Endotype-driven Co-module mechanisms of danhong injection in the Co-treatment of cardiovascular and cerebrovascular diseases: A modular-based drug and disease integrated analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular and cerebrovascular diseases are the leading causes of death worldwide and interact closely with each other. Danhong Injection (DHI) is a widely used preparation for the co-treatment of brain and heart diseases (CTBH). However, the underlying molecular endotype mechanisms of DHI in the CTBH remain unclear. AIM OF THIS STUDY: To elucidate the underlying endotype mechanisms of DHI in the CTBH. MATERIALS AND METHODS: In this study, we proposed a modular-based disease and drug-integrated analysis (MDDIA) strategy for elucidating the systematic CTBH mechanisms of DHI using high-throughput transcriptome-wide sequencing datasets of DHI in the treatment of patients with stable angina pectoris (SAP) and cerebral infarction (CI). First, we identified drug-targeted modules of DHI and disease modules of SAP and CI based on the gene co-expression networks of DHI therapy and the protein-protein interaction networks of diseases. Moreover, module proximity-based topological analyses were applied to screen CTBH co-module pairs and driver genes of DHI. At the same time, the representative driver genes were validated via in vitro experiments on hypoxia/reoxygenation-related cardiomyocytes and neuronal cell lines of H9C2 and HT22. RESULTS: Seven drug-targeted modules of DHI and three disease modules of SAP and CI were identified by co-expression networks. Five modes of modular relationships between the drug and disease modules were distinguished by module proximity-based topological analyses. Moreover, 13 targeted module pairs and 17 driver genes associated with DHI in the CTBH were also screened. Finally, the representative driver genes AKT1, EDN1, and RHO were validated by in vitro experiments. CONCLUSIONS: This study, based on clinical sequencing data and modular topological analyses, integrated diseases and drug targets. The CTBH mechanism of DHI may involve the altered expression of certain driver genes (SRC, STAT3, EDN1, CYP1A1, RHO, RELA) through various enriched pathways, including the Wnt signaling pathway.

Polyphyllin VII Promotes Apoptosis in Breast Cancer by Inhibiting MAPK/ERK Signaling Pathway through Downregulation of SOS1.

Polyphyllin VII is a biologically active herbal monomer extracted from the traditional Chinese herbal medicine Chonglou. Many studies have demonstrated the anticancer activity of polyphyllin VII against various types of cancers, such as colon, liver, and lung cancer, but its effect on breast cancer has not been elucidated. In this study, we demonstrate that polyphyllin VII inhibited proliferation, increased production of intracellular reactive oxygen species, and decreased mitochondrial membrane potential in breast cancer cells. Notably, polyphyllin VII also induced apoptosis via the mitochondrial pathway. Transcriptome sequencing was used to analyze the targets of PPVII in regulating breast cancer cells. Mechanistic studies showed that polyphyllin VII downregulated Son of Sevenless1 (SOS1) and inhibited the MAPK/ERK pathway. Furthermore, PPVII exerted strong antitumor effects in vivo in nude mice injected with breast cancer cells. Our results suggest that PPVII may promote apoptosis through regulating the SOS1/MAPK/ERK pathway, making it a possible candidate target for the treatment of breast cancer.

Betulinic acid inhibits the proliferation of human laryngeal carcinoma cells through reactive oxygen species-mediate mitochondrial apoptotic pathway.

Betulinic acid (BA), a natural pentacyclic triterpene, was extracted from the white birch tree, Triphyophyllum peltatum and the jujube tree. In a variety of human cancer cell lines, this substance displays anticancer properties. In this study, we examined how BA works to inhibit human laryngeal cancer growth. We discovered that BA minimally exhibited cytotoxicity in normal cells (human normal cell line GES-1), while remarkably inhibiting viability of AMC-HN-8, TU212, HEp-2 and M4e cells in a concentration-dependent manner. In AMC-HN-8 cancer cells, BA induced apoptosis, activated caspase-3/9/PARP, significantly reduced mitochondrial membrane potential (MMP), increased the expression of cytochrome C in the cytoplasm, transported Bax to the mitochondria, increased the production of reactive oxygen species (ROS), and the ROS scavenger N-acetylcysteine can reduce apoptosis. All data showed that BA triggered apoptosis via the mitochondrial pathway, in which ROS production was likely involved. The findings support the development of BA as a viable drug for the treatment of human laryngeal carcinoma.

