Epigallocatechin-3-gallate-induced tolerance to cadmium stress involves increased flavonoid synthesis and nutrient homeostasis in tomato roots.

Cadmium (Cd) is a toxic heavy metal, increasingly accumulating in the environment and its presence in various environmental compartments represents a significant risk to human health via the food chain. Epigallocatechin-3-Gallate (EGCG) is a prominent secondary metabolite, which can safeguard plants from biotic and abiotic stress. However, the role of EGCG in flavonoid synthesis, nutrient acquisition and reactive oxygen species (ROS) metabolism under Cd stress remains unclear. Here, we examined the effects of EGCG and Cd treatment on leaf photochemical efficiency, cell ultrastructure, essential element acquisition, antioxidant system, and secondary metabolism in tomato (Solanum lycopersicum L.). The results showed that O2•-, H2O2, and malondialdehyde levels increased after Cd treatment, but Fv/Fm decreased significantly, suggesting that Cd induced oxidative stress and photoinhibition. However, EGCG mitigated the adverse effects of Cd-induced phytotoxicity in both the roots and leaves. A decrease in ROS accumulation under EGCG + Cd treatment was mainly attributed to the significant enhancement in antioxidant enzyme activity, flavonoid content, and PHENYLALANINE AMMONIA-LYASE expression in roots. Moreover, EGCG reduced Cd content but increased some essential nutrient contents in tomato plants. Transmission electron microscopy-based observations revealed that EGCG treatment safeguards leaf and root cell ultrastructure under Cd stress. This implies that tomato plants subjected to Cd stress experienced advantageous effects upon receiving EGCG treatment. The present work elucidated critical mechanisms by which EGCG induces tolerance to Cd, thereby providing a basis for future investigations into environmentally sustainable agricultural practices in areas contaminated with heavy metals, for utilizing naturally occurring substances found in plants.

Effects of Differential Shading on Summer Tea Quality and Tea Garden Microenvironment.

Shading is an effective agronomic technique to protect tea plants from intense sunlight. However, there are currently very few studies on more effective shading methods to improve the quality of summer tea. In this study, 'Longjing43' plants were grown under four different shading treatments for 14 days, with no shading as the control. Among the four shading treatments, double-layer-net shadings had the most positive impact on the tea quality, resulting in higher levels of amino acids but lower levels of tea polyphenols. Additionally, double-layer-net shadings provided more suitable microenvironments for tea plants. The tea leaves in T4 (double nets 50 cm above the plant canopy) contained 16.13 mg∙g-1 of umami and sweet amino acids, which was significantly higher than in other treatments. T4 had the lowest air temperature and the most suitable and stable soil water content. Interestingly, the ratio of red light to far-red light in T4 was only 1.65, much lower than other treatments, which warrants further study. In conclusion, the microenvironment induced by shading can greatly affect the tea quality, and double-layer-net shading is better for improving the quality of summer tea.

Roles of rRNA N-methyladenosine modification in the function of ribosomes.

The N-methyladenosine (m6A) modification of ribosomal RNA (rRNA) plays critical roles in regulating the function of ribosomes, the essential molecular machines that translate genetic information from mRNA into proteins. Specifically, m6A modification affects ribosome biogenesis, stability, and function by regulating the processing and maturation of rRNA, the assembly and composition of ribosomes, and the accuracy and efficiency of translation. Furthermore, m6A modification allows for dynamic regulation of translation in response to environmental and cellular signals. Therefore, a deeper understanding of the mechanisms and functions of m6A modification in rRNA will advance our knowledge of ribosome-mediated gene expression and facilitate the development of new therapeutic strategies for ribosome-related diseases.

Relationship of sleep-quality and social-anxiety in patients with breast cancer: a network analysis.

