its translation from basic research into the clinic.

SOX on tumors, a comfort or a constraint?

The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family, composed of 20 transcription factors, is a conserved family with a highly homologous HMG domain. Due to their crucial role in determining cell fate, the dysregulation of SOX family members is closely associated with tumorigenesis, including tumor invasion, metastasis, proliferation, apoptosis, epithelial-mesenchymal transition, stemness and drug resistance. Despite considerable research to investigate the mechanisms and functions of the SOX family, confusion remains regarding aspects such as the role of the SOX family in tumor immune microenvironment (TIME) and contradictory impacts the SOX family exerts on tumors. This review summarizes the physiological function of the SOX family and their multiple roles in tumors, with a focus on the relationship between the SOX family and TIME, aiming to propose their potential role in cancer and promising methods for treatment.

Construction and validation of molecular subtype and signature of immune cell-related telomeric genes and prediction of prognosis and immunotherapy efficacy in ovarian cancer patients.

BACKGROUND: Ovarian cancer (OVC) has emerged as a fatal gynecological malignancy as a result of a lack of reliable methods for early detection, limited biomarkers and few treatment options. Immune cell-related telomeric genes (ICRTGs) show promise as potential biomarkers. METHODS: ICRTGs were discovered using weighted gene co-expression network analysis (WGCNA). ICRTGs were screened for significant prognosis using one-way Cox regression analysis. Subsequently, molecular subtypes of prognosis-relevant ICRTGs were constructed and validated for OVC, and the immune microenvironment's landscape across subtypes was compared. OVC prognostic models were built and validated using prognosis-relevant ICRTGs. Additionally, chemotherapy susceptibility drugs for OVC patients in the low- and high-risk groups of ICRTGs were screened using genomics of drug susceptibility to cancer (GDSC). Finally, the immunotherapy response in the low- and high-risk groups was detected using the data from GSE78220. We conducted an immune index correlation analysis of ICRTGs with significant prognoses. The MAP3K4 gene, for which the prognostic correlation coefficient is the highest, was validated using tissue microarrays for a prognostic-immune index correlation. RESULTS: WGCNA analysis constructed a gene set of ICRTGs and screened 22 genes with prognostic significance. Unsupervised clustering analysis revealed the best molecular typing for two subtypes. The Gene Set Variation Analysis algorithm was used to calculate telomere scores and validate the molecular subtyping. A prognostic model was constructed using 17 ICRTGs. In the The Cancer Genome Atlas-OVC training set and the Gene Expression Omnibus validation set (GSE30161), the risk score model's predicted risk groups and the actual prognosis were shown to be significantly correlated. GDSC screened Axitinib, Bexarotene, Embelin and the GSE78220 datasets and demonstrated that ICRTGs effectively distinguished the group that responds to immunotherapy from the non-responsive group. Additionally, tissue microarray validation results revealed that MAP3K4 significantly predicted patient prognosis. Furthermore, MAP3K4 exhibited a positive association with PD-L1 and a negative relationship with the M1 macrophage markers CD86 and INOS. CONCLUSIONS: ICRTGs may be reliable biomarkers for the molecular typing of patients with OVC, enabling the prediction of prognosis and immunotherapy efficacy.

Recent progress of particle electrode materials in three-dimensional electrode reactor: synthesis strategy and electrocatalytic applications.

With the complete promotion of a green, low-carbon, safe, and efficient economic system as well as energy system, the promotion of clean governance technology in the field of environmental governance becomes increasingly vital. Because of its low energy consumption, great efficiency, and lack of secondary pollutants, three-dimensional (3D) electrode technology is acknowledged as an environmentally beneficial and sustainable way to managing clean surroundings. The particle electrode is an essential feature of the 3D electrode reactor. This study provides an in-depth examination of the most current advancements in 3D electrode technology. The significance of 3D electrode technology is emphasized, with an emphasis on its use in a variety of sectors. Furthermore, the particle electrode synthesis approach and mechanism are summarized, providing vital insights into the actual implementation of this technology. Furthermore, by a metrological examination of the research literature in this sector, the paper expounds on the potential and obstacles in the development and popularization of future technology.