Diosmin ameliorates LPS-induced depression-like behaviors in mice: Inhibition of inflammation and oxidative stress in the prefrontal cortex.

Diosmin is a flavone glycoside with a confirmed therapeutic effectiveness on the chronic venous disorders. In this paper, the classical mouse depression model induced by LPS was established to explore the effect of Diosmin on depression. Firstly, we found that Diosmin could inhibit the inflammation and neuronal damage in the prefrontal cortex (PFC) of mice, and thus alleviating the LPS-induced depressive-like behaviors. Specifically, Diosmin treatment significantly suppressed the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß), reduced the activation of microglia, and inhibited the expression of NLRP3 inflammasome and its downstream effector caspase-1 in both PFC of mice and BV2 microglial cells exposed to LPS. Then, we demonstrated that pretreatment with Diosmin dramatically suppressed the LPS-induced oxidative stress in the PFC of mice, manifested in the decrease of reactive oxygen species and malondialdehyde while increase of catalase activity. Consistently, Diosmin also alleviated the oxidative stress in BV2 cells exposed to LPS. Finally, we confirmed that Diosmin effectively suppressed the activation of NF-κB signaling pathway in the PFC of LPS-treated mice. Further in vitro experiments also verified that Diosmin could prevent the p65 transposition to nucleus in LPS-treated BV2 cells, suggesting that the antidepressant effects of Diosmin are partially mediated by blocking of NF-κB signaling. Taken together, this study proposes the potential antidepressant effect of Diosmin, which provides useful support to the development of new therapies for depression.

Intraprocedural Cortisol Measurement Increases Adrenal Vein Cannulation Success Rate in Primary Aldosteronism: A Systematic Review and Meta-analysis.

BACKGROUND: This study aimed to explore the effectiveness of intraprocedural cortisol measurement (IPCM) for the technical success rates of bilateral adrenal vein, right adrenal vein (RAV), and left adrenal vein (LAV) cannulation during adrenal vein sampling (AVS). METHODS: Systematic searches of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were performed from database inception to May 10, 2023, without any restrictions. We estimated the overall effect estimates of outcomes using the Mantel-Haenszel random-effects model. We conducted subgroup analyses, meta-regression, and sensitivity analysis to explore the possible sources of between-study heterogeneity. RESULTS: In total, 3,485 patients from 11 studies (three prospective and eight retrospective) were enrolled. Bilateral selectivity in patients who underwent IPCM during AVS was significantly higher than that in patients who underwent a routine AVS procedure (84% vs. 64%, RR 1.42, 95% confidence interval [CI]: 1.27-1.59, P < 0.01), with significant heterogeneity (I2 = 68%). A 42% relative risk reduction in the failure rate of bilateral adrenal vein cannulation was found in the IPCM group. Moreover, pooled analysis showed a significant increase in the success rates of RAV cannulation (84% vs. 72%, RR 1.21, 95% CI 1.12-1.31, P < 0.01, I2 = 33%) and LAV cannulation (89% vs. 84%, RR 1.05, 95% CI 1.02-1.08, P < 0.01, I2 = 4%) when IPCM was implemented during the AVS procedure compared to the routine AVS procedure. CONCLUSIONS: An IPCM-based strategy during AVS appears to have a significant beneficial effect on improving the success rate of bilateral cannulation, RAV cannulation and LAV cannulation.

Novel dual targeting cubosomes modified with angiopep-2 for co-delivery GNA and PLHSpT to brain glioma.