BACKGROUND: There is a complex relationship between social anxiety and sleep quality. However, network analysis studies of associations between social anxiety and sleep quality are lacking, particularly among patients with breast cancer. The current study aimed to extend this research to a sample of patients with breast cancer and to examine symptom-level associations between social anxiety and sleep quality using network analysis. METHODS: Network analysis was conducted to explore their associations and identify bridge items of social anxiety and sleep quality. RESULTS: The network structure revealed 9 important edges between social anxiety and sleep quality. "Subjective sleep quality" had the highest EI value in the network. "Working difficulty under watching" and "Sleep disorders" had the highest BEI values in their own communities. CONCLUSION: There are complex pathological correlation pathways between social anxiety and sleep quality in breast cancer patients. "Subjective sleep quality", "Working difficulty under watching" and "Sleep disorders" have the potential to be intervention targets for sleep disorder-social anxiety comorbidity. Medical staff can take corresponding interventions according to the the centrality indices and bridge centrality indicators identified in this study, which is likely to effectively reduce the comorbidity of sleep disorders and social anxiety.

Medial prefrontal cortical PPM1F alters depression-related behaviors by modifying p300 activity via the AMPK signaling pathway.

AIMS: Protein phosphatase Mg2+/Mn2+-dependent 1F (PPM1F) is a serine/threonine phosphatase, and its dysfunction in depression in the hippocampal dentate gyrus has been previously identified. Nevertheless, its role in depression of another critical emotion-controlling brain region, the medial prefrontal cortex (mPFC), remains unclear. We explored the functional relevance of PPM1F in the pathogenesis of depression. METHODS: The gene expression levels and colocalization of PPM1F in the mPFC of depressed mice were measured by real-time PCR, western blot and immunohistochemistry. An adeno-associated virus strategy was applied to determine the impact of knockdown or overexpression of PPM1F in the excitatory neurons on depression-related behaviors under basal and stress conditions in both male and female mice. The neuronal excitability, expression of p300 and AMPK phosphorylation levels in the mPFC after knockdown of PPM1F were measured by electrophysiological recordings, real-time PCR and western blot. The depression-related behavior induced by PPM1F knockdown after AMPKα2 knockout or the antidepressant activity of PPM1F overexpression after inhibiting acetylation activity of p300 was evaluated. RESULTS: Our results indicate that the expression levels of PPM1F were largely decreased in the mPFC of mice exposed to chronic unpredictable stress (CUS). Behavioral alterations relevant to depression emerged with short hairpin RNA (shRNA)-mediated genetic knockdown of PPM1F in the mPFC, while overexpression of PPM1F produced antidepressant activity and ameliorated behavioral responses to stress in CUS-exposed mice. Molecularly, PPM1F knockdown decreased the excitability of pyramidal neurons in the mPFC, and restoring this low excitability decreased the depression-related behaviors induced by PPM1F knockdown. PPM1F knockdown reduced the expression of CREB-binding protein (CBP)/E1A-associated protein (p300), a histone acetyltransferase (HAT), and induced hyperphosphorylation of AMPK, resulting in microglial activation and upregulation of proinflammatory cytokines. Conditional knockout of AMPK revealed an antidepressant phenotype, which can also block depression-related behaviors induced by PPM1F knockdown. Furthermore, inhibiting the acetylase activity of p300 abolished the beneficial effects of PPM1F elevation on CUS-induced depressive behaviors. CONCLUSION: Our findings demonstrate that PPM1F in the mPFC modulates depression-related behavioral responses by regulating the function of p300 via the AMPK signaling pathway.

PPM1G promotes the progression of lung adenocarcinoma by inhibiting p38 activation via dephosphorylation of MEK6.

