Global acetylome profiling indicates EPA impedes but OA promotes prostate cancer motility through altered acetylation of PFN1 and FLNA.

Prostate cancer (PCa) is one of the leading causes of cancer morbidity and mortality in men. Metastasis is the main cause of PCa-associated death. Recent evidence indicated a significant reduction in PCa mortality associated with higher ω-3 polyunsaturated fatty acids (PUFAs) consumption. However, the underlying mechanisms remained elusive. In this study, we applied global acetylome profiling to study the effect of fatty acids treatment. Results indicated that oleic acid (OA, monounsaturated fatty acid, MUFA, 100 µM) elevates while EPA (eicosapentaenoic acid, 100 µM) reduces the acetyl-CoA level, which alters the global acetylome. After treatment, two crucial cell motility regulators, PFN1 and FLNA, were found with altered acetylation levels. OA increased the acetylation of PFN1 and FLNA, whereas EPA decreased PFN1 acetylation level. Furthermore, OA promotes while EPA inhibits PCa migration and invasion. Immunofluorescence assay indicated that EPA impedes the formation of lamellipodia or filopodia through reduced localization of PFN1 and FLNA to the leading edge of cells. Therefore, perturbed acetylome may be one critical step in fatty acid-affected cancer cell motility. This study provides some new insights into the response of ω-3 PUFAs treatment and a better understanding of cancer cell migration and invasion modulation.

Revealing the distinct clinical patterns and relapse risk factors in seronegative IgG4-RD patients: A retrospective cohort study over a decade.

OBJECTIVES: Our study aimed to investigate the distinct clinical patterns of seronegative IgG4-related disease (IgG4-RD) patients. METHODS: We retrospectively enrolled 698 treatment-naïve IgG4-RD patients in this study. Patients were divided into four different subgroups according to their baseline serum IgG4 levels. The distinct clinical patterns of seronegative IgG4-RD patients were revealed through the comparison of baseline clinical data and disease prognosis among the different subgroups. COX regression analyses were used to investigate the risk factors for disease relapse and to construct the nomogram model. RESULTS: Seronegative IgG4-RD patients account for a minority of IgG4-RD patients (49/698, 7.02%). The proportions of seronegative IgG-RD patients in our study and several Asian cohorts were significantly lower than those of the European and American cohorts. Seronegative IgG4-RD patients got lower serum IgG levels (p < 0.0001), lower eosinophil count (p < 0.0001), lower serum IgE levels (p < 0.0001)), lower IgG4-RD responder index (RI) scores (p < 0.0001), and fewer affected organ numbers (p < 0.0001) compared with other subgroups, whereas they were more likely to manifest fibrotic type with some special organ involvement. Younger age at onset, GCs monotherapy, elevated C-reactive protein level, and elevated erythrocyte sedimentation rate level are the risk factors for the disease relapse of seronegative IgG4-RD patients. An effective nomogram model predicting disease relapse of seronegative IgG4-RD patients was constructed. Seronegative IgG4-RD patients with scores >84.65 at baseline were susceptible to suffering from disease relapse. CONCLUSIONS: Distinct clinical features and multiple risk factors for disease relapse of seronegative IgG4-RD patients have been revealed in this study. A nomogram model was constructed to effectively predict disease relapse during the follow-up period.

Realizing high-efficiency third harmonic generation via accidental bound states in the continuum.

The bound states in the continuum (BICs) have attracted much attention in designing metasurface due to their high Q-factor and effectiveness in suppressing radiational loss. Here we report on the realization of the third harmonic generation (THG) at a near-ultraviolet wavelength (343 nm) via accidental BICs in a metasurface. The absolute conversion efficiency of the THG reaches 1.13 × 10-5 at a lower peak pump intensity of 0.7 GW/cm2. This approach allows the generation of an unprecedentedly high nonlinear conversion efficiency with simple structures.

Association between sleep apnea-specific hypoxic burden and severity of coronary artery disease.

