Diet and lifestyle behaviours simultaneously act on frailty: it is time to move the threshold of frailty prevention and control forward.

BACKGROUND: To analyse the association among the simultaneous effects of dietary intake, daily life behavioural factors, and frailty outcomes in older Chinese women, we predicted the probability of maintaining physical robustness under a combination of different variables. METHODS: The Fried frailty criterion was used to determine the three groups of "frailty", "pre-frailty", and "robust", and a national epidemiological survey was performed. The three-classification decision tree model was fitted, and the comprehensive performance of the model was evaluated to predict the probability of occurrence of different outcomes. RESULTS: Among the 1,044 participants, 15.9% were frailty and 50.29% were pre-frailty; the overall prevalence first increased and then decreased with age, reaching a peak at 70-74 years of age. Through univariate analysis, filtering, and embedded screening, eight significant variables were identified: staple food, spices, exercise (frequency, intensity, and time), work frequency, self-feeling, and family emotions. In the three-classification decision tree, the values of each evaluation index of Model 3 were relatively average; the accuracy, recall, specificity, precision, and F1 score range were between 75% and 84%, and the AUC was also greater than 0.800, indicating excellent performance and the best interpretability of the results. Model 3 takes exercise time as the root node and contains 6 variables and 10 types, suggesting the impact of the comprehensive effect of these variables on robust and non-robust populations (the predicted probability range is 6.67-93.33%). CONCLUSION: The combined effect of these factors (no exercise or less than 0.5 h of exercise per day, occasional exercise, exercise at low intensity, feeling more tired at work, and eating too many staple foods (> 450 g per day) are more detrimental to maintaining robustness.

Fecal transplantation of young mouse donors effectively improves enterotoxicity in elderly recipients exposed to triphenyltin.

Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors (IL-1ß, IL-6, TNF-α), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins (Claudin, Occludin, Muc2) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging.

Development of pH-freshness smart label based on gellan gum film incorporated with red cabbage anthocyanins extract and its application in postharvest mushroom.

Novel colorimetric films based on gellan gum (GG) containing red cabbage anthocyanins extract (RCAE) were prepared as pH-freshness smart labels for real-time visual detection of mushroom freshness. The GG/RCAE films had excellent pH and ammonia sensitivity. The GG/RCAE-0.2-0.3 films had the highest sensitivity to acetic acid. The SEM micrographs, AFM images, FT-IR and XRD spectra demonstrated that RCAE were successfully combined into the film-forming substrate. The incorporation of RCAE resulted in the increase of thermal stability, opacity and surface hydrophobicity of films. Meanwhile, the GG/RCAE-0.2 film exhibited stronger tensile strength and excellent color stability at 4℃. The color changes of GG/RCAE-0.2 film were visually easier to distinguish during the storage of mushroom. The results showed the GG/RCAE films could be used as pH-freshness smart labels to detect the freshness of fruits and vegetables.

Specific metabolic and cellular mechanisms of the vegetative desiccation tolerance in resurrection plants for adaptation to extreme dryness.

MAIN CONCLUSION: Substantial advancements have been made in our comprehension of vegetative desiccation tolerance in resurrection plants, and further research is still warranted to elucidate the mechanisms governing distinct cellular adaptations. Resurrection plants are commonly referred to as a small group of extremophile vascular plants that exhibit vegetative desiccation tolerance (VDT), meaning that their vegetative tissues can survive extreme drought stress (> 90% water loss) and subsequently recover rapidly upon rehydration. In contrast to most vascular plants, which typically employ water-saving strategies to resist partial water loss and optimize water absorption and utilization to a limited extent under moderate drought stress, ultimately succumbing to cell death when confronted with severe and extreme drought conditions, resurrection plants have evolved unique mechanisms of VDT, enabling them to maintain viability even in the absence of water for extended periods, permitting them to rejuvenate without harm upon water contact. Understanding the mechanisms associated with VDT in resurrection plants holds the promise of expanding our understanding of how plants adapt to exceedingly arid environments, a phenomenon increasingly prevalent due to global warming. This review offers an updated and comprehensive overview of recent advances in VDT within resurrection plants, with particular emphasis on elucidating the metabolic and cellular adaptations during desiccation, including the intricate processes of cell wall folding and the prevention of cell death. Furthermore, this review highlights existing unanswered questions in the field, suggests potential avenues for further research to gain deeper insights into the remarkable VDT adaptations observed in resurrection plants, and highlights the potential application of VDT-derived techniques in crop breeding to enhance tolerance to extreme drought stress.

