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Cadherin 2 (CDH2, N-cadherin) and cadherin 13 (CDH13, T-cadherin, H-cadherin) affect the progress and prognoses of many cancers. However, their roles in adrenocortical carcinoma (ACC), a rare endocrine cancer, remain unclear. To decipher the roles of these proteins in ACC and to identify their regulatory targets, we analyzed their expression levels, gene regulatory networks, prognostic value, and targets in ACC, using various bioinformatic analyses. CDH2 was strongly downregulated and CDH13 was strongly upregulated in patients with ACC; the expression levels of these genes affected the prognosis. In 75 patients, the expression of CDH2 and CDH13 was altered by 8% and 5%, respectively. CDH2 and CDH13, as well as their neighboring genes, were predicted to form a complex network of interactions, mainly through coexpression and physical and genetic interactions. CDH2 and its altered neighboring genes (ANGs) mainly affect tumor-related gene expression, cell cycle, and energy metabolism. The regulation of tumor-related integrin function, gene transcription, metabolism, and amide and phospholipid metabolism are the main functions of CDH13 and its ANGs. MiRNA and kinase targets of CDH2 and CDH13 in ACC were identified. CDH13 expression in patients with ACC was positively associated with immune cell infiltration. Anti-PD1/CTLA-4/PD-L1 immunotherapy significantly downregulated the expression of CDH13 in patients with ACC. Foretinib and elesclomol were predicted to exert strong inhibitory effects on SW13 cells by inhibiting the expression of CDH2 and CDH13. These data indicate that CDH2 and CDH13 are promising targets for precise treatment of ACC and may serve as new biomarkers for ACC prognosis.

BackgroundCombining genetic risk factors and plasma fatty acids (FAs) can be used as an effective method of precision medicine to prevent hypertension risk.MethodsA total of 195,250 participants in the UK Biobank cohort were included in this study from 2006–2010. Polygenic risk scores (PRSs) were calculated for hypertension using single-nucleotide polymorphisms (SNPs). Concentrations of plasma FAs, including polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs), were tested by nuclear magnetic resonance. The Cox model was used to test for the main effects of PRS, different plasma FAs and their joint effects on hypertension. Relative excess risk due to interaction (RERI) and the attributable proportion due to interaction (AP) were used to test the additive interaction.ResultsPlasma PUFAs, n-3 PUFAs, MUFAs and SFAs were related to the risk of hypertension (PUFAs: HR, 0.878; 95% CI, 0.868–0.888; MUFAs: HR, 1.13; 95% CI, 1.123–1.150; SFAs: HR, 1.086; 95% CI, 1.074–1.098; n-3 PUFAs: HR, 0.984; 95% CI, 0.973–0.995). Moreover, an additive interaction was found between PRS and plasma FAs, which could contribute to an approximately 10–18% risk of hypertension, and the associations between high plasma MUFAs and a high PRS of hypertension were the strongest positive [RERI: 0.178 (95% CI: 0.062, 0.294), AP: 0.079 (95% CI: 0.027, 0.130)].ConclusionIncreased plasma MUFAs or SFAs and decreased plasma PUFAs or n-3 PUFAs were associated with hypertension risk, especially among people at high genetic risk.

BackgroundAlthough the emerging NGS-based assays, metagenomic next-generation sequencing (mNGS) and targeted next-generation sequencing (tNGS), have been extensively utilized for the identification of pathogens in pulmonary infections, there have been limited studies systematically evaluating differences in the efficacy of mNGS and multiplex PCR-based tNGS in bronchoalveolar lavage fluid (BALF) specimens.MethodsIn this study, 85 suspected infectious BALF specimens were collected. Parallel mNGS and tNGS workflows to each sample were performed; then, we comparatively compared their consistency in detecting pathogens. The differential results for clinically key pathogens were confirmed using PCR.ResultsThe microbial detection rates of BALF specimens by the mNGS and tNGS workflows were 95.18% (79/83) and 92.77% (77/83), respectively, with no significant difference. mNGS identified 55 different microorganisms, whereas tNGS detected 49 pathogens. The comparative analysis of mNGS and tNGS revealed that 86.75% (72/83) of the specimens were complete or partial concordance. Particularly, mNGS and tNGS differed significantly in detection rates for some of the human herpesviruses only, including Human gammaherpesvirus 4 (P

