SOCS5-RBMX stimulates SREBP1-mediated lipogenesis to promote metastasis in steatotic HCC with HBV-related cirrhosis.

Abnormal lipid metabolism promotes hepatocellular carcinoma (HCC) progression, which engenders therapeutic difficulties owing to unclear mechanisms of the phenomenon. We precisely described a special steatotic HCC subtype with HBV-related cirrhosis and probed its drivers. Hematoxylin-eosin (HE) staining of 245 HCC samples revealed a special HCC subtype (41 cases) characterized by HBV-related cirrhosis and intratumoral steatosis without fatty liver background, defined as steatotic HCC with HBV-related cirrhosis (SBC-HCC). SBC-HCC exhibits a larger tumor volume and worse prognosis than non-SBC-HCC. Screening for driver genes promoting fatty acid (FA) biosynthesis in the Gao's HBV-related cirrhosis HCC cases and GSE121248' HBV-related HCC cases revealed that high expression of SOCS5 predicts increased FA synthesis and that SOCS5 is upregulated in SBC-HCC. Through proteomics, metabolomics, and both in vivo and in vitro experiments, we demonstrated that SOCS5 induces lipid accumulation to promote HCC metastasis. Mechanistically, through co-IP and GST-pulldown experiments, we found that the SOCS5-SH2 domain, especially the amino acids Y413 and D443, act as critical binding sites for the RBMX-RRM domain. SOCS5-RBMX costimulates the promoter of SREBP1, inducing de novo lipogenesis, while mutations in the SH2 domain, Y413, and D443 reverse this effect. These findings precisely identified SBC-HCC as a special steatotic HCC subtype and highlighted a new mechanism by which SOCS5 promotes SBC-HCC metastasis.

Metabolism-regulated ferroptosis in cancer progression and therapy.

Cancer metabolism mainly includes carbohydrate, amino acid and lipid metabolism, each of which can be reprogrammed. These processes interact with each other to adapt to the complicated microenvironment. Ferroptosis is a regulated cell death induced by iron-dependent lipid peroxidation, which is morphologically different from apoptosis, necrosis, necroptosis, pyroptosis, autophagy-dependent cell death and cuprotosis. Cancer metabolism plays opposite roles in ferroptosis. On the one hand, carbohydrate metabolism can produce NADPH to maintain GPX4 and FSP1 function, and amino acid metabolism can provide substrates for synthesizing GPX4; on the other hand, lipid metabolism might synthesize PUFAs to trigger ferroptosis. The mechanisms through which cancer metabolism affects ferroptosis have been investigated extensively for a long time; however, some mechanisms have not yet been elucidated. In this review, we summarize the interaction between cancer metabolism and ferroptosis. Importantly, we were most concerned with how these targets can be utilized in cancer therapy.

MEK-mediated CHPF2 phosphorylation promotes colorectal cancer cell proliferation and metastasis by activating NF-κB signaling.

The cytokine tumor necrosis factor (TNF) plays a crucial role in the proliferation and metastasis of colorectal cancer (CRC) cells, but the underlying mechanisms remain poorly understood. Here, we report that chondroitin polymerizing factor 2 (CHPF2) promotes CRC cell proliferation and metastasis mediated by TNF, independently of its enzymatic activity. CHPF2 is highly expressed in CRC, and its elevated expression is associated with poor prognosis of CRC patients. Mechanistically, upon TNF stimulation, CHPF2 is phosphorylated at the T588 residue by MEK, enabling CHPF2 to interact with both TAK1 and IKKα. This interaction enhances the binding of TAK1 and IKKα, leading to increased phosphorylation of the IKK complex and activation of NF-κB signaling. As a result, the expression of early growth factors (EGR1) is upregulated to promote CRC cell proliferation and metastasis. In contrast, introduction of a phospho-deficient T588A mutation in CHPF2 weakened the interaction between CHPF2 and TAK1, thus impairing NF-κB signaling. CHPF2 T588A mutation reduced the ability of CHPF2 to promote the proliferation and metastasis of CRC in vitro and in vivo. Furthermore, the NF-κB RELA subunit promotes CHPF2 expression, further amplifying TNF-induced NF-κB signaling activation. These findings identify a moonlighting function of CHPF2 in promoting tumor cell proliferation and metastasis and provide insights into the mechanism by which CHPF2 amplifies TNF-mediated NF-κB signaling activation. Our study provides a molecular basic for the development of therapeutic strategies for CRC treatment.