PURPOSE: Sleep apnea-specific hypoxic burden (SASHB) is a polysomnographic metric that comprehensively measures the degree of nocturnal desaturation caused by obstructive sleep apnea. This research was conducted to elucidate the relationship between SASHB and coronary artery disease (CAD) severity. METHODS: We carried out a prospective study of hospitalized patients with CAD of unstable angina who were expected to undergo invasive coronary angiography at Beijing Anzhen Hospital from February to September 2023. SASHB values were calculated using a self-programmed C + + program. Multivariable logistic regression analysis was applied to identify the association between SASHB and the prevalence of severe CAD, documented by the Gensini Score, and the SYNTAX (Synergy between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) Score. RESULTS: This study enrolled 137 patients with a median age of 59 years, 96 (70.1%) of whom were male. A total of 125 (91.2%) patients had coronary stenosis of ≥ 50% in at least one location. Patients with a high SASHB of ≥ 18% min/h had a significantly higher Gensini Score (32.0 vs. 18.5, P = 0.002) and SYNTAX Score (14.0 vs. 7.0, P = 0.002) than those with a low SASHB. After adjusting for multiple covariates, a high SASHB was significantly associated with the prevalence of severe CAD, determined by a Gensini Score ≥ 21 (OR 2.67, P = 0.008) or a SYNTAX Score > 22 (OR 4.03, P = 0.016). CONCLUSION: Our findings revealed a robust and independent association between SASHB and CAD severity in patients with unstable angina, highlighting the potential value of SASHB as a predictor of risk and a target for interventions aimed at preventing cardiovascular diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry No. ChiCTR2300067991 on February 2, 2023.

Flow field-flow fractionation coupled with multidetector: A robust approach for the separation and characterization of resistant starch.

The unique properties of resistant starch (RS) have made it applicable in the formulation of a broad range of functional foods. The physicochemical properties of RS play a crucial role in its applications. Recently, flow field-flow fractionation (FlFFF) has attracted increasing interest in the separation and characterization of different categories of RS. In this review, an overview of the theory behind FlFFF is introduced, and the controllable factors, including FlFFF channel design, sample separation conditions, and the choice of detector, are discussed in detail. Furthermore, the applications of FlFFF for the separation and characterization of RS at both the granule and molecule levels are critically reviewed. The aim of this review is to equip readers with a fundamental understanding of the theoretical principle of FlFFF and to highlight the potential for expanding the application of RS through the valuable insights gained from FlFFF coupled with multidetector analysis.

Dewdrop Metasurfaces and Dynamic Control Based on Condensation and Evaporation.

Dewdrops, the droplets of water naturally occurring on leaves and carapaces of insects, are a fascinating phenomenon in nature. Here, a man-made array of dewdrops with arbitrary shapes and arrangements, which can function as an electromagnetic metasurface, is demonstrated. The realization of the dewdrop array is enabled by a surface covered by a tailored pattern of hydrophilic and hydrophobic coatings, where tiny droplets of water can aggregate and form dewdrops on the former. Interestingly, this metasurface made of dewdrops can be modulated by the condensation and evaporation process. By increasing relative humidity and decreasing temperature, the dewdrop metasurface is gradually formed with increasing amounts of water. While the reverse operation can make it completely disappear. This idea is demonstrated through two examples with different functions of dynamically controllable microwave absorption and scattering. The work shows a principle to construct functional electromagnetic devices with dewdrops, as well as a mechanism of dynamic control based on condensation and evaporation, promising unprecedented applications.

Plant-Derived Extracellular Vesicles: A New Revolutionization of Modern Healthy Diets and Biomedical Applications.

Plant-derived extracellular vesicles (PDEVs) have recently emerged as a promising area of research due to their potential health benefits and biomedical applications. Produced by various plant species, these EVs contain diverse bioactive molecules, including proteins, lipids, and nucleic acids. Increasing in vitro and in vivo studies have shown that PDEVs have inherent pharmacological activities that affect cellular processes, exerting anti-inflammatory, antioxidant, and anticancer activities, which can potentially contribute to disease therapy and improve human health. Additionally, PDEVs have shown potential as efficient and biocompatible drug delivery vehicles in treating various diseases. However, while PDEVs serve as a potential rising star in modern healthy diets and biomedical applications, further research is needed to address their underlying knowledge gaps, especially the lack of standardized protocols for their isolation, identification, and large-scale production. Furthermore, the safety and efficacy of PDEVs in clinical applications must be thoroughly evaluated. In this review, we concisely discuss current knowledge in the PDEV field, including their characteristics, biomedical applications, and isolation methods, to provide an overview of the current state of PDEV research. Finally, we discuss the challenges regarding the current and prospective issues for PDEVs. This review is expected to provide new insights into healthy diets and biomedical applications of vegetables and fruits, inspiring new advances in natural food-based science and technology.

