Boosting the oxygen reduction activity of non-metallic catalysts via geometric and electronic engineering through nitrogen and chlorine dual-doping.

The development of heteroatom dual-doped porous carbon frameworks with uniform doping is highly desirable for achieving highly efficient oxygen reduction reaction (ORR) activity, due to their tunable chemical and electronic structures. Herein, porous covalent triazine-based frameworks (CTFs) incorporating nitrogen/chorine dual-doped porous carbon networks were fabricated by selecting 1,3-bis(4-cyanophenyl) imidazolium chloride as a building block, in a facile and controllable way via a bottom-up strategy. The resulting nitrogen/chorine dual-doped catalyst CCTF-700 exhibits excellent ORR performance with a more positive onset and half-wave potential (0.85 V vs. RHE), higher diffusion-limited current density and significantly improved stability in comparison with the benchmark commercial 20 wt% Pt/C catalyst. It is worth mentioning that CCTF-700 shows one of the best ORR performances among all the reported metal-free electrocatalysts under alkaline conditions. This work paves the way for a controllable and reliable strategy to craft highly efficient heteroatom dual-doped carbon catalysts for energy conversion.

Scutellarin alleviates microglia-mediated neuroinflammation and apoptosis after ischemic stroke through the PI3K/AKT/GSK3ß signaling pathway.

Microglia are resident immune cells in the central nervous system that are rapidly activated to mediate neuroinflammation and apoptosis, thereby aggravating brain tissue damage after ischemic stroke (IS). Although scutellarin has a specific therapeutic effect on IS, the potential target mechanism of its treatment has not been fully elucidated. In this study, we explored the potential mechanism of scutellarin in treating IS using network pharmacology. Lipopolysaccharide (LPS) was used to induce an in vitro BV-2 microglial cell model, while middle cerebral artery occlusion (MCAO) was used to induce an in vivo animal model. Our findings indicated that scutellarin promoted the recovery of cerebral blood flow in MCAO rats at 3 days, significantly different from that in the MCAO group. Western blotting and immunofluorescence revealed that scutellarin treatment of BV-2 microglial cells resulted in a significant reduction in the protein expression levels and incidence of cells immunopositive for p-NF-κB, TNF-α, IL-1ß, Bax, and C-caspase-3. In contrast, the expression levels of p-PI3K, p-AKT, p-GSK3ß, and Bcl-2 were further increased, significantly different from those in the LPS group. The PI3K inhibitor LY294002 had similar effects to scutellarin by inhibiting neuroinflammation and apoptosis in activated microglia. The results of the PI3K/AKT/GSK3ß signaling pathway and NF-κB pathway in vivo in MCAO models induced microglia at 3 days were consistent with those obtained from in vitro cells. These findings indicate that scutellarin plays a neuroprotective role by reducing microglial neuroinflammation and apoptosis mediated by the activated PI3K/AKT/GSK3ß/NF-κB signaling pathway.

ALKBH5 gene polymorphisms and risk of neuroblastoma in Chinese children from Jiangsu Province.

Background: Neuroblastoma is one of the most common extracranial malignant solid tumors in children. AlkB homolog 5 (ALKBH5) is an RNA N6-methyladenosine (m6A) demethylase that plays a critical role in tumorigenesis and development. We assessed the association between single nucleotide polymorphisms (SNPs) in ALKBH5 and the risk of neuroblastoma in a case-control study including 402 patients and 473 non-cancer controls. Methods: Genotyping was determined by the TaqMan method. The association between ALKBH5 polymorphisms (rs1378602 and rs8400) and the risk of neuroblastoma was evaluated using the odds ratio (OR) and 95% confidence interval (CI). Results: We found no strong association of ALKBH5 rs1378602 and rs8400 with neuroblastoma risk. Further stratification analysis by age, sex, primary site, and clinical stage showed that the rs1378602 AG/AA genotype was associated with a lower risk of neuroblastoma in males (adjusted OR = 0.58, 95% CI = 0.35-0.97, p = 0.036) and children with retroperitoneal neuroblastoma (adjusted OR = 0.58, 95% CI = 0.34-0.98, p = 0.040). Conclusions: ALKBH5 SNPs do not seem to be associated with neuroblastoma risk. More studies are required to confirm this negative result and reveal the relationship between gene polymorphisms of the m6A modifier ALKBH5 and neuroblastoma.

