Epigenome-wide association study of lung cancer among never smokers in two prospective cohorts in Shanghai, China.

BACKGROUND: The aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted. METHODS: We conducted a nested case-control study of 80 never-smoking incident lung cancer cases and 83 never-smoking controls within the Shanghai Women's Health Study and Shanghai Men's Health Study. DNAm was measured in prediagnostic oral rinse samples using Illumina MethylationEPIC array. Initially, we conducted an EWAS to identify differentially methylated positions (DMPs) associated with lung cancer in the discovery sample of 101 subjects. The top 50 DMPs were further evaluated in a replication sample of 62 subjects, and results were pooled using fixed-effect meta-analysis. RESULTS: Our study identified three DMPs significantly associated with lung cancer at the epigenome-wide significance level of p<8.22×10-8. These DMPs were identified as cg09198866 (MYH9; TXN2), cg01411366 (SLC9A10) and cg12787323. Furthermore, examination of the top 1000 DMPs indicated significant enrichment in epithelial regulatory regions and their involvement in small GTPase-mediated signal transduction pathways. Additionally, GrimAge acceleration was identified as a risk factor for lung cancer (OR=1.19 per year; 95% CI 1.06 to 1.34). CONCLUSIONS: While replication in a larger sample size is necessary, our findings suggest that DNAm patterns in prediagnostic oral rinse samples could provide novel insights into the underlying mechanisms of lung cancer in never smokers.

A nested case-control study of untargeted plasma metabolomics and lung cancer among never-smoking women within the prospective Shanghai Women's Health Study.

The etiology of lung cancer in never-smokers remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Here, we aimed to enhance our understanding of lung cancer pathogenesis among never-smokers using untargeted metabolomics. This nested case-control study included 395 never-smoking women who developed lung cancer and 395 matched never-smoking cancer-free women from the prospective Shanghai Women's Health Study with 15,353 metabolic features quantified in pre-diagnostic plasma using liquid chromatography high-resolution mass spectrometry. Recognizing that metabolites often correlate and seldom act independently in biological processes, we utilized a weighted correlation network analysis to agnostically construct 28 network modules of correlated metabolites. Using conditional logistic regression models, we assessed the associations for both metabolic network modules and individual metabolic features with lung cancer, accounting for multiple testing using a false discovery rate (FDR) < 0.20. We identified a network module of 121 features inversely associated with all lung cancer (p = .001, FDR = 0.028) and lung adenocarcinoma (p = .002, FDR = 0.056), where lyso-glycerophospholipids played a key role driving these associations. Another module of 440 features was inversely associated with lung adenocarcinoma (p = .014, FDR = 0.196). Individual metabolites within these network modules were enriched in biological pathways linked to oxidative stress, and energy metabolism. These pathways have been implicated in previous metabolomics studies involving populations exposed to known lung cancer risk factors such as traffic-related air pollution and polycyclic aromatic hydrocarbons. Our results suggest that untargeted plasma metabolomics could provide novel insights into the etiology and risk factors of lung cancer among never-smokers.

Age at lung cancer diagnosis in females versus males who never smoke by race and ethnicity.

BACKGROUND: We characterized age at diagnosis and estimated sex differences for lung cancer and its histological subtypes among individuals who never smoke. METHODS: We analyzed the distribution of age at lung cancer diagnosis in 33,793 individuals across 8 cohort studies and two national registries from East Asia, the United States (US) and the United Kingdom (UK). Student's t-tests were used to assess the study population differences (Δ years) in age at diagnosis comparing females and males who never smoke across subgroups defined by race/ethnicity, geographic location, and histological subtypes. RESULTS: We found that among Chinese individuals diagnosed with lung cancer who never smoke, females were diagnosed with lung cancer younger than males in the Taiwan Cancer Registry (n = 29,832) (Δ years = -2.2 (95% confidence interval (CI):-2.5, -1.9), in Shanghai (n = 1049) (Δ years = -1.6 (95% CI:-2.9, -0.3), and in Sutter Health and Kaiser Permanente Hawai'i in the US (n = 82) (Δ years = -11.3 (95% CI: -17.7, -4.9). While there was a suggestion of similar patterns in African American and non-Hispanic White individuals. the estimated differences were not consistent across studies and were not statistically significant. CONCLUSIONS: We found evidence of sex differences for age at lung cancer diagnosis among individuals who never smoke.

