A platform for whole-genome speed introgression from Aegilops tauschii to wheat for breeding future crops.

Breeding new and sustainable crop cultivars of high yields and desirable traits has been a major challenge for ensuring food security for the growing global human population. For polyploid crops such as wheat, introducing genetic variation from wild relatives of its subgenomes is a key strategy to improve the quality of their breeding pools. Over the past decades, considerable progress has been made in speed breeding, genome sequencing, high-throughput phenotyping and genomics-assisted breeding, which now allows us to realize whole-genome introgression from wild relatives to modern crops. Here, we present a standardized protocol to rapidly introgress the entire genome of Aegilops tauschii, the progenitor of the D subgenome of bread wheat, into elite wheat backgrounds. This protocol integrates multiple modern high-throughput technologies and includes three major phases: development of synthetic octaploid wheat, generation of hexaploid A. tauschii-wheat introgression lines (A-WIs) and homozygosis of the generated A-WIs. Our approach readily generates stable introgression lines in 2 y, thus greatly accelerating the generation of A-WIs and the introduction of desirable genes from A. tauschii to wheat cultivars. These A-WIs are valuable for wheat-breeding programs and functional gene discovery. The current protocol can be easily modified and used for introgressing the genomes of wild relatives to other polyploid crops.

Bibliometric Analysis of Global Research on Tumor Dormancy.

Tumor dormancy continues to be a research hotspot with numerous pressing problems that need to be solved. The goal of this study is to perform a bibliometric analysis of pertinent articles published in the twenty-first century. We concentrate on significant keywords, nations, authors, affiliations, journals, and literature in the field of tumor dormancy, which will help researchers to review the results that have been achieved and better understand the directions of future research. We retrieved research articles on tumor dormancy from the Web of Science Core Collection. This study made use of the visualization tools VOSviewer, CiteSpace, and Scimago Graphica, as visualization helps us to uncover the intrinsic connections between information. Research on tumor dormancy has been growing in the 21st century, especially from 2015 to the present. The United States is a leader in many aspects of this research area, such as in the number of publications, the number of partners, the most productive institutions, and the authors working in this field. Harvard University is the institution with the highest number of publications, and Aguirre-Ghiso, Julio A. is the author with the highest number of publications and citations. The keywords that emerged after 2017 were "early dissemination", "inhibition", "mechanism", "bone metastasis", and "promotion". We believe that research on tumor dormancy mechanisms and therapy has been, and will continue to be, a major area of interest. The exploration of the tumor dormancy microenvironment and immunotherapeutic treatments for tumor dormancy is likely to represent the most popular future research topics.

Pan-cancer analysis of PSAP identifies its expression and clinical relevance in gastric cancer.

Prosaposin (PSAP) plays a critical role in sphingolipid and cancer metabolism. Reports have shown that PSAP was involved in proliferation, tumorigenesis, and metastasis. However, the expression pattern of PSAP and its prognostic roles in gastric cancer remain elusive. PSAP expression pattern and its prognostic roles in gastric cancer (GC) were explored using data from the TCGA and Kaplan-Meier Plotter. Immunohistochemical staining of GC tissues was performed to validate the prognostic role of PSAP. TISIDB was used to analyze its correlation with immunomodulators. PSAP-associated genes, PDCD1, TGFB1, and CSF1R were used to build a risk model to evaluate immunotherapy outcomes of patients with stomach adenocarcinoma (STAD). Results showed that PSAP was highly expressed in GC. High PSAP expression in GC patients also significantly indicated a poor prognosis. The results of immunohistochemical staining showed that PSAP was an independent prognostic factor in GC patients. Based on three PSAP-associated genes, a risk model that could predict the prognosis and immunotherapy outcome of STAD was bulit. PSAP was an independent prognostic factor in GC. Our results have identified three prognosis-related genes which were useful to evaluate immunotherapy outcomes of STAD patients.

Thermodynamic properties, decomposition kinetics of 2-(5-amino-2H-tetrazol-1-yl)-4-amine-3,5-dinitropyridine.

