The relationship between the network of non-coding RNAs-molecular targets and N6-methyladenosine modification in tumors of urinary system.

N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating variable splicing, RNA maturation, transcription, and nuclear export, and also is vital for regulating RNA translation, stability, and cytoplasmic degradation. For example, m6A methylation can regulate pre-miRNA expression by affecting both splicing and maturation. Non-coding RNA (ncRNA), which includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), does not encode proteins but has powerful impacts on transcription and translation. Conversely, ncRNAs may impact m6A methylation by affecting the expression of m6A regulators, including miRNAs targeting mRNA of m6A regulators, or lncRNAs, and circRNAs, acting as scaffolds to regulate transcription of m6A regulatory factors. Dysregulation of m6A methylation is common in urinary tumors, and the regulatory role of ncRNAs is also important for these malignancies. This article provides a systematic review of the role and mechanisms of action of m6A methylation and ncRNAs in urinary tumors.

Gut microbiota's influence on erysipelas: evidence from a two-sample Mendelian randomization analysis.

Background: Previous studies have suggested a link between gut microbiota and skin diseases, including erysipelas, an inflammatory skin condition. Despite this, the precise nature of the relationship between erysipelas and gut microbiota remains unclear and subject to debate. Methods: We conducted a Mendelian Randomization (MR) analysis using publicly available summary data from genome-wide association studies (GWAS) to explore the potential causal relationship between gut microbiota and erysipelas. Instrumental variables (IVs) were identified using a comprehensive set of screening methods. We then performed MR analyses primarily using the Inverse Variance Weighted (IVW) method, complemented by alternative approaches such as MR Egger, weighted median, simple mode, and weighted mode. A series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test, and a leave-one-out test, were executed to ensure the robustness and validity of our findings. Results: We identified potential associations between erysipelas and various gut microbiota, including Alcaligenaceae (OR 1.23; 95% CI 1.06-1.43; p=0.006), Rikenellaceae (OR 0.77; 95% CI 0.67-0.90; p=0.001), and others. Notably, associations with Actinomyces, Lachnospiraceae NC2004 group, Ruminiclostridium 9, Ruminococcaceae UCG014, Odoribacter, and Actinobacteria were also observed. Sensitivity analyses confirmed the robustness of these associations. Conclusion: Our MR analysis suggests both potentially beneficial and harmful causal relationships between various gut microbiota and the incidence of erysipelas. This study provides new theoretical and empirical insights into the pathogenesis of erysipelas and underscores the potential for innovative preventive and therapeutic approaches.

Safety and clinical efficacy of immune checkpoint inhibitors in advanced gastric cancer in the real world.

BACKGROUND: To evaluate the clinical efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer in the real world. METHODS: The retrospective analysis was conducted on the clinical records of 402 patients with advanced gastric cancer who were admitted to the Nanjing Drum Tower Hospital between December 2017 and April 2022 and who had received immunotherapy. Observation target: drug use, treatment, adverse reaction type and grade, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). RESULTS: By retrospectively analyzing the data of patients with advanced gastric cancer treated with ICIs previously admitted to our medical center, we found some clinical characteristic factors associated with the occurrence of irAEs as well as the efficacy and prognosis: the presence or absence of hypertension, whether or not to receive targeted therapies can predict the occurrence of immune-related adverse events (irAEs), and the more the presence of irAEs, the better the prognosis. These can help clinicians in clinical drug selection. CONCLUSIONS: The results of this paper show that the occurrence of irAEs is associated with patients' OS. irAEs occurrence can prolong patients' OS. irAEs occurrence may serve as a surrogate marker for ICIs.

Nano vitamin E improved the antioxidant capacity of broiler chickens.