Bullying Victimization and Internalizing Problems among Adolescents: A Moderated Mediation Model of Peer Autonomy Support and Self-Esteem.

The present study employed the social-ecological diathesis-stress model as a theoretical framework to extend previous research by examining the underlying mechanism and conditional process that contribute to the positive association between bullying victimization and internalizing problems among adolescents. A moderated mediation model involving peer autonomy support and self-esteem was tested using a sample of 1723 adolescents (50.7% girls; M age = 12.79, SD = 1.58), who completed questionnaires assessing internalizing problems, bullying victimization, peer autonomy support, and self-esteem. The findings revealed that self-esteem partially mediated the positive association between bullying victimization and adolescents' internalizing problems. Specifically, bullying victimization was inversely related to self-esteem, which, in turn, was negatively associated with internalizing problems. Further moderation analyses demonstrated that these direct and indirect associations varied based on levels of peer autonomy support. Simple slope analyses specifically indicated that (a) peer autonomy support buffered against the negative association of bullying victimization with self-esteem and internalizing problems, and (b) peer autonomy support mitigated the negative association of self-esteem with internalizing problems. The elucidation of this mechanism and conditional process holds important implications for early interventions and prevention efforts aimed at mitigating the detrimental association of bullying victimization with adolescents' healthy emotional functions.

Identification of biomarkers associated with pediatric asthma using machine learning algorithms: A review.

Pediatric asthma is a complex disease with a multifactorial etiology. The identification of biomarkers associated with pediatric asthma can provide insights into the pathogenesis of the disease and aid in the development of novel diagnostic and therapeutic strategies. This study aimed to identify potential biomarkers for pediatric asthma using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning algorithms. We obtained gene expression data from publicly available databases and performed WGCNA to identify gene co-expression modules associated with pediatric asthma. We then used machine learning algorithms, including random forest, lasso regression algorithm, and support vector machine-recursive feature elimination, to classify asthma cases and controls based on the identified gene modules. We also performed functional enrichment analyses to investigate the biological functions of the identified genes.We detected 24,544 genes exhibiting differential expression between controlled and uncontrolled genes from the GSE135192 dataset. In the combined WCGNA analysis, a total of 104 co-expression genes were screened, both controlled and uncontrolled. After screening, 11 hub genes were identified. They were AK2, PDK4, PER3, GZMH, NUMBL, NRL, SCO2, CREBZF, LARP1B, RXFP1, and VDAC3P1. The areas under their receiver operating characteristic curve were above 0.78. Our study identified potential biomarkers for pediatric asthma using WGCNA and machine learning algorithms. Our findings suggest that 11 hub genes could be used as novel diagnostic markers and treatment targets for pediatric asthma. These findings provide new insights into the pathogenesis of pediatric asthma and may aid in the development of novel diagnostic and therapeutic strategies.

One-Step Pyrolysis Construction of Bimetallic Atom-Cluster Sites for Boosting Bifunctional Catalytic Activity in Zn-Air Batteries.

Due to their unique advantages, single atoms and clusters of transition metals are expected to achieve a breakthrough in catalytic activity, but large-scale production of active materials remains a challenge. In this work, a simple solvent-free one-step annealing method is developed and applied to construct diatomic and cluster active sites in activated carbon by utilizing the strong anchoring ability of phenanthroline to metal ions, which can be scaled for mass productions. Benefiting from the synergy between the different metals, the obtained sub-nano-bimetallic atom-cluster catalysts (FeNiAC -NC) exhibit high oxygen reduction reactions (ORR) activity (E1/2 = 0.936 V vs. RHE) and a small ORR/oxygen evolution reaction (OER) potential gap of only 0.594 V. An in-house pouch Zn-air battery is assembled using an FeNiAC -NC catalyst, which demonstrates a stability of 1000 h, outperforming previous reports. The existence of clusters and their effects on catalytic activity is analyzed by density functional theory calculations to reveal the chemistry of nano-bimetallic atom-cluster catalysts.

