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Abstract RAB3B is essential for the transportation and secretion within cells. Its increased expression is linked to the development and progression of various malignancies. However, understanding of RAB3B’s involvement in carcinogenesis is mostly limited to specific cancer subtypes. Hence, exploring RAB3B's regulatory roles and molecular mechanisms through comprehensive cancer datasets might offer innovative approaches for managing clinical cancer. To examine the potential involvement of RAB3B in the development of cancer, we analyzed data from various sources including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, HPA, UALCAN, and tissue microarray (TAM). Using bioinformatics techniques, we examined the correlation between RAB3B expression and prognosis, tumor heterogeneity, methylation modifications, and immune microenvironment across different cancer types. Our findings indicate that elevated RAB3B expression can independently predict prognosis in many tumors and has moderate accuracy for diagnosing most cancers. In most cancer types, we identified RAB3B mutations that showed a significant correlation with tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and microsatellite instability (MSI). Abnormal DNA methylation patterns were also observed in most cancers compared to normal tissues. Additionally, we found significant correlations between RAB3B expression, immune cell infiltration, and immune scores across various cancers. Through pan-cancer analysis, we observed significant differences in RAB3B expression levels between tumors and normal tissues, making it a potential primary factor for cancer diagnosis and prognosis. The IHC results revealed that the expression of RAB3B in six types of tumors was consistent with the results of the pan-cancer analysis of the database. Furthermore, RAB3B showed potential associations with tumor heterogeneity and immunity. Thus, RAB3B can be utilized as an auxiliary diagnostic marker for early tumor detection and a prognostic biomarker for various tumor types.

Abstract Background Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive. Results We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster. Conclusions A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL − Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.

Abstract Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.

Abstract Background Lipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis. Purpose Explore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3–5. Methods This is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3–5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness.. Results 255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis.. Conclusion Comprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3–5.

BackgroundChinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3–5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear.MethodsPatients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)

Abstract Background This study investigated the correlation between the expression of DARS2 and metabolic parameters of 18F-FDG PET/CT, and explored the potential mechanisms of DARS2 affecting the proliferation and glycolysis of lung adenocarcinoma (LUAD) cells. Methods This study used genomics and proteomics to analyze the difference in DARS2 expression between LUAD samples and control samples. An analysis of 62 patients with LUAD who underwent 18F-FDG PET/CT examinations before surgery was conducted retrospectively. The correlation between DARS2 expression and PET/CT metabolic parameters, including SUVmax, SUVmean, MTV, and TLG, was examined by Spearman correlation analysis. In addition, the molecular mechanism of interfering with DARS2 expression in inhibiting LUAD cell proliferation and glycolysis was analyzed through in vitro cell experiments. Results DARS2 expression was significantly higher in LUAD samples than in control samples (p

Abstract Background The insect hemolymph (blood-equivalent fluid), composed of a large number of hemocytes (blood cells) and a variety of soluble immune effectors, is hostile for pathogens including fungi. In order to survive in the insect hemocoel (body cavity), the entomopathogenic fungus (EPF) has evolved two classical coping strategies, namely evasion and suppression of the host immune reactions. However, it remains unclear whether EPF has other ways of coping with host immunity. Results In this study, we demonstrated that Metarhizium rileyi (an EPF) infection by injection of blastospores into the hemocoel enhanced the plasma antibacterial activity of cotton bollworm (Helicoverpa armigera), which was partially due to the enhanced expression of antimicrobial peptides (AMPs). The early stage of M. rileyi infection induced the translocation of gut bacteria into the hemocoel, where they were subsequently cleared due to the enhanced plasma antibacterial activity. Further, we showed that the enhanced plasma antibacterial activity and AMP expression were attributable to M. rileyi but not the invasive gut bacteria (opportunistic bacteria). Elevated ecdysone (major steroid hormone in insects) levels in the hemolymph at 48 h post-M. rileyi infection might contribute to the enhanced expression of AMPs. The fungus-elicited AMPs, such as cecropin 3 or lebocin, exhibited potent inhibitory activity against the opportunistic bacteria but not against hyphal bodies. In addition, the opportunistic bacteria competed with hyphal bodies for amino acid nutrients. Conclusions M. rileyi infection induced the translocation of gut bacteria, and then the fungi activated and exploited its host humoral antibacterial immunity to eliminate opportunistic bacteria, preventing them from competing for nutrients in the hemolymph. Unlike the classical strategies, EPF utilizes to evade or suppress host immunity, our findings reveal a novel strategy of interaction between EPF and host immunity. Video Abstract

Abstract Background The aim of this study was to determine the expression and function of heterogeneous nuclear ribonucleoprotein R (HNRNPR) in esophageal carcinoma (ESCA), the correlation between its expression and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computerized tomography scan (PET/CT)-related parameters. We also investigated whether 18F-FDG PET/CT can be used to predict the expression of HNRNPR in ESCA. Methods We analyzed patients with ESCA who underwent 18F-FDG PET/CT before surgery, and their tissues were stained with HNRNPR IHC. The associated parameters were derived using the 18F-FDG PET imaging data, and the correlation with the IHC score was evaluated. The Oncomine, TCGA, and GEO datasets were used to investigate HNRNPR expression in the pan- and esophageal cancers, as well as its relationship with N6-methyladenosine (m6A) modification and glycolysis. The R software, LinkedOmics, GeneMANIA, and StringOnline tools were used to perform GO/KEGG, GGI, and PPI analyses on the HNRNPR. Results HNRNPR is highly expressed in the majority of pan-cancers, including ESCA, and is associated with BMI, weight, and history of reflux in patients with ESCA. HNRNPR is somewhat accurate in predicting the clinical prognosis of ESCA. HNRNPR expression was positively correlated with SUVmax, SUVmean, and TLG in ESCA (p