Matte surfaces with broadband transparency enabled by highly asymmetric diffusion of white light.

The long-standing paradox between matte appearance and transparency has deprived traditional matte materials of optical transparency. Here, we present a solution to this centuries-old optical conundrum by harnessing the potential of disordered optical metasurfaces. Through the construction of a random array of meta-atoms tailored in asymmetric backgrounds, we have created transparent matte surfaces that maintain clear transparency regardless of the strength of disordered light scattering or their matte appearances. This remarkable property originates in the achievement of highly asymmetric light diffusion, exhibiting substantial diffusion in reflection and negligible diffusion in transmission across the entire visible spectrum. By fabricating macroscopic samples of such metasurfaces through industrial lithography, we have experimentally demonstrated transparent windows camouflaged as traditional matte materials, as well as transparent displays with high clarity, full color, and one-way visibility. Our work introduces an unprecedented frontier of transparent matte materials in optics, offering unprecedented opportunities and applications.

Widely targeted quantitative lipidomics reveal lipid remodeling in adipose tissue after long term of the combined exposure to bisphenol A and fructose.

Adipose tissue is the main organ that stores lipids and it plays important roles in metabolic balance in the body. We recently reported in Human and Experimental Toxicology that the combined exposure to BPA and fructose may interfere with energy metabolism of adipose tissue. However, it is still unclear whether the combined exposure to BPA and fructose has the possibility to induce lipid remodeling in adipose tissue. In the present study, we performed a widely targeted quantitative lipidomic analysis of the adipose tissue of rats after 6 months of BPA and fructose combined exposure. We totally determined 734 lipid molecules in the adipose tissue of rats. Principal component analysis (PCA) showed the group of the combined exposure to higher-dose (25 µg/kg every other day) BPA and fructose can be distinguished from the groups of control, higher-dose BPA exposure and fructose exposure clearly. Partial least squares-discriminant analysis (PLS-DA) and univariate statistical analysis displayed lipids of PC(18:0_ 20:3), TG(8:0_14:0_16:0), TG(12:0_14:0_16:1), TG(10:0_16:0_16:1), TG(12:0_ 14:0_18:1), TG(14:0_ 16:0_16:1), TG(14:0_14:1_16:1), TG(8:0_ 16:1_16:2), TG(14:1_16:1_ 16:1), TG(16:1_18:1_18:1), TG(16:0_16:1_20:4) and TG(15:0_18:1_ 24:1) may contributed the most to the discrimination. These findings indicated that combined exposure to BPA and fructose has the potential to cause lipid remodeling in adipose tissue.

Conditional knockout of Shank3 in the ventral CA1 by quantitative in vivo genome-editing impairs social memory in mice.

Individuals with autism spectrum disorder (ASD) have a higher prevalence of social memory impairment. A series of our previous studies revealed that hippocampal ventral CA1 (vCA1) neurons possess social memory engram and that the neurophysiological representation of social memory in the vCA1 neurons is disrupted in ASD-associated Shank3 knockout mice. However, whether the dysfunction of Shank3 in vCA1 causes the social memory impairment observed in ASD remains unclear. In this study, we found that vCA1-specific Shank3 conditional knockout (cKO) by the adeno-associated virus (AAV)- or specialized extracellular vesicle (EV)- mediated in vivo gene editing was sufficient to recapitulate the social memory impairment in male mice. Furthermore, the utilization of EV-mediated Shank3-cKO allowed us to quantitatively examine the role of Shank3 in social memory. Our results suggested that there is a certain threshold for the proportion of Shank3-cKO neurons required for social memory disruption. Thus, our study provides insight into the population coding of social memory in vCA1, as well as the pathological mechanisms underlying social memory impairment in ASD.

Amino acid metabolomics and machine learning for assessment of post-hepatectomy liver regeneration.