ECM1-associated miR-1260b promotes osteogenic differentiation by targeting GDI1.

Osteoporosis (OP) is a common disease among older adults. The promotion of osteoblast differentiation plays a crucial role in alleviating OP symptoms. Extracellular matrix protein 1 (ECM1) has been reported to be closely associated with osteogenic differentiation. In this study, we constructed U2OS cell lines with ECM1 knockdown and ECM1a overexpression based on knockdown, and identified the target miRNA (miR-1260b) by sequencing. Overexpression of miR-1260b promoted the osteogenic differentiation of U2OS and MG63 cells, as demonstrated by increased alkaline phosphatase (ALP) activity, matrix mineralization, and Runt-Related Transcription Factor 2 (RUNX2), Osteopontin (OPN), Collagen I (COL1A1), and Osteocalcin (OCN) protein expressions, whereas low expression of miR-1260b had the opposite effect. In addition, miR-1260b expression was decreased in OP patients than in non-OP patients. Next, we predicted the target gene of miRNA through TargetScan and miRDB and found that miR-1260b negatively regulated GDP dissociation inhibitor 1 (GDI1) by directly binding to its 3'-untranslated region. Subsequent experiments revealed that GDI1 overexpression decreased ALP activity and calcium deposit, reduced RUNX2, OPN, COL1A1, and OCN expression levels, and reversed the effects of miR-1260b on osteogenic differentiation. In conclusion, ECM1-related miR-1260b promotes osteogenic differentiation by targeting GDI1 in U2OS and MG63 cells. Thus, this study has significant implication for osteoporosis treatment.

Identification of novel F2-isoprostane metabolites by specific UDP-glucuronosyltransferases.

UDP-glucuronosyltransferases (UGTs) catalyze the conjugation of glucuronic acid with endogenous and exogenous lipophilic small molecules to facilitate their inactivation and excretion from the body. This represents approximately 35 % of all phase II metabolic transformations. Fatty acids and their oxidized eicosanoid derivatives can be metabolized by UGTs. F2-isoprostanes (F2-IsoPs) are eicosanoids formed from the free radical oxidation of arachidonic acid. These molecules are potent vasoconstrictors and are widely used as biomarkers of endogenous oxidative damage. An increasing body of evidence demonstrates the efficacy of measuring the ß-oxidation metabolites of F2-IsoPs rather than the unmetabolized F2-IsoPs to quantify oxidative damage in certain settings. Yet, the metabolism of F2-IsoPs is incompletely understood. This study sought to identify and characterize novel phase II metabolites of 15-F2t-IsoP and 5-epi-5-F2t-IsoP, two abundantly produced F2-IsoPs, in human liver microsomes (HLM). Utilizing liquid chromatography-mass spectrometry, we demonstrated that glucuronide conjugates are the major metabolites of these F2-IsoPs in HLM. Further, we showed that these molecules are metabolized by specific UGT isoforms. 15-F2t-IsoP is metabolized by UGT1A3, 1A9, and 2B7, while 5-epi-5-F2t-IsoP is metabolized by UGT1A7, 1A9, and 2B7. We identified, for the first time, the formation of intact glucuronide F2-IsoPs in human urine and showed that F2-IsoP glucuronidation is reduced in people supplemented with eicosapentaenoic and docosahexaenoic acids for 12 weeks. These studies demonstrate that endogenous F2-IsoP levels can be modified by factors other than redox mechanisms.