Abstract Objective This study aimed to investigate the role of cholesterol metabolism-related genes in nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) invading the cavernous sinus and analyze the differences in immune cell infiltration between invasive and noninvasive NF-PitNETs. Methods First, a retrospective analysis of single-center clinical data was performed. Second, the immune cell infiltration between invasive and noninvasive NF-PitNETs in the GSE169498 dataset was further analyzed, and statistically different cholesterol metabolism-related gene expression matrices were obtained from the dataset. The hub cholesterol metabolism-related genes in NF-PitNETs were screened by constructing machine learning models. In accordance with the hub gene, 73 cases of NF-PitNETs were clustered into two subtypes, and the functional differences and immune cell infiltration between the two subtypes were further analyzed. Results The clinical data of 146 NF-PitNETs were evaluated, and the results showed that the cholesterol (P = 0.034) between invasive and noninvasive NF-PitNETs significantly differed. After binary logistic analysis, cholesterol was found to be an independent risk factor for cavernous sinus invasion (CSI) in NF-PitNETs. Bioinformatics analysis found three immune cells between invasive and noninvasive NF-PitNETs were statistically significant in the GSE169498 dataset, and 34 cholesterol metabolism-related genes with differences between the two groups were obtained 12 hub genes were selected by crossing the two machine learning algorithm results. Subsequently, cholesterol metabolism-related subgroups, A and B, were obtained by unsupervised hierarchical clustering analysis. The results showed that 12 immune cells infiltrated differentially between the two subgroups. The chi-square test revealed that the two subgroups had statistically significance in the invasive and noninvasive samples (P = 0.001). KEGG enrichment analysis showed that the differentially expressed genes were mainly enriched in the neural ligand–receptor pathway. GSVA analysis showed that the mTORC signaling pathway was upregulated and played an important role in the two-cluster comparison. Conclusion By clinical data and bioinformatics analysis, cholesterol metabolism-related genes may promote the infiltration abundance of immune cells in NF-PitNETs and the invasion of cavernous sinuses by NF-PitNETs through the mTOR signaling pathway. This study provides a new perspective to explore the pathogenesis of cavernous sinus invasion by NF-PitNETs and determine potential therapeutic targets for this disease.

Background & Aims: Aflatoxin exposure increases the risk for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected individuals, particularly males. We investigated sex-based differences in the HCC genome and antitumor immunity. Methods: Whole-genome, whole-exome, and RNA sequencing were performed on 101 HCC patient samples (47 males, 54 females) that resulted from HBV infection and aflatoxin exposure from Qidong. Androgen on the expression of aflatoxin metabolism-related genes and nonhomologous DNA end joining (NHEJ) factors were examined in HBV-positive HCC cell lines, and further tested in tumor-bearing syngeneic mice. Results: Qidong HCC differed between males and females in genomic landscape and transcriptional dysfunction pathways. Compared with females, males expressed higher levels of aflatoxin metabolism-related genes, such as AHR and CYP1A1, and lower levels of NHEJ factors, such as XRCC4, LIG4, and MRE11, showed a signature of up-regulated type I interferon signaling/response and repressed antitumor immunity. Treatment with AFB1 in HBV-positive cells, the addition of 2 nmol/L testosterone to cultures significantly increased the expression of aflatoxin metabolism-related genes, but reduced NHEJ factors, resulting in more nuclear DNA leakage into cytosol to activate cGAS-STING. In syngeneic tumor-bearing mice that were administrated tamoxifen daily via oral gavage, favorable androgen signaling repressed NHEJ factor expression and activated cGAS-STING in tumors, increasing T-cell infiltration and improving anti–programmed cell death protein 1 treatment effect. Conclusions: Androgen signaling in the context of genotoxic stress repressed DNA damage repair. The alteration caused more nuclear DNA leakage into cytosol to activate the cGAS-STING pathway, which increased T-cell infiltration into tumor mass and improved anti–programmed cell death protein 1 immunotherapy in HCCs.