Vitamin E (VE) is a potent nutritional antioxidant that is critical in alleviating poultry oxidative stress. However, the hydrophobic nature and limited stability of VE restrict its effective utilization. Nanotechnology offers a promising approach to enhance the bioavailability of lipophilic vitamins. The objective of this experiment was to investigate the effects of different sources and addition levels of VE on the growth performance, antioxidant capacity, VE absorption site, and pharmacokinetics of Arbor Acres (AA) broilers. Three hundred and eighty-four 1-d-old AA chicks were randomly allocated into four groups supplemented with 30 and 75 IU/kg VE as regular or nano. The results showed that dietary VE sources had no significant impact on broiler growth performance. However, chickens fed 30 IU/kg VE had a higher average daily gain at 22 to 42 d and 1 to 42 d, and lower feed conversion ratio at 22 to 42 d than 75 IU/kg VE (P < 0.05). Under normal feeding conditions, broilers fed nano VE (NVE) displayed significantly higher superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) enzyme activities and lower malonic dialdehyde (MDA) concentration (P < 0.05). Similarly, NVE had a higher antioxidant effect in the dexamethasone-constructed oxidative stress model. It was found that nanosizing technology had no significant effect on the absorption of VE in the intestinal tract by examining the concentration of VE in the intestinal tract (P > 0.05). However, compared to broilers perfused with regular VE (RVE), the NVE group displayed notably higher absorption rates at 11.5 and 14.5 h (P < 0.05). Additionally, broilers perfused with NVE showed a significant increase in the area under the concentration versus time curve from zero to infinity (AUC0-∞), mean residence time (MRT0-∞), elimination half-life (t1/2z), and peak concentration (Cmax) of VE in plasma (P < 0.05). In summary, nanotechnology provides more effective absorption and persistence of VE in the blood circulation for broilers, which is conducive to the function of VE and further improves the antioxidant performance of broilers.

With the rapid development of intensive farming, factors such as high temperature, harmful gases, high-fat and high-protein diets, and changes in feeding methods have become causes of oxidative stress in animals. Studies have shown that oxidative stress decreases livestock feed intake and slows growth in animals, thereby affecting the quality of livestock products. Antioxidants and micronutrients are commonly added to animal feed to reduce the effects of oxidative stress. Since the progress in nanotechnology, nanovitamins have gained extensive recognition due to their novel qualities, including a high level of adsorption capacity and low toxicity. Therefore, the present study compared the effects of dietary supplementation with different sources of vitamin E (regular, RVE vs. nano, NVE) and varying inclusion levels on the growth performance, antioxidant capacity, VE absorption sites, and pharmacokinetics in AA broilers. The results indicated that supplementing broiler diets with NVE provides superior antioxidant benefits compared to RVE. This improvement is attributed to the enhanced absorption efficiency and extended half-life of NVE, both contributing to increased antioxidant performance of broilers.

IgA nephropathy in a child with X-linked agammaglobulinemia: a case report.

BACKGROUND: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the Bruton tyrosine kinase (BTK) gene. Individuals diagnosed with XLA are at an increased risk of developing autoimmune diseases. However, renal involvement are rare in cases of XLA. CASE PRESENTATION: In this report, we discussed a specific case involving a 6-year-old boy with XLA who experienced recurrent upper respiratory tract infections since the age of one. He presented with symptoms of hematuria and proteinuria, and renal pathology confirmed the presence of immunoglobulin (Ig) A nephropathy. Treatment comprised glucocorticoids, mycophenolate mofetil, and intermittent intravenous immunoglobulin replacement therapy. Consequently, there was a remission of proteinuria and a partial improvement in hematuria. CONCLUSIONS: In this study, we describe the first case of IgA nephropathy associated with XLA. This is an interesting phenotype found in XLA, and it provides valuable insights into the process of autoimmunity and the regulation of immune function in individuals with XLA. Based on our findings, we recommend the evaluation of immunoglobulin levels in patients diagnosed with IgA nephropathy.

A trapped covalent intermediate as a key catalytic element in the hydrolysis of a GH3 ß-glucosidase: An X-ray crystallographic and biochemical study.