Objective: Amino acid (AA) metabolism plays a vital role in liver regeneration. However, its measuring utility for post-hepatectomy liver regeneration under different conditions remains unclear. We aimed to combine machine learning (ML) models with AA metabolomics to assess liver regeneration in health and non-alcoholic steatohepatitis (NASH). Methods: The liver index (liver weight/body weight) was calculated following 70% hepatectomy in healthy and NASH mice. The serum levels of 39 amino acids were measured using ultra-high performance liquid chromatography-tandem mass spectrometry analysis. We used orthogonal partial least squares discriminant analysis to determine differential AAs and disturbed metabolic pathways during liver regeneration. The SHapley Additive exPlanations algorithm was performed to identify potential AA signatures, and five ML models including least absolute shrinkage and selection operator, random forest, K-nearest neighbor (KNN), support vector regression, and extreme gradient boosting were utilized to assess the liver index. Results: Eleven and twenty-two differential AAs were identified in the healthy and NASH groups, respectively. Among these metabolites, arginine and proline metabolism were commonly disturbed metabolic pathways related to liver regeneration in both groups. Five AA signatures were identified, including hydroxylysine, L-serine, 3-methylhistidine, L-tyrosine, and homocitrulline in healthy group, and L-arginine, 2-aminobutyric acid, sarcosine, beta-alanine, and L-cysteine in NASH group. The KNN model demonstrated the best evaluation performance with mean absolute error, root mean square error, and coefficient of determination values of 0.0037, 0.0047, 0.79 and 0.0028, 0.0034, 0.71 for the healthy and NASH groups, respectively. Conclusion: The KNN model based on five AA signatures performed best, which suggests that it may be a valuable tool for assessing post-hepatectomy liver regeneration in health and NASH.

The proteomic landscape of fall armyworm oral secretion reveals its role in plant adaptation.

BACKGROUND: The fall armyworm (FAW, Spodoptera frugiperda (J.E. Smith)) is a polyphagous agricultural pest with rapidly evolving adaptations to host plants. We found the oral secretion (OS) of FAW from different plants influences plant defense response differentially, suggesting its role in adapting to host plants. However, the protein expression profile of FAW OS respond to different plants is largely unknown. RESULTS: Here, from the mass spectrometry assay, we identified a total of 256 proteins in the OS of FAW fed on cotton (Gossypium hirsutum L.), tobacco (Nicotiana benthamiana Domin), maize (Zea mays L.) and artificial diet. The FAW OS primarily comprise of 60 proteases, 32 esterases and 92 non-enzymatic proteins. It displays high plasticity across different diets. We found that more than half of the esterases are lipases which have been reported as insect elicitors to enhance plant defense response. The lipase accumulation in cotton-fed larvae was the highest, followed by maize-fed larvae. In the presence of lipase inhibitors, the enhanced induction on defense genes in wounded leaves by OS was attenuated. However, the putative effectors were most highly accumulated in the OS from FAW larvae fed on maize compared to those fed on other diets. We identified that one of them (VRLP4) reduces the OS-mediated induction on defense genes in wounded leaves. CONCLUSION: Together, our investigation presents the proteomic landscape of the OS of FAW influenced by different diets and reveals diet-mediated plasticity of OS is involved in FAW adaptation to host plants. © 2024 Society of Chemical Industry.

Intracranial mesenchymal tumor with multiple extracranial metastases: A case report and literature review.

This study presents a rare case of an older woman with an intracranial mesenchymal tumor in the right frontal and parietal lobes. Despite prompt surgical intervention, her condition rapidly deteriorated because of tumor dissemination, leading to her demise. We highlight the tumor's marked invasiveness and heterogeneity, coupled with a propensity for distant systemic metastasis, which negatively impacted the patient's prognosis. This particular clinical behavior had not been previously reported, making this a novel observation. Thus, through a comprehensive review of relevant literature, we aim to provide valuable insights for further understanding, diagnosing, and treating such tumors.

Translocational attenuation mediated by the PERK-SRP14 axis is a protective mechanism of unfolded protein response.

