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.

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.

Non-volatile acylphloroglucinol components from Eucalyptus robusta inhibit Zika virus by impairing RdRp activity of NS5.

Eucalyptus is a large genus of the Myrtaceae family with high value in various fields of industry. Recently, attention has been focused on the functional properties of Eucalyptus extracts. These extracts have been traditionally used to combat various infectious diseases, and volatile oils are usually considered to play a major role. But the positive effects of non-volatile acylphloroglucinols, a class of specialized metabolites with relatively high content in Eucalyptus, should not be neglected. Herein, non-volatile acylphloroglucinols from leaves of Eucalyptus robusta were evaluated for their abilities to inhibit Zika virus (ZIKV) which is associated with severe neurological damage and complications. The results showed eucalyprobusone G, a new symmetrical acylphloroglucinol dimer, possessed the significant ability to inhibit ZIKV without inducing cytotoxicity. The EC50 values of eucalyprobusone G against the African lineage (MR766) and Asian lineage (SZ-WIV01) of ZIKV were 0.43 ± 0.08 and 10.10 ± 3.84 µM which were 110 times and 5.8 times better than those of the reference compound ribavirin, respectively. Further action mode research showed that eucalyprobusone G impairs the viral binding and RdRp activity of NS5. The results broaden the functional properties of Eucalyptus robusta and indicate acylphloroglucinol dimers could be developed as anti-ZIKV agents.

[Antiviral effects of the combination of glycyrrhizin and ribavirin against influenza A H1N1 virus infection in vivo].

Ribavirin is a broad-spectrum antiviral agent and glycyrrhizin has activities of anti-inflammation, immunoregulation and anti-viral infections. To enhance antiviral efficacy and weaken side-effects of ribavirin, antiviral effects of the combination of glycyrrhizin and ribavirin were studied in the present study. Firstly, a mouse model of viral pneumonia was established by inoculation of influenza H1N1 virus. Protective effects of glycyrrhizin and ribavirin used alone or in combination against H1N1 virus infection in mice were evaluated based on the survival rate, lung index and virus titer in lungs of mice. Results showed that the combination of glycyrrhizin and ribavirin significantly inhibited the lung consolidation with a 36% inhibition ratio on the lung swell of infected mice. The combination of the two drugs exhibited synergetic effects on survival of infected mice. The combination of 50 mg · kg(-1) · d(-1) glycyrrhizin and 40 mg · kg(-1) · d(-1) ribavirin resulted a 100% protection for infected mice with a synergetic value of 36, which was significantly higher than the control group and each drug alone. This combination also resulted a significant drop of lung virus titer (P < 0.01), as well as inhibition on the production of proinflammatory cytokines IL-6 (P < 0.01), TNF-α (P < 0.01) and IL-1ß (P < 0.05) induced by virus infection compared to the control. The treatment of ribavirin plus glycyrrhizin was more effective in influenza A infection in mice than either compound used alone, which suggested a potential clinical value of the combination of the two agents.

Chiral separation of racemic mandelic acids by use of an ionic liquid-mediated imprinted monolith with a metal ion as self-assembly pivot.

A new chiral stationary phase based on molecularly imprinted polymers (MIP) was prepared in ionic liquid by use of the metal pivot concept. Imprinted monoliths were synthesized by use of a mixture of R-mandelic acid (template), 4-vinylpyridine, ethylene glycol dimethacrylate, and several metal ions as pivot between the template and functional monomer. A ternary mixture of dimethyl sulfoxide-dimethylformamide-[BMIM]BF4 containing metal ions was used as the porogenic system. Separation of the enantiomers of rac-mandelic acid was successfully achieved on the MIP thus obtained, with resolution of 1.87, whereas no enantiomer separation was observed on the imprinted monolithic column in the absence of metal ions. The effects of polymerization conditions, including the nature of the metal ion and the ratios of template to metal ions and template to functional monomer, on the chiral separation of mandelic acid were investigated. The results reveal that use of metal ions as a pivot, in combination with ionic liquid, is an effective method for preparation of a highly efficient MIP stationary phase for chiral separation.

Foliar Zinc Application to Wheat May Lessen the Zinc Deficiency Burden in Rural Quzhou, China.