Deep ultraviolet high-resolution microscopic hyperspectral imager and its biological tissue detection.

Ultraviolet (UV) hyperspectral imaging technology is commonly used in the field of atmospheric remote sensing. In recent years, some in-laboratory research has been carried out for substance detection and identification. In this paper, UV hyperspectral imaging technology is introduced into microscopy to better utilize the obvious absorption characteristics of components, such as proteins and nucleic acids in biological tissues in the ultraviolet band. A deep UV microscopic hyperspectral imager based on the Offner structure with F # 2.5, low spectral keystone and smile is designed and developed. A 0.68 numerical aperture microscope objective is designed. The spectral range of the system is from 200 nm to 430 nm; the spectral resolution is better than 0.5 nm; and the spatial resolution is better than 1.3 µm. The K562 cells can be distinguished by transmission spectrum of nucleus. The UV microscopic hyperspectral image of the unstained mouse liver slices showed similar results to the microscopic image after hematoxylin and eosin staining, which could help to simplify the pathological examination process. Both results show a great performance in spatial and spectral detecting capabilities of our instrument, which has the potential for biomedical research and diagnosis.

Applications of Metal-Organic Frameworks and Their Derivatives in Electrochemical CO2 Reduction.

Electrochemically reducing CO2 to more reduced chemical species is a promising way that not only enables the conversion of intermittent energy resources to stable fuels, but also helps to build a closed-loop anthropogenic carbon cycle. Among various electrocatalysts for electrochemical CO2 reduction, multifunctional metal-organic frameworks (MOFs) have been employed as highly efficient and selective heterogeneous electrocatalysts due to their ultrahigh porosity and topologically diverse structures. Up to now, great progress has been achieved in the design and synthesis of highly active and selective MOF-related catalysts for electrochemical CO2 reduction reaction (CO2RR), and their corresponding reaction mechanisms have been thoroughly studied. In this review, we summarize the recent progress of applying MOFs and their derivatives in CO2RR, with a focus on the design strategies for electrocatalysts and electrolyzers. We first discussed the reaction mechanisms for different CO2RR products and introduced the commonly applied electrolyzer configurations in the current CO2RR system. Then, an overview of several categories of products (CO, HCOOH, CH4, CH3OH, and multi-carbon chemicals) generated from MOFs or their derivatives via CO2RR was discussed. Finally, we offer some insights and perspectives for the future development of MOFs and their derivatives in electrochemical CO2 reduction. We aim to provide new insights into this field and further guide future research for large-scale applications.

Efficacy and safety of Jinhua Qinggan granules in the treatment of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

OBJECTIVE: To evaluate, using meta-analysis, the efficacy and safety profile of Jinhua Qinggan granules (JHQG) in the treatment of novel coronavirus pneumonia. METHODS: We screened multiple publication databases (PubMed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang, and VIP), using parameters designed to identify articles detailing randomized controlled trials relating to the treatment of novel coronavirus pneumonia with JHQG. The inclusion period for each search was the point of database inception to November 2022. Each piece of literature identified in our initial screening was independently reviewed by 2 researchers, who extracted the relevant data and evaluated the bias risk associated with the study. The data was split in 2: the control group (containing patients who had received routine treatment or placebo) and the experimental group (containing patients treated with JHQG). The meta-analysis was performed using Revman 5.4 software. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Four articles were selected for this study and combined included a total of 582 patients, which were subdivided into experimental (n = 347) and control (n = 235) groups. The results showed that treatment with JHQG could significantly: enhance the improvement rate of primary symptoms [relative ratio (RR) = 1.26,95% confidence interval (CI) (1.07, 1.49), P = .007] and fever [RR = 1.48, 95% CI (1.07, 2.04), P = .02]; decrease the viral nucleic acid in patients with coronavirus disease 2019 (COVID-19) [RR = 2.04, 95% CI (1.15, 3.62), P = .02] and reduce the progression of pneumonia [RR = 0.34, 95% CI (0.17, 0.67), P = .002]. However, there was no significant difference between the 2 groups with regards to: the improvement rate of cough, nausea and vomiting, fatigue, computed tomography, or frequency of adverse reactions. CONCLUSIONS: Current evidence indicates that JHQG is effective in treating COVID-19, increasing the rate of improvement for fever, increasing the negative rate of viral nucleic acid in patients with COVID-19 and reducing the aggravation rate of pneumonia. These conclusions need to be verified by further rigorous studies, as the existing results were limited by the number and quality of the included studies.