A novel energetic material 2-(5-amino-2H-tetrazol-1-yl)-4-amine-3,5-dinitropyridine (ATDP) was synthesized and characterized by 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis. The research by differential scanning calorimetry (DSC) shows that ATDP decomposed about 290 °C. The calculating results of kinetic parameters using Ozawa method, Kissinger method, and Starink method were quite consistent. Self-accelerated decomposition temperature (TSADT), thermal ignition temperature (TTIT), and critical temperature of thermal explosion (Tb) were 272.55 °C, 121.71 °C, and 137.67 °C, respectively. Geometric optimization, heat of formation, detonation velocity (D), detonation pressure (P), bond dissociation energy (BDE), and electrostatic potential (ESP) were explored using Gaussian 16. The results show that ATDP has a much larger ΔHf,gas value than HMX(272.6 kJ mol-1). The D and P are predicted with the value of 7.50 km s-1 and 24.47 GPa, respectively. The relatively high BDE value (270.77 kJ mol-1) indicates that ATDP has moderate thermal stability.

AIFM1, negatively regulated by miR-145-5p, aggravates hypoxia-induced cardiomyocyte injury.

BACKGROUND: Hypoxia-induced apoptosis is linked to the pathogenesis of myocardial infarction. The role of apoptosis-inducing factor mitochondria associated 1 (AIFM1) in cardiomyocyte injury remains unclear. This study was aimed at probing into the role and the underlying regulatory mechanism of AIFM1 in myocardial injury. METHODS: H9c2 cardiomyocytes and C57BL/6 mice were used for myocardial hypoxic/ischemic injury and myocardial infarction animal models. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the expression levels of AIFM1 mRNA and miR-145-5p. Western blot was used for examining the expression levels of AIFM1, caspase-3, cleaved caspase-3, p-53, and γ-H2AX. Cell viability was examined by cell counting kit-8 (CCK-8) assay and BrdU assay. Interaction between AIFM1 and miR-145-5p was determined by bioinformatics analysis, qRT-PCR, Western blot, and dual-luciferase reporter assay. RESULTS: AIFM1 expression was markedly highly elevated, while miR-145-5p expression was significantly down-regulated in the myocardial infarction animal model and H9c2 cells under hypoxia. Augmentation of AIFM1 led to a dramatic decrease of cell viability, accompanied by an increase of the secretion of the inflammatory cytokines IL-1ß, TNF-α, IL-6, and the expression of cleaved caspase-3. Furthermore, AIFM1 was identified as a target of miR-145-5p. In addition, miR-145-5p/AIFM1 axis regulated the expression of p53. CONCLUSION: AIFM1 may exacerbate myocardial ischemic injury by promoting inflammation and the injury of cardiomyocytes, and its up-regulation may be partly due to the down-regulation of miR-145-5p.

Identification of Novel Drug Candidate for Epithelial Ovarian Cancer via In Silico Investigation and In Vitro Validation.

Epithelial ovarian cancer (EOC) has a poor prognosis and high mortality rate; patients are easy to relapse with standard therapies. So, there is an urgent need to develop novel drugs. In this study, differentially expressed genes (DEGs) of EOC were identified in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Enrichment and protein-protein interaction (PPI) analyses were performed. The drug candidate which has the possibility to treat EOC was predicted by Connectivity Map (CMAP) databases. Moreover, molecular docking was selected to calculate the binding affinity between drug candidate and hub genes. The cytotoxicity of drug candidates was assessed by MTT and colony formation analysis, the proteins coded by hub genes were detected by Western blots, and apoptosis analysis was evaluated by flow cytometry. Finally, 296 overlapping DEGs (|log 2 fold change|>1; q-value <0.05), which were principally involved in the cell cycle (p < 0.05), and cyclin-dependent kinase 1 (CDK1) were screened as the significant hub gene from the PPI network. Furthermore, the 21 drugs were extracted from CMAPs; among them, piperlongumine (PL) showed a lower CMAP score (-0.80, -62.92) and was regarded as the drug candidate. Furthermore, molecular docking results between PL and CDK1 with a docking score of -8.121 kcal/mol were close to the known CDK1 inhibitor (-8.24 kcal/mol). Additionally, in vitro experiments showed that PL inhibited proliferation and induced apoptosis via targeting CDK1 in EOC SKOV3 cells. Our results reveal that PL may be a novel drug candidate for EOC by inhibiting cell cycle.

A randomised trial on the therapeutic effectiveness of bronchoalveolar lavage under fiberoptic bronchoscopy in patients with severe lung infection living in the Tibetan plateau area.

