IKKα inactivation promotes Kras-initiated lung adenocarcinoma development through disrupting major redox regulatory pathways.

Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct and predominant types of human lung cancer. IκB kinase α (IKKα) has been shown to suppress lung SCC development, but its role in ADC is unknown. We found inactivating mutations and homologous or hemizygous deletions in the CHUK locus, which encodes IKKα, in human lung ADCs. The CHUK deletions significantly reduced the survival time of patients with lung ADCs harboring KRAS mutations. In mice, lung-specific Ikkα ablation (IkkαΔLu ) induces spontaneous ADCs and promotes KrasG12D-initiated ADC development, accompanied by increased cell proliferation, decreased cell senescence, and reactive oxygen species (ROS) accumulation. IKKα deletion up-regulates NOX2 and down-regulates NRF2, leading to ROS accumulation and blockade of cell senescence induction, which together accelerate ADC development. Pharmacologic inhibition of NADPH oxidase or ROS impairs KrasG12D-mediated ADC development in IkkαΔLu mice. Therefore, IKKα modulates lung ADC development by controlling redox regulatory pathways. This study demonstrates that IKKα functions as a suppressor of lung ADC in human and mice through a unique mechanism that regulates tumor cell-associated ROS metabolism

Perceived Value of Electronic Medical Records in Community Health Services: A National Cross-Sectional Survey of Primary Care Workers in Mainland China

Objective: To evaluate the degree to which electronic medical records (EMRs) were used in primary care and the value of EMRs as perceived by primary care workers in China. Methods: A cross-sectional survey was conducted on 2719 physicians (n = 2213) and nurses (n = 506) selected from 462 community health centres across all regions of mainland China except for Tibet. Regional differences in the responses regarding the functionality of existing EMR systems and the perceived value of EMRs were examined using Chi-square tests and ordinal regression analyses. Results: Less than 59% of the community health centres had adopted EMRs. More than 89% of the respondents believed that it was necessary to adopt EMRs in primary care. Of the existing EMR systems, 50% had access to telehealth support for laboratory, imaging or patient consultation services. Only 38.4% captured data that met all task needs and 35.4% supported referral arrangements. “Management of chronic conditions” was voted (66%) as the top preferred feature of EMRs. Higher levels of recognition of the value of EMRs were found in the relatively more developed eastern region compared with their counterparts in other regions. Conclusions: Rapid EMR adoption in primary care is evident in mainland China. The low level of functionality in data acquisition and referral arrangements runs counter to the requirements for “management of chronic conditions”, the most preferred feature of EMRs in primary care. Regional disparities in the realised value of EMRs in primary care deserve policy attention

GHRH, PRP-PACAP and GHRHR Target Sequencing via an Ion Torrent Personal Genome Machine Reveals an Association with Growth in Orange-Spotted Grouper (Epinephelus coioides)

Growth hormone-releasing hormone (GHRH) and the receptor, GHRHR, constitute important components of the hypothalamus-pituitary growth axis and act on the downstream growth hormone (GH). PACAP-related peptide/pituitary adenylate cyclase activating polypeptide (PRP-PACAP) is a paralog of GHRH. These genes all play key roles in development and growth patterns. To improve the quality of cultured fish strains, natural genetic variation must be examined and understood. A mixed linear model has been widely used in association mapping, taking the population structures and pairwise kinship patterns into consideration. In this study, a mass cross population of orange-spotted grouper (Epinephelus coioides) was examined. These candidate genes were found to harbor low nucleotide diversity (θw from 0.00154 to 0.00388) and linkage disequilibrium levels (delay of 50% within 2 kbp). Association mapping was employed, and two single-nucleotide polymorphisms (KR269823.1:g.475A>C and KR269823.1:g.2143T>C) were found to be associated with growth (false discovery rate Q < 0.05), explaining 9.0%–17.0% of the phenotypic variance. The association of KR269823.1:g.2143T>C was also found via haplotype-based association (p < 0.05). The identified associations offer new insights into gene functions, and the associated single-nucleotide polymorphisms (SNPs) may be used for breeding purposes

Reduce operational costs of thermal power units in power systems using the flexibility of district cooling systems

