Insight into Conformational Change for 14-3-3σ Protein by Molecular Dynamics Simulation

14-3-3σ is a member of a highly conserved family of 14-3-3 proteins that has a double-edged sword role in human cancers. Former reports have indicated that the 14-3-3 protein may be in an open or closed state. In this work, we found that the apo-14-3-3σ is in an open state compared with the phosphopeptide bound 14-3-3σ complex which is in a more closed state based on our 80 ns molecular dynamics (MD) simulations. The interaction between the two monomers of 14-3-3σ in the open state is the same as that in the closed state. In both open and closed states, helices A to D, which are involved in dimerization, are stable. However, large differences are found in helices E and F. The hydrophobic contacts and hydrogen bonds between helices E and G in apo-14-3-3σ are different from those in the bound 14-3-3σ complex. The restrained and the mutated (Arg56 or Arg129 to alanine) MD simulations indicate that the conformation of four residues (Lys49, Arg56, Arg129 and Tyr130) may play an important role to keep the 14-3-3σ protein in an open or closed state. These results would be useful to evaluate the 14-3-3σ protein structure-function relationship

Localization Transformation of Five Coordinate Milling Machine

AbstractAs five coordinates gantry milling machine is not able to meet the requirements of the parts of precision and efficient processing, for the machine tool's electrical function degradation, mechanical part aging, CNC system backward, now it needs to upgrade the whole electrification and fix the mechanical part by Huangzhong, HNC - 848 c/M bus type numerical control system. Though the machine localization reformation, the precision and efficiency of the machine tool are improved, thus the application of domestic CNC system and functional components in the machine tool are promoted

Analysis of Dynamic Variation Characteristics and Influential Factors of PM2.5 on Subway Platforms under Air-Conditioning Condition and Ventilation Condition

The purpose of this study is to investigate the main influential factors of the subway Particulate Matter (PM) pollutants under the air-conditioning condition and ventilation condition, by an on-site field measurement in a subway station in Shanghai. It is found that the dust accumulation at fresh air shaft was the secondary dusting action under the influence of fresh air flow, leading to a higher concentration of the PM in the subway station than in the outdoor air even when the outdoor air quality was good. In addition, in the morning rush hour the PM 2.5 value near the platform screen door our is highest of the day

Exogenous brassinosteroids alleviate calcium deficiency-induced tip-burn by maintaining cell wall structural stability and higher photosynthesis in mini Chinese Cabbage

Tip-burn has seriously affected the yield, quality and commodity value of mini Chinese cabbage. Calcium (Ca2+) deficiency is the main cause of tip-burn. In order to investigate whether exogenous brassinosteroids (BRs) can alleviate tip-burn induced by calcium (Ca2+) deficiency and its mechanism, in this study, Ca2+ deficiency in nutrient solution was used to induced tip-burn, and then distilled water and BRs were sprayed on leaves to observe the tip-burn incidence of mini Chinese cabbage. The tip-burn incidence and disease index, leaf area, fluorescence parameters (Fv/Fm, NPQ, qP andφPSII) and gas exchange parameters (Tr, Pn, Gs and Ci), pigment contents, cell wall components, mesophyll cell ultrastructure and the expression of genes related to chlorophyll degradation were measured. The results showed that exogenous BRs reduced the tip-burn incidence rate and disease index of mini Chinese cabbage, and the tip-burn incidence rate reached the highest on the ninth day after treatment. Exogenous BRs increased the contents of cellulose, hemifiber, water-soluble pectin in Ca2+ deficiency treated leaves, maintaining the stability of cell wall structure. In addition, BRs increased photosynthetic rate by increasing the activities of Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and fructose 1,6-bisphosphatase (FBPase) related to Calvin cycle, maintaining relatively complete chloroplast structure and higher chlorophyll content via down-regulating the expression of BrPPH1 and BrPAO1 genes related to chlorophyll degradation. In conclusion, exogenous BRs alleviated calcium deficiency-induced tip-burn by maintaining cell wall structural stability and higher photosynthesis

Gobi agriculture: an innovative farming system that increases energy and water use efficiencies. A review

International audienceAbstractIn populated regions/countries with fast economic development, such as Africa, China, and India, arable land is rapidly shrinking due to urban construction and other industrial uses for the land. This creates unprecedented challenges to produce enough food to satisfy the increased food demands. Can the millions of desert-like, non-arable hectares be developed for food production? Can the abundantly available solar energy be used for crop production in controlled environments, such as solar-based greenhouses? Here, we review an innovative cultivation system, namely “Gobi agriculture.” We find that the innovative Gobi agriculture system has six unique characteristics: (i) it uses desert-like land resources with solar energy as the only energy source to produce fresh fruit and vegetables year-round, unlike conventional greenhouse production where the energy need is satisfied via burning fossil fuels or electrical consumption; (ii) clusters of individual cultivation units are made using locally available materials such as clay soil for the north walls of the facilities; (iii) land productivity (fresh produce per unit land per year) is 10–27 times higher and crop water use efficiency 20–35 times greater than traditional open-field, irrigated cultivation systems; (iv) crop nutrients are provided mainly via locally-made organic substrates, which reduce synthetic inorganic fertilizer use in crop production; (v) products have a lower environmental footprint than open-field cultivation due to solar energy as the only energy source and high crop yields per unit of input; and (vi) it creates rural employment, which improves the stability of rural communities. While this system has been described as a “Gobi-land miracle” for socioeconomic development, many challenges need to be addressed, such as water constraints, product safety, and ecological implications. We suggest that relevant policies are developed to ensure that the system boosts food production and enhances rural socioeconomics while protecting the fragile ecological environment

