Rust Prevention Property of a New Organic Inhibitor under Different Conditions.

The corrosion resistance properties of a new type of environmentally-friendly organic inhibitor containing amino ketone molecules are presented in this paper. To evaluate the prevention effect of the inhibitor on corrosion of reinforcement, the electrochemical characteristics of steels in the simulated concrete pore solution (SPS) were investigated under varied conditions of the relevant parameters, including concentrations of the inhibitor and NaCl, pH value, and temperature. The inhibition efficiency of the material was characterized through electrochemical impedance spectroscopy (EIS), potentiodynamic polarization, and the weight loss of steels. The results reveal a significant improvement in the corrosion resistance of steels with the inhibitor. A maximum resistance value of 89.07% was achieved at an inhibitor concentration of 4%. Moreover, the new organic inhibitor exhibited good corrosion protection capability for steels under different NaCl concentrations. Its inhibition efficiency was determined to be 65.62, 80.06, and 66.30% at NaCl concentrations of 2, 3.5 and 5%, respectively. On the other hand, it was found that an alkaline environment was favorable for an enhanced corrosion prevention effect, and an optimal pH value of 11.3 was observed in this work. Besides, the inhibition efficiencies at different temperatures showed a trend of 25 > 35 > 40 > 20 > 30 °C, with a maximum value of 81.32% at 25 °C. The above results suggest that the new organic material has high potential to be used as an eco-friendly and long-term durable inhibitor for steel corrosion prevention under complex conditions.

Enhancing Escherichia coli Inactivation: Synergistic Mechanism of Ultraviolet Light and High-Voltage Electric Field.

This study investigated the bactericidal effects of ultraviolet (UV) radiation, a high-voltage electric field (HVEF), and their combination on Escherichia coli. The results indicated that UV and combined disinfection were more effective with longer exposure, leading to significant reductions in microbial activity. Specifically, the single UV disinfection alone reduced activity by 3.3 log after 5 min, while combined disinfection achieved a 4.2 log reduction. In contrast, short-term HVEF treatment did not exhibit significant bactericidal effects, only achieving a reduction of 0.17 log in 5 min. Furthermore, prolonged exposure to both UV disinfection and an HVEF was found to damage cell membranes, ultimately causing cell death, while shorter durations did not. Despite rapid cell count decreases, flow cytometry did not detect apoptotic or necrotic cells, likely due to rapid cell rupture. This study suggests that combining UV radiation and an HVEF could be a promising approach for inhibiting bacterial reproduction, with HVEF enhancing UV effects. These findings provide insights for using combined HVEF and UV disinfection in food safety and preservation.

METTL5 promotes gastric cancer progression via sphingomyelin metabolism.

BACKGROUND: The treatment of gastric cancer (GC) has caused an enormous social burden worldwide. Accumulating studies have reported that N6-methyladenosine (m6A) is closely related to tumor progression. METTL5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of cells. However, its aberrant regulation in GC has not been fully elucidated. AIM: To excavate the role of METTL5 in the development of GC. METHODS: METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry, western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical samples. The tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays, colony formation assays, scratch healing assays, transwell assays and flow cytometry. The tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor model. The EpiQuik m6A RNA Methylation Quantification Kit was used for m6A quantification. Next, liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism, which was confirmed by Enzyme-linked immunosorbent assay and rescue tests. In addition, we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell experiments. RESULTS: Our research revealed substantial upregulation of METTL5, which suggested a poor prognosis of GC patients. Increased METTL5 expression indicated distant lymph node metastasis, advanced cancer stage and pathological grade. An increased level of METTL5 correlated with a high degree of m6A methylation. METTL5 markedly promotes the proliferation, migration, and invasion of GC cells in vitro. METTL5 also promotes the growth of GC in animal models. METTL5 knockdown resulted in significant changes in sphingomyelin metabolism, which implies that METTL5 may impact the development of GC via sphingomyelin metabolism. In addition, high METTL5 expression led to cisplatin resistance. CONCLUSION: METTL5 was found to be an oncogenic driver of GC and may be a new target for therapy since it facilitates GC carcinogenesis through sphingomyelin metabolism and cisplatin resistance.