BackgroundTime-restricted feeding (TRF) has become a popular weight loss method in recent years. It is widely used in the nutritional treatment of normal obese people and obese people with chronic diseases such as diabetes mellitus and hypertension, and has shown many benefits. However, most TRF studies have excluded chronic kidney disease (CKD) patients, resulting in a lack of sufficient evidence-based practice for the efficacy and safety of TRF therapy for CKD. Therefore, we explore the efficacy and safety of TRF in overweight and obese patients with moderate-to-severe stage CKD through this pilot study, and observe patient compliance to assess the feasibility of the therapy.MethodsThis is a prospective, non-randomized controlled short-term clinical trial. We recruited overweight and obese patients with CKD stages 3-4 from an outpatient clinic and assigned them to either a TRF group or a control diet (CD) group according to their preferences. Changes in renal function, other biochemical data, anthropometric parameters, gut microbiota, and adverse events were measured before the intervention and after 12 weeks.ResultsThe change in estimated glomerular filtration rate (eGFR) before and after intervention in the TRF group (Δ = 3.1 ± 5.3 ml/min/1.73m2) showed significant improvement compared with the CD group (Δ = -0.8 ± 4.4 ml/min/1.73m2). Furthermore, the TRF group had a significant decrease in uric acid (Δ = -70.8 ± 124.2 μmol/L), but an increase in total protein (Δ = 1.7 ± 2.5 g/L), while the changes were inconsistent for inflammatory factors. In addition, the TRF group showed a significant decrease in body weight (Δ = -2.8 ± 2.9 kg) compared to the CD group, and body composition indicated the same decrease in body fat mass, fat free mass and body water. Additionally, TRF shifted the gut microbiota in a positive direction.ConclusionPreliminary studies suggest that overweight and obese patients with moderate-to-severe CKD with weight loss needs, and who were under strict medical supervision by healthcare professionals, performed TRF with good compliance. They did so without apparent adverse events, and showed efficacy in protecting renal function. These results may be due to changes in body composition and alterations in gut microbiota.

Abstract Background Chronic kidney disease (CKD) is a major global health problem. Short-term self-management has been considered to effect some renal and psychological endpoints. However, there are currently very few studies about self-management for CKD that a) have been scientifically designed by a theory-based framework and b) that evaluate the long-term effects and working mechanism. This study presents the rationale and design of a theory-based cohort study to explore how this self-management intervention works and its effectiveness on the Chinese CKD population. Methods In this ambispective intervention cohort study,1,200 patients with CKD stages 1–5 will be recruited from July 2015 to July 2024 in 3 branches of Guangdong Provincial Hospital of Chinese Medicine (GPHCM) in Guangdong province, China. The patients in the self-management cohort will choose to receive an intervention that consists of education, nutrition/diet modification, lifestyle change recommendation, medication review, and psychology support based on Social Cognition Theory (SCT). The patients in the control cohort will do regular follow-ups based on the clinic rules. All the patients will be followed up for 5 years, or until the occurrence of a primary outcome. Detailed clinical, laboratory markers, nutritional status, psychological exposures and outcome questionaries will be collected semiannually in CKD stage 1–2 and trimonthly in stage 3–5 patients. The primary outcome is the occurrence of composite clinical endpoints (doubling of serum creatinine level, ESKD, loss of renal function (≥ 40% decline in GFR from baseline), death, major cardiovascular or cerebrovascular events). The main secondary outcomes include the absolute change and slope of eGFR, absolute changes of urinary protein creatinine ratio, 24-h urine proteinuria, intact parathyroid hormone level, and self-management adherence rate and quality of life from baseline to end of the study. The effectiveness of self-management will be analyzed and the association between longitudinal trajectories of self-management and renal outcomes will be evaluated. Discussion This study aims to provide further evidence for the effectiveness of theory-based self-management in CKD patients and to improve the lives of patients with CKD by slowing progression, improving psychological well-being and overall quality of life. Trial registration Chinese Clinical Trial Register (ChiCTR1900024633). 19 July, 2019. http://www.chictr.org.cn/showproj.aspx?proj=38378

In this paper, we propose three physical images, namely, asymmetric external inputs, discretization of the low rate region, and secondary outbreak, to understand the mystery of the relative timescales in the coevolution dynamics on multiplex networks. We carry out our analysis on an irreversible information-epidemic coevolution dynamics. In this dynamics, we found five kinds of anomalous behaviors, which are that with the increase of relative information processing speed, the final epidemic size may be monotonically increasing, monotonically decreasing, first decreasing and then increasing, first increasing and then decreasing but increasing again, and suddenly increasing with large fluctuation. Such complex behavior can be fully explained by our three physical images. Moreover, these five behaviors may transform into one another, which is far more complex than cyclic dynamics. Of course, our physical images easily provide an explanation for the results of cyclic coevolution dynamics. Since our discussion does not rely on specific dynamics and networks, our research may readily be extended to a broader field, rather than the network epidemiology in this paper.