Glycoside hydrolases (GHs) are industrially important enzymes that hydrolyze glycosidic bonds in glycoconjugates. In this study, we found a GH3 ß-glucosidase (CcBgl3B) from Cellulosimicrobium cellulans sp. 21 was able to selectively hydrolyze the ß-1,6-glucosidic bond linked glucose of ginsenosides. X-ray crystallographic studies of the ligand complex ginsenoside-specific ß-glucosidase provided a novel finding that support the catalytic mechanism of GH3. The substrate was clearly identified within the catalytic center of wild-type CcBgl3B, revealing that the C1 atom of the glucose was covalently bound to the Oδ1 group of the conserved catalytic nucleophile Asp264 as an enzyme-glycosyl intermediate. The glycosylated Asp264 could be identified by mass spectrometry. Through site-directed mutagenesis studies with Asp264, it was found that the covalent intermediate state formed by Asp264 and the substrate was critical for catalysis. In addition, Glu525 variants (E525A, E525Q and E525D) showed no or marginal activity against pNPßGlc; thus, this residue could supply a proton for the reaction. Overall, our study provides an insight into the catalytic mechanism of the GH3 enzyme CcBgl3B.

Knowledge mapping and current trends of m6A methylation in the field of cancer.

Background: Cancer is a serious threat to people's lives and health, killing millions of people every year. Here, we performed a bibliometric analysis of tumor N6-methyladenosine methylation data between 2001 and 2022 to understand research trends and potential future directions. Methods: A total of 890 papers published in the Web of Science core collection database between January 1, 2001 and December 31, 2022 were analyzed. Bibliometric analysis was performed using VOSviewer software to explore citations, co-authorship, co-citations, and co-occurrence. Results: Although few papers were published before 2018, there was a rapid increase in publications after 2018. The People's Republic of China published 810 papers with 16,957 citations, both ranking first in the word. Sun Yat Sen University had the highest number of citations and published articles (67 published papers and 2702 citations), indicative of its active collaborative research status. Wang Xiao was the most co-cited author with 546 co-citations. Huang Yufei and Meng Jia ranked first with a link strength of 22, making them the most active collaborative authors. Frontiers in Oncology and Nature were the most active and co-cited journals, with 57 papers and 1953 co-citations, respectively. Studies of tumor N6-methyladenosine methylation can be divided into three categories: "tumor metabolism", "tumor bioinformatics and immunity", and "tumor progression". Conclusions: This study systematically summarized the research on tumor N6-methyladenosine methylation during the past 20 years and suggested potential ways to explore its biomarkers and immunotherapy in the future.

Research progress on and molecular mechanism of vacuum sealing drainage in the treatment of diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are common chronic wounds and a common complication of diabetes. The foot is the main site of diabetic ulcers, which involve small and medium-sized arteries, peripheral nerves, and microcirculation, among others. DFUs are prone to coinfections and affect many diabetic patients. In recent years, interdisciplinary research combining medicine and material science has been increasing and has achieved significant clinical therapeutic effects, and the application of vacuum sealing drainage (VSD) in the treatment of DFUs is a typical representative of this progress, but the mechanism of action remains unclear. In this review, we integrated bioinformatics and literature and found that ferroptosis is an important signaling pathway through which VSD promotes the healing of DFUs and that System Xc-GSH-GPX4 and NAD(P)H-CoQ10-FSP1 are important axes in this signaling pathway, and we speculate that VSD is most likely to inhibit ferroptosis to promote DFU healing through the above axes. In addition, we found that some classical pathways, such as the TNF, NF-κB, and Wnt/ß-catenin pathways, are also involved in the VSD-mediated promotion of DFU healing. We also compiled and reviewed the progress from clinical studies on VSD, and this information provides a reference for the study of VSD in the treatment of DFUs.

Case report: A case of advanced gastric cancer with multiple skin metastases, with significant relief from immunotherapy.