Zinc (Zn) malnutrition is a common health problem, especially in developing countries. The human health and economic benefits of the replacement of conventional flour with Zn-biofortified wheat flour in rural household diets were assessed. One hundred forty-five wheat flour samples were collected from rural households in Quzhou County. Then, field experiments were conducted on wheat at two Zn levels (0 and 0.4% ZnSO4 · 7H2O foliar application) under 16 diverse agricultural practices in Quzhou County. Foliar Zn application significantly increased the Zn concentration and bioavailability in wheat grain and flour. If rural households consumed Zn-biofortified flour instead of self-cultivated flour or flour purchased from supermarkets, 257-769 or 280-838, 0.46-1.36 million or 0.50-1.49 million disability-adjusted life years (DALYs) lost, respectively, could be saved in Quzhou County and China. Amounts of 2.3-12.0 million and 5.5-22.6 billion RMB could be obtained via Zn-biofortified flour in Quzhou County and China, respectively. The current study indicates that Zn-biofortified flour via foliar Zn application is a win-win strategy to maintain the yield and combat human Zn deficiency in rural households in China. More health and economic benefits could be obtained in rural household dependent on wheat flour purchased from supermarkets than in those dependent on self-cultivated wheat flour.

The responses of soil enzyme activities, microbial biomass and microbial community structure to nine years of varied zinc application rates.

Zinc (Zn) fertilizer application can certainly improve the production and nutritional quality of cereal crops. However, Zn accumulation in the soil may lead to some deleterious environmental impacts in agroecosystems. The effects of long-term Zn application on soil microbial properties remain unclear, but it is imperative to understand such effects. In this study, we collected soil samples from a nine-year field experiment in a wheat-maize system that continuously received Zn applied at various rates (0, 2.3, 5.7, 11.4, 22.7 and 34.1 kg ha-1) to evaluate the soil enzymes, microbial biomass and microbial community structure. The results showed that Zn application at the rate of 5.7 kg ha-1 significantly increased the activities of urease, invertase, alkaline phosphatase and catalase in the soil, while the rate of 34.1 kg ha-1 significantly decreased the evaluated enzyme activities. The microbial biomass carbon (C) and nitrogen (N) were not affected by Zn application rates, although an increase in the microbial biomass C was observed in the 11.4 kg ha-1 treatment. Moreover, the alpha diversity of the bacterial and fungal communities did not vary among the nil Zn, optimal Zn (5.7 kg ha-1) and excess Zn (34.1 kg ha-1) treatments. However, the bacterial communities in the soil receiving the optimal and excess Zn application rates were slightly changed. Compared to the nil Zn treatment, the other Zn application rates increased the relative abundances of the Rhodospirillales, Gaiellales and Frankiales orders and decreased the abundance of the Latescibacteria phylum. The redundancy analysis further indicated that the soil bacterial community composition significantly correlated with the concentrations of soil DTPA-Zn and total Zn. These results highlight the importance of optimal Zn application in achieving high production and high grain quality while concurrently promoting soil microbial activity, improving the bacterial community and further maintaining the sustainability of the agroecological environment.

Responses in Zinc Uptake of Different Mycorrhizal and Non-mycorrhizal Crops to Varied Levels of Phosphorus and Zinc Applications.

Negative effects of high phosphorus (P) application on zinc (Zn) nutrition have been observed in many crops. This study investigated the Zn responses of three typical crops to varied P and Zn applications. A pot experiment was conducted using two mycorrhizal crops (maize and soybean) and one non-mycorrhizal crop (oilseed rape) under three levels of P, two levels of Zn, and two levels of benomyl. Results showed that P application significantly decreased shoot and root Zn concentrations, Zn uptake, and Zn acquisition efficiency (ZnAE) of the three crops irrespective of Zn rate, and that these reductions were greater for maize and soybean than for oilseed rape. Zn application alleviated the P inhibition of Zn uptake in the three crops. The arbuscular mycorrhizal fungi (AMF) colonization of maize and soybean contributed most to the negative effects of increasing P application on Zn uptake, explaining 79-89 and 64-69% of the effect, respectively. For oilseed rape, root dry weight and root Zn concentration explained 90% of the decrease in Zn uptake caused by P application. These results suggest that there is another pathway in addition to the mycorrhizal pathway regulating Zn uptake under mediation by P supply.

Health risk assessment associated with heavy metal accumulation in wheat after long-term phosphorus fertilizer application.

