LHPP promotes the intracellular reactive oxygen species accumulation and sensitivity of gastric cancer to cisplatin via JNK and p38 MAPK pathways

Background. Cisplatin is the first-line chemotherapy drug for the treatment of gastric cancer (GC) patients. However, GC patients who are resistant to cisplatin often do not benefit from it. Therefore, finding a key molecule that affects cisplatin sensitivity is expected to enhance the efficacy of cisplatin in GC treatment. Methods. The human GC cell lines SGC-7901 and BGC-823 were used. The protein chip array was used to screen the cisplatin-resistance genes from the complete response and non-complete response GC patients’ tissues, then, the differential gene expression analysis, GO function annotation analysis, and KEGG pathway enrichment analysis were performed. The GC tissue chip in the GEO database was analyzed to screen the target gene. Flow cytometry, Hoechst 33342 staining assay, Western Blot, MTT, tumor sphere formation, cell cycle, and apoptosis assays were performed to explore the effect of Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP) on the apoptosis, stemness, and reactive oxygen species (ROS) accumulation of cisplatin-resistant GC cells treated with cisplatin. In vivo, the cisplatin-resistant GC cell lines transfected with pcDNA-LHPP or si-LHPP were injected subcutaneously into mice to construct GC subcutaneous xenograft GC models. Results. Based on protein chip array and bioinformatics analysis, it was found that LHPP is the core molecule in the cisplatin resistance regulatory network in GC, and its expression is down-regulated in GC cisplatin-resistant tissues and cells. In vitro and in vivo experimental results show that the up-regulated expression of LHPP is closely related to the increase in sensitivity of GC to cisplatin. Mechanically, we found that overexpression of LHPP may inhibit the activation of the JNK and p38 MAPK pathways, promote cisplatininduced ROS accumulation, suppress stemness, and enhance the sensitivity of GC to cisplatin. Conclusions. Up-regulation of LHPP may inhibit the activation of the JNK and p38 MAPK pathways, attenuate stemness, and enhance the accumulation of intracellular ROS, thereby promoting cisplatin-mediated GC cell apoptosis and enhancing cisplatin sensitivity

An expanded evaluation of protein function prediction methods shows an improvement in accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent. Keywords: Protein function prediction, Disease gene prioritizationpublishedVersio

An Expanded Evaluation of Protein Function Prediction Methods Shows an Improvement In Accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent

Study on Relationship between Environmental Regulation and Green Total Factor Productivity from the Perspective of FDI—Evidence from China

The existing literature has paid less attention to the key role of FDI in the realization of Porter’s hypothesis. Based on China’s provincial panel data from 2007 to 2020, this paper uses the SBM function and the Luenberger productivity index to measure the green total factor productivity (GTFP) of China’s provinces while considering energy consumption and undesired output. Using FDI as the mediating variable and threshold variable, this paper studies the relationship between environmental regulation (ENV), FDI, and GTFP. The research results show that: (1) There is a U-shaped relationship between ENV and GTFP. China is currently on the left side of the U-shaped inflection point. Further improving the intensity of ENV can promote the growth of GTFP. (2) The mediating effect of FDI is significantly established. ENV and FDI show a significant U-shaped relationship. Further development of FDI can promote GTFP. (3) FDI has a threshold effect. When FDI is at a low level of development, ENV and GTFP are negatively correlated and insignificant; when FDI is at a high level of development, ENV can significantly promote the growth of GTFP. The marginal effect on green TFP increases with FDI growth. The results of this paper show that FDI is a necessary prerequisite for the Porter hypothesis to become a reality in China. The research of this paper has important reference value for realizing the sustainable development of environment, economy, and society

Has the Construction of National High-Tech Zones Promoted Regional Economic Growth?—Empirical Research from Prefecture-Level Cities in China

