Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

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. On the other hand, 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. This article is protected by copyright. All rights reserved.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

Indole-3-Aldehyde Reduces Inflammatory Responses and Restores Intestinal Epithelial Barrier Function Partially via Aryl Hydrocarbon Receptor (AhR) in Experimental Colitis Models.

Purpose: Indole-3-aldehyde (IAld) has been shown to improve intestinal epithelial barrier (IEB) function through the aryl hydrocarbon receptor (AhR) in murine colitis models. However, the impact of IAld on intestinal tissue inflammation remains unexplored. This study aimed to investigate the effects of IAld on the inflammatory responses of the gut both in vivo and in vitro and probe the mechanisms by which IAld attenuates colitis. Methods: The effects of IAld on phenotypic changes, pro-inflammatory cytokines, IEB functions and the faecal bacterial composition in mice with dextran sulfate sodium salt (DSS)-induced colitis were assessed. Macrophage cells and intestinal epithelial cells were stimulated with lipopolysaccharide (LPS), and the effects of IAld on the inflammatory responses and IBE functions were measured. Results: IAld reduced IL-6, IL-1ß and TNF-α protein levels in both colonic tissues from the mice with colitis and LPS-stimulated macrophage cells. The IAld-mediated reduction of IL-6 but not IL-1ß and TNF-α was through AhR activation. Furthermore, nuclear factor-κB pathway was found to be inhibited by IAld treatment via AhR activation both in vivo and in vitro. Gut permeability was significantly improved by IAld in both DSS-treated mice and LPS-stimulated Caco-2 cells. This observation is consistent with downregulation of phosphorylated myosin light chain through AhR activation. IAld did not appear to have an effect on the bacterial composition in mice with colitis despite the reduced colonic inflammatory responses. Conclusion: IAld improved DSS-induced colitis by inhibiting the inflammatory responses and restoring IEB function, partially via AhR activation. This work provided insight into the function of IAld in modulating gut inflammation.

The effect of fructose exposure on amino acid metabolism among Chinese community residents and its possible multi-omics mechanisms.

The consumption of fructose has increased dramaticly during the last few decades, inducing a great increase in the risk of intrahepatic lipid accumulation, hypertriglyceridemia, hyperuricemia and cancer. However, the underlying mechanism has not yet been fully elucidated. Amino acid metabolism may play an important role in the process of the diseases caused by fructose, but there is still a lack of corresponding evidence. In present study, we provide an evidence of how fructose affects amino acids metabolism in 1895 ordinary residents in Chinese community using UPLC-QqQMS based amino acid targeted metabolomics and the underlying mechanism of fructose exposure how interferes with amino acid metabolism related genes and acetylated modification of proteome in the liver of rats model. We found people with high fructose exposure had higher levels of Asa, EtN, Asp, and Glu, and lower levels of 1MHis, PEtN, Arg, Gln, GABA, Aad, Hyl and Cys. The further mechanism study displayed amino acid metabolic genes of Aspa, Cndp1, Dbt, Dmgdh, and toxic metabolites such as N-acetylethanolamines accumulation, interference of urea cycle, as well as acetylated modification of key enzymes in glutamine metabolic network and glutamine derived NEAAs synthesis pathway in liver may play important roles in fructose caused reprogramming in amino acid metabolism. This research provides novel insights of the mechanism of amino acid metabolic disorder caused by fructose and supplies new targets for clinical therapy.

Association between a family history of cancer and multiple primary lung cancer risks: a population-based analysis from China.