YZL-51N functions as a selective inhibitor of SIRT7 by NAD+ competition to impede DNA damage repair.

The NAD+-dependent deacetylase SIRT7 is a pivotal regulator of DNA damage response (DDR) and a promising drug target for developing cancer therapeutics. However, limited progress has been made in SIRT7 modulator discovery. Here, we applied peptide-based deacetylase platforms for SIRT7 enzymatic evaluation and successfully identified a potent SIRT7 inhibitor YZL-51N. We initially isolated bioactive YZL-51N from cockroach (Periplaneta americana) extracts and then developed the de novo synthesis of this compound. Further investigation revealed that YZL-51N impaired SIRT7 enzymatic activities through occupation of the NAD+ binding pocket. YZL-51N attenuated DNA damage repair induced by ionizing radiation (IR) in colorectal cancer cells and exhibited a synergistic anticancer effect when used in combination with etoposide. Overall, our study not only identified YZL-51N as a selective SIRT7 inhibitor from insect resources, but also confirmed its potential use in combined chemo-radiotherapy by interfering in the DNA damage repair process.

Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children: A five-center case-control study.

Objective: Nucleotide excision repair (NER) plays a vital role in maintaining genome stability, and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation. This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children. Methods: In this five-center case-control study, we enrolled 966 subjects from East China (193 hepatoblastoma patients and 773 healthy controls). The TaqMan method was used to genotype 19 single nucleotide polymorphisms (SNPs) in NER pathway genes, including ERCC1, XPA, XPC, XPD, XPF, and XPG. Then, multivariate logistic regression analysis was performed, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized to assess the strength of associations. Results: Three SNPs were related to hepatoblastoma risk. XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model (adjusted OR=1.49, 95% CI=1.07-2.08, P=0.019; adjusted OR=1.66, 95% CI=1.12-2.45, P=0.012, respectively). However, XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model (adjusted OR=0.68, 95% CI=0.49-0.95; P=0.024). Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups. Moreover, there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) analysis. Conclusions: In summary, NER pathway gene polymorphisms (XPC rs2229090, XPD rs3810366, and XPD rs238406) are significantly associated with hepatoblastoma risk, and further research is required to verify these findings.

FDG Avid Intracholecystic Papillary Neoplasm Mimicking Hepatic Metastasis in a Patient with Head-and-neck Cancer.

A 75-year-old male with head-and-neck squamous cell cancer received a staging f-18-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) scan which showed additional focal abnormal uptake in the right hepatic lobe. The patient was treated for probable metastatic disease. Restaging FDG PET/CT scan revealed resolution of uptake in the head-and-neck and persistent focal uptake in the presumed liver metastasis. An abdominal CT with intravenous contrast revealed an enhancing mass in the gallbladder, without extension into the liver. Cholecystectomy revealed an intracholecystic papillary neoplasm of the gallbladder. The initial appearance of hepatic metastasis was due to a misregistration artifact.

Age over sex: evaluating gut microbiota differences in healthy Chinese populations.

Age and gender have been recognized as two pivotal covariates affecting the composition of the gut microbiota. However, their mediated variations in microbiota seem to be inconsistent across different countries and races. In this study, 613 individuals, whom we referred to as the "healthy" population, were selected from 1,018 volunteers through rigorous selection using 16S rRNA sequencing. Three enterotypes were identified, namely, Escherichia-Shigella, mixture (Bacteroides and Faecalibacterium), and Prevotella. Moreover, 11 covariates that explain the differences in microbiota were determined, with age being the predominant factor. Furthermore, age-related differences in alpha diversity, beta diversity, and core genera were observed in our cohort. Remarkably, after adjusting for 10 covariates other than age, abundant genera that differed between age groups were demonstrated. In contrast, minimal differences in alpha diversity, beta diversity, and differentially abundant genera were observed between male and female individuals. Furthermore, we also demonstrated the age trajectories of several well-known beneficial genera, lipopolysaccharide (LPS)-producing genera, and short-chain fatty acids (SCFAs)-producing genera. Overall, our study further elucidated the effects mediated by age and gender on microbiota differences, which are of significant importance for a comprehensive understanding of the gut microbiome spectrum in healthy individuals.

Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to achieve low-toxicity and low-immunogenicity targeted delivery. Signaling pathways related to exosome contents can also be used for safer and more effective immunotherapy against tumors. Exosomes are derived from a wide range of sources, and exhibit different biological characteristics as well as clinical application advantages in different cancer therapies. In this review, we analyzed the main sources of exosomes that have great potential and broad prospects in cancer diagnosis and therapy. Moreover, we compared their therapeutic advantages, providing new ideas for the clinical application of exosomes.

Riparian plant-soil-microbial C:N:P stoichiometry: are they conserved at plant functional group level?

As a consequence of the tight linkages between plants, soil, and microorganisms, we hypothesized the variations in plant species would change soil and microbial stoichiometry. Here, we examined the plant leaf carbon (C):nitrogen (N):phosphorus (P) ratios of nine species coming from three plant functional groups (PFGs) in the riparian zones of Hulunbuir steppe during near-peak biomass. The soil C:N:P, microbial biomass carbon (MBC):microbial biomass nitrogen (MBN), and extracellular enzyme's C:N:P were also assessed using the soils from each species. We found that plant tissue, soil nutrient, microbial, and enzyme activity stoichiometry significantly differed among different PFGs. Plant leaf and soil nutrient ratios tended to be similar (p > 0.05) between different species within the same PFGs. The variations in leaf C:N:P significantly correlated with the changes in soil C:N:P and MBC:MBN ratios. The homeostatic coefficients (H) < 1 suggested the relationships between plants and their resources C:N:P ratios might be non-homeostatic in the examined riparian zone. By assessing plant tissue and its soil nutrient stoichiometry, this study provided a perspective to understand the linkages of plant community, soil nutrient, and microbial characteristics.

Design, synthesis, and evaluation of benzodioxolane compounds for antitumor activity.

This study reports the design, synthesis, and comprehensive biological evaluation of 13 benzodioxolane derivatives, derived from the core structure of piperine, a natural product with established antitumor properties. Piperine, primarily found in black pepper, has been noted for its diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Leveraging piperine's antitumor potential, we aimed to enhance its efficacy through structural modifications. Among the synthesized compounds, HJ1 emerged as the most potent, exhibiting a 4-fold and 10-fold increase in inhibitory effects on HeLa and MDA-MB-231 cell lines, respectively, compared to piperine. Furthermore, HJ1 demonstrated a favorable safety profile, characterized by significantly lower cytotoxicity towards the human normal cell line 293T. Mechanistic investigations revealed that HJ1 markedly inhibited clonogenicity, migration, and adhesion of HeLa cells. In vivo studies utilizing the chick embryo chorioallantoic membrane (CAM) model substantiated the robust antitumor activity of HJ1, evidenced by its ability to suppress tumor angiogenesis and reduce tumor weight. These results suggest that HJ1 holds significant promise as a lead compound for the development of novel antitumor therapies.

Effects of common eye diseases in children and their treatment measures on ocular surface homeostasis: A review.

Ocular surface homeostasis plays a vital role in maintaining of eye health. Dry eye disease is one of the prominent and typical manifestations of disruption of ocular surface homeostasis that leads to the worsening of ocular surface homeostasis that leads to the worsening of ocular surface disease when it interacts with other pathogenic factors. However, disruption in ocular surface homeostasis in children is often overlooked because of the current methods of assessing ocular surface homeostasis. This review summarizes the main factors affecting ocular surface homeostasis in children, with the aim of drawing the attention of clinicians to the disruption of ocular surface homeostasis in children when dealing with such diseases. Ocular surface homeostasis involves several interrelated components, each of which plays a nonnegligible role in ocular surface homeostasis. Unlike adults, children have a stronger lacrimal gland secretion capacity and milder symptoms when there is a slight disruption of the ocular surface homeostasis. In addition, children's expressive abilities were weaker. Therefore, dry eye in children is often ignored by doctors and parents, and clinicians should pay more attention to the protection of ocular surface homeostasis when treating children with these diseases. Therefore, there is a need for diagnostic criteria for dry eye disease specific to children.