The unfolded protein response (UPR) relieves endoplasmic reticulum (ER) stress through multiple strategies, including reducing protein synthesis, increasing protein folding capabilities, and enhancing misfolded protein degradation. After a multi-omics analysis, we find that signal recognition particle 14 (SRP14), an essential component of the SRP, is markedly reduced in cells undergoing ER stress. Further experiments indicate that SRP14 reduction requires PRKR-like ER kinase (PERK)-mediated eukaryotic translation initiation factor 2α (eIF2α) phosphorylation but is independent of ATF4 or ATF3 transcription factors. The decrease of SRP14 correlates with reduced translocation of fusion proteins and endogenous cathepsin D. Enforced expression of an SRP14 variant with elongation arrest capability prevents the reduced translocation of cathepsin D in stressed cells, whereas an SRP14 mutant without the activity does not. Finally, overexpression of SRP14 augments the UPR and aggravates ER-stress-induced cell death. These data suggest that translocational attenuation mediated by the PERK-SRP14 axis is a protective measure for the UPR to mitigate ER stress.

Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance.

Fetuin-A, a hepatokine secreted by hepatocytes, binds to insulin receptors and consequently impairs the activation of the insulin signaling pathway, leading to insulin resistance. Apigenin, a flavonoid isolated from plants, has beneficial effects on insulin resistance; however, its regulatory mechanisms are not fully understood. In the present study, we investigated the molecular mechanisms underlying the protective effects of apigenin on insulin resistance. In Huh7 cells, treatment with apigenin decreased the mRNA expression of fetuin-A by decreasing reactive oxygen species-mediated casein kinase 2α (CK2α)-nuclear factor kappa-light-chain-enhancer of activated B activation; besides, apigenin decreased the levels of CK2α-dependent fetuin-A phosphorylation and thus promoted fetuin-A degradation through the autophagic pathway, resulting in a decrease in the protein levels of fetuin-A. Moreover, apigenin prevented the formation of the fetuin-A-insulin receptor (IR) complex and thereby rescued the PA-induced impairment of the insulin signaling pathway, as evidenced by increased phosphorylation of IR substrate-1 and Akt, and translocation of glucose transporter 2 from the cytosol to the plasma membrane. Similar results were observed in the liver of HFD-fed mice treated with apigenin. Collectively, our findings revealed that apigenin ameliorates obesity-induced insulin resistance in the liver by targeting fetuin-A.

Prohibitin 1 inhibits cell proliferation and induces apoptosis via the p53-mediated mitochondrial pathway in vitro.

BACKGROUND: Prohibitin 1 (PHB1) has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed, and it participates in a variety of essential cellular functions, including apoptosis, cell cycle regulation, proliferation, and survival. Emerging evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma (HCC). However, the role of PHB1 in HCC is controversial. AIM: To investigate the effects of PHB1 on the proliferation and apoptosis of human HCC cells and the relevant mechanisms in vitro. METHODS: HCC patients and healthy individuals were enrolled in this study according to the inclusion and exclusion criteria; then, PHB1 levels in the sera and liver tissues of these participates were determined using ELISA, RT-PCR, and immunohistochemistry. Human HepG2 and SMMC-7721 cells were transfected with the pEGFP-PHB1 plasmid and PHB1-specific shRNA (shRNA-PHB1) for 24-72 h. Cell proliferation was analysed with an MTT assay. Cell cycle progression and apoptosis were analysed using flow cytometry (FACS). The mRNA and protein expression levels of the cell cycle-related molecules p21, Cyclin A2, Cyclin E1, and CDK2 and the cell apoptosis-related molecules cytochrome C (Cyt C), p53, Bcl-2, Bax, caspase 3, and caspase 9 were measured by real-time PCR and Western blot, respectively. RESULTS: Decreased levels of PHB1 were found in the sera and liver tissues of HCC patients compared to those of healthy individuals, and decreased PHB1 was positively correlated with low differentiation, TNM stage III-IV, and alpha-fetoprotein ≥ 400 µg/L. Overexpression of PHB1 significantly inhibited human HCC cell proliferation in a time-dependent manner. FACS revealed that the overexpression of PHB1 arrested HCC cells in the G0/G1 phase of the cell cycle and induced apoptosis. The proportion of cells in the G0/G1 phase was significantly increased and the proportion of cells in the S phase was decreased in HepG2 cells that were transfected with pEGFP-PHB1 compared with untreated control and empty vector-transfected cells. The percentage of apoptotic HepG2 cells that were transfected with pEGFP-PHB1 was 15.41% ± 1.06%, which was significantly greater than that of apoptotic control cells (3.65% ± 0.85%, P < 0.01) and empty vector-transfected cells (4.21% ± 0.52%, P < 0.01). Similar results were obtained with SMMC-7721 cells. Furthermore, the mRNA and protein expression levels of p53, p21, Bax, caspase 3, and caspase 9 were increased while the mRNA and protein expression levels of Cyclin A2, Cyclin E1, CDK2, and Bcl-2 were decreased when PHB1 was overexpressed in human HCC cells. However, when PHB1 was upregulated in human HCC cells, Cyt C expression levels were increased in the cytosol and decreased in the mitochondria, which indicated that Cyt C had been released into the cytosol. Conversely, these effects were reversed when PHB1 was knocked down. CONCLUSION: PHB1 inhibits human HCC cell viability by arresting the cell cycle and inducing cell apoptosis via activation of the p53-mediated mitochondrial pathway.