Gastric cancer is the fifth leading cause of cancer-related mortality worldwide, with a low 5-year survival rate in advanced stages. Cutaneous metastasis is rare in gastric cancer, with only 0.8-1% incidence. We reported a rare case of female gastric cancer. The patient had undergone subtotal gastrectomy and chemotherapy 13 years ago, followed by a subsequent surgery of residual stomach, partial jejunum, and partial colon resection 11 years later. The pathological examination revealed poorly differentiated stomach adenocarcinoma, Lauren classification: diffuse type. The patient received 2 cycles of SOX chemotherapy. Two years later, cauliflower-like skin nodules, which were surgically excised, appeared on the back. The histopathological examination showed a spindle cell tumor; no specific anti-tumor treatment was administered. Six months later, the skin lesions increased in size and number, spreading to the neck, chest, and abdomen, presenting as erythematous patches with some cauliflower-like elevations. A skin biopsy of a 1cm0.5cm0.3cm lesion on the left abdomen was performed, and based on the immunohistochemistry, clinical history, and the possibility of metastatic or infiltrating adenocarcinoma, the gastrointestinal origin was highly suspected. Genetic testing was performed on the gastric recurrence and skin lesions, revealing 103 shared genetic variations, further suggesting the skin metastasis originated from gastric cancer. Subsequently, the patient received 10 cycles of immunotherapy combined with intravenous chemotherapy (200mg Tislelizumab and 100mg albumin-bound paclitaxel). The treatment response was evaluated as partial remission, with significant improvement in the skin lesions compared to before. This case highlights the possibility of tumor metastasis in patients with extensive skin lesions in advanced gastric cancer. Early examination, diagnosis, skin biopsy, immunohistochemistry, and genetic sequencing are recommended.

The effects of resonance acoustic mixing modulation on the structural and emulsifying properties of pea protein isolate.

The effects of resonant acoustic mixing (RAM) with different treatment times (0, 5, 10, 15, 20 and 30 min) on the structural and emulsifying properties of pea protein isolate (PPI) were investigated for the first time. Increasing the RAM treatment time from 0 to 20 min decreased the α-helix/ß-sheet ratio and particle size of the PPI samples by 37.84 % and 46.44 %, respectively, accompanied by an increase in solubility from 54.79 % to 71.80 % (P < 0.05). Consequently, the emulsifying activity index of PPI (from 10.45 m2/g to 14.2 m2/g) and the physical stability of RAM-PPI emulsions were effectively enhanced, which was confirmed by the small and uniformly distributed oil droplets in the micrographs of the emulsions. However, excessive RAM treatment (30 min) diminished the effectiveness of the aforementioned improvements. Therefore, obviously enhanced solubility and emulsifying properties of PPI can be attained through proper RAM treatment (15-20 min).

Impacts of glutamate, an exercise-responsive metabolite on insulin signaling.

AIMS: Disruption of the insulin signaling pathway leads to insulin resistance (IR). IR is characterized by impaired glucose and lipid metabolism. Elevated levels of circulating glutamate are correlated with metabolic indicators and may potentially predict the onset of metabolic diseases. Glutamate receptor antagonists have significantly enhanced insulin sensitivity, and improved glucose and lipid metabolism. Exercise is a well-known strategy to combat IR. The aims of our narrative review are to summarize preclinical and clinical findings to show the correlations between circulating glutamate levels, IR and metabolic diseases, discuss the causal role of excessive glutamate in IR and metabolic disturbance, and present an overview of the exercise-induced alteration in circulating glutamate levels. MATERIALS AND METHODS: A literature search was conducted to identify studies on glutamate, insulin signaling, and exercise in the PubMed database. The search covered articles published from December 1955 to January 2024, using the search terms of "glutamate", "glutamic acid", "insulin signaling", "insulin resistance", "insulin sensitivity", "exercise", and "physical activity". KEY FINDINGS: Elevated levels of circulating glutamate are correlated with IR. Excessive glutamate can potentially hinder the insulin signaling pathway through various mechanisms, including the activation of ectopic lipid accumulation, inflammation, and endoplasmic reticulum stress. Glutamate can also modify mitochondrial function through Ca2+ and induce purine degradation mediated by AMP deaminase 2. Exercise has the potential to decrease circulating levels of glutamate, which can be attributed to accelerated glutamate catabolism and enhanced glutamate uptake. SIGNIFICANCE: Glutamate may act as a mediator in the exercise-induced improvement of insulin sensitivity.