Herein, we report a case of retroperitoneal clear cell carcinoma (RCCC) with an unknown primary site that was confirmed via pathology. A 46-year-old man presented with low-grade fever, hyperhidrosis, and nightly fatigue that had occurred for the last 20 days. His weight had decreased significantly within the past 2 months (approximately 12 kg). On abdominal ultrasound, a mass was observed near the left renal hilum. In addition, enhanced magnetic resonance imaging (MRI) of the abdomen revealed a retroperitoneal nodular mass; however, no abnormalities in either kidney or adrenal glands were observed. 18F-fludeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) demonstrated an intensely FDG-avid retroperitoneal mass, the maximum standardized uptake value (SUVmax) was 19.6. On March 8, 2021, left retroperitoneal lesion resection, retroperitoneal lymph node dissection, and double kidney exploration were performed under general anesthesia. A post-operative pathological examination revealed Poorly differentiated clear cell carcinoma (left retroperitoneal) and metastatic lymph nodes. Immunohistochemical findings showed that the tumor originated from the kidney. At 6-month follow-up, reexamination of the patient revealed retroperitoneal lesion recurrence; however, no abnormalities were observable via enhanced computed tomography (CT) of both kidneys. To our knowledge, there have been no previous reports of RCCC of unknown origin.

BackgroundThe targeted therapy for lung cancer relies on prognostic genes and requires further research. No research has been conducted to determine the effect of endothelin-converting enzyme 2 (ECE2) in lung cancer.MethodsWe analyzed the expression of ECE2 in lung adenocarcinoma (LUAD) and normal adjacent tissues and its relationship with clinicopathological characteristics from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). Immunohistochemical staining was used to further validate the findings. GO/KEGG enrichment analysis and gene set enrichment analysis (GSEA) of ECE2 co-expression were performed using R software. Data from TIMER, the GEPIA database, and TCGA were analyzed to determine the relationship between ECE2 expression and LUAD immune infiltration. To investigate the relationship between ECE2 expression levels and LUAD m6A modification, TCGA data and GEO data were analyzed.ResultsECE2 is highly expressed in various cancers including LUAD. ECE2 showed high accuracy in distinguishing tumor and normal sample results. The expression level of ECE2 in LUAD was significantly correlated with tumor stage and prognosis. GO/KEGG enrichment analysis showed that ECE2 was closely related to mitochondrial gene expression, ATPase activity and cell cycle. GSEA analysis showed that ECE2-related differential gene enrichment pathways were related to mitotic cell cycle, MYC pathway, PLK1 pathway, DNA methylation pathway, HIF1A pathway and Oxidative stress-induced cellular senescence. Analysis of the TIMER, GEPIA database, and TCGA datasets showed that ECE2 expression levels were significantly negatively correlated with B cells, CD4+ cells, M2 macrophages, neutrophils, and dendritic cells. TCGA and GEO datasets showed that ECE2 was significantly associated with m6A modification-related genes HNRNPC, IGF2BP1, IGF2BP3 and RBM1.ConclusionECE2 is associated with m6A modification and immune infiltration and is a prognostic biomarker in LUAD.

Background: NPM1 is highly expressed in a variety of solid tumors and promotes tumor development. However, there are few comprehensive studies on NPM1 analysis in gastrointestinal cancer.Methods: We used bioinformatics tools to study the expression difference of NPM1 between gastrointestinal cancer and control group, and analyzed the relationship between its expression level and the diagnosis, prognosis, functional signaling pathway, immune infiltration, m6A and cuproptosis related genes of gastrointestinal cancer. At the same time, the expression difference of NPM1 between esophageal carcinoma (ESCA) samples and control samples was verified by in vitro experiments.Results: NPM1 was overexpressed in gastrointestinal cancer. In vitro experiments confirmed that the expression of NPM1 in ESCA samples was higher than that in normal samples. The expression of NPM1 has high accuracy in predicting the outcome of gastrointestinal cancer. The expression of NPM1 is closely related to the prognosis of multiple gastrointestinal cancers. Go and KEGG enrichment analysis showed that NPM1 co-expressed genes involved in a variety of biological functions. NPM1 expression is potentially associated with a variety of immune cell infiltration, m6A and cuproptosis related genes in gastrointestinal cancers.Conclusion: NPM1 can be used as a diagnostic and prognostic marker of gastrointestinal cancer, which is related to the immune cell infiltration and the regulation of m6A and cuproptosis.

Kidney injuries may trigger renal fibrosis and lead to chronic kidney disease (CKD), but effective therapeutic strategies are still limited. Quercetin is a natural flavonoid widely distributed in herbal medicines. A large number of studies have demonstrated that quercetin may protect kidneys by alleviating renal toxicity, apoptosis, fibrosis and inflammation in a variety of kidney diseases. Therefore, quercetin could be one of the promising drugs in the treatment of renal disorders. In the present study, we review the latest progress and highlight the beneficial role of quercetin in kidney diseases and its underlying mechanisms. The pharmacokinetics and bioavailability of quercetin and its proportion in herbal medicine will also be discussed.