Exposure to triphenyltin impairs gut integrity, disturbs gut microbiota, and alters fecal metabolites.

Triphenyltin is an environmental contaminant widely used in antifouling paints and can cause toxicity in various organs in living organisms. However, its effects on intestinal function and the microbiome of the gut remain unknown. The objective of this study was to explore the intestinal toxicity of triphenyltin in mice by orally administering 0, 1.875, 3.75, and 7.5 mg/Kg to adult male mice for 8 weeks. Results showed that triphenyltin caused ileum tissue damage, induced oxidative stress, upregulated inflammation-related gene expression and increased serum tumor-necrosis factor α (TNF-α) levels in mice. Triphenyltin impaired ileum barrier function by downregulating Muc2, ZO-1, Occludin and their protein levels at 3.75 and 7.5 mg/Kg. TPT exposure led to partial inflammation and decreased mucin mRNA expression in the colon. Triphenyltin altered intestinal micro-ecological balance and fecal metabolome in mice. In conclusion, triphenyltin alters the mouse gut microbiota and fecal metabolome.

Circular RNA circATP9A promotes non-small cell lung cancer progression by interacting with HuR and by promoting extracellular vesicles-mediated macrophage M2 polarization.

BACKGROUND: CircRNA is recognized for its significant regulatory function across various cancers. However, its regulatory role in non-small cell lung cancer (NSCLC) is still largely uncharted. METHODS: Analysis based on public databases is completed using R software. circATP9A was identified by two circRNA datasets of NSCLC from the Gene Expression Omnibus database. To examine the impact of circATP9A on the phenotype of NSCLC, we conducted both in vitro and in vivo functional experiments. The mRNA and protein levels of specific molecules were determined through quantitative real-time PCR and western blot assays. RNA pulldown and RNA immunoprecipitation assays were performed to verify the interaction between RNA and protein. The functional role of extracellular vesicles (EVs)-circATP9A on tumor-associated macrophage (TAM) polarization was assessed using co-culture system and cell flow cytometry. RESULTS: Here, we elucidates the functional role of circATP9A in NSCLC. We demonstrated that circATP9A can foster the progression of NSCLC through in vivo and in vitro experiments. From a mechanistic standpoint, circATP9A can interact with the HuR protein to form an RNA-protein complex, subsequently amplifying the mRNA and protein levels of the target gene NUCKS1. Further, the PI3K/AKT/mTOR signaling was identified as the downstream pathways of circATP9A/HuR/NUCKS1 axis. More notably, hnRNPA2B1 can mediate the incorporation of circATP9A into EVs. Subsequently, these EVs containing circATP9A induce the M2 phenotype of TAMs, thereby facilitating NSCLC development. CONCLUSIONS: Our discoveries indicate that circATP9A could serve as a promising diagnostic indicator and a therapeutic target for NSCLC.

Integrase Interactor 1 (INI1) Deficiency in a Lung Cancer Patient Presents Nonresponse to Immunotherapy and Tazemetostat: A Case Report.