Adjuvant transarterial chemoembolization timing after radical resection is an independent prognostic factor for patients with hepatocellular carcinoma.

Background: It has been reported that postoperative adjuvant TACE (PA-TACE) treatment decreases recurrence and significantly improves the survival of patients who undergo radical resection of hepatocellular carcinoma (HCC) with high-risk recurrence factors. However, when to perform PA-TACE has not been fully studied. Methods: We retrospectively collected the clinicopathologic characteristics of the patients with HCC between October 2013 and June 2020. The optimal cutoff value for PA-TACE time was determined based on the R package "maxstat". Logistic regression and Cox regression analysis were used to determine the effect of the choice of PA-TACE timing on prognosis. Results: The analysis was performed on 789 patients with HCC, and 484 patients were finally involved and were divided into training cohort (378) and validation cohort (106). The PA-TACE timing was found to be associated with survival outcomes. Multivariate logistic analysis found independent predictors of the PA-TACE timing, including gender and history of HBV. Multivariate Cox analysis showed that Ki-67, tumor size, MVI and the PA-TACE timing were independent prognostic factors for RFS in HCC patients. Conclusions: Based on this study, HCC patients with high-risk recurrence factors can receive personalized assistance in undergoing PA-TACE treatment and improve their survival outcomes.

STX5 Inhibits Hepatocellular Carcinoma Adhesion and Promotes Metastasis by Regulating the PI3K/mTOR Pathway.

Background and Aims: Syntaxin 5 (STX5) is a member of the syntaxin or target-soluble SNAP receptor (t-SNARE) family and plays a critical role in autophagy. However, its function and molecular mechanism in tumor cell migration are still unknown. The role of STX5 in influencing hepatocellular carcinoma (HCC) is an important topic in our research. Methods: By using quantitative reverse transcription polymerase chain reaction (qPCR), western blotting, and immunohistochemical analysis of RNA and protein in tissues, we comprehensively evaluated data sets from public databases and clinical patient cohorts for STX5. The correlation of STX5 expression with the clinicopathological characteristics of HCC patients were assessed. In addition, we predicted signal pathways from differentially expressed genes (DEGs) and the Cancer Genome Atlas (TCGA) databases, and confirmed the prediction using integrated transcriptome and RNA-seq. We further investigated the underlying mechanisms of STX5 in the migration and adhesion of HCC cells both in vitro and in vivo. Results: In the TCGA dataset and our patient cohort, STX5 levels were significantly higher in HCC tissues than in adjacent normal liver tissues. At the same time, high expression of STX5 predicted worse prognosis in patients with liver cancer. High expression of STX5 indicates the decrease of adhesion and the increase of migration of HCC cells, and the conversion of epithelial-mesenchymal transition (EMT) in vitro via PI3K/mTOR pathway activation. Conversely, when Sirolimus, a phosphoinositide 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) inhibitor acts on cells simultaneously, STX5 overexpression-mediated enhancement of HCC metastasis is reversed. Double-negative regulation of STX5 and mTOR further enhanced the inhibitory effect of STX5 on HCC metastasis. In vivo, STX5 knockdown inhibited the metastasis of HCC cells. Conclusions: Our study demonstrates a novel research result that STX5 promotes HCC metastasis through PI3K/mTOR pathway. We believe that combined inhibition of STX5 and mTOR is a potential treatment for effectively prolonging patient survival and inhibiting HCC metastasis.

Chinese herbal bath therapy for the treatment of Atopic dermatitis in children: A meta-analysis and systematic review.