BackgroundSolute carrier family 17 member 9 (SLC17A9) encodes a member of a family of transmembrane proteins that are involved in the transport of small molecules. SLC17A9 is involved in the occurrence and development of various cancers, but its biological role in liver hepatocellular carcinoma (LIHC) is unclear.MethodsThe expression level of SLC17A9 was assessed using The Cancer Genome Atlas (TCGA) database and immunohistochemistry of tumor tissues and adjacent normal liver tissues. The receiver operating characteristic (ROC) and R software package performed diagnosis and prognosis. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes functional enrichment and co-expression of SLC17A9, gene–gene interaction (GGI), and protein–protein interaction (PPI) networks were performed using R, GeneMANIA, and STRING. Western blot, real-time quantitative PCR (RT-qPCR), immunofluorescence, colony formation, wound scratch assay, ATP production assays, and high connotation were applied to determine the effect of SLC17A9 knockdown on HEPG2 (hepatocellular liver carcinoma) cells. TIMER, GEPIA, and TCGA analyzed the relationship between SLC17A9 expression and immune cells, m6A modification, and ferroptosis.ResultsSLC17A9 expression in LIHC tissues was higher than in normal liver tissues (p < 0.001), and SLC17A9 was related to sex, DSS (disease-specific survival), and PFI (progression-free interval) (p = 0.015, 0.006, and 0.023). SLC17A9 expression has diagnostic (AUC: 0.812; CI: 0.770–0.854) and prognostic potential (p = 0.015) in LIHC. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) functional enrichment analysis showed that SLC17A9 was closely related to neuronal cell body, presynapse, axonogenesis, PI3K/Akt signaling pathway. GGI showed that SLC17A9 was closely related to MYO5A. PPI showed that SLC17A9 was closely related to SLC18A3. SLC17A9 silencing inhibited HepG2 cells proliferation, migration, colony formation, and reduced their ATP level. SLC17A9 expression level was related to immune cells: B cells (r = 0.094, P = 8.06E-02), CD4+ T cells (r = 0.184, P = 5.95E-04), and macrophages (r = 0.137, P = 1.15E-02); m6A modification: HNRNPC (r = 0.220, p < 0.001), METTL3 (r = 0.180, p < 0.001), and WTAP (r = 0.130, p = 0.009); and ferroptosis: HSPA5 (r = 0.240, p < 0.001), SLC7A11 (r = 0.180, p < 0.001), and FANCD2 (r = 0.280, p < 0.001).ConclusionOur data show that SLC17A9 may influence LIHC progression. SLC17A9 expression correlates with tumor immune infiltration, m6A modification, and ferroptosis in LIHC and may have diagnostic and prognostic value in LIHC.

In this paper, we investigate the effect of self-awareness (interlayer interaction) for information-epidemic dynamics with simplicial complexes both near and away from the epidemic threshold. It is shown that, contrary to previous views, self-awareness plays a key role near the epidemic threshold. In small homogeneous networks, multiple susceptibility peaks can emerge in the susceptibility of the epidemic layer under the combined effect of simplicial complexes and self-awareness, even two types of multiple susceptibility peaks with completely opposite mechanisms. This means that one needs to be very careful when obtaining epidemic thresholds based on susceptibility. Moreover, the self-awareness can regulate the presence or absence of bistable phenomena both in epidemic prevalence and epidemic threshold. We also found that the time series of disease may be nonmonotonic, with a peak, and that self-awareness is one of the factors controlling the relative height between maximum and steady state. In addition, we modify heterogeneous mean-field theory and partial effective degree theory to accommodate the introduction of simplicial complexes in dynamics. We believe that our study has implications for other dynamics concerning higher-order and interlayer interactions.

A 62-year-old female patient with pathologically confirmed left lung small cell neuroendocrine carcinoma. The patient was referred to our positron emission tomography (PET)/CT center to look for possible metastatic diseases. After fasting for 8 h, the fasting blood glucose level of the patient was 7.1 mmol/L. The patient was intravenously injected with a 6.42 mCi (238 MBq) 18F-fluorodeoxyglucose (FDG) imaging agent. After the patient rested for 1 h, we scanned the patient with SIEMENS Biograph mCT 64 PET/CT camera. In addition to lung tumors and lymph node diseases, abnormal tracer uptake in the patient's thyroid was also found. PET/CT also showed situs inversus totalis of the patient, including the dextrocardia, liver on the left side, stomach, and spleen on the right side of the patient's body. The identification of anatomical variations and abnormalities by PET/CT imaging is very important to develop the best treatment for lung cancer.

Background: YTHDF1 is highly expressed in multiple tumors and affects tumor progression. However, there are only a few comprehensive studies on the analysis of YTHDF1 in esophageal cancer.Methods: We analyzed YTHDF1 expression in pan-cancer by comparing both the GEPIA and TCGA cohorts, and further verified the differences in YTHDF1 expression between the ESCA and normal groups by the GEO ESCA cohort and in vitro experiments. The correlation of YTHDF1 expression and the clinical characteristics of ESCA patients was analyzed using the TCGA ESCA clinical data. The GO and KEGG enrichment analyses of the YTHDF1 coexpressed genes were completed by bioinformatics analysis, and the GGI and PPI were constructed for the YTHDF1, respectively. The relationship between YTHDF1 expression and the infiltration of ESCA immune cells was analyzed by using the TIMER database and the TCGA ESCA cohort. The relationships between YTHDF1 expression levels and glycolysis and ferroptosis-related genes were analyzed using the TCGA and GEPIA ESCA cohorts. Finally, the ceRNA network that may be involved in YTHDF1 in ESCA was predicted and constructed through a variety of databases.Results: YTHDF1 was overexpressed in various cancers, and in vitro experiments confirmed that YTHDF1 expression was higher in ESCA samples than in normal samples. The expression of YTHDF1 has some accuracy in predicting the tumor outcome. Expression of YTHDF1 was significantly associated with multiple clinical features in ESCA patients. GO and KEGG enrichment analyses indicated that YTHDF1 coexpressed genes involved multiple biological functions. There is a potential association between YTHDF1 expression and multiple immune cell infiltration, glycolysis, and ferroptosis-related genes in ESCA. YTHDF1 may be involved in multiple ceRNA regulatory networks in ESCA, including PAXIP1-AS1/hsa-miR-376c-3p/YTHDF1 axis, THUMPD3-AS1/hsa-miR-655-3p/YTHDF1 axis, and SNHG20/hsa-miR-655-3p/YTHDF1 axis, respectively.Conclusion: YTHDF1 can serve as a biomarker of ESCA, related to the immune cell infiltration of ESCA, regulation of glycolysis and ferroptosis, and the ceRNA regulatory network.