Necroptosis throws novel insights on patient classification and treatment strategies for hepatocellular carcinoma

IntroductionNecroptosis is a novel pattern of immunogenic cell death and has triggered an emerging wave in antitumor therapy. More evidence has suggested the potential associations between necroptosis and intra-tumoral heterogeneity. Currently, the underlying role of necroptosis remains elusive in hepatocellular carcinoma (HCC) at antitumor immunity and inter-tumoral heterogeneity.MethodsThis study enrolled a total of 728 HCC patients and 139 immunotherapy patients from eight public datasets. The consensus clustering approach was employed to depict tumor heterogeneity of cancer necroptosis. Subsequently, our study further decoded the heterogeneous clinical outcomes, genomic landscape, biological behaviors, and immune characteristics in necroptosis subtypes. For each patient, providing curative clinical recommendations and developing potential therapeutic drugs were used to promote precise medicine.ResultsWith the use of the weighted gene coexpression network analysis (WGCNA) algorithm, necroptosis-associated long non-coding RNAs (lncRNAs) (NALRs) were identified in HCC. Based on the NALR expression, two heterogeneous subtypes were decoded with distinct clinical outcomes. Compared to patients in C1, patients in C2 harbored superior pathological stage and presented more unfavorable overall survival and recurrence-free survival. Then, the robustness and reproducibility of necroptosis subtypes were further validated via the nearest template prediction (NTP) approach and classical immune phenotypes. Through comprehensive explorations, C1 was characterized by enriched immune-inflammatory and abundant immune infiltration, while C2 possessed elevated proliferative and metabolic activities and highly genomic instability. Moreover, our results indicated that C1 was more prone to obtain desirable benefits from immunotherapy. For patients in C2, numerous underlying therapeutic agents were developed, which might produce significant efficacy.ConclusionThis study identified two necroptosis subtypes with distinct characteristics, decoding the tumor heterogeneity. For an individualized patient, our work tailored corresponding treatment strategies to improve clinical management

CD8+ T cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinoma

IntroductionMounting evidence has revealed that the interactions and dynamic alterations among immune cells are critical in shaping the tumor microenvironment and ultimately map onto heterogeneous clinical outcomes. Currently, the underlying clinical significance of immune cell evolutions remains largely unexplored in hepatocellular carcinoma (HCC).MethodsA total of 3,817 immune cells and 1,750 HCC patients of 15 independent public datasets were retrieved. The Seurat and Monocle algorithms were used to depict T cell evolution, and nonnegative matrix factorization (NMF) was further applied to identify the molecular classification. Subsequently, the prognosis, biological characteristics, genomic variations, and immune landscape among distinct clusters were decoded. The clinical efficacy of multiple treatment approaches was further investigated.ResultsAccording to trajectory gene expression, three heterogeneous clusters with different clinical outcomes were identified. C2, with a more advanced pathological stage, presented the most dismal prognosis relative to C1 and C3. Eight independent external cohorts validated the robustness and reproducibility of the three clusters. Further explorations elucidated C1 to be characterized as lipid metabolic HCC, and C2 was referred to as cell-proliferative HCC, whereas C3 was defined as immune inflammatory HCC. Moreover, C2 also displayed the most conspicuous genomic instability, and C3 was deemed as “immune-hot”, having abundant immune cells and an elevated expression of immune checkpoints. The assessments of therapeutic intervention suggested that patients in C1 were suitable for transcatheter arterial chemoembolization treatment, and patients in C2 were sensitive to tyrosine kinase inhibitors, while patients in C3 were more responsive to immunotherapy. We also identified numerous underlying therapeutic agents, which might be conducive to clinical transformation in the future.ConclusionsOur study developed three clusters with distinct characteristics based on immune cell evolutions. For specifically stratified patients, we proposed individualized treatment strategies to improve the clinical outcomes and facilitate the clinical management

Variation of cataract surgery costs in four different graded providers of China

<p>Abstract</p> <p>Background</p> <p>China has the largest population of cataract patients in the world. However, the cataract surgery rate per million remains low in China. We carried out a survey on costs of cataract surgery from four different graded providers in China and analyzed differences in cost among these clinics.</p> <p>Methods</p> <p>1,189 patients were recruited for the study in four eye clinics, located in two provinces, Guangdong province in southern China and Hubei province in central China. The average cost of each cataract surgery episode was calculated including cost of intraocular lens, cost of drugs and facility cost. We also collected information on reimbursement and disposable annual income of local residents.</p> <p>Results</p> <p>Mean total cost per cataract intervention of four different providers varied considerably, ranging from US$1,293 in Union Hospital to US$ 536 in Jingshan County Hospital. In all providers, except for Jingshan County Hospital, the cost exceeded annual disposable income of local rural residents. As to the proportion of patients with reimbursement, the figure for Union Hospital was only 36%, while for other three clinics it was more than 60%. There was a significant difference between mean reimbursement ratios, with the highest ratio in Zhongshan Ophthalmic Center being 71%.</p> <p>Conclusions</p> <p>Significant differences in costs of cataract surgery were found among the 4 different graded providers. A part of the cost was borne by patients. Proportion of patients with reimbursement and mean reimbursement ratios were higher in economically developed regions than in economically developing regions. Much more financial support should be directed into the rural New Cooperative Medical Scheme to raise the reimbursement ratio in rural China.</p