Association between F2-Isoprostane Metabolites and Weight Change in Older Women: A Longitudinal Analysis.

INTRODUCTION: Theoretically, some metabolic traits may predispose older individuals to weight loss during aging, leading to increased all-cause mortality and many serious health issues. Biomarkers to robustly predict progressive weight loss during aging are, however, lacking. We prospectively assessed if urinary levels of F2-isoprostanes and their peroxisomal ß-oxidation metabolite, 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-IsoP-M), were associated with subsequent weight loss in middle-aged and older women. METHODS: Included in the analysis were 2,066 women aged 40-70 years, a subset of a prospective cohort study. F2-isoprostanes (F2-IsoPs) and its ß-oxidation metabolite, F2-IsoP-M, were measured in urine using gas chromatography-mass spectrometry. Measurements of anthropometry and exposures to major determinants of body weight were performed at baseline and repeated thrice over 15-year follow-up. The longitudinal associations of F2-IsoP-M and the F2-IsoP-M to its parent compound, F2-IsoP, ratio (MPR) with repeatedly measured weight changes were examined using linear mixed-effect models. RESULTS: After adjusting for time-varying covariates: energy intake, physical activity, and comorbidity index, among others, levels of F2-IsoP-M and the MPR were both inversely associated with percentage of weight change. Weight in the highest quartile of these two biomarkers was 1.33% (95% CI = -2.41, -0.24) and 1.09% (95% CI = -2.16, -0.02) lower than those in the lowest quartile group, with p for trend of 0.01 and 0.03, respectively. The inverse association was consistently seen across follow-up periods, although appearing stronger with prolonged follow-up. There was no association between the parent compound, F2-IsoPs, and weight change. CONCLUSION: This study demonstrates the first piece of evidence to associate F2-IsoP metabolism, peroxisomal ß-oxidation, with weight loss in older women. Further investigations into the role of lipid peroxidation and peroxisomal ß-oxidation in weight change among older individuals are warranted.

Bimetallic Nanozyme: A Credible Tag for In Situ-Catalyzed Reporter Deposition in the Lateral Flow Immunoassay for Ultrasensitive Cancer Diagnosis.

The lateral flow immunoassay (LFIA) is a sought-after point-of-care testing platform, yet the insufficient sensitivity of the LFIA limits its application in the detection of tumor biomarkers. Here, a colorimetric signal amplification method, bimetallic nanozyme-mediated in situ-catalyzed reporter deposition (BN-ISCRD), was designed for ultrasensitive cancer diagnosis. The bimetallic nanozyme used, palladium@iridium core-shell nanoparticles (Pd@Ir NPs), had ultrahigh enzyme-like activity, which was further explained by the electron transfer of Pd@Ir NPs and the change in the Gibbs free energy during catalysis through density functional theory calculations. With gastric cancer biomarkers pepsinogen I and pepsinogen II as model targets, this assay could achieve a cutoff value of 10 pg/mL, which was 200-fold lower than that without signal enhancement. The assay was applied to correctly identify 8 positive and 28 negative clinical samples. Overall, this BN-ISCRD-based LFIA showed great merits and potential in the application of ultrasensitive disease diagnosis.

Structural and signaling mechanisms of TAAR1 enabled preferential agonist design.

Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D3.32 for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second binding pocket (SBP) allowed modulation of signaling preference. In addition to traditional drug-induced Gs signaling, Gq activation by EAM or synthetic compounds is beneficial to schizophrenia treatment. Our results provided a structural and signaling framework for molecular recognition by TAAR1, which afforded structural templates and signal clues for TAAR1-targeted candidate compounds design.

Association between leptin receptor polymorphisms and polycystic ovary syndrome risk: a meta-analysis based on 11 studies.