Integrase interactor 1 (INI1)-deficient lung cancer is extremely rare, often with poor prognosis, and lacks effective treatment. Previous studies have reported the efficacy of immunotherapy and enhancer of the zeste homolog 2 (EZH2) inhibitor tazemetostat in various types of INI1-deficient tumors, such as sarcomas. However, the effectiveness of these treatments in INI1-deficient lung cancer has not yet been verified. We hereby report a case of a patient who was diagnosed with advanced squamous lung cancer with INI1 deficiency and received chemotherapy, immunotherapy, and tazemetostat treatments successively. The patient showed optimal response in the initial chemotherapy combined with anti-programmed cell death protein 1 (PD-1) immunotherapy, made rapid progress in the subsequent stage of maintenance immunotherapy, and showed nonresponse to tazemetostat. To the best of our knowledge, this is the first case of a lung cancer patient with INI1 deficiency who received tazemetostat treatment.

Alfalfa MsATG13 Confers Cold Stress Tolerance to Plants by Promoting Autophagy.

Autophagy is a conserved cellular process that functions in the maintenance of physiological and metabolic balance. It has previously been demonstrated to improve plant tolerance to abiotic stress. Numerous autophagy-related genes (ATGs) that regulate abiotic stress have been identified, but there have been few functional studies showing how ATGs confer cold stress tolerance. The cold transcriptome data of the crown buds that experienced overwintering of the alfalfa (Medicago sativa L.) showed that MsATG13 is upregulated in response to cold stress. In the present study, we found that MsATG13 transgenic tobacco enhanced cold tolerance compared to wild-type (WT) plants. Transmission electron microscopy demonstrated that transgenic tobacco overexpressing MsATG13 formed more autophagosomes than WT plants in response to cold stress conditions. The transgenic tobacco increased autophagy levels due to upregulation of other ATGs that were necessary for autophagosome production under cold stress conditions. MsATG13 transgenic tobacco also increased the proline contents and antioxidant enzyme activities, enhancing the antioxidant defense capabilities under cold stress conditions. Furthermore, MsATG13 overexpression decreased levels of superoxide anion radicals and hydrogen peroxide under cold stress conditions. These findings demonstrate the role of MsATG13 in enhancing plant cold tolerance through modulation of autophagy and antioxidant levels.

Ginkgetin suppresses ovarian cancer growth through inhibition of JAK2/STAT3 and MAPKs signaling pathways.

BACKGROUND: Ginkgo biloba L., a kind of traditional Chinese medicine, is always used to treat various diseases. Ginkgetin is an active biflavonoid isolated from leaves of Ginkgo biloba L., which exhibits diverse biological activities, including anti-tumor, anti-microbial, anti-cardiovascular and cerebrovascular diseases, and anti-inflammatory effects. However, there are few reports on the effects of ginkgetin on ovarian cancer (OC). HYPOTHESIS/PURPOSE: OC is one of the most common cancers with high mortality in women. The purpose of this study was to find out how ginkgetin inhibited OC and which signal transduction pathways was involved to suppress OC. METHODS: The OC cell lines, A2780, SK-OV-3 and CP70, were used for in vitro experiments. MTT assay, colony formation, apoptosis assay, scratch wound assay and cell invasion assay were used to determine the inhibitory effect of ginkgetin. BALB/c nude female mice were injected with A2780 cells subcutaneously, then treated with ginkgetin by intragastric administration. Western blot experiment was used to verify the inhibitory mechanism of OC in vitro and in vivo. RESULTS: We found that ginkgetin inhibited the proliferation and induced apoptosis in OC cells. In addition, ginkgetin reduced migration and invasion of OC cells. In vivo study showed that ginkgetin significantly reduced tumor volume in the xenograft mouse model. Furthermore, the anti-tumor effects of ginkgetin were associated with a down regulation of p-STAT3, p-ERK and SIRT1 both in vitro and in vivo. CONCLUSION: Our results suggest that ginkgetin exhibits anti-tumor activity in OC cells via inhibiting the JAK2/STAT3 and MAPK pathways and SIRT1 protein. Ginkgetin could be a potential candidate for the treatment of OC.