Phosphorus (P) fertilizer is widely used to increase wheat yield. However, it remains unclear whether prolonged intake of wheat grain that received long-term P application may promote human health risks by influencing heavy metal(loid)s (HMs) accumulation. A 10-year field experiment was conducted to evaluate the effects of continuous P application (0, 25, 50, 100, 200, and 400 kg P ha-1) on human health risks of HMs, including zinc (Zn), copper (Cu), cadmium (Cd), lead (Pb), arsenic (As), nickel (Ni), and chromium (Cr), by ingesting wheat grain. The results showed that P application facilitated Zn, Pb, Cd, and As accumulation in the topsoil. The Zn, Cu, Pb, and Ni concentrations in grain were decreased, while Cd and As were increased by P application. All HMs concentrations of both soil and grain were in the ranges of corresponding safety thresholds at different P levels. The accumulation abilities of Zn, Cu, Pb, and Ni from soil and straw to grain were suppressed by P addition while of As was enhanced. There was no significant difference in the hazard index (HI) of the investigated HMs in all treatments except 25 kg ha-1. The threshold cancer risk (TCR) associated with As and Cd was enhanced, while that of Pb was alleviated as P application increased. Behaviors of Cr from soil to wheat and to humans were not affected by P application. Phosphorus application at a rate of 50 kg ha-1 decreased total non-cancer and cancer risks by 15% and 21%, respectively, for both children and adults, compared to the highest value. In conclusion, long-term optimal application of 50 kg P ha-1 to wheat did not result in additional adverse effects on the total non-carcinogenic or carcinogenic risk caused by the studied HMs to humans through the ingestion of wheat grain.

Health risk assessment of heavy metals (Zn, Cu, Cd, Pb, As and Cr) in wheat grain receiving repeated Zn fertilizers.

Soil application of Zn fertilizer is an effective approach to improve yield and Zn accumulation in wheat grain. However, it remains unclear whether repeated Zn application can result in high accumulation of heavy metals (HMs) in soils and grains and thus represents a potential risk for human consumption. This study aimed to evaluate the health risk assessment of HMs in a wheat production system which had continuously received 8 years of Zn application at varying rates (0, 2.3, 5.7, 11.4, 22.7, 34.1 kg Zn ha-1). The results showed that Zn application significantly increased the soil total Zn concentration without affecting concentrations of As, Pb, Cd, Cu and Cr. Across Zn rates, Zn application increased grain concentrations of Zn, Pb and Cd by 75%, 51% and 14%, respectively, and reduced grain As concentration by 14%. The human health risk assessment revealed that the threshold hazard quotients for the individual HM were below 1, independent of Zn rates. The hazard index (HI) values at Zn rates of 11.4, 22.7 and 34.1 kg Zn ha-1 were significantly greater than that at null Zn treatment. Furthermore, exposures to As, Cu and Zn accounted for 97% of HI at all Zn rates. Analysis of the threshold cancer risk with Pb and As showed that ingestion of wheat grain even from highest Zn application rate wouldn't bring the lifetime carcinogenic risk. In contrast, long-term Zn application significantly reduced the carcinogenic risk of As by 9.7-26.5%. In conclusion, repeated soil applications of Zn at optimal rate (5.7 kg Zn ha-1) didn't cause health risk for Zn, Cu, Cd, Pb, Cr, and As, while improving productivity and grain Zn concentration of wheat to meet human recruitment. Our study highlights the importance of appropriate Zn fertilizer management in improving grain quality while reducing HMs risks from human consumption.

Physiological and developmental traits associated with the grain yield of winter wheat as affected by phosphorus fertilizer management.