OBJECTIVES: The incidence of multiple primary lung cancer (MPLC) has increased in recent years. The risk factors of MPLC are not well studied, especially in the Asian population. This case-control study investigated the association between a family history of cancer and MPLC risk. METHODS: We used data from people who surgically confirmed MPLC with at least 2 nodes of Fujian Medical University Union Hospital and matched 1:2 normal individuals as controls between 2016 and 2017. Information on age, sex, lifestyle, personal history, and family history of cancer was collected using a self-administered questionnaire, and odds ratios (OR) were estimated using unconditional logistic regression. RESULTS: We included 2 104 patients. In total, 321 patients with histologically confirmed MPLC and 642 healthy controls were studied. The significantly higher ratio of current smokers was observed for the cases than the controls (54.1% vs. 30.0%). A family history of LC in first-degree relatives of the cases reported a significantly higher proportion than in the controls (15.3% vs. 8.6%). Family history of all cancers and LC significantly increased the risk of MPLC (OR = 1.64, P = 0.009 and OR = 2.59, P = 0.000, respectively). The multivariate analysis identified a significantly increased risk of MPLC (OR = 2.45, P = 0.000) associated with parents and siblings influenced by LC history. The younger age (aged < 55 years) of LC cases at diagnosis exhibited a significantly increased risk of MPLC (OR = 2.39, P = 0.000). A significant association with a family history of LC was found for male squamous carcinoma and male adenocarcinoma (OR = 1.59, p = 0.037 and OR = 1.64, p = 0.032, respectively). A positive association with LC history was only observed for female adenocarcinoma (OR = 2.23, p = 0.028). The risk of MPLC was not significantly associated with A family history of cancers in non-smokers (OR = 0.91, P = 0.236). Ever-smokers with a positive family history of cancer or LC had a significantly elevated risk of MPLC (OR = 4.01, P = 0.000 and OR = 6.49, P = 0.000, respectively). We also observed a very elevated risk for smokers with no family history (OR = 3.49, P = 0.000). Such a positive association was also observed in ever-smokers with no family history of LC (OR = 3.55, P = 0.000). Adenocarcinoma in females was prevalent and significantly associated with a family history of LC in risk of MPLC compared with other histologic subtypes. CONCLUSIONS: Our findings suggest an association between a family history of LC and MPLC risk among an Asian population. Smoking status and family history of LC have a synergistic effect on MPLC. These findings indicate that MPLC exhibits familiar aggregation and that inherited genetic susceptibility may contribute to the development of MPLC.

Association Between Olfactory Dysfunction and Cognitive Impairment in Dementia-Free Older Adults: A Prospective Cohort Study in Taiwan.

BACKGROUND: Previous studies assessing olfactory function and cognition have mostly been cross-sectional, and few have investigated the Asian geriatric population. OBJECTIVE: To examine the relationships of olfaction with global or domain-specific cognitive function in Taiwanese community-dwelling older adults. METHODS: This cohort study (2015-2019) is part of the Taiwan Initiative for Geriatric Epidemiological Research. The Taiwanese version of the Montreal Cognitive Assessment (MoCA-T) and a battery of neuropsychological tests were assessed at baseline and at a two-year follow-up. The cross-culture modified Sniffin' Sticks Identification Test (SSIT) was utilized to measure olfactory function. Generalized linear mixed models were used to examine the association of olfaction with cognitive performance over two years. RESULTS: Data were collected from 376 participants (55.1% women), with a mean age of 75.6 years. A one-point decrease in the SSIT score (worsening of olfaction) was associated with worse global cognition (MoCA-T: ߈= -0.13), memory (߈= -0.08 to -0.06), and verbal fluency (߈= -0.07). Compared with an SSIT score ≥ 11 (normosmia), an SSIT score < 8 (anosmia) was associated with worse global cognition (MoCA-T: ߈= -0.99), memory (߈= -0.48 to -0.42), executive function (Trail Making Test A: ߈= -0.36), attention (digit span backward: ߈= -0.34), and verbal fluency (߈= -0.45). After stratified analyses, the associations remained in older adults ≥ 75 years, males, and non-carriers of apolipoprotein E ɛ4 in terms of global cognition, memory, and verbal fluency. CONCLUSIONS: Odor identification deficits were associated with poor global or domain-specific cognitive function in a four-year cohort of community-dwelling older adults. Cognitive assessments should be conducted in dementia-free elderly individuals with impaired odor identification.