Comparison of patient-controlled analgesia and sedation (PCAS) with remifentanil and propofol versus total intravenous anesthesia (TIVA) with midazolam, fentanyl, and propofol for colonoscopy.

BACKGROUND: Colonoscopy is a commonly performed gastroenterological procedure in patients associated with anxiety and pain. Various approaches have been used to provide sedation and analgesia during colonoscopy, including patient-controlled analgesia and sedation (PCAS). This study aims to evaluate the feasibility and efficiency of PCAS administered with propofol and remifentanil for colonoscopy. METHODS: This randomized controlled trial was performed in an authorized and approved endoscopy center. A total of 80 outpatients were recruited for the colonoscopy studies. Patients were randomly allocated into PCAS and total intravenous anesthesia (TIVA) groups. In the PCAS group, the dose of 0.1 ml/kg/min of the mixture was injected after an initial bolus of 3 ml mixture (1 ml containing 3 mg of propofol and 10 µg of remifentanil). Each 1 ml of bolus was delivered with a lockout time of 1 min. In the TIVA group, patients were administered fentanyl 1 µg/kg, midazolam 0.02 mg/kg, and propofol (dosage titrated). Cardiorespiratory parameters and auditory evoked response index were continuously monitored during the procedure. The recovery from anesthesia was assessed using the Aldrete scale and the Observer's Assessment of Alertness/Sedation Scale. The Visual Analogue Scale was used to assess the satisfaction of patients and endoscopists. RESULTS: No statistical differences were observed in the Visual Analogue Scale scores of the patients (9.58 vs 9.50) and the endoscopist (9.43 vs 9.30). A significant decline in the mean arterial blood pressure, heart rate, and auditory evoked response index parameters was recorded in the TIVA group (P < 0.05). The recovery time was significantly shorter in the PCAS group than in the TIVA group (P = 0.00). CONCLUSION: The combination of remifentanil and propofol could provide sufficient analgesia, better hemodynamic stability, lighter sedation, and faster recovery in the PCAS group of patients compared with the TIVA group.

Enhancing the Weld Quality of Polylactic Acid Biomedical Materials Using Rotary Friction Welding.

Polylactic acid (PLA) stands out as a biomaterial with immense potential, primarily owing to its innate biodegradability. Conventional methods for manufacturing PLA encompass injection molding or additive manufacturing (AM). Yet, the fabrication of sizable medical devices often necessitates fragmenting them into multiple components for printing, subsequently requiring reassembly to accommodate the constraints posed by the dimensions of the AM platform. Typically, laboratories resort to employing nuts and bolts for the assembly of printed components into expansive medical devices. Nonetheless, this conventional approach of jointing is susceptible to the inherent risk of bolts and nuts loosening or dislodging amid the reciprocating movements inherent to sizable medical apparatus. Hence, investigation into the joining techniques for integrating printed components into expansive medical devices has emerged as a critical focal point within the realm of research. The main objective is to enhance the joint strength of PLA polymer rods using rotary friction welding (RFW). The mean bending strength of welded components, fabricated under seven distinct rotational speeds, surpasses that of the underlying PLA substrate material. The average bending strength improvement rate of welding parts fabricated by RFW with three-stage transformation to 4000 rpm is about 41.94% compared with the average bending strength of PLA base material. The average surface hardness of the weld interface is about 1.25 to 3.80% higher than the average surface hardness of the PLA base material. The average surface hardness of the weld interface performed by RFW with variable rotational speed is higher than the average surface hardness of the weld interface performed at a fixed rotating friction speed. The temperature rise rate and maximum temperature recorded during RFW in the X-axis of the CNC turning machine at the outer edge of the welding part surpassed those observed in the internal temperature of the welding part. Remarkably, the proposed method in this study complies with the Sustainable Development Goals due to its high energy efficiency and low environmental pollution.

Enhancing the Cooling Efficiency of Aluminum-Filled Epoxy Resin Rapid Tool by Changing Inner Surface Roughness of Cooling Channels.