Background: Overexpression of solute carrier family 2 member 1 (SLC2A1) promotes glycolysis and proliferation and migration of various tumors. However, there are few comprehensive studies on SLC2A1 in colorectal cancer (CRC).Methods: Oncomine, The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases were used to analyze the expression of SLC2A1 in pan-cancer and CRC and analyzed the correlation between SLC2A1 expression and clinical characteristics of TCGA CRC samples. The expression level of SLC2A1 in CRC was certified by cell experiments and immunohistochemical staining analysis. The Genome Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses of SLC2A1 relative genes were completed by bioinformatics analysis. The correlation between SLC2A1 expression level and CRC immune infiltration cell was analyzed by Tumor IMmune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and TCGA database. The correlation between SLC2A1 expression level and ferroptosis and m6A modification of CRC was analyzed by utilizing TCGA and GEO cohort. Finally, the possible competing endogenous RNA (ceRNA) networks involved in SLC2A1 in CRC are predicted and constructed through various databases.Results: SLC2A1 is highly expressed not only in CRC but also in many other tumors. ROC curve indicated that SLC2A1 had high predictive accuracy for the outcomes of tumor. The SLC2A1 expression in CRC was closely correlated with tumor stage and progression free interval (PFI). GO, KEGG, and GSEA analysis indicated that SLC2A1 relative genes were involved in multiple biological functions. The analysis of TIMER, GEPIA, and TCGA database indicated that the SLC2A1 mRNA expression was mainly positively associated with neutrophils. By the analysis of the TCGA and GEO cohort, we identified that the expression of SLC2A1 is closely associated to an m6A modification relative gene Insulin Like Growth Factor 2 MRNA Binding Protein 3 (IGF2BP3) and a ferroptosis relative gene Glutathione Peroxidase 4 (GPX4).Conclusion: SLC2A1 can be used as a biomarker of CRC, which is associated to immune infiltration, m6A modification, ferroptosis, and ceRNA regulatory network of CRC.

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Background: Hexokinase 2 not only plays a role in physiological function of human normal tissues and organs, but also plays a vital role in the process of glycolysis of tumor cells. However, there are few comprehensive studies on HK2 in esophageal carcinoma (ESCA) needs further study.Methods: Oncomine, Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were used to analyze the expression differences of HK2 in Pan-cancer and ESCA cohort, and to analyze the correlation between HK2 expression level and clinicopathological features of TCGA ESCA samples. GO/KEGG, GGI, and PPI analysis of HK2 was performed using R software, LinkedOmics, GeneMANIA and STRING online tools. The correlation between HK2 and ESCA immune infiltration was analyzed TIMER and TCGA ESCA cohort. The correlation between HK2 expression level and m6A modification of ESCA was analyzed by utilizing TCGA ESCA cohort.Results: HK2 is highly expressed in a variety of tumors, and its high expression level in ESCA is closely related to the weight, cancer stages, tumor histology and tumor grade of ESCA. The analysis results of GO/KEGG showed that HK2 was closely related to cell adhesion molecule binding, cell-cell junction, ameboidal-type cell migration, insulin signaling pathway, hif-1 signaling pathway, and insulin resistance. GGI showed that HK2 associated genes were mainly involved in the glycolytic pathway. PPI showed that HK2 was closely related to HK1, GPI, and HK3, all of which played an important role in tumor proliferation. The analysis results of TIMER and TCGA ESCA cohort indicated that the HK2 expression level was related to the infiltration of various immune cells. TCGA ESCA cohort analyze indicated that the HK2 expression level was correlated with m6A modification genes.Conclusion: HK2 is associated with tumor immune infiltration and m6A modification of ESCA, and can be used as a potential biological target for diagnosis and therapy of ESCA.

BackgroundOverexpression of NPM1 can promote the growth and proliferation of various tumor cells. However, there are few studies on the comprehensive analysis of NPM1 in lung adenocarcinoma (LUAD).MethodsTCGA and GEO data sets were used to analyze the expression of NPM1 in LUAD and clinicopathological analysis. The GO/KEGG enrichment analysis of NPM1 co-expression and gene set enrichment analysis (GSEA) were performed using R software package. The relationship between NPM1 expression and LUAD immune infiltration was analyzed using TIMER, GEPIA database and TCGA data sets, and the relationship between NPM1 expression level and LUAD m6A modification and glycolysis was analyzed using TCGA and GEO data sets.ResultsNPM1 was overexpressed in a variety of tumors including LUAD, and the ROC curve showed that NPM1 had a certain accuracy in predicting the outcome of tumors and normal samples. The expression level of NPM1 in LUAD is significantly related to tumor stage and prognosis. The GO/KEGG enrichment analysis indicated that NPM1 was closely related to translational initiation, ribosome, structural constituent of ribosome, ribosome, Parkinson disease, and RNA transport. GSEA showed that the main enrichment pathway of NPM1-related differential genes was mainly related to mTORC1 mediated signaling, p53 hypoxia pathway, signaling by EGFR in cancer, antigen activates B cell receptor BCR leading to generation of second messengers, aerobic glycolysis and methylation pathways. The analysis of TIMER, GEPIA database and TCGA data sets showed that the expression level of NPM1 was negatively correlated with B cells and NK cells. The TCGA and GEO data sets analysis indicated that the NPM1 expression was significantly correlated with one m6A modifier related gene (HNRNPC) and five glycolysis related genes (ENO1, HK2, LDHA, LDHB and SLC2A1).ConclusionNPM1 is a prognostic biomarker involved in immune infiltration of LUAD and associated with m6A modification and glycolysis. NPM1 can be used as an effective target for diagnosis and treatment of LUAD.