The high volatility of wind generation causes the thermal power units to start up and shut down frequently because there is a lack of flexibility in the power systems, which poses a challenge to economic operation. With the increase in cooling demand, district cooling systems (DCSs) have received attention in recent years and have been built in many regions, which offer a novel option to alleviate the above problems by utilizing the complementarity between power and cooling systems. In a typical DCS, the cooling source is a key component that generates cooling energy for the entire cooling system. Utilization of the cooling storage capacity of cooling sources in DCSs is an economical and efficient measure for more operational flexibility of power systems. Therefore, this paper proposes a unit commitment model with combined power systems and DCSs to reduce the operational costs of thermal power units and wind curtailment. In this model, an accurate model of a cooling source with an ice storage tank, where the cooling characteristics and energy transmission process are reflected, is built to fully excavate the flexibility potential of DCSs. Finally, numerical simulations are performed to show that the proposed method reduces the operational costs by 15.78% within a scheduling day and makes the wind curtailment close to zero. The results of the above comparison demonstrate that the method can improve the operational economy and encourage wind power integration while assuring an adequate supply of electricity and cooling

The above literatures all proved that the trace elements in the lipid soluble extracts of ants also played a role in the anti-cadmium poisoning

In order to study the quasi black prickly ant extracts antioxidant mechanism, test the completely random method is adopted to 160 rats, and randomly divided into 8 groups, divided into control group, cadmium poisoning group, cadmium and extracts from petroleum ether to black prickly ant group (divided into high, medium and low dose group), cadmium to higher doses of anhydrous ethanol extracts from black prickly ant group, higher dose of petroleum ether to black prickly ant extract group, only higher doses of anhydrous ethanol extracts from black prickly ant group. The mice were fed for 21 days, and the clinical symptoms of the mice were observed every day. On the 22nd day, the liver, spleen, kidney and sexual organs of the mice were dissected and separated, and the organ coefficients of the mice were calculated. After grinding treatment, the contents of MDA, SOD, CAT and T-AOC in kidney and spleen of mice were determined according to the instructions of the kit. Results showed that the mice of the sex organs of liver, spleen, kidney, organ coefficient were elevated compared with control group (P<0.05), cadmium poisoning group mice kidney, spleen MDA levels were elevated compared with control group (P<0.05), cadmium poisoning group mice kidney, spleen SOD, T–AOC,CAT content decreased (P<0.05), The results indicated that the lipid soluble extract of C. nigra had antioxidant ability, and the low and medium dose of lipid soluble extract of C. nigra had less cadmium toxicity than the high doseThe curative effect in mice was remarkable and the anti-inflammatory function was achieved

Chromosome Genome Assembly of Cromileptes altivelis Reveals Loss of Genome Fragment in Cromileptes Compared with Epinephelus Species

The humpback grouper (Cromileptes altivelis), an Epinephelidae species, is patchily distributed in the reef habitats of Western Pacific water. This grouper possesses a remarkably different body shape and notably low growth rate compared with closely related grouper species. For promoting further research of the grouper, in the present study, a high-quality chromosome-level genome of humpback grouper was assembled using PacBio sequencing and high-throughput chromatin conformation capture (Hi-C) technology. The assembled genome was 1.013 Gb in size with 283 contigs, of which, a total of 143 contigs with 1.011 Gb in size were correctly anchored into 24 chromosomes. Moreover, a total of 26,037 protein-coding genes were predicted, of them, 25,243 (96.95%) genes could be functionally annotated. The high-quality chromosome-level genome assembly will provide pivotal genomic information for future research of the speciation, evolution and molecular-assisted breeding in humpback groupers. In addition, phylogenetic analysis based on shared single-copy orthologues of the grouper species showed that the humpback grouper is included in the Epinephelus genus and clustered with the giant grouper in one clade with a divergence time of 9.86 Myr. In addition, based on the results of collinearity analysis, a gap in chromosome 6 of the humpback grouper was detected; the missed genes were mainly associated with immunity, substance metabolism and the MAPK signal pathway. The loss of the parts of genes involved in these biological processes might affect the disease resistance, stress tolerance and growth traits in humpback groupers. The present research will provide new insight into the evolution and origin of the humpback grouper

Stearoyl-CoA Desaturase 1 Potentiates Hypoxic plus Nutrient-Deprived Pancreatic Cancer Cell Ferroptosis Resistance