The p38 MAP kinase (MAPK) signaling pathway is a key signal transduction cascade that cancer cells employ to sense and adapt to a plethora of environmental stimuli and has attracted much attention as a promising target for cancer therapy. Although the kinases that phosphorylate p38 have been extensively studied, the negative regulation of p38 phosphorylation remains to be elucidated. Here, we found that PPM1G was highly expressed in lung adenocarcinoma (LUAD) compared to normal tissues, and higher levels of PPM1G were observed in adverse staged LUAD. Furthermore, the higher levels of PPM1G were highly correlated with poor prognosis, according to the Cancer Genome Atlas cohort. Most importantly, we identified phospho-MEK6 as a direct substrate of PPM1G. PPM1G, a metal-dependent protein phosphatase family phosphatase, could reduce p38 phosphorylation via MEK6 dephosphorylation and contribute to the proliferation, invasion and metastasis of LUAD. Our study highlighted the essential role of PPM1G in LUAD and shed new light on unveiling the regulation of p38 activity via direct dephosphorylation of MEK6 in malignant transformation. Together, this study provides new insight into the complexity of regulating the versatile p38 signaling and suggests new directions in intervening in p38 MAPK signaling.

NiAlP@Cobalt substituted nickel carbonate hydroxide heterostructure engineered for enhanced supercapacitor performance.

Transitional metal phosphides with high electrical conductivity and superb physicochemical features have been recognized as ideal battery-type electrode materials for outstanding performance supercapacitors. However, their specific capacities and structural stability are needed to be enhanced for large-scale practical applications. To overcome these shortcomings, we fabricated heterostructured NiAlP@cobalt substituted nickel carbonate hydroxide (Co-NiCH) nanosheet arrays by sequential a hydrothermal reaction, a phosphorization treatment, and a second hydrothermal reaction. Profiting from its core-shell porous nanostructure and synergistic effect of NiAlP with high electrical conductivity and Co-NiCH with high redox reactivity, the resultant NiAlP@Co-NiCH electrode delivers a large specific capacity of 825.7C g-1 at 1 A g-1, excellent rate capability with 78.9% capacity retention and long lifespan, superior to those of pure NiAlP and Co-NiCH electrodes. Additionally, an aqueous asymmetric supercapacitor device is constructed by NiAlP@Co-NiCH and lotus pollen-derived hierarchical porous carbon, which demonstrates a large energy density of 82.3 Wh kg-1 at a power density of 739.8 W kg-1, and wonderful cycle stability with 88.2% capacity retention after 10,000 cycles. This work proposes a feasible strategy on construction of transitional metal phosphide-based heterojunctions for advanced asymmetric supercapacitor devices.

Potential of Kazakhstan's grain export trade / O potencial do comércio de exportação de grãos do Cazaquistão

ABSTRACT: Kazakhstan is located in the hinterland of Central Asia. Its virtuous geographical advantages and huge grain production potential make it one of the most important grain exporters in the world. The research on the problem of the grain trade in Kazakhstan is of great significance for food security. This study measured its international competitiveness using the International Market Share Index, the Revealed Comparative Advantage Index, Trade competitiveness index and calculated the international competitiveness and analyzed the influencing factors of grain export by constructing an extended gravity model and measured its export potential. Results showed that Kazakhstan has a low share of the international grain market; however, wheat, barley, and buckwheat have strong export advantages; the level of economic development and economic distance has significantly promoted the scale of grain exports. While geographical distance, the difference in GDP per capita, and the fact whether trading partner countries have joined the Eurasian Economic Union have caused obstacles to grain exports. Kazakhstan's export potential to 6 countries including Russia, Kyrgyzstan and China shows an upward" trend, its export potential to 6 countries including Tajikistan and Ukraine showing a "stable" trend, and its export to 9 countries included Poland and Germany. The potential showed a "declining" trend.