Although researchers have determined that attaining high grain yields of winter wheat depends on the spike number and the shoot biomass, a quantitative understanding of how phosphorus (P) nutrition affects spike formation, leaf expansion and photosynthesis is still lacking. A 3-year field experiment with wheat with six P application rates (0, 25, 50, 100, 200, and 400 kg P ha-1) was conducted to investigate this issue. Stem development and mortality, photosynthetic parameters, dry matter accumulation, and P concentration in whole shoots and in single tillers were studied at key growth stages for this purpose. The results indicated that spike number contributed the most to grain yield of all the yield components in a high-yielding (>8 t/ha) winter wheat system. The main stem (MS) contributed 79% to the spike number and tiller 1 (T1) contributed 21%. The 2.7 g kg-1 tiller P concentration associated with 15 mg kg-1 soil Olsen-P at anthesis stage led to the maximal rate of productive T1s (64%). The critical shoot P concentration that resulted in an adequate product of Pn and LAI was identified as 2.1 g kg-1. The thresholds of shoot P concentration that led to the maximum productive ability of T1 and optimal canopy photosynthetic capacity at anthesis were very similar. In conclusion, the thresholds of soil available P and shoot P concentration in whole plants and in single organs (individual tillers) were established for optimal spike formation, canopy photosynthetic capacity, and dry matter accumulation. These thresholds could be useful in achieving high grain yields while avoiding excessive P fertilization.

Beclin1 inhibition enhances paclitaxel­mediated cytotoxicity in breast cancer in vitro and in vivo.

Beclin1, a key regulator of autophagy, has been demonstrated to be associated with cancer cell resistance to chemotherapy. Paclitaxel is a conventional chemotherapeutic drug used in the clinical treatment of breast cancer. However, the function and mechanism of Beclin1 in paclitaxel­mediated cytotoxicity in breast cancer are not well defined. The present study demonstrated that paclitaxel suppressed cell viability and Beclin1 expression levels in BT­474 breast cancer cells in a dose­ and time­dependent fashion. Compared with the control, the knockdown of Beclin1 significantly enhanced breast cancer cell death via the induction of caspase­dependent apoptosis following paclitaxel treatment in vitro (P<0.05). In a BT­474 xenograft model, paclitaxel achieved substantial inhibition of tumor growth in the Beclin1 knockdown group compared with the control group. Furthermore, analysis of the publicly available Gene Expression Omnibus datasets revealed a clinical correlation between Beclin1 levels and the response to paclitaxel therapy in patients with breast cancer. Collectively, the present results suggest that Beclin1 protects breast cancer cells from apoptotic death. Thus, the inhibition of Beclin1 may be a novel way to improve the effect of paclitaxel. Additionally, Beclin1 may function as a favorable prognostic biomarker for paclitaxel treatment in patients with breast cancer.

Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer.

Overexpression of drug efflux transport ABCB1 is correlated with multidrug resistance (MDR) among cancer cells. Upregulation of ABCB1 accounts for the recurrence of resistance to docetaxel therapy in ovarian cancer with poor survival. Erastin is a novel and specific small molecule that targets SLC7A11 to induce ferroptosis. In the present research, we explored the synergistic effect of erastin and docetaxel in ovarian cancer. We confirmed that the co-delivery of erastin with docetaxel significantly decreased cell viability, promoted cell apoptosis, and induced cell cycle arrest at G2/M in ovarian cancer cells with ABCB1 overexpression. Mechanistically, erastin dominantly elevated the intracellular ABCB1 substrate levels by restricting the drug-efflux activity of ABCB1 without alteration of the expression of ABCB1. Consequently, erastin can reverse ABCB1-mediated docetaxel resistance in ovarian cancer, revealing that the combination of erastin and docetaxel may potentially offer an effective administration for chemo-resistant patients suffering from ovarian cancers.

[Nutrient Distribution Characteristics of the Sediment-water System in the Xiangxi River During the Impoundment of TGR].

This study characterizes the nutrient distribution of the sediment-water system in the Xiangxi River (XXR) during the impoundment of the Three Gorges Reservoir (TGR). In 2016, the research group obtained samples in the Xiangxi River, analyzed the distribution of nitrogen, phosphorus, and O.M. (organic matter) in the sediment-water system, explored the characteristics of "source-sink" between the interstitial water and overlying water, and carried out a cluster analysis for the sampling sites. The results showed that ρ(TN) in the sediments was higher than in the estuary, and the ρ(TN) was close to that in the middle and downstream samples of the river. The ρ(TP) in the upstream sample was the highest of all sites, ρ(O.M.) presented low distribution characteristics in the downstream, and the maximum value of ρ(O.M.) exceeded the critical point (1.5%) within a depth of 10 cm, and there was a certain risk of release. For the distribution in the overlying water, ρ(DTN) and ρ(DTP) were the largest in the estuary, ρ(DTN) decreased from the estuary to the upstream, and ρ(DTP) did not change along the river. During the study, DTN, NH4+-N, and DTP in all sites (except CJ point) were released as nutrients to the overlaying water as the "source," but some points for NO3--N and PO43--P presented as "sources," and some of them presented as "sinks." The "source-sink" process of nitrogen was stronger than that of phosphorus. This was due to the difference between the oxidation environment at the bottom of the XXR and the stream flow backward depth of the Xiangxi bay during impoundment. Based on the results of a cluster analysis, the characteristics of CJ, 1, and 2 indicated similar sediment-water systems, while the characteristics of 3 and 4 were similar.