3Glioblastoma multiforme is the most aggressive malignant brain tumor. However, the treatment of glioblastoma multiforme faces great challenges owing to difficult penetration of the blood-brain barrier. Therefore, more effective treatment strategies are desired quite urgently. In our study, a dual-targeting drug delivery system for co-loading with hydrophobic Gambogenic acid and hydrophilic PLHSpT was developed by cubosomes with angiopep-2 decorating. The Ang-cubs-(GNA + PLHSpT) was prepared by high-temperature emulsification-low-temperature solidification demonstrating excellent physical properties.Transmission electron microscopy revealed that Ang-cubs-(GNA + PLHSpT) was nearly spherical with a "core-shell" double-layer structure. Differential scanning calorimetry suggested that a new phase was formed. Small-angle X-ray scattering also verified that Ang-cubs-(GNA + PLHSpT) retains the Pn3m cubic. Moreover, laser confocal indicated that Ang-cubs-(GNA + PLHSpT) was capable of crossing BBB via binding to lipoprotein receptor-related protein-1, likely suggesting the potential tumor-specific targeting characteristic. Compared to free drug and cubs-(GNA + PLHSpT), Ang-cubs-(GNA + PLHSpT) was easily taken up by C6 cell and exhibited better anti-glioma effects in vitro. Importantly, GNA and PLHSpT co-loaded Ang-cubs could suppress tumor growth and significantly prolong survival in vivo. In conclusion, Ang-cubs-(GNA + PLHSpT) acts as a new dual-targeting drug delivery system for the treatment of GBM.

[Role of lymphatic system in coronary heart disease based on theory of combined phlegm and stasis].

According to the traditional Chinese medicine(TCM) theory, coronary heart disease(CHD) is mainly caused by heart vessel obstruction due to Qi stagnation, blood stasis, and phlegm turbidity. Chest impediment with combined phlegm and stasis is a common syndrome of CHD, with the manifestations of chest tightness, chest pain, and asthma. Lymphatic system is one of the important immune systems in the human body and has a close relationship with the Qi and blood movement in TCM. The dysfunction of the lymphatic system may lead to metabolism disorders, the generation of dampness pathogen which turns into sticky and difficult-to-dissolve phlegm turbidity. Moreover, it can affect blood circulation and coagulation, causing slow blood flow, increased blood viscosity, and microcirculation disorders. Alterations in lymphatic hydrodynamics may affect the interaction between blood circulation and the lymphatic system. A variety of small molecule drugs and TCM can treat cardiovascular diseases by targeting the lymphatic system. This review discusses the role of the lymphatic system in CHD based on the theory of combined phlegm and stasis, involving the influences of mechanical factors on lymphatic function and the effects and pharmacological mechanisms of TCM and chemicals that target lymphocyte function and lymphatic circulation. By expounding the development process of combined phlegm and stasis in CHD from the lymphatic system, this paper aims to provide new ideas for deciphering pharmacological mechanisms of TCM for resolving phlegm and stasis.

Clinical significance of expression level of ZNF471 in gastric cancer.

BACKGROUND: As a tumor suppressor gene, zinc finger protein 471 (ZNF471) has an essential role in tumor occurrence and development. Due to promoter hypermethylation, it can be underexpressed or silenced in gastric cancer (GC) cell lines. In this study, we investigated relationships between clinical characteristics and ZNF471 expression levels in tissues of patients with GC. METHODS: We used immunohistochemistry (IHC) to detect ZNF471 expression in paraffin tissue specimens, and quantitative real-time PCR (qRT-PCR) and western blot (WB) analysis to measure expression levels of ZNF471 in fresh tissue specimens. We analyzed relationships between ZNF471 expression levels and characteristics, such as tumor size, gender, age, TNM stage, and lymph node metastasis. RESULTS: Immunohistochemistry revealed the expression of ZNF471 protein from paraffin blocks of GC tissues was significantly lower than that of adjacent tissues. Expression levels of ZNF471 mRNA and protein in fresh GC tissues were markedly lower than those in adjacent tissues and in normal gastric mucosal tissues from healthy subjects. ZNF471 expression was significantly correlated with tumor size, lymph node metastasis, and TNM stage (all P<0.05). There were no significant associations with gender, age, distant metastasis, or pathologic type. Expression of ZNF471 mRNA and protein was not significantly different between adjacent tissues of patients with GC and normal gastric mucosal tissue from healthy subjects. CONCLUSION: ZNF471 functions as a tumor suppressor during the pathogenesis of GC. Thus, it is a promising biomarker for diagnosis and therapy of GC.