RESUMO: O Cazaquistão está localizado no interior da Ásia Central. Suas virtuosas vantagens geográficas e grande potencial de produção de grãos a tornam um dos exportadores de grãos mais importantes do mundo. A pesquisa sobre o problema do comércio de grãos no Cazaquistão é de grande importância para a segurança alimentar. Este estudo mede sua competitividade internacional por meio do índice IMS, índice RCA, índice TC e calcula a competitividade internacional e analisa os fatores influenciadores da exportação de grãos por meio da construção de um modelo gravimétrico estendido e mede seu potencial exportador. Os resultados mostram que o Cazaquistão tem uma baixa participação no mercado internacional de grãos; no entanto, trigo, cevada e trigo sarraceno têm fortes vantagens de exportação; o nível de desenvolvimento econômico e a distância econômica têm promovido significativamente a escala das exportações de grãos. Embora a distância geográfica, a diferença no PIB per capita e o fato de os países parceiros comerciais terem aderido à União Econômica da Eurásia têm causado obstáculos às exportações de grãos. O potencial de exportação do Cazaquistão para seis países, incluindo Rússia, Quirguistão e China mostra uma tendência de "alta", seu potencial de exportação para seis países, incluindo Tajiquistão e Ucrânia, mostra uma tendência" estável "e sua exportação para nove países, incluindo Polônia e Alemanha. O potencial mostra uma tendência de "declínio".

Rational synthesis of CoFeP@nickel-manganese sulfide core-shell nanoarrays for hybrid supercapacitors.

Transition metal phosphide electrodes, particularly those with unique morphologies and micro-/nanostructures, have demonstrated desirable capabilities for hybrid supercapacitor applications by virtue of their superior electrical conductivity and high electrochemical activity. Here, three-dimensional hierarchical CoFeP@nickel-manganese sulfide nanoarrays were in situ constructed on a flexible carbon cloth via a hydrothermal method, a phosphorization process, followed by an electrodeposition approach. In this smart nanoarchitecture, CoFeP nanorods grown on carbon cloth act as the conductive core for rapid electron transfer, while the nickel-manganese sulfide nanosheets decorated on the surface of CoFeP serve as the shell for efficient ion diffusion, forming a stable core-shell heterostructure with enhanced electrical conductivity. Benefiting from the synergy of the two components and the generation of a heterointerface with a modified electronic structure, The CoFeP@nickel-manganese sulfide electrodes deliver a high capacity of 260.7 mA h g-1 at 1 A g-1, excellent rate capability, and good cycling stability. More importantly, an aqueous hybrid supercapacitor based on CoFeP@nickel-manganese sulfide as a positive electrode and a lotus pollen-derived hierarchical porous carbon as a negative electrode is constructed to display a maximum energy density of 60.1 W h kg-1 at 371.8 W kg-1 and a good cycling stability of 85.7% capacitance retention after 10 000 cycles.

The association between soy-based food and soy isoflavone intake and the risk of gastric cancer: a systematic review and meta-analysis.

Soy contains many bioactive phytochemicals, such as isoflavones, which have the effect of preventing many cancers. Some studies have shown the beneficial effect of soy-based food and isoflavone intake on gastric cancer (GC), while others claimed no effect. Therefore, whether the beneficial effect of soy-based food is related to its fermentation or whether its protective effect comes from isoflavones still remains inconclusive. Our aim was to investigate the relationship between total soybean, fermented soybean, non-fermented soybean and isoflavone intake, and the risk of GC. Ten cohort studies and 21 case-control studies involving 916 354 participants were included. The association between soy-based food and isoflavone intake and the risk of GC was calculated with the pooled relative risks (RRs) for the highest versus lowest intake categories. The results showed that isoflavone intake might be a protective factor to GC, but the result was not statistically significant (RR = 0.92; 95% CI: 0.79-1.07). However, total soybean intake could significantly decrease the risk of GC by 36% (RR = 0.64; 95% CI: 0.51-0.80), which might be credited to non-fermented soybean products (RR = 0.79; 95% CI: 0.71-0.87). In contrast, high intake of fermented soybean products could increase the risk of GC (RR = 1.19; 95% CI: 1.02-1.38). High intake of total soybean and non-fermented soybean products could reduce the risk of GC, and high intake of fermented soybean products could increase the risk, which indicated that the beneficial effect of soy-based food might be related to its non-fermentation. However, high intake of isoflavones may not be associated with the incidence of GC. © 2021 Society of Chemical Industry.