Adaptor protein CEMIP reduces the chemosensitivity of small cell lung cancer via activation of an SRC-YAP oncogenic module.

Small cell lung cancer (SCLC) is a recalcitrant malignancy with dismal prognosis due to rapid relapse after an initial treatment response. More effective treatments for SCLC are desperately needed. Our previous studies showed that cell migration-inducing hyaluronan binding protein (CEMIP) functionally promotes SCLC cell proliferation and metastasis. In this study, we investigated whether and how CEMIP regulates the chemosensitivity of SCLC. Through the GDSC database, we found that CEMIP expression levels were positively correlated with the IC50 values of several commonly used chemotherapeutic drugs in SCLC cells (cisplatin, gemcitabine, 5-fluorouracil and cyclophosphamide). We demonstrated that overexpression or knockdown of CEMIP in SCLC cells resulted in a notable increase or reduction in the IC50 value of cisplatin or etoposide, respectively. We further revealed that CEMIP functions as an adaptor protein in SCLC cells to interact with SRC and YAP through the 1-177 aa domain and 820-1361 aa domain, respectively, allowing the autophosphorylation of Y416 and activation of SRC, thus facilitating the interaction between YAP and activated SRC, and resulting in increased phosphorylation of Y357, protein stability, nuclear accumulation and transcriptional activation of YAP. Overexpressing SRC or YAP counteracted the CEMIP knockdown-mediated increase in the sensitivity of SCLC cells to cisplatin and etoposide. The combination of the SRC inhibitor dasatinib or the YAP inhibitor verteporfin and cisplatin/etoposide (EP regimen) displayed excellent synergistic antitumor effects on SCLC both in vitro and in vivo. This study demonstrated that targeted therapy against the CEMIP/SRC/YAP complex is a potential strategy for SCLC and provides a rationale for the development of future clinical trials with translational prospects.

Effects of uranium mining on the rhizospheric bacterial communities of three local plants on the Qinghai-Tibet Plateau.

In this study, we used 16S high-throughput sequencing to investigate the effects of uranium mining on the rhizospheric bacterial communities and functions of three local plant species, namely, Artemisia frigida, Acorus tatarionwii Schott., and Salix oritrepha Schneid. The results showed that uranium mining significantly reduced the diversity of rhizospheric bacteria in the three local plant species, including the Shannon index and Simpson index (P < 0.05). Interestingly, we found that Sphingomonas and Pseudotrichobacter were enriched in the rhizosphere soil of the three local plants from uranium mining areas, indicating their important ecological role. The three plants were enriched in various dominant rhizospheric bacterial populations in the uranium mining area, including Vicinamidobacteriaceae, Nocardioides, and Gaiella, which may be related to the unique microecological environment of the plant rhizosphere. The rhizospheric bacterial community of A. tatarionwii plants from tailings and open-pit mines also showed a certain degree of differentiation, indicating that uranium mining is the main factor driving the differentiation of plant rhizosphere soil communities on the plateau. Functional prediction revealed that rhizospheric bacteria from different plants have developed different functions to cope with stress caused by uranium mining activities, including enhancing the translational antagonist Rof, the translation initiation factor 2B subunit, etc. This study explores for the first time the impact of plateau uranium mining activities on the rhizosphere microecology of local plants, promoting the establishment of effective soil microecological health monitoring indicators, and providing a reference for further soil pollution remediation in plateau uranium mining areas.

Validation of IGA*BSA in Assessing Disease Severity and Response in Patients with Atopic Dermatitis: A Retrospective Cohort Study in China.