Screening of anti-cancer compounds from Vaccariae Semen by lung cancer A549 cell fishing and UHPLC-LTQ Orbitrap MS.

Vaccariae Semen, derived from the dried ripe seed of Vaccaria segetalis (Neck.) Garcke, has various therapeutic characteristics in traditional Chinese medicine (TCM), containing promoting blood circulation and unblocking meridians. It exhibits significant anti-cancer activity and is therapeutically utilized to treat and reduce chemotherapy adverse effects in cancer patients, notably those with lung cancer. However, the active ingredients responsible for its anti-lung cancer efficacy remain unknown. In this study, we used A549 cell fishing in conjunction with UHPLC-LTQ Orbitrap MS to screen for anti-lung cancer active components in Vaccariae Semen. The cell counting Kit-8 (CCK-8) assay revealed that the n-butanol extract substantially reduced A549 cell growth. Through the cell fishing assay, we found 14 A549 cell-binding compounds in the n-butanol extract, all of which were identified as triterpenoid saponins. The total saponins of Vaccariae Semen were subsequently purified using macroporous adsorption resin (MAR), and they showed a significant inhibitory effect on the proliferation of A549 lung cancer cells, as well as alterations in cell morphology, apoptosis, and fragmentation. In conclusion, saponins were discovered as the key active components responsible for the anti-lung cancer activity of Vaccariae Semen.

Advancements in Analyzing Tumor Metabolites through Chemical Derivatization-Based Chromatography.

Understanding the metabolic abnormalities of tumors is crucial for early diagnosis, prognosis, and treatment. Accurate identification and quantification of metabolites in biological samples are essential to investigate the relationship between metabolite variations and tumor development. Common techniques like LC-MS and GC-MS face challenges in measuring aberrant metabolites in tumors due to their strong polarity, isomerism, or low ionization efficiency during MS detection. Chemical derivatization of metabolites offers an effective solution to overcome these challenges. This review focuses on the difficulties encountered in analyzing aberrant metabolites in tumors, the principles behind chemical derivatization methods, and the advancements in analyzing tumor metabolites using derivatization-based chromatography. It serves as a comprehensive reference for understanding the analysis and detection of tumor metabolites, particularly those that are highly polar and exhibit low ionization efficiency.

Identification of the susceptible genes and mechanism underlying the comorbid presence of coronary artery disease and rheumatoid arthritis: a network modularization analysis.