OBJECTIVE: Published evidence indicated that the leptin receptor (LEPR) gene polymorphisms are associated with polycystic ovary syndrome (PCOS) risk. However, studies on the association between the polymorphisms of LEPR gene are inconsistent or even controversial. MATERIAL AND METHODS: We conducted this meta-analysis to explore the more precise relationship between LEPR polymorphisms and PCOS risk. Relevant articles were searched with five online databases up to March 1 2023. Odds ratios (OR) with 95% confidence intervals (CI) were selected to examine the statistical strength of each genetic model. Moreover, RNA secondary structure and variant effects of these loci were examined with in silico analysis. RESULTS: Overall, 11 publications were analyzed, and the pooled results did not present any significant association between rs1137101 A/G polymorphism and PCOS risk in general population and some subgroup analysis. But the significant association were observed in Asian population (AG vs. AA: OR = 0.51, 95%CI = 0.32-0.81, p = .01, I2=0%; AG + GG vs. AA: OR = 0.41, 95%CI = 0.26-0.65, p < .01, I2=25.9%). Moreover, similar positive associations were also observed in rs1805096 polymorphism with PCOS risk. CONCLUSION: In summary, our meta-analysis suggested that the LEPR gene polymorphisms might be associated with PCOS susceptibility. Owing to the limited studies and small sample size in our meta-analysis, more well-designed studies from different races were needed to be conducted to verify the current results.

Associations between Longer Leukocyte Telomere Length and Increased Lung Cancer Risk among Never Smokers in Urban China.

BACKGROUND: The complex relationship between measured leukocyte telomere length (LTL), genetically predicted LTL (gTL), and carcinogenesis is exemplified by lung cancer. We previously reported associations between longer pre-diagnostic LTL, gTL, and increased lung cancer risk among European and East Asian populations. However, we had limited statistical power to examine the associations among never smokers by gender and histology. METHODS: To investigate further, we conducted nested case-control analyses on an expanded sample of never smokers from the prospective Shanghai Women's Health Studies (798 cases and 792 controls) and Shanghai Men's Health Studies (161 cases and 162 controls). We broke the case-control matching and used multivariable unconditional logistic regression models to estimate the ORs and 95% confidence intervals (CI) of incident lung cancer and adenocarcinoma (LUAD), in relation to LTL measured using quantitative PCR and gTL determined using a polygenic score. In addition, we conducted Mendelian randomization (MR) using MR-PRESSO. RESULTS: We found striking dose-response relationships between longer LTL and gTL, and increased lung cancer risk among never-smoking women (P trendLTL = 4×10-6; P trendgTL = 3×10-4). Similarly, among never-smoking men, longer measured LTL was associated with over triple the risk compared with those with the shortest (OR, 3.48; 95% CI, 1.85-6.57). The overall results were similar for LUAD among women and men. MR analyses supported causal associations with LUAD among women (OR1 SD gTL, 1.19; 95% CI, 1.03-1.37; P = 0.03). CONCLUSIONS: Longer pre-diagnostic LTL is associated with increased lung cancer risk among never smokers. IMPACT: Our findings firmly support the role of longer telomeres in lung carcinogenesis.

miR-196b-5p promotes myoblast proliferation and differentiation.