Liquid-solid ratio during hydrothermal carbonization affects hydrochar application potential in soil: Based on characteristics comparison and economic benefit analysis.

Returning straw-like agricultural waste to the field by converting it into hydrochar through hydrothermal carbonization (HTC) is an important way to realize resource utilization of waste, soil improvement, and carbon sequestration. However, the large-scale HTC is highly limited by the large water consumption and waste liquid pollution. Here, we propose strategies to optimize the liquid-solid ratio (LSR) of HTC, and comprehensively evaluate the stability, soil application potential, and economic benefits of corn stover-based hydrochar under different LSRs. The results showed that the total amount of dissolved organic carbon of hydrochars increased by 55.0% as LSR reducing from 10:1 to 2:1, while the element content, thermal stability, carbon fixation potential, specific surface area, pore volume, and functional group type were not obviously affected. The specific surface area and pore volume of hydrochar decreased by 61.8% and 70.9% as LSR reduced to 1:1, due to incomplete carbonization. According to the gray relation, hydrochar derived at LSR of 10:1 and followed by 2:1 showed greatest relation degree of 0.80 and 0.70, respectively, indicating better soil application potential. However, reducing LSR from 10:1 to 2:1 made the income of single process production increased from -388 to 968 ¥, and the wastewater generation decreased by 80%. Considering the large-scale application of HTC in fields for farmland improvement and environmental remediation, the comprehensive advantages of optimized LSR will be further highlighted.

Disseminated Talaromyces marneffei infection after renal transplantation: A case report and literature review.

We reported a 31-year-old man who received renal transplantation for more than 2 years. He was admitted to our hospital on 9 March 2022 due to intermittent diarrhea accompanied by leukopenia for more than 1 month. The patient successively developed high fever, cough, anemia, weight loss, gastrointestinal bleeding, and liver function impairment. Computed tomography (CT) revealed a slight inflammation in the lower lobes of both lungs, enlargement of the lymph nodes in the retroperitoneal and the root of mesenteric areas, and hepatosplenomegaly. Talaromyces marneffei was detected by metagenomics next-generation sequencing (mNGS) in blood and bronchoalveolar lavage fluid, and the pathogen was subsequently verified by blood culture. After endoscopic hemostatic therapy and antifungal therapy with voriconazole and amphotericin B cholesteryl sulfate complex, the patient was successfully discharged. Oral voriconazole was given regularly after discharge. Diarrhea, fever, enlargement of the lymph nodes, and endoscopic evidence of erosion may indicate intestinal T. marneffei infection. Although the mortality of T. marneffei infection after renal transplantation is very high, timely and effective antifungal therapy with amphotericin B cholesteryl sulfate complex is still expected to improve its prognosis.

Rapid response in relapsed follicular lymphoma with massive chylous ascites to anti-CD19 CAR T therapy using Piggy Bac: A case report.

CD19-directed chimeric antigen receptor (CAR) T cell therapy has been shown to achieve a considerably durable response in patients with refractory or relapsed B cell non-Hodgkin lymphomas, as seen from the results of Zuma-1, Zuma-5, and other clinical trials. Most of these CARs were generated by lentivirus or reverse adenovirus. It is rare to see CARs using non-viral vectors, such as Piggy Bac (pb), in treating lymphoma patients with active diseases. Generally, patients with a high tumor burden tend to have a higher rate of severe cytokine release syndrome (CRS) or neurological events as reported in the literature. Patients with symptomatic pleural effusions are excluded from the Zuma-1 trial because of the risk of severe CRS. We report here that a patient with relapsed follicular lymphoma with bulky disease and massive chylous ascites failed several lines of chemotherapy. After infusion of the CD19-directed pbCAR-T cells at 6 × 106 cells/kg, the patient had a rapid response and achieved a nearly complete metabolic remission on day 28. There was only grade 1 CRS, and no neurotoxicity occurred. The CAR-T cells reached a peak level on day 14 and spread into the ascites and expanded for 3 months. This might be the first case reported for pbCAR-T cells to treat relapsed follicular lymphoma directly. The long-term efficacy will be observed, and more patients be tested in the future. Clinical Trial Registration: https://ClinicalTrials.gov, identifier NCT05472610.