Versatile Janus Composite Nonwoven Solar Absorbers with Salt Resistance for Efficient Wastewater Purification and Desalination.

Solar steam generation is an efficient way of harvesting solar energy for water purification. Developing a versatile solar absorber with salt resistance and the capability to purify an oil-in-water emulsion is a grand challenge. Herein, a polypropylene (PP) nonwoven fabric-based photothermal absorber is fabricated by the combination of carbon nanotubes (CNTs), polypyrrole (PPy), and a fluorinated hydrophobic coating in a layer-by-layer approach. The specially designed architecture displays a hierarchical microstructure and Janus wetting properties, facilitating solar absorption and heat generation on the evaporation surface, and can effectively prevent salt crystallization. The water layer formed on the superhydrophilic/underwater superoleophobic bottom surface could repel oil droplets and form a channel to advect concentrated salt back into bulk water, which enabled high purity separation of an oil-in-water emulsion and continuous desalinization of seawater without the reduction of the evaporation rate. As a result, the solar absorber can achieve a remarkable evaporation rate of 1.61 kg m-2 h-1 and an energy efficiency of 91.2% under 1 sun irradiation and shows extraordinary performance in the purification of contaminated wastewater (over 99.8% purity). The strategy proposed provides a pathway for developing versatile high-performance solar absorbers for the sustainable treatment of saline water, wastewater, and oil-containing water.

PPM1F in hippocampal dentate gyrus regulates the depression-related behaviors by modulating neuronal excitability.

Major depressive disorder (MDD) is a common, serious, debilitating mental illness. Protein phosphatase Mg2+/Mn2+-dependent 1F (PPM1F), a serine/threonine phosphatase, has been reported to have multiple biological and cellular functions. However, the effects of PPM1F and its neuronal substrates on depressive behaviors remain largely unknown. Here, we showed that PPM1F is widely distributed in the hippocampus, and chronic unpredictable stress (CUS) can induce increased expression of PPM1F in the hippocampus, which was correlated with depression-associated behaviors. Overexpression of PPM1F mediated by adeno-associated virus (AAV) in the dentate gyrus (DG) produced depression-related behaviors and enhanced susceptibility to subthreshold CUS (SCUS) in both male and female mice, while, knockout of PPM1F in DG produced antidepressant phonotypes under stress conditions. Whole-cell patch-clamp recordings demonstrated that overexpression of PPM1F increased the neuronal excitability of the granule cells in the DG. Consistent with neuronal hyperexcitability, overexpression of PPM1F regulated the expression of certain ion channel genes and induced decreased phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CAMKII) and Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in hippocampus. These results suggest that PPM1F in the DG regulates depression-related behaviors by modulating neuronal excitability, which might be an important pathological gene for depression or other mental diseases.

pH-Responsive Cascaded Nanocatalyst for Synergistic Like-Starvation and Chemodynamic therapy.

A tumor microenvironment (TME) responsive cascade nanocatalyst was built based on copper-embedded hollow mesoporous silica (HMSN-Cu) decorated with glucose oxidase (GOD) on the surface, realizing tumor-selected cascade catalyst for elegant combination of starving therapy and chemodynamic therapy. Specifically, benefited from the strong demand for glucose metabolism in tumor cells, this HMSN-Cu-GOD could catalyze rich glucose into H2O2 in the presence of O2, along with localized declined pH in situ to in turn degrade HMSN-Cu and thus release Cu2+/Cu+. Importantly, abound hydroxyl radical (•OH) with high oxidative activity generated in the Fenton reaction between H2O2 and Cu2+/Cu+. Interesting, the high-expressed GSH and exacerbated hypoxia in tumor cells, will facilitate accumulation of Cu+ with much higher reaction efficiency, further enhanced Chemodynamic therapy (CDT) efficiency. Compared with monotherapy, in vitro and vivo tumor inhibition experiments demonstrated the superior synergistic effect of CDT and starving therapy based on a simple but effective biodegradable nanosystem.