MicroRNAs (miRNAs) are a class of non-coding single-stranded RNA molecules about 22 nucleotides in length and are encoded by endogenous genes, and are involved in the regulation of post-transcriptional gene expression in animals and plants. Many studies have shown that microRNAs regulate the development of skeletal muscle, mainly manifested in the activation of muscle satellite cells and biological processes such as proliferation, differentiation, and formation of muscle tubes. In this study, miRNA sequencing screening of longissimus dorsi (LD, mainly fast-twitch fibers) and soleus muscle (Sol, dominated by slow-twitch fibers) identified the miR-196b-5p as a differentially expressed and highly conserved sequence in different skeletal muscles. Studies of miR-196b-5p in skeletal muscle have not been reported. In this study, miR-196b-5p mimics and inhibitor were used in miR-196b-5p overexpression and interference experiments in C2C12 cells. The effect of miR-196b-5p on myoblast proliferation and differentiation was analyzed by western blotting, real-time quantitative RT-PCR, flow cytometry, immunofluorescence staining, and the target gene of miR-196b-5p was identified by bioinformatics prediction and analyzed by dual luciferase reporter assays. The results showed that overexpression of miR-196b-5p could significantly increase the mRNA and protein expression of Cyclin B, Cyclin D and Cyclin E (P<0.05); Cell cycle analysis showed that overexpression of miR-196b-5p significantly increased the proportion of cells in the S phase (P<0.05), indicating that miR-196b-5p could accelerate cell cycle progress. Results of EdU staining showed that overexpression of miR-196b-5p significantly promoted cell proliferation. Conversely, inhibition of miR-196b-5p expression could significantly reduce the proliferation capacity of myoblasts. Further, overexpression of miR-196b-5p could significantly increase the expression levels of myogenic marker genes MyoD, MoyG and MyHC (P<0.05), thereby promoting myoblast fusion and accelerating C2C12 cell differentiation. Bioinformatics predictions and dual luciferase experiments demonstrated that miR-196b-5p could target and inhibit the expression of the Sirt1 gene. Altering the Sirt1 expression could not rescue the effects of miR-196b-5p on the cell cycle, but could weaken the promoting effects of miR-196b-5p on myoblast differentiation, suggesting that miR-196b-5p promoted myoblast differentiation by targeting Sirt1.

Visual and Electrochemical Detection of let-7a: A Tumor Suppressor and Biomarker.

Let-7a, a type of low-expressed microRNAs in cancer cells, has been investigated as a promising biomarker and therapeutic target for tumor suppression. Developing simple and sensitive detection methods for let-7a is important for cancer diagnosis and treatment. In this work, the hybridization chain reaction (HCR) was initiated by let-7a via two hairpin primers (H1 and H2). After the HCR, the remaining hairpin H1 was further detected by lateral flow assay (LFA) and electrochemical impedance spectroscopy. For LFA, biotin-modified H1(bio-H1) and free H2 were used for HCR. With the decrease of let-7a concentration, the color of T line gradually increased. As for electrochemical methods, the H1'-AuNP-modified electrode was used for detection of bio-H1 based on the difference of impedance (ΔRct) detected without and with different concentrations of let-7a participating in the HCR. This method could detect let-7a in the range of 10.0 fM and 1.0 nM with detection limits of 4.2 fM.

The feedback loop of AURKA/DDX5/TMEM147-AS1/let-7 drives lipophagy to induce cisplatin resistance in epithelial ovarian cancer.

Platinum-taxane chemotherapy is the first-line standard-of-care treatment administered to patients with epithelial ovarian cancer (EOC), and faces the major challenge of cisplatin resistance. Aurora Kinase A (AURKA) is a serine/threonine kinase, acting as an oncogene by participating in microtubule formation and stabilization. In this study, we demonstrate that AURKA binds with DDX5 directly to form a transcriptional coactivator complex to induce the transcription and upregulation of an oncogenic long non-coding RNA, TMEM147-AS1, which sponges hsa-let-7b/7c-5p leading to the increasing expression of AURKA as a feedback loop. The feedback loop maintains EOC cisplatin resistance via activation of lipophagy. These findings underscore the feedback loop of AURKA/DDX5/TMEM147-AS1/let-7 provides mechanistic insights into the combined use of TMEM147-AS1 siRNA and VX-680, which can help improve EOC cisplatin treatment. Our mathematical model shows that the feedback loop has the potential to act as a biological switch to maintain on- (activated) or off- (deactivated) status, implying the possible resistance of single use of VX-680 or TMEM147-AS1 siRNA. The combined use reduces both the protein level of AURKA using TMEM147-AS1 siRNA and its kinase activity using VX-680, showing more significant effect than the use of TMEM147-AS1 siRNA or VX-680 alone, which provides a potential strategy for EOC treatment.