In low-pressure wax injection molding, cooling time refers to the period during which the molten plastic inside the mold solidifies and cools down to a temperature where it can be safely ejected without deformation. However, cooling efficiency for the mass production of injection-molded wax patterns is crucial. This work aims to investigate the impact of varying surface roughness on the inner walls of the cooling channel on the cooling efficiency of an aluminum-filled epoxy resin rapid tool. It was found that the cooling time for the injection-molded products can be determined by the surface roughness according to the proposed prediction equation. Employing fiber laser processing on high-speed steel rods allows for the creation of microstructures with different surface roughness levels. Results demonstrate a clear link between the surface roughness of cooling channel walls and cooling time for molded wax patterns. Employing an aluminum-filled epoxy resin rapid tool with a surface roughness of 4.9 µm for low-pressure wax injection molding can save time, with a cooling efficiency improvement of approximately 34%. Utilizing an aluminum-filled epoxy resin rapid tool with a surface roughness of 4.9 µm on the inner walls of the cooling channel can save the cooling time by up to approximately 60%. These findings underscore the significant role of cooling channel surface roughness in optimizing injection molding processes for enhanced efficiency.

Clinical features and risk factors of primary Sjögren's syndrome complicated with severe pneumonia: a case-control study.

OBJECTIVES: To analyze clinical characteristics, risk factors, pathogen distribution, and prognostic markers in primary Sjögren's syndrome (pSS) patients with severe pneumonia (SP) compared to those without severe pneumonia (NSP). METHODS: This case-control study included 24 hospitalized pSS patients with SP and 96 NSP at the first affiliated hospital of Soochow university from June 2014 to May 2023. Data encompassing demographics, comorbidities, treatments, and laboratory results were retrospectively collected. Univariate and multivariate regression analyses, ROC curves, and statistical analyses using SPSS 23.0 assessed risk factors. The study retrospectively analyzed clinical features and risk factors, highlighting distinct parameters between pSS patients with and without SP. RESULTS: Marked differences were observed in several parameters: pSS activity(P < 0.001), white blood cell (P = 0.043), lymphocyte (P < 0.001), neutrophils (P = 0.042), C-reactive protein (P = 0.042), and CD8+ T cell (P = 0.017). Notably, lymphocyte count and SS activity demonstrated robust discrimination ability (AUC > 0.85). C-reactive protein (CRP), procalcitonin, CD4+ T cell, and IgA showed significant associations with SP; higher CRP levels correlated with increased risk, while lower CD4+ T cell and IgA levels associated with increased risk. SS activity significantly impacted outcomes. Various biomarkers exhibited diverse discriminatory abilities but lacked strong predictive associations with outcomes. CONCLUSION: pSS patients with SP exhibited higher disease activity and altered immune profiles compared to those NSP. Lymphocyte count and SS activity emerged as robust discriminators. Higher CRP levels correlated with increased risk of SP, while lower CD4+T cell and IgA levels associated with increased risk. SS activity significantly impacted patient outcomes. Key Points • pSS patients with SP exhibited higher disease activity and altered immune profiles compared to those NSP. • Lymphocyte count and SS activity emerged as robust discriminators. • Higher CRP levels correlated with increased risk of SP, while lower CD4+ T cell and IgA levels associated with decreased risk. • SS activity significantly impacted patient outcomes.

SIRT4 loss reprograms intestinal nucleotide metabolism to support proliferation following perturbation of homeostasis.

The intestine is a highly metabolic tissue, but the metabolic programs that influence intestinal crypt proliferation, differentiation, and regeneration are still emerging. Here, we investigate how mitochondrial sirtuin 4 (SIRT4) affects intestinal homeostasis. Intestinal SIRT4 loss promotes cell proliferation in the intestine following ionizing radiation (IR). SIRT4 functions as a tumor suppressor in a mouse model of intestinal cancer, and SIRT4 loss drives dysregulated glutamine and nucleotide metabolism in intestinal adenomas. Intestinal organoids lacking SIRT4 display increased proliferation after IR stress, along with increased glutamine uptake and a shift toward de novo nucleotide biosynthesis over salvage pathways. Inhibition of de novo nucleotide biosynthesis diminishes the growth advantage of SIRT4-deficient organoids after IR stress. This work establishes SIRT4 as a modulator of intestinal metabolism and homeostasis in the setting of DNA-damaging stress.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases.