Hypoxia and nutrient starvation (H/NS) microenvironment, a notable characteristic of pancreatic carcinoma, plays a critical role in cell death resistance and tumor recurrence. However, its role in ferroptosis remains to be classified. Here, we found that H/NS contributed to the pancreatic cancer cell ferroptosis resistance depending on the altered intracellular lipid compositions. Mechanistically, H/NS induced the upregulation of stearoyl-CoA desaturase 1 (SCD1), which promoted monounsaturated fatty acids (MUFAs) synthesis and protected against lipid peroxidation. Surprisingly, SCD1 showed a strong correlation with antiferroptosis gene expression. Moreover, short-hairpin RNA-based knockdown of SCD1 enhanced erastin-induced ferroptosis in vitro under H/NS. Finally, our results demonstrate the synergistic effect of erastin and A939572, a special SCD1 inhibitor, in dictating pancreatic carcinoma subcutaneous ferroptotic death. Taken together, our findings reveal a new role of the H/NS microenvironment against ferroptosis and suggest a potential therapeutic strategy for overcoming ferroptosis resistance in pancreatic cancer cells

Signatures of selection in tilapia revealed by whole genome resequencing

Natural selection and selective breeding for genetic improvement have left detectable signatures within the genome of a species. Identification of selection signatures is important in evolutionary biology and for detecting genes that facilitate to accelerate genetic improvement. However, selection signatures, including artificial selection and natural selection, have only been identified at the whole genome level in several genetically improved fish species. Tilapia is one of the most important genetically improved fish species in the world. Using next-generation sequencing, we sequenced the genomes of 47 tilapia individuals. We identified a total of 1.43 million high-quality SNPs and found that the LD block sizes ranged from 10–100 kb in tilapia. We detected over a hundred putative selective sweep regions in each line of tilapia. Most selection signatures were located in non-coding regions of the tilapia genome. The Wnt signaling, gonadotropin-releasing hormone receptor and integrin signaling pathways were under positive selection in all improved tilapia lines. Our study provides a genome-wide map of genetic variation and selection footprints in tilapia, which could be important for genetic studies and accelerating genetic improvement of tilapia.Published versio

Genetic Polymorphisms Associated with Prothrombin Time and Activated Partial Thromboplastin Time in Chinese Healthy Population

(1) Background: The purpose of this study was to evaluate the effect of gene polymorphisms on prothrombin time (PT) and activated partial thromboplastin time (APTT) in a healthy Chinese population. (2) Methods: A total of 403 healthy volunteers from a series of novel oral anticoagulants (NOACs) bioequivalence trials in China were included. Coagulation tests for PT and APTT were performed in the central lab at Peking University First Hospital. Whole-exome sequencing (WES) and genome-wide association analysis were performed. (3) Results: In the correlation analysis of PT, 105 SNPs from 84 genes reached the genome-wide significance threshold (p &lt; 1 &times; 10&minus;5). Zinc Finger Protein 594 (ZNF594) rs184838268 (p = 4.50 &times; 10&minus;19) was most significantly related to PT, and Actinin Alpha 1 (ACTN1) was found to interact most with other candidate genes. Significant associations with previously reported candidate genes Aurora Kinase B (AURKB), Complement C5(C5), Clock Circadian Regulator (CLOCK), and Histone Deacetylase 9(HDAC9) were detected in our dataset (p &lt; 1 &times; 10&minus;5). PiggyBac Transposable Element Derived 2(PGBD2) rs75935520 (p = 4.49 &times; 10&minus;6), Bromodomain Adjacent To Zinc Finger Domain 2A(BAZ2A) rs199970765 (p = 5.69 &times; 10&minus;6) and Protogenin (PRTG) rs80064850 (p = 8.69 &times; 10&minus;6) were significantly correlated with APTT (p &lt; 1 &times; 10&minus;5). The heritability values of PT and APTT were 0.83 and 0.64, respectively; (4) Conclusion: The PT and APTT of healthy populations are affected by genetic polymorphisms. ZNF594 and ACTN1 variants could be novel genetic markers of PT, while PRTG polymorphisms might be associated with APTT levels. The findings could be attributed to ethnic differences, and need further investigation