A new phenolic compound from Persicaria capitata.

Persicaria capitata was a frequently used Hmong medicinal flora in China. In this study, one new phenolic compound, capitaone A (1) together with 20 known ones, were isolated from the whole herb of P. capitata. Among them, 7 components (4, 9-11, 15-16, 20-21) were discovered from P. capitata for the first time. Their chemical structures were elucidated on the basis of extensive NMR and MS spectrum. Furthermore, three compounds (15, 20, 21) displayed remarkable cytotoxic activities against two human cancer cell lines (A549 and HepG2).

Brunonianines A-C, C20-diterpenoid alkaloids with cyano group from Delphinium brunonianum Royle.

Cyano tends to have better biological activity, but it is rarely reported in natural products, especially in the C20-diterpene alkaloids. Herein, three unprecedented C20-diterpenoid alkaloids, brunonianines A-C (1-3), possessing rare cyano functional group as well as an atisine backbone constructed from a phenethyl substituent and a tetrahydropyran ring, along with four C19-alkaloids (4-7) and one amide alkaloids (8), were isolated from the whole plant of Delphinium brunonianum Royle. Compounds 1-3 are also the first atisine type diterpenoid alkaloids with cyano group obtained from nature. The structures of the previously undescribed compounds were elucidated by HR-ESI-MS, 1D/2D NMR spectroscopic data and electronic circular dichroism calculations and single-crystal X-ray diffraction. Reasonable speculations have also been made regarding the biogenic synthetic pathways of compounds 1-3. In addition, the inhibitory activity of all compounds was also tested against four tumor lines: A549, Caco-2, H460 and Skov-3, where compound 2 (IC50 2.20 ± 0.21 µM) showed better inhibitory activity against Skov-3 cells than the hydroxycamptothecin. Using flow cytometry, cell staining, migration and invasion analysis, and Western blot, compound 2 was found to arrest cells in the G2/M phase and was able to effectively inhibit cell motility to achieve potent anti-tumor effects. In addition, compound 2 can effectively induce apoptosis by activating the Bax/Bcl-2/Caspase-3 signaling pathway.

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.

Heat shock factor 1 directly regulates transsulfuration pathway to promote prostate cancer proliferation and survival.

There are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and is an actionable target. In this manuscript, we identify that HSF1 regulates the conversion of homocysteine to cystathionine in the transsulfuration pathway by altering levels of cystathionine-ß-synthase (CBS). We find that HSF1 directly binds the CBS gene and upregulates CBS mRNA levels. Targeting CBS decreases PCa growth and induces tumor cell death while benign prostate cells are largely unaffected. Combined inhibition of HSF1 and CBS results in more pronounced inhibition of PCa cell proliferation and reduction of transsulfuration pathway metabolites. Combination of HSF1 and CBS knockout decreases tumor size for a small cell PCa xenograft mouse model. Our study thus provides new insights into the molecular mechanism of HSF1 function and an effective therapeutic strategy against advanced PCa.