BACKGROUND: Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality, with the liver being the primary organ of metastasis. Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases (CRLMs). Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy. However, the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy. Body mass index (BMI) is one of the factors affecting the tumorigenesis and progression of colorectal cancer as well as prognosis after various antitumour therapies. Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight, particularly when receiving first-line chemotherapy regimens in combination with bevacizumab. AIM: To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs. METHODS: A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023. Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response. The Kaplan-Meier method with log rank test was used to compare progression-free survival (PFS) between patients with high and low BMI. BMI < 24.0 kg/m2 was defined as low BMI, and tumour regression grade 1-2 was defined as complete tumour response. RESULTS: Low BMI was observed in 74 (58.7%) patients and complete tumour response was found in 27 (21.4%) patients. The rate of complete tumour response was significantly higher in patients with low BMI (29.7% vs 9.6%, P = 0.007). Multivariate analysis revealed that low BMI [odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.42-14.63, P = 0.011], targeted therapy with bevacizumab (OR = 3.02, 95%CI: 1.10-8.33, P = 0.033), preoperative carcinoembryonic antigen level < 10 ng/mL (OR = 3.84, 95%CI: 1.19-12.44, P = 0.025) and severe sinusoidal dilatation (OR = 0.17, 95%CI: 0.03-0.90, P = 0.037) were independent predictive factors for complete tumour response. The low BMI group exhibited a significantly longer median PFS than the high BMI group (10.7 mo vs 4.7 mo, P = 0.011). CONCLUSION: In CRLM patients receiving preoperative chemotherapy, a low BMI may be associated with better tumour response and longer PFS.

Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer.

BACKGROUND: A growing number of clinical examples suggest that coronavirus disease 2019 (COVID-19) appears to have an impact on the treatment of patients with liver cancer compared to the normal population, and the prevalence of COVID-19 is significantly higher in patients with liver cancer. However, this mechanism of action has not been clarified. AIM: To investigate the disease relevance of COVID-19 in liver cancer. METHODS: Gene sets for COVID-19 (GSE180226) and liver cancer (GSE87630) were obtained from the Gene Expression Omnibus database. After identifying the common differentially expressed genes (DEGs) of COVID-19 and liver cancer, functional enrichment analysis, protein-protein interaction network construction and screening and analysis of hub genes were performed. Subsequently, the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed. RESULTS: Of 518 common DEGs were obtained by screening for functional analysis. Fifteen hub genes including aurora kinase B, cyclin B2, cell division cycle 20, cell division cycle associated 8, nucleolar and spindle associated protein 1, etc., were further identified from DEGs using the "cytoHubba" plugin. Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation, cell cycle and other functions, and they may serve as potential molecular markers for COVID-19 and liver cancer. Finally, we selected 10 of the hub genes for in vitro expression validation in liver cancer cells. CONCLUSION: Our study reveals a common pathogenesis of liver cancer and COVID-19. These common pathways and key genes may provide new ideas for further mechanistic studies.

Abnormal expression of PRKAG2-AS1 in endothelial cells induced inflammation and apoptosis by reducing PRKAG2 expression.

PRKAG2 is required for the maintenance of cellular energy balance. PRKAG2-AS1, a long non-coding RNA (lncRNA), was found within the promoter region of PRKAG2. Despite the extensive expression of PRKAG2-AS1 in endothelial cells, the precise function and mechanism of this gene in endothelial cells have yet to be elucidated. The localization of PRKAG2-AS1 was predominantly observed in the nucleus, as revealed using nuclear and cytoplasmic fractionation and fluorescence in situ hybridization. The manipulation of PRKAG2-AS1 by knockdown and overexpression within the nucleus significantly altered PRKAG2 expression in a cis-regulatory manner. The expression of PRKAG2-AS1 and its target genes, PRKAG2b and PRKAG2d, was down-regulated in endothelial cells subjected to oxLDL and Hcy-induced injury. This finding suggests that PRKAG2-AS1 may be involved in the mechanism behind endothelial injury. The suppression of PRKAG2-AS1 specifically in the nucleus led to an upregulation of inflammatory molecules such as cytokines, adhesion molecules, and chemokines in endothelial cells. Additionally, this nuclear suppression of PRKAG2-AS1 facilitated the adherence of THP1 cells to endothelial cells. We confirmed the role of nuclear knockdown PRKAG2-AS1 in the induction of apoptosis and inhibition of cell proliferation, migration, and lumen formation through flow cytometry, TUNEL test, CCK8 assay, and cell scratching. Finally, it was determined that PRKAG2-AS1 exerts direct control over the transcription of PRKAG2 by its binding to their promoters. In conclusion, downregulation of PRKAG2-AS1 suppressed the proliferation and migration, promoted inflammation and apoptosis of endothelial cells, and thus contributed to the development of atherosclerosis resulting from endothelial cell injury.