As a “special economic zone” and “policy test field” in the region, the national high-tech zone is an important strategy for the country to promote the development of high-tech industries and regional economy, but its effect needs to be verified. This paper uses panel data of 281 prefecture-level cities in China from 1994 to 2019, and uses the differences-in-differences method to study the impact of high-tech zones on regional economic development. On this basis, the heterogeneity effects of different types of high-tech zones on regional economic growth are explored. The empirical research results show that the national high-tech zone promotes regional economic growth, and this conclusion still holds after conducting multiple robustness tests. Further research found that the promotion of national high-tech zones to economic development showed the law of “diminishing marginal effect”: Compared with higher-level cities, lower-level cities gained faster development from the construction of national high-tech zones. Compared with the developed regions in the east, the underdeveloped regions in the west have achieved faster development from the construction of the national high-tech zone. In addition, this paper finds that growth-type high-tech zones have a greater marginal contribution to regional economic growth than mature high-tech zones; multi-zone high-tech zones have a greater marginal contribution to regional economic growth than single-zone high-tech zones. The research of this paper shows that the national high-tech zones as “policy test fields” and “special economic zones” can not only drive economic development, but also help narrow the economic development gap between regions through their rational distribution. This provides important inspiration for the future layout of the national high-tech zone and the establishment of other related policies

Progress on the hydraulic measures for grid slotting and fracking to enhance coal seam permeability

A method of hydraulic grid slotting and hydraulic fracturing was proposed to enhance the permeability of low permeability coal seam in China. Micro-structural development and strength characteristics of coal were analysed to set up the failure criterion of coal containing water and gas, which could describe the destruction rule of coal containing gas under the hydraulic measures more accurately. Based on the theory of transient flow and fluid grid, the numerical calculation model of turbulence formed by high pressure oscillating water jet was used. With the high speed photography test, dynamic evolution and pulsation characteristics of water jet water analysed which laid a foundation for mechanism analysis of rock damage under water jet. Wave equation of oscillating water jet slotting was established and the mechanism of coal damage by the impact stress wave under oscillation jet was revealed. These provide a new method to study the mechanism of porosity and crack damage under high pressure jet. Fracture criterion by jet slotting was established and mechanism of crack development controlled by crack zone between slots was found. The fractures were induced to extend along pre-set direction, instead of being controlled by original stress field. The model of gas migration through coal seams after the hydraulic measures for grid slotting and fracking was established. The key technology and equipment for grid slotting and fracking with high-pressure oscillating jet were developed and applied to coal mines in Chongqing and Henan in China. The results show that the gas permeability of coal seam is enhanced by three orders of magnitude, efficiency of roadway excavation and mining is improved by more than 57% and the cost of gas control is reduced by 50%. Keywords: Coal seam permeability, High pressure water jet, Grid slotting and fracking, Gas extractio

Association of peroxisome proliferator-activated receptor delta and additional gene–smoking interaction on cardiovascular disease

Aims: To investigate the impact of peroxisome proliferator–activator receptor delta (PPARD) gene polymorphism and additional gene–smoking interaction on cardiovascular disease (CVD) risk based on this Chinese population. Methods: A total of 1048 subjects (617 males, 431 females) with a mean age of 52.9 ± 14.1 years old were selected, including 520 CVD patients and 528 normal control subjects. The logistic regression model was used to examine the association between three SNPs and CVD risk, odds ratio (OR), and 95% confident interval (95%CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to investigate the gene–smoking interaction. Results: Genotypes of variants in rs2016520 and rs9794 were associated with decreased CVD risk, and CVD risk was significantly lower in carriers of C allele of the rs2016520 polymorphism than those with the TT genotype (TC+CC versus TT), adjusted OR (95%CI) = 0.71 (0.56–0.86). In addition, we also found that CVD risk was also significantly lower in carriers of the G allele of the rs9794 polymorphism than those with the CC genotype (CG+ GG versus CC), adjusted OR (95%CI) = 0.69 (0.53–0.86). GMDR analysis suggested a potential gene–environment interaction between rs2016520 and smoking. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 62.17%, and never smokers with TC or CC of the rs2016520 genotype have the lowest CVD risk, compared to smokers with TT of rs2016520, OR (95%CI) was 0.42 (0.23–0.66). Conclusions: The minor allele of rs2016520 and rs9794 in PPAR-δ and interaction between rs2016520 and non-smoking were associated with decreased risk of CVD