Application of Price Competition Model Based on Computational Neural Network in Risk Prediction of Transnational Investment.

Aiming at the scenario where edge devices rely on cloud servers for collaborative computing, this paper proposes an efficient edge-cloud collaborative reasoning method. In order to meet the application's specific requirements for delay or accuracy, an optimal division point selection algorithm is proposed. A kind of multichannel supply chain price game model is constructed, and nonlinear dynamics theory is introduced into the research of the multichannel supply chain market. According to the actual competition situation, the different business strategies of retailers are considered in the modeling, which makes the model closer to the actual competition situation. Taking the retailer's profit as an indicator, the influence of the chaos phenomenon on the market performance is analyzed. Compared with the previous studies, this thesis uses nonlinear theory to better reveal the operating laws of the economic system. This paper selects company A in the financial industry to acquire company B in Sweden. It is concluded that company B is currently facing financial difficulties, but its brand and technical advantages are far superior to company A. The indirect financial risk index of company B, that is, the investment environment, is analyzed, and the final investment environment score of the country where company B is located is 90 points, which is an excellent grade by scoring the investment environment of the target enterprise. Combining the investment environment score and the alarm situation prediction score, it is concluded that the postmerger financial risk warning level of company A is in serious alarm.

A Quantitative Model of International Trade Based on Deep Neural Network.

This paper is an in-depth study of international trade quantification models based on deep neural networks. Based on an in-depth analysis of global trade characteristics, a summary of existing problems, and a comparative analysis of various prediction methods, this paper constructs the ARIMA model, BP neural network (BPNN) model, and deep neural network (DNN) model to make a comprehensive comparison of international trade quantification. The results show that the nonlinear model has a global trade quantification has some advantages over linear models, and the deep model shows better prediction performance than the shallow model. In addition, preprocessing of the time series is considered to improve the prediction accuracy or shorten the model training time. The empirical modal analysis method (EMD) is introduced to decompose the time series into eigenmodal functions (IMFs) of different scales. Then the decomposed IMF series are arranged into a matrix using principal component analysis (PCA) to reduce the dimensionality and extract the data containing the most stock index information features; these features are then input into BPNN and DNN for combined prediction, thus constructing the combined models EMD-PCA-BPNN and EMD-PCA-DNN. Based on Melitz's heterogeneous firm trade theory and its development by Chaney, a quantitative trade model incorporating production heterogeneity is constructed through a multisector extension. This paper adopts a general equilibrium analysis, which makes the modeling process pulse clear. The completed model has high flexibility and scalability, which can be applied to quantitative analysis of various problems.

Correction: Silence of cancer susceptibility candidate 9 inhibits gastric cancer and reverses chemoresistance.

[This corrects the article DOI: 10.18632/oncotarget.14871.].

Biomechanics of the lead straight punch of different level boxers.