Assessing the effectiveness of the expanded hepatitis A vaccination program in China: an interrupted time series design.

INTRODUCTION: China initialised the expanded hepatitis A vaccination programme (EHAP) in 2008. However, the effectiveness of the programme remains unclear. We aimed to comprehensively evaluate the effectiveness of EHAP in the country. METHODS: Based on the provincial data on the incidence of hepatitis A (HepA), the population and meteorological variables in China, we developed interrupted time series (ITS) models to estimate the effectiveness of EHAP with the autocorrelation, seasonality and the meteorological confounders being controlled. Results were also stratified by economic zones, age groups and provinces. RESULTS: We found a 0.9% reduction (RR=0.991, 95% CI: 0.990 to 0.991) in monthly HepA incidence after EHAP, which was 0.3% greater than the reduction rate before EHAP in China. Across the three economic regions, we found a 1.1% reduction in HepA incidence in both central and western regions after EHAP, which were 0.3% and 1.2% greater than the reduction rates before EHAP, respectively. We found a decreased reduction rate for the eastern region. In addition, we found generally increased reduction rate after EHAP for age groups of 0-4, 5-14 and 15-24 years. However, we found decreased reduction rate among the 25-64 and ≥65 years groups. We found a slight increased rate after EHAP in Shanxi Province but not elsewhere. CONCLUSION: Our finding provides comprehensive evidence on the effectiveness of EHAP in China, particularly in the central and western regions, and among the population aged 0-24 years old. This study has important implications for the adjustment of vaccination strategies for other regions and populations.

Disturbance rejection of offshore drilling platforms: An equivalent-input-disturbance-based dynamic positioning control method.

Offshore drilling platforms are exposed to wind, waves, currents, and other unknown disturbances. Accurately estimating and rejecting these disturbances is the key to ensuring reliable station-keeping of the platforms. In this study, a novel dynamic positioning method using an improved equivalent-input-disturbance (EID) approach is proposed for offshore drilling platforms. An improved EID estimator is employed to estimate and suppress unknown disturbances, significantly enhancing the disturbance-rejection performance of the dynamic positioning system. The input channels are decoupled through linear transformation, and the parameter tuning process of the observer and controller is optimized, thus improving system performance. The bounded-input bounded-output stability of the closed-loop system is proved. This study provides insights into the design of dynamic positioning systems for offshore drilling platforms.

Corrigendum: In vitro and in vivo evaluation of alginate hydrogel-based wound dressing loaded with green chemistry cerium oxide nanoparticles.

[This corrects the article DOI: 10.3389/fchem.2023.1298808.].

Real-time dual-modal photoacoustic and fluorescence small animal imaging.

By combining optical absorption contrast and acoustic resolution, photoacoustic imaging (PAI) has broken the barrier in depth for high-resolution optical imaging. Meanwhile, Fluorescence imaging (FLI), owing to advantages of high sensitivity and high specificity with abundant fluorescence agents and proteins, has always been playing a key role in live animal studies. Based on different optical contrast mechanisms, PAI and FLI can provide important complementary information to each other. In this work, we uniquely designed a Photoacoustic-Fluorescence (PA-FL) imaging system that provides real-time dual modality imaging, in which a half-ring ultrasonic array is employed for high quality PA tomography and a specially designed optical window allows simultaneous whole-body fluorescence imaging. The performance of this dual modality system was demonstrated in live animal studies, including real-time monitoring of perfusion and metabolic processes of fluorescent dyes. Our study indicates that the PA-FL imaging system has unique potential for live small animal research.

YAP promotes the healing of ischemic wounds by reducing ferroptosis in skin fibroblasts through inhibition of ferritinophagy.