Structural basis of peptide recognition and activation of endothelin receptors.

Endothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes-endothelin receptor A (ETAR) and B (ETBR). Since ET-1, the first endothelin, was identified in 1988 as one of the most potent endothelial cell-derived vasoconstrictor peptides with long-lasting actions, the endothelin system has attracted extensive attention due to its critical role in vasoregulation and close relevance in cardiovascular-related diseases. Here we present three cryo-electron microscopy structures of ETAR and ETBR bound to ET-1 and ETBR bound to the selective peptide IRL1620. These structures reveal a highly conserved recognition mode of ET-1 and characterize the ligand selectivity by ETRs. They also present several conformation features of the active ETRs, thus revealing a specific activation mechanism. Together, these findings deepen our understanding of endothelin system regulation and offer an opportunity to design selective drugs targeting specific ETR subtypes.

Asperolide A induces apoptosis and cell cycle arrest of human hepatoma cells with p53-Y220C mutant through p38 mediating phosphorylation of p53 (S33).

Asperolides A (AA), one of the new tetranorlabdane diterpenoids, is proved to inhibit the proliferation of lung cancer cells and bone metastasis of breast cancer cells. Herein, we report that AA induces apoptosis and cell cycle arrest of hepatoma cells. It intensely inhibits proliferation of Huh-7 cell, compared with HepG-2 and L02 cells. AA elevates the activity of mitogen-activated protein kinases (MAPKs), in which the activation of ERK and JNK improves cell survival. However, phosphorylation of p53 at S33 by p38 activation could be a principal factor in the AA-induced apoptosis and G2/M cell cycle arrest of Huh-7 cells. The S33 site of p53-Y220C mutant, as the specific activation site of p38, reactivates the wild-type function of mutant p53 protein, which leads to a higher sensitivity of Huh-7 cells to AA. These results provide new insights into the molecular mechanisms of AA as a developing mutant p53 rescue drug.

First report of Fusarium meridionale causing Fusarium head blight of wheat in Henan Province, China.

Fusarium graminearum and F. asiaticum have been found as a major cause of Fusarium head blight (FHB) of wheat (Triticum aestivum L.), especially in Henan Province of China (Zhang et al. 2014; Xu et al. 2021). In May 2021, a survey to determine the composition of Fusarium species infecting wheat heads was conducted in commercial fields in Henan. A total of 395 diseased spikes with premature whitening symptom were collected from 31 commercial fields in Henan. Symptomatic spikelets were excised, surface-sterilized for 10 s in 70% ethanol followed by 1 min in 3% sodium hypochlorite, rinsed three times with autoclaved distilled water, and then plated onto potato dextrose agar (PDA) medium. Isolated colonies that resembled Fusarium species were transferred to fresh PDA plates and purified using a single spore method. Species were identified based on sequence analysis of the translation elongation factor-1α (TEF) and trichothecene 3-Oacetyltransferase (Tri 101) gene (Proctor et al. 2009). The results indicated that F. graminearum (43.3%), F. asiaticum (47.8%), F. pseudograminearum (6.6%) were the main causal agents of FHB in Henan. However, nine isolates (2.3%) were found to be identical to F. meridionale by sequence comparison in GenBank, and eight isolates of which came from three fields with 1% to 2% diseased spikes near Reservoir Luhun (34.1255° N, 112.1111° E, altitude: 388 m above sea level), Songxian County of Henan. The isolates of F. meridionale were transferred onto carnation leaf agar (CLA) and incubated at 20℃ under black light blue illumination. Macroconidia were abundant, relatively slender, curved to almost straight, commonly six- to seven-septate, and 27.0 to 61.0 (average 44.0) µm × 3.2 to 6.8 (average 5.3) µm. Microconidia were not observed. The TEF sequences (Accession nos. OM460748 to OM460756) and the Tri 101 sequences (OM460759 to OM460767) of the nine isolates showed 99 to 100% similarity with the TEF and Tri 101 sequences of F. meridionale NRRL 28436 and NRRL 28723 (AF212435 and AF212436 (TEF); AF212582 and AF212683 (Tri 101)). To complete Koch's postulates, the pathogenicity of the fungus was tested by using the single floret inoculation method by injecting 20-µl conidial suspension (5 × 105 conidia per milliliter) into healthy inflorescences of wheat cultivar Bainong 207 at anthesis in the field. Another 30 healthy inflorescences were injected with sterile distilled water. The heads were covered with polyethylene bags that were removed after 2 days. Twenty days after inoculation, while control inflorescences were asymptomatic, the F. meridionale-inoculated inflorescences showed 12% bleached spikelets per spike. By using the methodology described above, the fungus was re-isolated from infected spikelets of inoculated wheat heads but not from the controls. Although F. meridionale has frequently been reported in association with Fusarium ear rot (FER) of maize in Chongqing City and Gansu Province (Zhang et al. 2014; Zhou et al. 2018), and rice FER in Sichuan Province (Dong et al. 2020), to our knowledge, this is the first report of F. meridionale from diseased wheat heads in Henan, China. Further investigation is needed to gain a better understanding of this species by collecting isolates from different cropping system in Henan, which maize-wheat and rice-wheat rotation fields have coexisted in the region.