Renal fibrosis is one of the most characterized pathological features in chronic kidney disease (CKD). Progressive fibrosis eventually leads to renal failure, leaving dialysis or allograft transplantation the only clinical option for CKD patients. Transforming growth factor-β (TGF-β) is the key mediator in renal fibrosis and is an essential regulator for renal inflammation. Therefore, the general blockade of the pro-fibrotic TGF-β may reduce fibrosis but may risk promoting renal inflammation and other side effects due to the diverse role of TGF-β in kidney diseases. Long non-coding RNAs (lncRNAs) are RNA transcripts with more than 200 nucleotides and have been regarded as promising therapeutic targets for many diseases. This review focuses on the importance of TGF-β and lncRNAs in renal inflammation, fibrogenesis, and the potential applications of TGF-β and lncRNAs as the therapeutic targets and biomarkers in renal fibrosis and CKD are highlighted.

BackgroundGlucose transporter 1 (GLUT1) is encoded by the solute carrier family 2A1 (SLC2A1) gene and is one of the glucose transporters with the greatest affinity for glucose. Abnormal expression of GLUT1 is associated with a variety of cancers. However, the biological role of GLUT1 in esophageal carcinoma (ESCA) remains to be determined.MethodsWe analyzed the expression of GLUT1 in pan-cancer and ESCA as well as clinicopathological analysis through multiple databases. Use R and STRING to perform GO/KEGG function enrichment and PPI analysis for GLUT1 co-expression. TIMER and CIBERSORT were used to analyze the relationship between GLUT1 expression and immune infiltration in ESCA. The TCGA ESCA cohort was used to analyze the relationship between GLUT1 expression and m6A modification in ESCA, and to construct a regulatory network in line with the ceRNA hypothesis.ResultsGLUT1 is highly expressed in a variety of tumors including ESCA, and is closely related to histological types and histological grade. GO/KEGG functional enrichment analysis revealed that GLUT1 is closely related to structural constituent of cytoskeleton, intermediate filament binding, cell-cell adheres junction, epidermis development, and P53 signaling pathway. PPI shows that GLUT1 is closely related to TP53, GIPC1 and INS, and these three proteins all play an important role in tumor proliferation. CIBERSORT analysis showed that GLUT1 expression is related to the infiltration of multiple immune cells. When GLUT1 is highly expressed, the number of memory B cells decreases. ESCA cohort analysis found that GLUT1 expression was related to 7 m6A modifier genes. Six possible crRNA networks in ESCA were constructed by correlation analysis, and all these ceRNA networks contained GLUT1.ConclusionGLUT1 can be used as a biomarker for the diagnosis and treatment of ESCA, and is related to tumor immune infiltration, m6A modification and ceRNA network.

Abstract Background Mermithid nematodes, such as Ovomermis sinensis, display a broad host range including some lepidopteran pests. Infective juveniles penetrate their host through the cuticle, complete their growth within the hemocoel and eventually kill the host upon their emergence. Hence, mermithid nematodes are considered potential biological control agents of insect pests. Our previous data indicate that the infection rate of O. sinensis on cotton bollworm (Helicoverpa armigera) is low, which may be largely due to the strong immune system of the host. However, current knowledge on the interactions of mermithid nematodes with their hosts and the mechanisms employed by hosts to defend themselves against mermithid nematodes is limited. Results Here, we investigated the response of H. armigera to O. sinensis infection. Parasitism by O. sinensis caused a sharp decline in the survival rate of H. armigera. The hemocytic phagocytosis ability, antibacterial activity, and phenoloxidase (PO) activity in plasma of H. armigera increased at 1 d post parasitism (dpp) but decreased at 3 dpp. Further, we investigated gene expression in the fat body of parasitized and non-parasitized H. armigera larvae at 1, 3, and 5 dpp using a digital gene expression system. In total, 41, 60 and 68 immune-related differentially expressed genes were identified at 1, 3, and 5 dpp, respectively. These genes encoded pattern recognition receptors (PRRs), antimicrobial peptides (AMPs), serine proteases (SPs), SP inhibitors, mucins and other immune-related proteins. The expression of most PRRs, AMPs, SPs, and mucins was upregulated in the fat body of larvae at 1 dpp, downregulated at 3 dpp, and then again upregulated at 5 dpp by O. sinensis. The increased expression of SP inhibitors may contribute to the inhibited PO activity at 5 dpp. Conclusions This study demonstrates that parasitism by O. sinensis modulates the immune reaction of the host H. armigera by altering the expression of immune-related genes. Our data provide a basis for future investigation of the molecular mechanisms employed by the mermithid nematode O. sinensis to modulate the immunity of the host H. armigera. These data will also likely facilitate the improvement of success in parasitism of H. armigera by O. sinensis.