BACKGROUND: People living in plateau areas are prone to upper respiratory tract infections and secondary lung infections. The current study aimed to explore the effects of bronchoalveolar lavage under fiberoptic bronchoscope for the treatment of patients with severe pulmonary infection living in plateau areas. METHODS: 148 patients with severe lung infection admitted to the intensive care unit of Shigatse People's Hospital (Shigatse, Tibet Autonomous Region, China) between July 2019 and January 2021 were enrolled. Patients were randomly assigned to the observational group or the control group. For all patients, basic clinical data including sex, age, body mass index (BMI), blood pressure, diabetes history, stroke history, presence or absence of chronic obstructive pulmonary disease, lung infection (gram-positive bacterial infection, gram-negative bacterial infection, fungal infection, acute lung abscess), surgical history, and postoperative inhalation injury. were collected. The control group received conventional treatment, and the observational group received bronchoalveolar lavage under fiberoptic bronchoscopy. Pearson's correlation was used to analyze the correlations between bronchoalveolar lavage under fiberoptic bronchoscopy and inflammatory factors levels. Logistic regression was used to investigate the correlation between bronchoalveolar lavage under fiberoptic bronchoscopy and the effectiveness of the treatment. RESULTS: Before treatment, no significant difference existed in the basic data of the observational group and the control group. After treatment, the parameters of respiratory mechanics and inflammatory factors in the 2 groups were significantly improved compared with those before treatment (P<0.05). At the same time, in the observational group, the clinical parameters were significantly higher than those of the control group, and the levels of inflammatory factors were significantly lower than those of the control group (all P<0.05). After full adjustment for age, sex, BMI, gram-negative infection, diabetes, and acute lung abscess, compared with the control group, the therapeutic effectiveness in the observational group was increased by 23% (OR =1.23, 95% CI: 1.09-1.51, P=0.007). CONCLUSIONS: For patients with severe lung infection who are resident in high altitude areas, compared with conventional treatments, bronchoalveolar lavage under fiberoptic bronchoscopy can significantly improve chest, lung, and total dynamic compliance, as well as reduce the levels of the inflammatory factors procalcitonin (PCT) and transforming growth factor-ß, thus increasing the effectiveness of the treatment.

Theoretical Studies on the Performance of HMX with Different Energetic Groups.

Forty nitramines by incorporating -C=O, -NH2, -N3, -NF2, -NHNO2, -NHNH2, -NO2, -ONO2, -C(NO2)3, and -CH(NO2)2 groups based on a 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX) framework were designed. Their electronic structures, heats of formation (HOFs), detonation properties, thermal stabilities, electrostatic potential, and thermodynamic properties were systematically investigated by density functional theory. The comprehensive relationships between the structures and performance of different substituents were studied. Results indicate that -C(NO2)3 has the greatest effect on improvement of HOFs among the whole substituted groups. Thermodynamic parameters, such as standard molar heat capacity (C p,m θ), standard molar entropy (S m θ), and standard molar enthalpy (H m θ), of all designed compounds increase with the increasing number of energetic groups, and the volumes of energetic groups have a great influence on standard molar enthalpy. Except for -NH2(R1), -NHNH2(R5), and B3, all of the designed compounds have higher detonation velocities and pressures than HMX. Among them, E7 exhibits an extraordinarily high detonation performance (D = 10.89 km s-1, P = 57.3 GPa), E1 exhibits a relatively poor detonation performance (D = 8.93 km s-1, P = 35.5 GPa), and -NF2 and -C(NO2)3 are the best ones in increasing the density by more or less 12%.

Pressure induced structural behavior of energetic cocrystal TNT/TNB: a density functional theory study.

In order to find out the relationship between external pressures and properties of energetic materials, we used the density functional theory (DFT) method to investigate the structural, electronic, and absorption properties of crystalline 2,4,6-trinitrotoluene (TNT)/2,4,6-trinitrotoluene (TNB) under hydrostatic compression of 0-100 GPa. By analyzing the change of lattice constants (a, b, and c) of TNT/TNB under compression conditions, we found that variation tendency of the lattice constants was anisotropic. The b-axis is much stiffer than that along the a- and c-axes, which indicates that the TNT/TNB crystal is anisotropic within a certain pressure region. The pressure-induced structure transformation results in the new covalent bonds O11-C13, O12-C11, O8-C4, and O1-C12 at 60 GPa, and O4-C5 at 80 GPa, respectively. By analyzing the band structure and density of states of TNT/TNB in the pressure range over 40 GPa, the electronic structure of TNT/TNB changed to metallic system, which indicated it becomes more sensitivity under high pressures. The pressure-induced structure transformation of TNT/TNB also contributed to the relatively high optical activity of TNT/TNB at 70 GPa.