Ketogenic diet-produced ß-hydroxybutyric acid accumulates brain GABA and increases GABA/glutamate ratio to inhibit epilepsy.

Ketogenic diet (KD) alleviates refractory epilepsy and reduces seizures in children. However, the metabolic/cell biologic mechanisms by which the KD exerts its antiepileptic efficacy remain elusive. Herein, we report that KD-produced ß-hydroxybutyric acid (BHB) augments brain gamma-aminobutyric acid (GABA) and the GABA/glutamate ratio to inhibit epilepsy. The KD ameliorated pentetrazol-induced epilepsy in mice. Mechanistically, KD-produced BHB, but not other ketone bodies, inhibited HDAC1/HDAC2, increased H3K27 acetylation, and transcriptionally upregulated SIRT4 and glutamate decarboxylase 1 (GAD1). BHB-induced SIRT4 de-carbamylated and inactivated glutamate dehydrogenase to preserve glutamate for GABA synthesis, and GAD1 upregulation increased mouse brain GABA/glutamate ratio to inhibit neuron excitation. BHB administration in mice inhibited epilepsy induced by pentetrazol. BHB-mediated relief of epilepsy required high GABA level and GABA/glutamate ratio. These results identified BHB as the major antiepileptic metabolite of the KD and suggested that BHB may serve as an alternative and less toxic antiepileptic agent than KD.

Tryptophanylation of insulin receptor by WARS attenuates insulin signaling.

Increased circulating amino acid levels have been linked to insulin resistance and development of type 2 diabetes (T2D), but the underlying mechanism remains largely unknown. Herein, we show that tryptophan modifies insulin receptor (IR) to attenuate insulin signaling and impair glucose uptake. Mice fed with tryptophan-rich chow developed insulin resistance. Excessive tryptophan promoted tryptophanyl-tRNA synthetase (WARS) to tryptophanylate lysine 1209 of IR (W-K1209), which induced insulin resistance by inhibiting the insulin-stimulated phosphorylation of IR, AKT, and AS160. SIRT1, but not other sirtuins, detryptophanylated IRW-K1209 to increase the insulin sensitivity. Collectively, we unveiled the mechanisms of how tryptophan impaired insulin signaling, and our data suggested that WARS might be a target to attenuate insulin resistance in T2D patients.

Jeans and language: kin networks and reproductive success are associated with the adoption of outgroup norms.

Traditional norms of human societies in rural China may have changed owing to population expansion, rapid development of the tourism economy and globalization since the 1990s; people from different ethnic groups might adopt cultural traits from outside their group or lose their own culture at different rates. Human behavioural ecology can help to explain adoption of outgroup cultural values. We compared the adoption of four cultural values, specifically speaking outgroup languages/mother tongue and wearing jeans, in two co-residing ethnic groups, the Mosuo and Han. Both groups are learning outgroup traits, including each other's languages through contact in economic activities, education and kin networks, but only the Mosuo are starting to lose their own language. Males are more likely to adopt outgroup values than females in both groups. Females of the two groups are no different in speaking Mandarin and wearing jeans, whereas males do differ, with Mosuo males being keener to adopt them than Han males. The reason might be that Mosuo men experience more reproductive competition over mates, as Mosuo men have larger reproductive skew than others. Moreover, Mosuo men but not others gain fitness benefits from the adoption of Mandarin (they start reproducing earlier than non-speakers). This article is part of the theme issue 'Social norm change: drivers and consequences'.

Modulation of temporal and occipital cortex by acupuncture in non-menstrual MWoA patients: a rest BOLD fMRI study.