OBJECTIVE: The comorbidities of coronary artery disease (CAD) and rheumatoid arthritis (RA) are mutual risk factors, which lead to higher mortality, but the biological mechanisms connecting the two remain unclear. Here, we aimed to identify the risk genes for the comorbid presence of these two complex diseases using a network modularization approach, to offer insights into clinical therapy and drug development for these diseases. METHOD: The expression profile data of patients CAD with and without RA were obtained from the GEO database (GSE110008). Based on the differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA) was used to construct a gene network, detect co-expression modules, and explore their relation to clinical traits. The Zsummary index, gene significance (GS), and module membership (MM) were utilized to screen the important differentiated modules and hub genes. The GO and KEGG pathway enrichment analysis were applied to analyze potential mechanisms. RESULT: Based on the 278 DEGs obtained, 41 modules were identified, of which 17 and 24 modules were positively and negatively correlated with the comorbid occurrence of CAD and RA (CAD&RA), respectively. Thirteen modules with Zsummary < 2 were found to be the underlying modules, which may be related to CAD&RA. With GS ≥ 0.5 and MM ≥ 0.8, 49 hub genes were identified, such as ADO, ABCA11P, POT1, ZNF141, GPATCH8, ATF6 and MIA3, etc. The area under the curve values of the representative seven hub genes under the three models (LR, KNN, SVM) were greater than 0.88. Enrichment analysis revealed that the biological functions of the targeted modules were mainly involved in cAMP-dependent protein kinase activity, demethylase activity, regulation of calcium ion import, positive regulation of tyrosine, phosphorylation of STAT protein, and tissue migration, etc. CONCLUSION: Thirteen characteristic modules and 49 susceptibility hub genes were identified, and their corresponding molecular functions may reflect the underlying mechanism of CAD&RA, hence providing insights into the development of clinical therapies against these diseases.

Gasotransmitters in non-alcoholic fatty liver disease: just the tip of the iceberg.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by fatty lesions and fat accumulation in hepatic parenchymal cells, which is in the absence of excessive alcohol consumption or definite liver damage factors. The exact pathogenesis of NAFLD is not fully understood, but it is now recognized that oxidative stress, insulin resistance, and inflammation are essential mechanisms involved in the development and treatment of NAFLD. NAFLD therapy aims to stop, delay or reverse disease progressions, as well as improve the quality of life and clinical outcomes of patients with NAFLD. Gasotransmitters are produced by enzymatic reactions, regulated through metabolic pathways in vivo, which can freely penetrate cell membranes with specific physiological functions and targets. Three gasotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide have been discovered. Gasotransmitters exhibit the effects of anti-inflammatory, anti-oxidant, vasodilatory, and cardioprotective agents. Gasotransmitters and their donors can be used as new gas-derived drugs and provide new approaches to the clinical treatment of NAFLD. Gasotransmitters can modulate inflammation, oxidative stress, and numerous signaling pathways to protect against NAFLD. In this paper, we mainly review the status of gasotransmitters research on NAFLD. It provides clinical applications for the future use of exogenous and endogenous gasotransmitters for the treatment of NAFLD.

The gut microbes in inflammatory bowel disease: Future novel target option for pharmacotherapy.

Gut microbes constitute the main microbiota in the human body, which can regulate biological processes such as immunity, cell proliferation, and differentiation, hence playing a specific function in intestinal diseases. In recent years, gut microbes have become a research hotspot in the pharmaceutical field. Because of their enormous number, diversity, and functional complexity, gut microbes have essential functions in the development of many digestive diseases. Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease with a complex etiology, the exact cause and pathogenesis are unclear. There are no medicines that can cure IBD, and more research on therapeutic drugs is urgently needed. It has been reported that gut microbes play a critical role in pathogenesis, and there is a tight and complex association between gut microbes and IBD. The dysregulation of gut microbes may be a predisposing factor for IBD, and at the same time, IBD may exacerbate gut microbes' disorders, but the mechanism of interaction between the two is still not well defined. The study of the relationship between gut microbes and IBD is not only important to elucidate the pathogenesis but also has a positive effect on the treatment based on the regimen of regulating gut microbes. This review describes the latest research progress on the functions of gut microbes and their relationship with IBD, which can provide reference and assistance for further research. It may provide a theoretical basis for the application of probiotics, fecal microbiota transplantation, and other therapeutic methods to regulate gut microbes in IBD.

Interactions between Verticillium dahliae and cotton: pathogenic mechanism and cotton resistance mechanism to Verticillium wilt.