Background: Accurate evaluation of atopic dermatitis (AD) severity is crucial to determine and adjust treatment options. Previous studies have found the product of Investigator's Global Assessment (IGA) and affected body surface area (BSA) to be a simple tool, which requires further verification. Objective: To determine the validity of IGA*BSA in assessing the severity of AD across all age, sex, BMI and disease severity groups. Method: We performed a retrospective study of AD using data from a national cohort (China Type II Inflammatory Skin Disease Clinical Research and Standardized Diagnosis and Treatment Project). Results: Overall, 3051 participants were included in the final analysis. IGA*BSA correlated better with objective measures than with subjective measures. IGA*BSA significantly correlated with Eczema Area and Severity Index (EASI) (r = 0.81), which was stronger than either IGA or BSA alone with EASI, regardless of age, sex, Body Mass Index (BMI), and disease severity groups. Besides, IGA*BSA mild, moderate, and severe groups were associated with significantly higher scores of other assessments and had moderate to fair concordance with other assessments severity strata. At follow-up, the concordance of improvement between IGA*BSA 50/75/90 and EASI 50/75/90 was observed (ĸ = 0.65, 0.62, 0.58, respectively). Conclusion: IGA*BSA appears to be a valid objective assessment of AD severity and improvement over time across all age, sex, BMI, and disease severity subgroups in the clinical practice.

[Relationship between lipid metabolism molecules in plasma and carotid atheroscle-rotic plaques, traditional cardiovascular risk factors, and dietary factors].

OBJECTIVE: To explore the relationship between lipid metabolism molecules in plasma and carotid atherosclerotic plaques, traditional cardiovascular risk factors and possible dietary related factors. METHODS: Firstly, among 1 312 community people from those who participated in a 10-year follow-up study of subclinical atherosclerosis cohort in Shijingshan District, Beijing, 85 individuals with 2 or more carotid soft plaques or mixed plaques and 89 healthy individuals without plaques were selected according to the inclusive and the exclusive criteria (< 70 years, not having clinical cardiovascular disease and other diseases, etc.). Secondly, 10 cases and 10 controls were randomly selected in the above 85 and 89 individuals respectively. Carotid plaques were detected using GE Vivid i Ultrasound Machine with 8L detector. Lipid metabolism molecules were detected by high performance liquid chromatography-mass spectrometry. The detection indexes included 113 lipid metabolism molecules. Traditional cardiovascular risk factors were collected by unified standard questionnaires, and dietary related factors were collected by main dietary frequency and weight scale. The difference of lipid metabolism molecules between the case group and the control group was analyzed by Wilcoxin rank test. In the control group, the Spearman correlation method was used to analyze the correlation between statistically significant lipid metabolism molecules and traditional cardiovascular risk factors and dietary factors. RESULTS: Among the 113 lipid metabolism molecules, 53 lipid metabolism molecules were detected. C24:0 sphingomyelin (SM), C22:0/ C24:0 ceramide molecules, C18:0 phosphoethanolamine (PE) molecules, and C18:0/C18:2 (Cis) phosphatidylcholine (PC) were significantly higher in the carotid atherosclerotic plaque group than in the control group. The correlation analysis showed that C24:0 SM was significantly positively correlated with low density lipoprotein cholesterol (LDL-C, r=0.636, P < 0.05), C18:2 (Cis) PC (DLPC) was significantly positively correlated with systolic pressure (r=0.733, P < 0.05), C18:0 PE was significantly positively correlated with high sensitivity C-response protein (r=0.782, P < 0.01), C22:0, C24:0 ceramide and C18:0 PE were negatively correlated with vegetable intake (r=-0.679, P < 0.05;r=-0.711, P < 0.05;r=-0.808, P < 0.01), C24:0 ceramide was also negatively correlated with beans food intake (r=-0.736, P < 0.05) in the control group. CONCLUSIONS: The increase of plasma C24:0 SM, C22:0, C24:0 ceramide, C18:0 PE, C18:2 (Cis) PC (DLPC), C18:0 PC (DSPC) may be new risk factors for human atherosclerotic plaques. These molecules may be related to blood lipid, blood pressure or inflammatory level and the intake of vegetables and soy products, but the nature of the association needs to be verified in a larger sample population.

N6-methyladenosine modification of circMARK2 enhances cytoplasmic export and stabilizes LIN28B, contributing to the progression of Wilms tumor.