OBJECTIVE: To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). METHODS: Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed. RESULTS: Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P < 0.01, P = 0.015). The DC values of the right inferior temporal area were positively correlated with the pain degree at TP1 in Group 1 (r = 0.371; P = 0.008). CONCLUSION: Spontaneous brain activity and network changes in young women with non-menstrual MwoA were altered by acupuncture. The right temporal area may be an important target for acupuncture modulated brain function in young women with non-menstrual MwoA.

Fufang Luohanguo Qingfei granules reduces influenza virus susceptibility via MAVS-dependent type I interferon antiviral signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. AIM OF THE STUDY: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. MATERIALS AND METHODS: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs-/-) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. RESULTS: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-ß transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. CONCLUSION: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-ß antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.

Analysis of the potential biological value of pyruvate dehydrogenase E1 subunit ß in human cancer.

BACKGROUND: The pyruvate dehydrogenase E1 subunit ß (PDHB) gene which regulates energy metabolism is located in mitochondria. However, few studies have elucidated the role and mechanism of PDHB in different cancers. AIM: To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in cancer. In vitro experiments were performed to examine the biological regulation of PDHB in liver cancer. METHODS: Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas (TCGA) database. Analysis of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset databases. Cox regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer patients. The correlation between PDHB and receiver operating characteristic diagnostic curve, clinicopathological staging, somatic mutation, tumor mutation burden (TMB), microsatellite instability (MSI), DNA methylation, and drug susceptibility in pan-cancer was also analyzed. Various algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment, as well as the co-expression analysis of PDHB and immune checkpoint (ICP) genes. The expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing, and the functional enrichment analysis of PDHB-related genes was performed. The study also validated the level of mRNA or protein expression of PDHB in several cancers. Finally, in vitro experiments verified the regulatory effect of PDHB on the proliferation, migration, and invasion of liver cancer. RESULTS: PDHB was significantly and differently expressed in most cancers. PDHB was significantly associated with prognosis in patients with a wide range of cancers, including kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, breast invasive carcinoma, and brain lower grade glioma. In some cancers, PDHB expression was clearly associated with gene mutations, clinicopathological stages, and expression of TMB, MSI, and ICP genes. The expression of PDHB was closely related to the infiltration of multiple immune cells in the immune microenvironment and the regulation of tumor chemotaxis environment. In addition, single-cell sequencing results showed that PDHB correlated with different biological phenotypes of multiple cancer single cells. This study further demonstrated that down-regulation of PDHB expression inhibited the proliferation, migration, and invasion functions of hepatoma cells. CONCLUSION: As a member of pan-cancer, PDHB may be a novel cancer marker with potential value in diagnosing cancer, predicting prognosis, and in targeted therapy.

Development of a Silicone Rubber Mold with an Innovative Waterfall Cooling Channel.

A conformal cooling channel (CCC) follows the mold core or cavity profile to carry out uniform cooling in the cooling stage. However, the significant pressure drop along the cooling channels is a distinct disadvantage of the CCC. In this study, an innovative waterfall cooling channel (WCC) was proposed and implemented. The WCC cools the injected products via surface contact, replacing the conventional line contact to cool the injected products. The WCC was optimized using numerical simulation software. Silicone rubber molds with two kinds of cooling channels were designed and implemented. The cooling time of the molded part was evaluated using a low-pressure wax injection molding machine. The experimental results of the cooling time of the molded part were compared with the simulation results from numerical simulation software. The results showed that the optimal mesh element count was about 1,550,000 with a mesh size of 1 mm. The simulation software predicted the filling time of the water cup injection-molded product to be approximately 2.008 s. The cooling efficiency for a silicone rubber mold with a WCC is better than that of the silicone rubber mold with a CCC since the core and cavity cooling efficiency is close to 50%. The pressure drop of the WCC is smaller than that of the CCC, which reduces the pressure drop by about 56%. Taking a water cup with a mouth diameter of 70 mm, a height of 60 mm, and a thickness of 2 mm as an example, the experimental results confirmed that the use of the WCC can save the cooling time of the product by about 265 s compared with the CCC. This shows how a WCC can increase cooling efficiency by approximately 17.47%.