Triptriolide (T11) is a natural diterpene diepoxide that derived from Chinese traditional herb medicine (TCHM) Tripterygium wilfordii Hook.F (TWHF). From a structural point of view, T11 is very similar to triptolide (T9), one of the most effectively compounds in TWHF that have already been systematically investigated in the past decades. However, the basic functions and medicinal properties of T11 have not yet been well investigated mainly due to its low abundance in its plant organ. The present study aimed to investigate the protective effects of T11 on puromycin aminonucleoside (PAN) induced apoptotic mouse podocytes and the underlying mechanism. The results showed that T11 had no significant toxicity in podocytes in high dosage, and showed prominent protective effects on PAN induced podocytes injury. Further studies indicated that T11 might exert its protective effects by inhibiting of apoptosis and restoring of survival in PAN induced podocytes.

BackgroundE2F transcription factors (E2Fs) are a group of genes encoding a family of transcription factors in higher eukaryotes. They are involved in a variety of cellular functions and are up-regulated in many tissues and organs. However, the expression level, genetic variation, molecular mechanism, and biological function of different E2Fs in PAAD and its relationship with the prognosis and immune infiltration in patients with PAAD have not been fully elucidated.MethodsIn this study, we investigated the mRNA expression level, genetic variation, prognostic value and gene–gene interaction network of E2Fs in PAAD using the Oncomine, GEPIA, Kaplan Meier plotter, cBioPortal, GeneMANIA, STRING and Metascape database. Then, the relationship between E2Fs expression and tumor immune invasion was studied by using the TIMER database. Finally, we confirmed the expression of E2Fs in PAAD by IHC.ResultsThe transcription levels of E2F1/3/5/8 are obviously up-regulated in PAAD and the high expression of E2F2/3/6/8 was apparently associated with the tumor stage of patients with PAAD. The abnormal expression of E2F1/2/3/4/5/7/8 in PAAD patients is related to the clinical outcome of PAAD patients. We also found that PAAD tissues have higher expression levels of E2F1/3/5/8 compared with adjacent normal tissues. The function of E2Fs and its neighboring genes is mainly related to the transcription initiation of the RNA polymerase II promoter. The functions of E2Fs and its neighboring proteins are mainly related to cell cycle, virus carcinogenesis, FoxO signaling pathway, TGF-β signaling pathway, transcriptional disorders in cancer and Wnt signaling pathway. We also found that the expression of E2Fs was significantly correlated with immune infiltrates, including B cells, CD8+ T cells, CD4+T cells, neutrophils, macrophages, and dendritic cells.ConclusionsOur study may provide new insights into the choice of immunotherapy targets and prognostic biomarkers in PAAD patients.

Diabetic kidney disease (DKD) is the most common diabetic complication and is a leading cause of end-stage kidney disease. Increasing evidence shows that DKD is regulated not only by many classical signaling pathways but also by epigenetic mechanisms involving chromatin histone modifications, DNA methylation, and non-coding RNA (ncRNAs). In this review, we focus on our current understanding of the role and mechanisms of ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the pathogenesis of DKD. Of them, the regulatory role of TGF-β/Smad3-dependent miRNAs and lncRNAs in DKD is highlighted. Importantly, miRNAs and lncRNAs as biomarkers and therapeutic targets for DKD are also described, and the perspective of ncRNAs as a novel therapeutic approach for combating diabetic nephropathy is also discussed.

Kidneys are one of the targets for SARS-CoV-2, it is reported that up to 36% of patients with SARS-CoV-2 infection would develop into acute kidney injury (AKI). AKI is associated with high mortality in the clinical setting and contributes to the transition of AKI to chronic kidney disease (CKD). Up to date, the underlying mechanisms are obscure and there is no effective and specific treatment for COVID-19-induced AKI. In the present study, we investigated the mechanisms and interactions between Quercetin and SARS-CoV-2 targets proteins by using network pharmacology and molecular docking. The renal protective effects of Quercetin on COVID-19-induced AKI may be associated with the blockade of the activation of inflammatory, cell apoptosis-related signaling pathways. Quercetin may also serve as SARS-CoV-2 inhibitor by binding with the active sites of SARS-CoV-2 main protease 3CL and ACE2, therefore suppressing the functions of the proteins to cut the viral life cycle. In conclusion, Quercetin may be a novel therapeutic agent for COVID-19-induced AKI. Inhibition of inflammatory, cell apoptosis-related signaling pathways may be the critical mechanisms by which Quercetin protects kidney from SARS-CoV-2 injury.

Inflammation and fibrosis are two pathological features of chronic kidney disease (CKD). Transforming growth factor-β (TGF-β) has been long considered as a key mediator of renal fibrosis. In addition, TGF-β also acts as a potent anti-inflammatory cytokine that negatively regulates renal inflammation. Thus, blockade of TGF-β inhibits renal fibrosis while promoting inflammation, revealing a diverse role for TGF-β in CKD. It is now well documented that TGF-β1 activates its downstream signaling molecules such as Smad3 and Smad3-dependent non-coding RNAs to transcriptionally and differentially regulate renal inflammation and fibrosis, which is negatively regulated by Smad7. Therefore, treatments by rebalancing Smad3/Smad7 signaling or by specifically targeting Smad3-dependent non-coding RNAs that regulate renal fibrosis or inflammation could be a better therapeutic approach. In this review, the paradoxical functions and underlying mechanisms by which TGF-β1 regulates in renal inflammation and fibrosis are discussed and novel therapeutic strategies for kidney disease by targeting downstream TGF-β/Smad signaling and transcriptomes are highlighted.