BACKGROUND: The potential involvement of circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification in the progression of Wilms tumor (WT) has not been fully elucidated. This study investigates the regulatory mechanisms and clinical significance of m6A-modified circMARK2 and its role in WT progression. METHODS: We identified dysregulated circRNAs through deep sequencing and validated their expression by qRT-PCR in WT tissues. The biological functions of circMARK2 were assessed using clone formation, transwell migration, and orthotopic animal models. To dissect the underlying mechanisms, we employed RNA immunoprecipitation, RNA pull-down, dual-luciferase reporter assays, Western blotting, and immunofluorescence and immunohistochemical staining. RESULTS: CircMARK2, upregulated in WT tissues, was found to be m6A-modified and promoted cytoplasmic export. It facilitated WT progression by stabilizing LIN28B mRNA through the circMARK2/IGF2BP2 interaction. In vitro and in vivo studies demonstrated that circMARK2 enhances the malignant behavior of WT cells. Clinically, higher circMARK2 levels in tumor tissues of WT patients were linked to increased tumor aggressiveness and reduced survival rates. CONCLUSIONS: Our study provides the first comprehensive evidence that m6A-modified circMARK2 contributes to WT progression by enhancing LIN28B mRNA stability, promoting cellular aggressiveness. CircMARK2 emerges as a potential biomarker for prognosis and a promising target for therapeutic intervention in WT, underscoring the clinical relevance of m6A modification in pediatric renal cancer.

Identification of novel biomarkers for lupus nephritis.

Lupus nephritis (LN) is an autoimmune disease that rapidly progresses as a secondary consequence of systemic lupus erythematosus (SLE) and has a very poor prognosis. Therefore, this study aimed to identify characteristics of immune cell infiltration and investigate potential therapeutic targets using bioinformatics methods and the Murphy Roths Large/lymphoproliferation (MRL/lpr) mouse model. In this study, a total of 2,810 differentially expressed genes (DEGs) were identified, which were primarily enriched in inflammatory and immune regulation pathways. From these DEGs, 226 immune-related genes (IRGs) were also identified. The single-sample gene set enrichment analysis (ssGSEA) revealed that patients with LN had increased infiltration of effector memory CD4+ T cells, effector memory CD8+ T cells, gamma delta T cells, myeloid-derived suppressor cells (MDSC), follicular helper T cells, Th1 cells, and Th2 cells, and this was closely correlated with the DEG-IRGs. Furthermore, the potential therapeutic biomarkers, CD244, S100 calcium binding protein P (S100P), and vascular endothelial growth factor C (VEGFC), were identified by Random Forest Approach (RFA), which were validated in LN mice. These findings provide new evidence and insights for further research on diagnosis and treatment of LN by identifying critical genes and their associations with immune infiltration.

Analysis of infrared radiation emitted by moxibustion devices made of different materials using Fourier transform infrared spectroscopy.

Moxibustion has a long history of use as a traditional Chinese medicine therapy. Infrared radiation is an important and effective factor in moxibustion. Instead of the time-consuming and laborious process of holding moxa sticks in the hand, moxibustion devices are commonly used as moxibustion methods and tools in modern times. With the publication of the international standard of moxibustion devices (ISO18666:2021, Traditional Chinese Medicine - General requirements of moxibustion devices) published, moxibustion devices of various materials are now sold in the pharmacies and online stores. However, the influence of moxibustion devices on the therapeutic effect of moxibustion has not been studied. Therefore, this research was aimed to evaluate the infrared radiation of moxibustion devices, in order to select the moxibustion device that delivered infrared radiation closest to that of moxa stick combustion. The combination of combustion stability and infrared radiation intensity showed that cardboard tubes and silicone were better materials for moxibustion devices. In the mid-far infrared wave band, the moxibustion devices made from cardboard tubes and silica gels can better maintain the thermal effect generated by moxibustion and enable it to be more easily absorbed by the human body. The infrared radiation intensity of the cardboard moxibustion devices increased rapidly and steadily and could be maintained for the longest time. In conclusion, cardboard tubes are the better material for moxibustion devices with respect to infrared radiation.

The metabolomics analysis of cecal contents elucidates significant metabolites involved in the therapeutic effects of total flavonoids derived from Sonchus arvensis L. in male C57BL/6 mice with ulcerative colitis.