Discovery of cyanopyridine scaffold as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors through virtual screening and preliminary hit optimisation.

With the aim of discovering novel IDO1 inhibitors, a combined similarity search and molecular docking approach was employed to the discovery of 32 hit compounds. Testing the screened hit compounds has led to several novel submicromolar inhibitors. Especially for compounds LVS-019 with cyanopyridine scaffold, showed good IDO1 inhibitory activity. To discover more compounds with similar structures to LVS-019, a shape-based model was then generated on the basis of it and the second-round virtual screening was carried out leading to 23 derivatives. Molecular docking studies suggested a possible binding mode of LVS-019, which provides a good starting point for the development of cyanopyridine scaffold compounds as potent IDO1 inhibitor. To improve potency of these hits, we further designed and synthesised another 14 derivatives of LVS-019. Among these compounds, LBJ-10 showed improved potency compared to the hits and displayed comparable potency to the control GDC-0919 analogue. LBJ-10 can serve as ideal leads for further modifications as IDO1 inhibitors for cancer treatment.

Osthole decreases tau protein phosphorylation via PI3K/AKT/GSK-3ß signaling pathway in Alzheimer's disease.

AIM: Alzheimer's disease (AD), a neurodegenerative disease, was characterized by the loss of memory and progressive cognitive deterioration. Up to now, there has no effective drugs to cure or delay the state of illness. Increasing evidence indicates that hyperphosphorylated tau protein plays a pivotal role in the occurrence and development of AD. Therefore, in present study, we aim to investigate whether osthole (OST) could decrease hyperphosphorylated tau protein in AD and the underlying mechanism. MAIN METHODS: The ability of learning and memory was detected by Morris Water Maze. The pathological changes were detected by H&E staining. The percentage of cells apoptosis was detected by TUNEL assay in vivo and Flow Cytometry in intro. The expressions of tau protein and related proteins in PI3K/Akt/GSK-3ß signaling pathway were detected by Western Blot. KEY FINDINGS: We found that OST could significantly improve learning and memory dysfunction, ameliorate the histology structure of damaged neural cells in hippocampal area. Moreover, we also found that OST could decrease tau protein phosphorylation as well as inhibit cells apoptosis. To explore the underlying mechanism, we used LY294002 to block PI3K/Akt/GSK-3ß signaling pathway, the results from Western bolt showed that the expression of related proteins in PI3K signaling pathway were decreased with LY294002 treated. SIGNIFICANCE: Taken together, the results indicated that OST could decrease phosphorylated tau levels via activation of PI3K/Akt/GSK-3ß signaling pathway. Thus, this study demonstrated that OST might be a potential candidate for the treatment of AD.

Synthesis and Antitumor Activity Evaluation of a Novel Combi-nitrosourea Prodrug: BGCNU.

Chloroethylnitrosoureas (CENUs) are an important type of alkylating agent employed in the clinical treatment of cancer. However, the anticancer efficacy of CENUs is greatly decreased by a DNA repairing enzyme, O6-alkylguanine-DNA alkyltransferase (AGT), by preventing the formation of interstrand cross-links (ICLs). In this study, a combi-nitrosourea prodrug, namely, N-(2-chloroethyl)-N'-2-(O6-benzyl-9-guanine)ethyl-N-nitrosourea (BGCNU), which possesses an O6-benzylguanine (O6-BG) derivative and CENU pharmacophores simultaneously, was synthesized and evaluated for its ability to induce ICLs. The target compound is markedly more cytotoxic in human glioma cells than the clinically used CENU chemotherapies ACNU, BCNU, and their respective combinations with O6-BG. In the AGT-proficient cells, significantly higher levels of DNA ICLs were observed in the groups treated by BGCNU than those by ACNU and BCNU, which indicated that the activity of AGT was effectively inhibited by the O6-BG derivatives released from BGCNU.