We analyze and compare the differences in the biomechanical parameters between the lead straight punch and the index of force development of the lower extremities of boxers of different levels of ability. This can bridge the technical gap and provide insight and information for training strategies and athlete selection. To this end, a synchronized Vicon infrared 3D motion-capture system, two Kistler force platforms, and Kistler 8 target sensors were used for analysis. Sixteen boxers were recruited and sorted into an elite group (height 181.14 ± 3.01 cm, body mass 76.00 ± 10.028 kg) and a junior group (179.67 ± 5.84 cm, body mass 75.47 ± 12.19 kg), and their lead straight punch was then compared and analyzed. Three punch velocity indexes-peak velocity, contact velocity and Punching deceleration rate-six strength indexes-impulse, peak force, relative strength, peak time (frame), rate of force development (RFD), and movement time-and five exertion of both legs indexes- peak force, peak force/body mass, peak time, RFD index, and RFD/body mass index-were selected for analysis. Significant differences in the peak punch velocity and contact velocity were found between the two groups (7.162 ± 0.475 m•s-1vs. 6.317 ± 0.415 m•s-1, Cohen's d = 1.89, p < 0.01, 5.557 ± 0.606 m•s-1 vs. 4.874 ± 0.385 m•s-1, Cohen's d = 1.34, p < 0.05). Furthermore, significant differences were noted in the peak force [(1507.99 ± 411) N vs. (1035.45 ± 220) N, Cohen's d = 1.43, p < 0.01], relative strength [(21.04 ± 5.88) N•kg-1 vs. (15.61 ± 2.53) N•kg-1, Cohen's d = 1.19, p < 0.05], impulse [(88.61 ± 25.88) N•ms-1 and (60.53 ± 9.03) N•ms-1, Cohen's d = 1.45, p < 0.05], and RFD [(88.61 ± 25.88) N•ms-1 and (60.53 ± 9.03) N•ms-1, Cohen's d = 1.45, p < 0.05]. Among the four indexes of the lower extremities from two embedded Kistler force platforms, there were significant differences in the lead leg's peak force/body mass [(19.68 ± 4.096) N•kg-1vs. (13.320 ± 2.223) N•kg-1, t = 3.902, Cohen's d = 1.92, p < 0.01], RFD index [(16.90 ± 3.269) N•ms-1vs. (10.28 ± 4.313) N•ms-1, Cohen's d = 1.72, p < 0.01], and RFD/body mass index [(23.47 ± 4.09%) N•ms-1Kg-1 vs. (15.38 ± 5.65%) N•ms-1Kg-1, Cohen's d = 1.64, p < 0.01]. There were no significant differences in the four indexes on the rear leg between the two groups (p > 0.05). Based on the disparity in the effect of the lead straight punch and the biomechanical parameters of both lower extremities, the boxers must attach importance to sequential acceleration-braking training to improve the terminal velocity of the hand, and thus improve the contact velocity. Furthermore, it is advised that coaches and practitioners carefully consider increasing start-up strength training of the lead leg and attempt to improve the peak velocity of the lead straight punch. In addition, these biomechanical parameters can be used as criteria for the selection of boxers.

Comparative analysis of physiological, agronomic and transcriptional responses to drought stress in wheat local varieties from Mongolia and Northern China.

Drought is one of the major abiotic stresses that threaten wheat production worldwide, especially in the Mongolian Plateau and adjacent regions. This study aims to find local wheat varieties with high yields and drought resistance at various developmental stages based on agronomic traits and drought resistance indices analysis and explore the underlining molecular mechanisms by transcriptome analysis. Our results revealed that drought stress started at the seedling stage has a greater impact on crop yields. Four types of drought responses were found among the tested varieties. Type 1 and type 2 show low tolerance to drought stress despite high or low yield in control condition, type 3 exhibits high yield under control condition but dropped significantly after drought, and type 4 displays relatively high and stable yields under control and drought conditions. Transcriptome analysis performed with the representative varieties of the four types revealed GO terms and KEGG pathways enriched among drought-triggered differential expressed genes (DEGs). A network containing 18 modules was constructed using weighted gene co-expression analysis (WGCNA). Ten modules were significantly correlated to yield by module-trait correlation, and 3 modules showed Darkhan 144 specific gene expression patterns. C2H2 zinc finger factor-recognized motifs were identified from the promoters of genes in these modules. qRT-PCR confirmed several key DEGs with specific expression patterns and physiological measurements validated the relatively low oxidative damage and high antioxidant capacity in the drought tolerant variety Dankhan 144. These findings provide an important basis for local agriculture and breeding of drought-tolerant high yield wheat varieties.