Associations of lifestyle with physical, hearing, visual, and mental functional impairments among older adults: Findings from two prospective cohort studies.

OBJECTIVE: To examine the associations between lifestyle habits and functional impairments among older adults. METHODS: The study includes 20,545 women and 14,374 men aged 70 years or older at the time of the function assessment. Participants were from two prospective cohort studies: the Shanghai Women's Health Study (SWHS, enrollment from 1996 to 2000) and the Shanghai Men's Health Study (SMHS, enrollment from 2002 to 2006). Lifestyle information was collected at study enrollment and a healthy lifestyle score (HLS) was derived. Functional impairment information was collected at the follow-up survey conducted in 2012-2017. Logistic regression analyses were applied to estimate the associations of HLS with functional impairments. RESULTS: The average age at lifestyle and functional impairment assessment was 62.3 (range: 49.9-70.9) and 77.7 (range: 70.0-89.4) for women and 67.5 (range: 55.1-74.9) and 77.4 (range: 70.0-88.6) for men. After a median follow-up of 14.4 years, we found that the HLS was inversely associated with overall severe functional impairment: odds ratio (95% confidence interval), 0.78(0.71-0.86) and individual severe functional impairment: 0.67(0.62-0.73) for independent walking, 0.85(0.77-0.94) for hearing/vision, 0.79(0.70-0.88) for memory, and 0.74(0.67-0.82) for decision-making impairment, comparing the highest with the lowest HLS categories. Such associations were similar among individuals with/without cardiometabolic diseases at baseline. The associations between each lifestyle factor and functional impairments differed. CONCLUSION: A healthy lifestyle was associated with reduced odds of physical and mental impairment among older Chinese adults, emphasizing the importance of promoting and maintaining a healthy lifestyle to prevent or postpone age-related functional impairments.

PDCD10 promotes proliferation, migration, and invasion of osteosarcoma by inhibiting apoptosis and activating EMT pathway.