BACKGROUND: To conduct a systematic review of the efficacy of Chinese herbal bath therapy on children with Atopic dermatitis. METHODS: We searched Chinese databases (CNKI, VIP, and Wanfang) and English databases (PubMed, Embase, Web of science, Cochrane library) for studies from the establishment of the database to September 2022. The included literature was randomized control studies investigating the treatment of Atopic dermatitis in children by Chinese herbal bath therapy. The outcomes included the cure rate, scoring atopic dermatitis (SCORAD) index, adverse reactions and recurrence rate. RevMan 5.4 was used to analyze the extracted data. RESULTS: A total of 8 related studies were included containing 854 cases. The meta-analysis showed that Chinese herbal bath therapy group was superior to control group in terms of cure rate, SCORAD index, adverse reactions and recurrence rate in children with Atopic dermatitis [RR = 1.11, 95%(1.02, 1.21), P = .01; SMD = -0.77, 95%(-0.99, -0.55), P < .00001; RR = 0.44, 95%CI(0.28,0.67), P = .0002; RR = 0.25, 95%CI(0.10, 0.59), P = .0002]. CONCLUSION: The present study shows that Chinese herbal bath therapy is an effective treatment for children with Atopic dermatitis in China.

SOCS5 knockdown suppresses metastasis of hepatocellular carcinoma by ameliorating HIF-1α-dependent mitochondrial damage.

The Pringle maneuver (PM) is widely used during hepatocellular carcinoma (HCC) resection. However, it inevitably leads to ischemia and hypoxia, which promotes tumor metastasis. In this study, immunohistochemical staining of specimens from 130 HCC patients revealed that long-time PM significantly affected the prognosis of patients with high expression of suppressor of cytokine signaling 5 (SOCS5), but did not affect the prognosis of patients with low expression of SOCS5. The TCGA database showed that patients with high expression of SOCS5 had higher hypoxia scores, and it was proved that SOCS5 could promote the expression of hypoxia-inducible factor 1 subunit alpha (HIF-1α) protein by clinical tissue samples, cell experiments, lung metastases, and subcutaneous tumorigenesis experiments. Then, we used CoCl2 to construct a hypoxia model, and confirmed that SOCS5 knockdown resisted hypoxia-induced mitochondrial damage by inhibiting the expression of HIF-1α, thereby inhibiting the invasion and migration of HCC cells by immunofluorescence, electron microscopy, migration, invasion, and other experiments. We performed rescue experiments using LY294002 and rapamycin and confirmed that the knockdown of SOCS5-inhibited HCC cell invasion and migration by inhibiting the PI3K/Akt/mTOR/HIF-1α signaling axis. More importantly, we obtained consistent conclusions from clinical, cellular, and animal studies that the hypoxia-induced invasion and migration ability of SOCS5-inhibited HCC were weaker than that of normal HCC. In conclusion, we identified a novel role for SOCS5 in regulating HIF-1α-dependent mitochondrial damage and metastasis through the PI3K/Akt/mTOR pathway. The development of a SOCS5-specific inhibitor, an indirect inhibitor of HIF-1α, might be effective at controlling PM-induced tumor micrometastases during HCC resection.

Parental Autonomy Support and Mental Health among Chinese Adolescents and Emerging Adults: The Mediating Role of Self-Esteem.

Guided by the dual-factor model and self-determination theory, this study explored the relationship between parental autonomy support and mental health (i.e., life satisfaction and emotional problems) in adolescents and emerging adults, with a focus on the mediating role of self-esteem. We conducted two studies among independent samples in China, including 1617 adolescents aged 10 to 17 years (Mage =12.79, SD = 1.63; 50.7% girls; Study 1) and 1274 emerging adults aged 17 to 26 years (Mage = 20.31, SD = 1.63; 56.6% women; Study 2). All participants completed a set of self-reported questionnaires. The results of both studies validated our hypothesis; specifically, parental autonomy support was positively associated with life satisfaction, but negatively associated with emotional problems (emotional symptoms in Study 1 and depressive symptoms in Study 2). Meanwhile, self-esteem partially mediated the positive relationship between parental autonomy support and life satisfaction (R2 = 0.33 in Study 1; R2 = 0.38 in Study 2), and partially mediated the negative relationship between parental autonomy support and emotional problems (R2 = 0.16 in Study 1; R2 = 0.42 in Study 2). In summary, this suggests that the common antecedents of positive and negative indicators of mental health addressed in this study are prevalent in adolescents and emerging adults. These findings have important implications for preventive and interventional efforts aimed at mental health problems in both demographics.