Background: Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. Methods: The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min−1·1.73 m−2, aged 18–70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. Results: A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (−13.0–24.1) and 11.7 (−2.6–42.9) μmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was −0.2 (−4.3–2.7) and −2.2 (−5.7–0.8) ml·min−1·1.73 m−2, respectively (Z = −2.408, P = 0.016). There were no significant differences in adverse events between the groups. Conclusions: Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. Trial Registration: Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.

Triptolide(T9) is a predominant bioactive component extracted from Chinese herb Tripterygium wilfordii Hook F. (TwHF), and has multiple pharmacological activities, such as immunosuppressive and anti-inflammatory activities, et al. However, severe adverse effects and toxicity, particularly nephrotoxicity, limit its clinical application. It has been demonstrated that the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway could alleviate T9-induced nephrocyte damage. The aim of this study was to investigate the potential protective role of triptriolide (T11) against T9-induced nephrocyte apoptosis in vitro and in vivo. Renal injury models were established in human kidney 2 (HK2) cells and BALB/c mice using T9, and the protective effects of T11 were probed in vitro and in vivo, respectively. T9 induced nephrocyte damage in HK2 cells and BALB/c mice by induction of reactive oxygen species (ROS), lactate dehydrogenase (LDH), malondialdehyde (MDA) and glutathione (GSH) and reduction of superoxide dismutase (SOD), which resulted in the apoptosis of nephrocyte and injury of renal function. While, pretreatment of T11 effectively reversed these changes, resulting in the obvious decrease of oxidative stress and renal function parameters, ameliorated nephrocyte apoptosis, improved cell morphology, and higher increase of Nrf2, NAD(P)H: quinine oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) protein levels in vitro and in vivo. Altogether, T11 protected against T9-induced nephrocyte apoptosis possibly via suppressing oxidative stress.

Nrf2 (Nuclear Factor Erythroid 2 Related Factor 2) transcription factor not only regulates oxidative stress response, but also represses inflammation by regulating cytokines production and cross-talking with NF-κB signaling pathways. Nrf2 plays an essential role in liver injury induced by oxidative stress and inflammation. Triptriolide (T11) is a minor component of Tripterygium wilfordii Hook F. (TwHF), which can be obtained by hydrolysis reaction of triptolide (T9). The major purpose of this study is to clarify the regulating effects of T11 on oxidative stress and inflammation in vivo and in vitro. LPS-stimulated RAW 264.7 cells were used to verify the regulating effects of T11 on oxidative stress (ROS and Nrf2 signaling pathway) and inflammatory cytokines production (TNF-α, IL-6 and IL-1β). The antioxidant responsive element (ARE) luciferase assay was employed to evaluate Nrf2 activation effect of T11 in HEK-293T cells. Lipopolysaccharides (LPS) induced acute liver injury (ALI) in BALB/c mice were used to study the protective effects (ALT, AST, MDA, SOD, histopathology and neutrophils/macrophages filtration) and the underlying protection mechanisms of ALI amelioration (Nrf2 and NF-κB signaling pathway) of T11. Firstly, the results showed that T11 can not only effectively decrease the productions of inflammatory cytokines (TNF-α, IL-6 and IL-1β), ROS and NO in LPS-stimulated RAW 264.7 cells, but also further significantly increase the activity of Nrf2 in HEK-293T cells. Secondly, the results suggested that T11 could dramatically decrease the oxidative stress responses (SOD and MDA) and inflammation (histopathology, neutrophils/macrophages filtration, TNF-α, IL-6 and IL-1β production) in LPS-induced ALI in BALB/c mice. Finally, the results implied that T11 could dramatically increase Nrf2 protein expression and decrease p-TAK1, p-IκBα and NF-κB protein expression both in vivo and in vitro. In conclusion, our findings indicated that T11 could alleviate LPS induced oxidative stress and inflammation by regulating Nrf2 and NF-κB signaling pathways in vitro and in vivo, which offers a novel insights for the application of TwHF in clinical.

Bupi Yishen Formula (BYF), a Chinese medicine preparation, has been clinically applied for the recovery of chronic kidney disease and for delaying its progress. Nevertheless, the chemical components in BYF have yet to be fully clarified. Ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MSn) and triple-quadrupole tandem mass spectrometry (UHPLC-TQ-MS/MS) methods were developed for qualitative chemical profiling and multi-components quantitative analysis in BYF. The chromatographic separation was performed on a Phenomenex Kinetex C18 column (2.1 × 100 mm i.d., 1.7 μm) using gradient elution of water (A) and acetonitrile (B) both containing 0.1% formic acid. Eighty-six compounds, including flavones, saponins, phenolic acids, and other compounds were authenticated or temporarily deduced according to their retention behaviors, mass mensuration, and characteristic fragment ions with those elucidated reference substances or literatures. Among the herbal medicinal materials of the formula, Astragali Radix, Codonopsis Radix, Salviae Miltiorrhizae Radix Rhizoma, and Polygoni Multiflori Radix Praeparata contributed to the bulk of the dissolved metabolites of the formula extraction. In addition, seven analytes were simultaneously determined by UHPLC-TQ-MS/MS, which was validated and has managed to determine major components in BYF. The study indicated that the established qualitative and quantitative methods would be potent and dependable analytical tools for characterizing multi-constituent in complex prescriptions decoction and provided a basis for the evaluation of bioactive components in BYF.