Cotton is widely grown in many countries around the world due to the huge economic value of the total natural fiber. Verticillium wilt, caused by the soil-borne pathogen Verticillium dahliae, is the most devastating disease that led to extensive yield losses and fiber quality reduction in cotton crops. Developing resistant cotton varieties through genetic engineering is an effective, economical, and durable strategy to control Verticillium wilt. However, there are few resistance gene resources in the currently planted cotton varieties, which has brought great challenges and difficulties for breeding through genetic engineering. Further revealing the molecular mechanism between V. dahliae and cotton interaction is crucial to discovering genes related to disease resistance. In this review, we elaborated on the pathogenic mechanism of V. dahliae and the resistance mechanism of cotton to Verticillium wilt. V. dahliae has evolved complex mechanisms to achieve pathogenicity in cotton, mainly including five aspects: (1) germination and growth of microsclerotia; (2) infection and successful colonization; (3) adaptation to the nutrient-deficient environment and competition of nutrients; (4) suppression and manipulation of cotton immune responses; (5) rapid reproduction and secretion of toxins. Cotton has evolved multiple physiological and biochemical responses to cope with V. dahliae infection, including modification of tissue structures, accumulation of antifungal substances, homeostasis of reactive oxygen species (ROS), induction of Ca2+ signaling, the mitogen-activated protein kinase (MAPK) cascades, hormone signaling, and PAMPs/effectors-triggered immune response (PTI/ETI). This review will provide an important reference for the breeding of new cotton germplasm resistant to Verticillium wilt through genetic engineering.

Effects of insecticidal proteins of Enterobacter cloacae NK on cellular immunity of Galleria mellonella larvae.

Enterobacter cloacae produces insecticidal proteins capable of causing toxicity in pests, but the insecticidal mechanisms of these proteins for insect control remain unclear. To elucidate the mechanisms, the purified insecticidal protein from E. cloacae NK was administered to Galleria mellonella larvae either by intraperitoneal injection or by feeding. The number of hemocytes, apoptosis in immune cells, and polyphenol oxidase (PO) activity of G. mellonella larvae were detected by hemocytometer, Annexin V-FITC/PI, and UV-vis spectrophotometer, respectively. With the extension of the invasion time of NK insecticidal protein, the number of hemocytes in G. mellonella larvae decreased significantly (p < 0.05), whereas the apoptosis rate of hemocytes increased. The activity of PO showed a trend of rising-peak-sharp decline and the melanization reaction was deepened simultaneously. Moreover, the phagocytosis and coating capabilities of hemocytes decreased, and the intraperitoneal injection method was more effective than the feeding method. Taking together, the insecticidal protein of E. cloacae NK inhibits and destroys the cellular immune response of G. mellonella larvae, which suggests an important role in killing the host insect.

TCMFP: a novel herbal formula prediction method based on network target's score integrated with semi-supervised learning genetic algorithms.

Traditional Chinese medicine (TCM) has accumulated thousands years of knowledge in herbal therapy, but the use of herbal formulas is still characterized by reliance on personal experience. Due to the complex mechanism of herbal actions, it is challenging to discover effective herbal formulas for diseases by integrating the traditional experiences and modern pharmacological mechanisms of multi-target interactions. In this study, we propose a herbal formula prediction approach (TCMFP) combined therapy experience of TCM, artificial intelligence and network science algorithms to screen optimal herbal formula for diseases efficiently, which integrates a herb score (Hscore) based on the importance of network targets, a pair score (Pscore) based on empirical learning and herbal formula predictive score (FmapScore) based on intelligent optimization and genetic algorithm. The validity of Hscore, Pscore and FmapScore was verified by functional similarity and network topological evaluation. Moreover, TCMFP was used successfully to generate herbal formulae for three diseases, i.e. the Alzheimer's disease, asthma and atherosclerosis. Functional enrichment and network analysis indicates the efficacy of targets for the predicted optimal herbal formula. The proposed TCMFP may provides a new strategy for the optimization of herbal formula, TCM herbs therapy and drug development.

Noncoding RNAs: Master Regulator of Fibroblast to Myofibroblast Transition in Fibrosis.