Clinical Practice of Targeted Capture Sequencing to Identify Actionable Alterations in Cholangiocarcinoma.

The early diagnosis and treatment of cholangiocarcinoma (CCA) remain a challenge worldwide. Genetic testing promises to solve these problems. Due to the different mutation landscapes across populations and the paucity of sequencing data of Chinese patients with CCA, the existing mutation landscape is insufficient to reflect the mutation characteristics of Chinese patients. Thus, we retrospectively analyzed 72 Chinese patients with CCA who had received genetic testing of targeted capture sequencing. A total of 2152 somatic mutations were detected in 56 (77.78%) patients, of which, the frequently mutated driver genes were TP53 (27.78%), KMT2D (23.81%), KMT2C (20.63%), BCOR (18.06%), APC (15.28%), BAP1 (13.89%), ARID1A (12.50%), NF1 (12.50%), PIK3CA (12.50%), KRAS (11.11%), and LRP1B (11.11%). Most mutations were enriched in NRF2, TP53, and TGF-Beta oncogenic signaling pathways and cadherin repeat domains which were associated with intercellular adhesion. Based on cancer-related public databases and multiple protein function prediction algorithms, we identified 118 novel pathogenic or likely pathogenic somatic mutations and 77 actionable alterations. Molecular analysis of tumors from a precision oncology perspective can provide potential targets for early diagnosis and treatment of CCA and assist physicians in clinical decision making.

A new nomogram model for prognosis of hepatocellular carcinoma based on novel gene signature that regulates cross-talk between immune and tumor cells.

BACKGROUND: The combined application of immune cells and specific biomarkers related to the tumor immune microenvironment has a better predictive value for the prognosis of HCC. The purpose of this study is to construct a new prognostic model based on immune-related genes that regulate cross-talk between immune and tumor cells to assess the prognosis and explore possible mechanisms. METHOD: The immune cell abundance ratio of 424 cases in the TCGA-LIHC database is obtained through the CIBERSORT algorithm. The differential gene analysis and cox regression analysis is used to screen IRGs. In addition, the function of IRGs was preliminarily explored through the co-culture of M2 macrophages and HCC cell lines. The clinical validation, nomogram establishment and performing tumor microenvironment score were validated. RESULTS: We identified 4 immune cells and 9 hub genes related to the prognosis. Further, we identified S100A9, CD79B, TNFRSF11B as an IRGs signature, which is verified in the ICGC and GSE76427 database. Importantly, IRGs signature is closely related to the prognosis, tumor microenvironment score, clinical characteristics and immunotherapy, and nomogram combined with clinical characteristics is more conducive to clinical promotion. In addition, after co-culture with M2 macrophages, the migration capacity and cell pseudopod of MHCC97H increased significantly. And CD79B and TNFRSF11B were significantly down-regulated in MHCC97H, Huh7 and LM3, while S100A9 was up-regulated. CONCLUSION: We constructed an IRGs signature and discussed possible mechanisms. The nomogram established based on IRGs can accurately predict the prognosis of HCC patients. These findings may provide a suitable therapeutic target for HCC.

Traditional Chinese Medicine Based Acupoint Application for Asthma Treatment in Children: A Meta-Analysis and Systematic Review.

Objective: By conducting a systematic review of the efficacy of acupoint application on children with asthma. Methods: We searched Chinese databases (CNKI, VIP, and Wanfang) and English databases (PubMed, Embase, and Cochrane Library) for studies from the establishment of the database to October 2021. The included literature studies were randomized control studies investigating the treatment of asthma in children by acupoint application. The primary outcomes included the cure rate, the resolution time of cough, and the resolution time of wheezing. The secondary outcomes included pulmonary function and interleukins. Stata 15 and RevMan 5.4 were used to analyze the extracted data. Results: A total of 24 related studies were included containing 2716 cases. The meta-analysis showed that TCM group was superior to control group in terms of cure rate, pulmonary function (FEV1), and resolution time of wheezing in children with asthma [RR = 1.26,95% (1.21,1.31), P < 0.05; SMD = 0.81, 95%CI (0.05,1.56), P < 0.05; WMD = -1.40, 95%CI (-1.75, -1.05), P < 0.05]. Conclusions: The present study shows that acupoint application is an effective treatment for children with asthma in China, especially in alleviating wheezing and improving quality of life.