Ulcerative colitis (UC), an inflammatory disease affecting the colon and rectal mucosa, is characterized by chronic and heterogeneous behavior of unknown origin. The primary cause of UC is chronic inflammation, which is closely linked to the development of colorectal cancer. Sonchus arvensis L. (SAL), a plant consumed worldwide for its nutritional and medicinal properties, holds significance in this context. In this study, we employed the total flavone in SAL as a treatment for male C57BL/6 mice with UC. The cecal contents metabolic profile of C57BL/6 mice in different groups, including UC (group ML; n = 5), UC treated with aspirin (group AN; n = 5), UC treated with the total flavone in SAL (group FE; n = 5), and healthy male C57BL/6 mice (group CL; n = 5), was examined using UHPLC-Triple-TOF-MS. Through the identification of variations in key metabolites associated with UC and the exploration of their underlying biological mechanisms, our understanding of the pathological processes underlying this condition has been enhanced. This study identified a total of seventy-three metabolites that have a significant impact on UC. Notably, the composition of total flavone in SAL, a medication used for UC treatment, differs from that of aspirin due to the presence of four distinct metabolites (13,14-Dihydro-15-keto-PGE2, Prostaglandin I2 (PGI2), (20R,22R)-20,22-dihydroxycholesterol, and PS (18:1(9Z)/0:0)). These metabolites possess unique characteristics that set them apart. Moreover, the study identified a total of eleven pathways that were significantly enriched in mice with UC, including Aminoacyl-tRNA biosynthesis, Valine, leucine and isoleucine biosynthesis, Linoleic acid metabolism, PPAR signaling pathway, mTOR signaling pathway, Valine, leucine and isoleucine degradation, Lysine degradation, VEGF signaling pathway, Melanogenesis, Endocrine and other factor-regulated calcium reabsorption, and Cocaine addiction. These findings contribute to a better understanding of the metabolic variations in UC following total flavonoids of SAL therapy and provide valuable insights for the treatment of UC.Keywords: Ulcerative colitis; Total flavonoids of Sonchus arvensis L.; Key metabolites; Metabonomics; Cecal contents of male C57BL/6 mice.

Integrin-Linked Kinase in the Development of Gastric Tumors Induced by Helicobacter pylori: Regulation and Prevention Potential.

BACKGROUND: Integrin-linked kinase (ILK) is crucial in solid tumors by regulating the Hippo-Yes-associated protein 1 (YAP) pathway. This study aimed to uncover how Helicobacter pylori influences ILK levels and its role in regulating YAP during H. pylori-induced gastric cancer. MATERIALS AND METHODS: GES-1 cells with stable Ilk knockdown and overexpression and a mouse carcinogenesis model for H. pylori infection were constructed. And ILK, the phosphorylated mammalian STE20-like protein kinase 1 (MST1), large tumor suppressor 1 (LATS1; S909, T1079), and YAP (S109, S127) were detected in cells, and mice by western blotting, as well as fluorescence intensity of YAP were assayed by immunofluorescence. YAP downstream genes Igfbp4 and Ctgf, the pathological changes and tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1ß), and nitric oxide (NO) levels in mice gastric tissues were detected by real-time PCR, H&E, and ELISA assays. RESULTS: In this study, stable Ilk knockdown cells exhibited significantly higher phosphorylated levels of MST1, LATS1, and YAP, as well as increased YAP in the nuclei of GES-1 cells. Conversely, cells with Ilk overexpression showed opposite results. H. pylori infection led to decreased ILK levels in gastric epithelial cells but increased ILK levels in gastric cancer cell lines (MGC803, SGC7901) and gastric cancer tissues in mice. Treatment with the ILK inhibitor OST-T315 elevated the phosphorylated MST, LATS1, and YAP levels, and inhibited the mRNA levels of Igfbp4 and Ctgf at 44, 48 week-aged mice. OST-T315 also reduced the release of TNF-α, IL-6, IL-1ß, and NO, as well as the progression of gastric cancer caused by H. pylori and N-Nitroso-N-methylurea (NMU) treatment. CONCLUSION: Upon initiation of gastric tumorigenesis signals, H. pylori increases ILK levels and suppresses Hippo signaling, thereby promoting YAP activation and gastric cancer progression. ILK can serve as a potential prevention target to impede H. pylori-induced gastric cancer.