BACKGROUND: Osteosarcoma, a common primary malignant tumor, occurs in children and adolescents with a poor prognosis. The current treatment methods are various, while the five-year survival rate of patients has not been significantly improved. As a member of the programmed death factor (PDCD) family, programmed death factor 10 (PDCD10) plays a role in regulating cell apoptosis. Several studies of PDCD10 in CCM and cancers have been reported before. However, there are no relevant research reports on the effects of PDCD10 on osteosarcoma. METHODS: We used bioinformatics analysis, IHC, and clinical data to confirm the expression of PDCD10 and its correlation with prognosis in osteosarcoma. Then, we used shRNAs and cDNA to knock down or overexpress PDCD10 in U2OS and MG63 cell lines. A series of function assays such as CCK8, Wound healing test, Plate cloning formation assay, and Transwell were done to confirm how PDCD10 affects osteosarcoma. Animal assays were done to confirm the conclusions in cell lines. At last, WB was used to measure the protein expression levels of apoptosis and the EMT pathway. RESULTS: PDCD10 was highly expressed in patients with osteosarcoma and correlated with prognosis; PDCD10 knockdown inhibited osteosarcoma growth, proliferation, migration, and invasion; PDCD10 overexpression promoted osteosarcoma growth, proliferation, migration, and invasion. In vivo experiments confirmed the conclusions in cell lines; PDCD10 inhibited apoptosis and activated the EMT pathway. CONCLUSIONS: In this study, it was found that PDCD10 was highly expressed in patients with osteosarcoma, and it was closely related to patient prognosis. PDCD10 inhibited tumor cell apoptosis and promoted tumor progression by activating the EMT pathway. These findings may provide a potential target for gene therapy of osteosarcoma.

First report of Fusarium falciforme causing root rot of soybean (Glycine max L.) in Henan, China.

Soybean (Glycine max L.) is an important crop in China owing to its high oil and protein content, with approximately 9.88 million ha of production in 2020. In September 2021, soybean plants showing wilting, root necrosis, and brown discoloration were observed, with an average incidence of approximately 36% in seven fields in Yongcheng City and Shangqiu City, Henan, China. Fungi were isolated from small pieces of symptomatic root tissues after being surface-sterilized (70% ethanol for 50 s followed by 3% NaClO for 1.0 min), rinsed three times in sterile distilled water, and then placed on PDA and incubated at 25℃ for 5 days in the dark. Single-spore cultures of twenty isolates were obtained by dilution plating (Leslie and Summerell 2006), and then were cultured on carnation leaf agar at 25℃ for 14 days. Macroconidia were mostly 3-septate, hyaline, falcate, with slightly curved apexes, with well-developed foot cells and blunt apical cells, and measured 29.3 to 45.0 (average 34.7) µm × 4.6 to 8.0 (average 6.0) µm. Microconidia were one to two celled, hyaline, and measured 11.9 to 29.0 (average 20.1) µm × 3.9 to 7.6 (average 5.7) µm. These morphological characteristics were consistent with previous descriptions of the Fusarium solani species complex (FSSC) (Leslie and Summerell 2006; Summerell et al. 2003). Partial sequences of translation elongation factor-1α (TEF) and RNA polymerase II subunit (RPB2) gene were PCR amplified using region specific primers as described by O'Donnell et al. (2008). The nucleotide sequences obtained from twenty isolates were deposited in GenBank with accession numbers of ON375405-ON375423, ON697187 (TEF) and ON331917-ON331936 (RPB2). Phylogenetic analysis revealed the isolates were nested within F. falciforme based on the DNA sequences of the above two genes (Chitrampalam and Nelson 2016). Pathogenicity tests of two representative isolates (21BeanYC3-3 and 21BeanYC7-5) were performed on two-week-old healthy soybean seedlings (cv. Shengdou 101) by injecting and cutting root method with a conidial suspension (1×106 conidia per mL) of F. falciforme (2 mL to one seedling). Control seedlings were inoculated with 2 mL distilled water. After 40 days under 25℃, 16h light/8h dark, the root system of all inoculated soybean plants exhibited dark brown lesions over the entire taproot, while control plants remained healthy. The fungus was reisolated from inoculated plants and identified as F. falciforme based on morphological characteristics and molecular methods described above. To our knowledge, this is the first report of root rot in soybean (Glycine max L.) caused by F. falciforme in Henan, China. The results are important for soybean production and breeding programs.