The impaired healing of chronic wounds is often attributed to the ischemic and hypoxic microenvironment, leading to increased cell death. Ferroptosis, a novel form of cell death unveiled in recent years, could potentially be linked with the process of wound healing. In this study, we explored the significance and mechanism of ferroptosis in ischemic wounds. Using transmission electron microscopy, Western blot, flow cytometry, immunofluorescence, and glutathione (GSH) assay, we observed that the death of primary mouse skin fibroblasts induced by oxygen and glucose deprivation (OGD) was associated with ferroptosis. Specifically, we observed elevated intracellular Fe2+ and lipid peroxidation levels and decreased GSH levels in vitro, indicative of ferroptosis. Importantly, we found that ferroptosis in OGD-treated skin fibroblasts was dependent on autophagy, as the autophagy inhibitor chloroquine phosphate (CHQ) significantly reduced ferroptosis induced by OGD. Moreover, our study revealed that NCOA4-mediated ferritinophagy significantly contributed to the occurrence of ferroptosis induced by OGD in skin fibroblasts. Additionally, we identified the involvement of YAP in the regulation of ferritinophagy, with YAP suppressing NCOA4 expression in OGD-treated skin fibroblasts, thereby reducing ferroptosis. Furthermore, in ischemic wound models in mice, both inhibitors of ferroptosis and autophagy promoted wound healing, while a YAP inhibitor, verteporfin, delayed wound healing. In conclusion, these findings indicate that ferroptosis, regulated by YAP through ferritinophagy inhibition, presents a novel mechanism responsible for the delayed healing of ischemic wounds. Understanding this process could offer promising therapeutic targets to improve wound healing in ischemic conditions.

New concepts drive the development of delivery tools for sustainable treatment of diabetic complications.

Diabetic complications, especially diabetic retinopathy, diabetic nephropathy and painful diabetic neuropathy, account for a large portion of patients with diabetes and display rising global prevalence. They are the leading causes of blindness, kidney failure and hypersensitivity to pain caused by diabetes. Current approved therapeutics against the diabetic complications are few and exhibit limited efficacy. The enhanced cell-specificity, stability, biocompatibility, and loading capacity of drugs are essential for the mitigation of diabetic complications. In the article, we have critically discussed the recent studies over the past two years in material sciences and biochemistry. The insightful concepts in these studies drive the development of novel nanoparticles and mesenchymal stem cells-derived extracellular vesicles to meet the need for treatment of diabetic complications. Their underlying biochemical principles, advantages and limitations have been in-depth analyzed. The nanoparticles discussed in the article include double-headed nanodelivery system, nanozyme, ESC-HCM-B system, soft polymer nanostars, tetrahedral DNA nanostructures and hydrogels. They ameliorate the diabetic complication through attenuation of inflammation, apoptosis and restoration of metabolic homeostasis. Moreover, mesenchymal stem cell-derived extracellular vesicles efficiently deliver therapeutic proteins to the retinal cells to suppress the angiogenesis, inflammation, apoptosis and oxidative stress to reverse diabetic retinopathy. Collectively, we provide a critical discussion on the concept, mechanism and therapeutic applicability of new delivery tools to treat these three devastating diabetic complications.

Emerging strategy for the treatment of urothelial carcinoma: Advances in antibody-drug conjugates combination therapy.

Urothelial carcinoma (UC) is a prevalent malignant tumor involving the urinary system. Although there are various treatment modalities, including surgery, chemotherapy, and immune checkpoint inhibitor (ICI) therapy, some patients experience disease recurrence and metastasis with poor prognosis and dismal long-term survival. Antibody-drug conjugates (ADCs), which combine the targeting ability of antibody drugs with the cytotoxicity of chemotherapeutic drugs, have recently emerged as a prominent research focus in the development of individualized precision cancer therapy. Although ADCs have improved the overall response rate in patients with UC, their effectiveness remains limited. Currently, ADC-based combination therapies, particularly ADC combined with ICIs, have demonstrated promising efficacy. This combination approach has advanced the treatment of UC, exhibiting the potential to become the standard first-line therapy for advanced UC in the future. This article reviewed clinical trials involving ADC-based combination therapy for UC and discussed the possible challenges and future perspectives to provide guidance for the clinical treatment of UC.