Myofibroblasts escape apoptosis and proliferate abnormally under pathological conditions, especially fibrosis; they synthesize and secrete a large amount of extracellular matrix (ECM), such as α-SMA and collagen, which leads to the distortion of organ parenchyma structure, an imbalance in collagen deposition and degradation, and the replacement of parenchymal cells by fibrous connective tissues. Fibroblast to myofibroblast transition (FMT) is considered to be the main source of myofibroblasts. Therefore, it is crucial to explore the influencing factors regulating the process of FMT for the prevention, treatment, and diagnosis of FMT-related diseases. In recent years, non-coding RNAs, including microRNA, long non-coding RNAs, and circular RNAs, have attracted extensive attention from scientists due to their powerful regulatory functions, and they have been found to play a vital role in regulating FMT. In this review, we summarized ncRNAs which regulate FMT during fibrosis and found that they mainly regulated signaling pathways, including TGF-ß/Smad, MAPK/P38/ERK/JNK, PI3K/AKT, and WNT/ß-catenin. Furthermore, the expression of downstream transcription factors can be promoted or inhibited, indicating that ncRNAs have the potential to be a new therapeutic target for FMT-related diseases.

A molecular classification of gastric cancer associated with distinct clinical outcomes and validated by an XGBoost-based prediction model.

Gastric cancer (GC) is a heterogeneous disease and a leading cause of cancer-related deaths. Discovering robust, clinically relevant molecular classifications is critical for guiding personalized therapies for GC. Here, we propose a refined molecular classification scheme for GC using integrated optimal algorithms and multi-omics data. Based on the important features of mRNA, microRNA, and DNA methylation data selected by the multivariate Cox regression model, three subtypes linked to distinct clinical outcomes were identified by combining similarity network fusion and consensus clustering methods. Three subtypes were validated by an extreme gradient boosting machine learning prediction model with 125 differentially expressed genes in multiple independent cohorts. The molecular characteristics of mutation signatures, characteristic gene sets, driver genes, and chemotherapy sensitivity for each subtype were also identified: subtype 1 was associated with favorable prognosis and characterized by high ARID1A and PIK3CA mutations, subtype 2 was associated with a poor prognosis and harbored high recurrent TP53 mutations, and subtype 3 was associated with high CHD1, APOA1 mutations, and a poor prognosis. The proposed three-subtype scheme achieved a better clinical prediction performance (area under the curve value = 0.71) than The Cancer Genome Atlas classification, which may provide a practical subtyping framework to improve the treatment of GC.

Boosting the Areal Capacity of Titanium-Manganese Single Flow Battery by Fe2+ /Fe3+ Redox Mediator.

Aqueous manganese-based flow batteries (AMFBs) have attracted great attention due to the advantages of low cost and environmental friendliness. Extending the cycle life of AMFBs has long been a challenging theme. The titanium-manganese single-flow batteries (TMSFB) are promising due to their special structure and electrolyte composition. However, TMSFB with high areal capacity faces capacity decay for unknown reasons. In this work, the capacity decay mechanism (accumulation and growth of MnO2 ) is clarified by a homemade in situ microscope system. Given that, a redox mediator of Fe2+ /Fe3+ is specially designed to boost the areal capacity of TMSFB without side reaction. The directional promoting principle of the Fe2+ /Fe3+ is elaborated in detail. Fe2+ chemically reacts with the residual MnO2 to form Fe3+ , which is reduced to Fe2+ by the electrochemical reaction. And then Fe2+ continues reacting with MnO2 until MnO2 is consumed completely. As a result, the TMSFB with the areal capacity of ≈55 mA h cm-2 can stably operate at a current density of 40 mA cm-2 , which is the highest areal capacity reported in aqueous manganese-based batteries. This work provides a new strategy for boosting the capacity of manganese-based batteries, shedding light on the improvement of other deposition-type batteries.