Crizotinib synergizes with cisplatin in preclinical models of ovarian cancer.

Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene. However, the anticancer effect of crizotinib on ovarian cancer is still unclear. In this study, our data show that crizotinib can actively induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreasing phosphorylation of the downstream signaling effectors AKT and ERK in human ovarian cancer cells. Crizotinib also increases the intracellular reactive oxidative species (ROS) levels, and pretreating with ROS scavenger N-acety-L-cysteine partially reverses crizotinib-induced apoptosis. Moreover, crizotinib can synergistically inhibit ovarian cancer cells growth in vitro and in vivo when combines with cisplatin. Altogether, crizotinib potently potentiates the activity of cisplatin in ovarian cancer, suggesting the synergistic effect of crizotinib and cisplatin may be valuable for ovarian cancer patients' treatment.

Preparation of polyhedral oligomeric silsesquioxane based imprinted monolith.

Polyhedral oligomeric silsesquioxane (POSS) was successfully applied, for the first time, to prepare imprinted monolithic column with high porosity and good permeability. The imprinted monolithic column was synthesized with a mixture of PSS-(1-Propylmethacrylate)-heptaisobutyl substituted (MA 0702), naproxon (template), 4-vinylpyridine, and ethylene glycol dimethacrylate, in ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM]BF4). The influence of synthesis parameters on the retention factor and imprinting effect, including the amount of MA 0702, the ratio of template to monomer, and the ratio of monomer to crosslinker, was investigated. The greatest imprinting factor on the imprinted monolithic column prepared with MA 0702 was 22, about 10 times higher than that prepared in absence of POSS. The comparisons between MIP monoliths synthesized with POSS and without POSS were made in terms of permeability, column efficiency, surface morphology and pore size distribution. In addition, thermodynamic and Van Deemter analysis were used to evaluate the POSS-based MIP monolith.

Cyclin-dependent kinase inhibitor dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer.

Ovarian cancer is one of the most lethal of woman cancers, and its clinical therapeutic outcome currently is unsatisfied. Dinaciclib, a novel small molecule inhibitor of CDK1, CDK2, CDK5 and CDK9, is assessed in clinical trials for the treatment of several types of cancers. In this study, we investigated the anticancer effects and mechanisms of dinaciclib alone or combined with cisplatin in ovarian cancer. Dinaciclib alone actively induced cell growth inhibition, cell cycle arrest and apoptosis with the increased intracellular ROS levels, which were accompanied by obvious alterations of related proteins such as CDKs, Cyclins, Mcl-1, XIAP and survivin. Pretreatment with N-acety-L-cysteine significantly blocked ROS generation but only partially rescued apoptosis triggered by dinaciclib. Moreover, the combination of dinaciclib with cisplatin synergistically promoted cell cycle arrest and apoptosis, and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. Altogether, dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer, indicating this beneficial combinational therapy may be a promising strategy for treatment of ovarian cancer.

Piperlongumine induces apoptosis and synergizes with cisplatin or paclitaxel in human ovarian cancer cells.

Piperlongumine (PL), a natural alkaloid from Piper longum L., possesses the highly selective and effective anticancer property. However, the effect of PL on ovarian cancer cells is still unknown. In this study, we firstly demonstrate that PL selectively inhibited cell growth of human ovarian cancer cells. Furthermore, PL notably induced cell apoptosis, G2/M phase arrest, and accumulation of the intracellular reactive oxidative species (ROS) in a dose- and time-dependent manner. Pretreatment with antioxidant N-acety-L-cysteine could totally reverse the PL-induced ROS accumulation and cell apoptosis. In addition, low dose of PL/cisplatin or paclitaxel combination therapies had a synergistic antigrowth effect on human ovarian cancer cells. Collectively, our study provides new therapeutic potential of PL on human ovarian cancer.