RIPK4 Suppresses the Invasion and Metastasis of Hepatocellular Carcinoma by Inhibiting the Phosphorylation of STAT3.

Receptor interacting serine/threonine kinase 4 (RIPK4) is a member of the threonine/serine protein kinase family; it plays related functions in a variety of tumours, but its biological function has not been fully revealed. It has been reported that it is differentially expressed in hepatocellular carcinoma (HCC). Our research aimed to reveal the role of RIPK4 in the progression of HCC and to reveal the biological behaviour of RIPK4 in HCC. We analysed the differences in RIPK4 expression in HCC by using a publicly available data set. By using PCR, Western blotting and immunohistochemical staining methods, we detected the expression level of RIPK4 in HCC patient specimens and studied the relationship between the expression of RIPK4 and the clinicopathological features of HCC patients. The prognostic data were combined to analyse the relationship between RIPK4 and HCC patient survival and tumour recurrence. We found that the expression level of RIPK4 in nontumour tissues was significantly higher than that in tumour tissues, and the level of RIPK4 was significantly positively correlated with postoperative survival and recurrence in HCC patients. Further, our study found that RIPK4 inhibits the progression of HCC by influencing the invasion and metastasis of HCC and that overexpression of RIPK4 reduces the invasion and metastasis of HCC by inhibiting epithelial-mesenchymal transition (EMT) and the STAT3 pathway. In in vivo experiments, overexpression of RIPK4 stably inhibited HCC metastasis. To summarize, our research revealed the relationship between RIPK4 and the prognosis of patients with HCC. We discovered that RIPK4 affects the invasion and metastasis of HCC through the EMT and STAT3 pathways. Targeted inhibition of the RIPK4 gene and the STAT3 pathway may be potential therapeutic strategies for inhibiting the postoperative recurrence and metastasis of HCC.

Temperature Plays an Essential Regulatory Role in the Tumor Immune Microenvironment.

In recent years, emerging immunotherapy has been included in various malignant tumor treatment standards. Temperature has been considered to affect different pathophysiological reactions such as inflammation and cancer for a long time. However, in tumor immunology research, temperature is still rarely considered a significant variable. In this review, we discuss the effects of room temperature, body temperature, and the local tumor temperature on the tumor immune microenvironment from multiple levels and perspectives, and we discuss changes in the body's local and whole-body temperature under tumor conditions. We analyze the current use of ablation treatment-the reason for the opposite immune effect. We should pay more attention to the therapeutic potential of temperature and create a better antitumor microenvironment that can be combined with immunotherapy.

Tectorigenin inhibits inflammation and pulmonary fibrosis in allergic asthma model of ovalbumin-sensitized guinea pigs.

OBJECTIVES: The aim of this study was to evaluate the effect of tectorigenin on treating allergic asthma model of guinea pigs and investigate the underlying mechanisms. METHODS: Allergic asthma model of guinea pigs was established by sensitizing with ovalbumin (OVA). Then OVA-sensitized guinea pigs were injected with 10 mg/kg tectorigenin, 25 mg/kg tectorigenin or dexamethasone to investigate the effect of tectorigenin. KEY FINDINGS: High dose of tectorigenin effectively decreased the number of coughs, the number of inflammatory cells and the levels of pro-inflammatory factors. Moreover, tectorigenin could inhibit pulmonary fibrosis in guinea pigs sensitized with OVA. In addition, the functions of tectorigenin were realized through downregulating profibrotic factors of transforming growth factor (TGF)-ß1, phosphorylated (p)-Smad2/3 and Smad4, upregulating fibrosis-inhibitor of Smad7 and decreasing pro-inflammatory factors of vascular endothelial growth factor A (VEGFA), tumour necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), p-inhibitor of nuclear factor-kappa B (NF-κB) kinase ß (p-IKKß) and NF-κB. CONCLUSIONS: Tectorigenin could inhibit pulmonary fibrosis and airway inflammation through TGF-ß1/Smad signalling pathway and TLR4/NF-κB signalling pathway. Therefore, tectorigenin might be a promising medicine to treat allergic asthma.