Infusion of GMSCs relieves autoimmune arthritis by suppressing the externalization of neutrophil extracellular traps via PGE2-PKA-ERK axis.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic autoimmune disease with limited treatment success, characterized by chronic inflammation and progressive cartilage and bone destruction. Accumulating evidence has shown that neutrophil extracellular traps (NETs) released by activated neutrophils are important for initiating and perpetuating synovial inflammation and thereby could be a promising therapeutic target for RA. K/B × N serum transfer-induced arthritis (STIA) is a rapidly developed joint inflammatory model that somehow mimics the inflammatory response in patients with RA. Human gingival-derived mesenchymal stem cells (GMSCs) have been previously shown to possess immunosuppressive effects in arthritis and humanized animal models. However, it is unknown whether GMSCs can manage neutrophils in autoimmune arthritis. OBJECTIVES: To evaluate whether infusion of GMSCs can alleviate RA by regulating neutrophils and NETs formation. If this is so, we will explore the underlying mechanism(s) in an animal model of inflammatory arthritis. METHODS: The effects of GMSCs on RA were assessed by comparing the symptoms of the K/B × N serum transfer-induced arthritis (STIA) model administered either with GMSCs or with control cells. Phenotypes examined included clinical scores, rear ankle thickness, paw swelling, inflammation, synovial cell proliferation, and immune cell frequency. The regulation of GMSCs on NETs was examined through immunofluorescence and immunoblotting in GMSCs-infused STIA mice and in an in vitro co-culture system of neutrophils with GMSCs. The molecular mechanism(s) by which GMSCs regulate NETs was explored both in vitro and in vivo by silencing experiments. RESULTS: We found in this study that adoptive transfer of GMSCs into STIA mice significantly ameliorated experimental arthritis and reduced neutrophil infiltration and NET formation. In vitro studies also showed that GMSCs inhibited the generation of NETs in neutrophils. Subsequent investigations revealed that GMSCs secreted prostaglandin E2 (PGE2) to activate protein kinase A (PKA), which ultimately inhibited the downstream extracellular signal-regulated kinase (ERK) pathway that is essential for NET formation. CONCLUSION: Our results demonstrate that infusion of GMSCs can ameliorate inflammatory arthritis mainly by suppressing NET formation via the PGE2-PKA-ERK signaling pathway. These findings further support the notion that the manipulation of GMSCs is a promising stem cell-based therapy for patients with RA and other autoimmune and inflammatory diseases.

Curcumin attenuates diphenyl phosphate-induced apoptosis in GC-2spd(ts) cells through activated autophagy via the Nrf2/P53 pathway.

Diphenyl phosphate (DPhP) is one of the frequently used derivatives of aryl phosphate esters and is used as a plasticizer in industrial production. Like other plasticizers, DPhP is not chemically bound and can easily escape into the environment, thereby affecting human health. DPhP has been associated with developmental toxicity, reproductive toxicity, neurodevelopmental toxicity, and interference with thyroid homeostasis. However, understanding of the underlying mechanism of DPhP on the reproductive toxicity of GC-2spd(ts) cells remains limited. For the first time, we investigated the effect of DPhP on GC-2spd(ts) cell apoptosis. By decreasing nuclear factor erythroid-derived 2-related factor (Nrf2)/p53 signaling, DPhP inhibited autophagy and promoted apoptosis. DPhP reduced total antioxidant capacity and nuclear Nrf2 and its downstream target gene expression. In addition, we investigated the protective effects of Curcumin (Cur) against DPhP toxicity. Cur attenuated the DPhP-induced rise in p53 expression while increasing Nrf2 expression. Cur inhibited DPhP-induced apoptosis in GC-2spd(ts) cells by activating autophagy via Nrf2/p53 signaling. In conclusion, our study provides new insights into the reproductive toxicity hazards of DPhP and demonstrates that Cur is an important therapeutic agent for alleviating DPhP-induced reproductive toxicity by regulating Nrf2/p53 signaling.