A sustainable phosphorus management in agriculture: Assessing trade-offs between human health risks and nutritional yield regarding heavy metals in maize grain.

High-quality products in sustainable agriculture require both limited health risks and sufficient dietary nutrients. Phosphorus (P) as a finite and non-renewable resource is widely used in agriculture, usually exerting influence on the accumulation of heavy metals (HMs) in soil and crops. The present research explores, for the first time, the combined effects of long-term P fertilizer and repeated zinc (Zn) application in field on the human health risks and nutritional yield regarding trace elements in maize grain. A field experiment was conducted using maize with six P application rates (0, 12.5, 25, 50, 100, and 200 kg P ha-1) and two Zn application rates (0 and 11.4 kg Zn ha-1). The results showed that the concentrations of Zn, copper (Cu), and lead (Pb) in the maize grain were significantly affected by P application and can be further affected by Zn application. The concentrations of chromium (Cr) and arsenic (As) showed opposite tendency as affected by P fertilizer rates while did not affected by additional Zn application. Zn application decreased the cadmium (Cd) concentration at high P levels and Pb concentration at low P levels, particularly. No HMs contamination or direct health risk was found in maize grain after receiving long-term P and repeated Zn fertilizer. The threshold hazard quotient of an individual and all investigated HMs in this study were acceptable for human digestion of maize grain. While the carcinogenic risk of Cr was non-negligible in case of maize was taken as one of daily staple food for local residents. Combination use of P (25 kg ha-1) and Zn fertilizer on maize enhanced its nutritional supply ability regarding Zn and Cu, and simultaneously mitigated potential human health risks associated with Cd and Pb.

NDUFC1 Is Upregulated in Gastric Cancer and Regulates Cell Proliferation, Apoptosis, Cycle and Migration.

Gastric cancer is one of the most common primary tumors of the digestive system. NADH: ubiquinone oxidoreductase subunit C1 (NDUFC1), which is an accessory subunit of the NADH dehydrogenase (complex I), is responsible for the transportation of electrons from NADH to the respiratory chain essential for the oxidative phosphorylation. However, little is known about the roles of NDUFC1 in carcinogenesis. In this study, NDUFC1 protein level in NSCLC tissues was tested by immunohistochemistry (IHC) staining. NDUFC1 mRNA level in gastric cancer cell lines was determined by qRT-PCR. MGC-803 and SGC-7901 cells were transfected with shNDUFC1 lentivirus designed to silence NDUFC1. MTT assay, CCK8 assay, wound healing assay and transwell migration assay were conducted. Cell cycle and apoptosis were detected by flow cytometry. In vivo experiments were performed using nude mice. The results indicated that overexpressed NDUFC1 in gastric cancer was related to more serious tumor infiltrates, a higher risk of lymphatic metastasis, a higher proportion of positive lymph nodes, and a more advanced tumor stage. Compared with shCtrl groups, MGC-803 and SGC-7901 of shNDUFC1 groups had lower abilities of proliferation and migration, higher levels of apoptosis. NDUFC1 knockdown also inhibited SGC-7901 cell growth in vivo and suppressed Ki67 expression in xenograft tumors. More importantly, we found that NDUFC1 downregulation made the levels of P-Akt, P-mTOR, CCND1, CDK6, PIK3CA, Bcl-2, Survivin, and XIAP decreased, and that PI3K/AKT signaling pathway agonist SC79 rescued the inhibitory effects on cell proliferation and migration, reversed the promoted effects on cell apoptosis caused by NDUFC1 knockdown. More importantly, compared with NDUFC1 knockdown group, the expression of P-Akt, Bcl-2, Survivin, and XIAP was raised in shNDUFC1 + SC79 group. Thus, our suspicion was that NDUFC1 exacerbates NSCLC progression via PI3K/Akt pathway. Taken together, our study indicated that targeting NDUFC1 could open innovative perspectives for new multi-targeting approaches in the treatment of gastric cancer.