In order to further grasp the contamination level of Alternaria toxins in red date, this study took commercially available red date and its products as the research objects, explored the extraction method of mycotoxins with QuChERS as the core and established ultra-high performance liquid chromatography-tandem mass spectrometry analysis technology for five kinds of Alternaria toxins in red dates, and analyzed the pollution level of Alternaria toxin in red jujube and its products. Results showed that the recovery of Alternaria toxins in solid samples by QuChERS method ranged from 74.89% to 98.04%, and in liquid samples by solid-phase extraction method ranged from 68.35% to 99.63% with the relative standard deviations less than 10%. After the determination of five Alternaria toxins in Jun-date from Aksu, Kashi and Hotan regions, two toxins, TeA and AOH, were detected. Among them, the TeA in Jun-date in Kashgar was the highest, reaching 5.12~10.76 μg/kg. Three Alternaria toxins, TeA, AOH and ALT, were detected in 11 kinds of products of red date, among which TeA in red date wine reached 127.08 μg/kg and AOH was detected only in amethyst date, with content ranging from 34.76 to 98.61 μg/kg. ALT was detected in freeze-dried red dates slices, fried red dates and amethyst date, with content ranging from 2.04 to 399.64 μg/kg. In this paper, a UPLC-MS/MS method was developed to meet the requirements for the determination of Alternaria toxins in date samples with different forms, it would provide a theoretical basis for the edible safety of red dates.

Abstract Background Toxoplasma gondii has been reported to be associated with higher mortality in patients with schizophrenia. This study aimed to explore the relationship between T. gondii infection and 25-year mortality based on data from the Third National Health and Nutrition Examination Survey (NHANES III) database. Methods Cases with serum T. gondii antibody test results were included in this study and the corresponding mortality dataset was obtained from the US National Center for Health Statistics (NCHS). Propensity score matching (PSM) was used to match age and sex between groups. The Cox proportional hazards model was used to evaluate the effect of T. gondii infection on mortality. Results A total of 14,181 cases were included in the analysis, of which 3831 (27.0%) were seropositive for T. gondii antibody. The median follow-up time of the whole cohort was 22.5 (interquartile range 16.3, 24.5) years. A total of 5082 deaths were observed in this cohort, a mortality rate of 35.8%. All-cause mortality was significantly higher in the seropositive group than in the seronegative group (50.0% vs 30.6%, P

Objective: The aim of this study was to evaluate the incidence and duratio n of delayed hyponatremia and to assess the factors influencing the developme nt of delayed hyponatremia after transsphenoidal surgery (TSS) in pituitary a denomas. Methods: We retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. Univariable and multivariable statistics wer e carried out to identify factors independently associated with the occurrence of delayed hyponatremia. Results: Of the 285 patients with pituitary adenoma who underwent micro scopic TSS, 44 (15.4%) developed postoperative-delayed hyponatremia and 241 (84.6%) did not. The onset of delayed hyponatremia occurred an average of 5.84 d ays post-surgery and persisted for an average of 5.36 days. Logistic regression anal ysis showed the highest risk of delayed hyponatremia in patients with significant change in tumor cavity height (odds ratio (OR), 1.158; 95% CI, 1.062, 1.262; P = 0.001), preoperative hypothalamus– pituitary–thyroid axis hypofunction (OR, 3.112; 95% CI, 1.481, 6.539; P = 0.003), and significant difference in blood sodium levels before and 2 days a fter TSS (OR, 1.101; 95% CI, 1.005, 1.206; P = 0.039). Conclusions: Preoperative hypothyroidism, difference in blood sodium levels before and 2 days after TSS, and the change in tumor cavity height after T SS played important roles in predicting postoperative-delayed hyponatremia onset in patients with pituitary adenomas.

BackgroundBromodomain and extracellular terminal (BET) family (including BRD2, BRD3, and BRD4) is considered to be a major driver of cancer cell growth and a new target for cancer therapy. Currently, more than 30 targeted inhibitors have shown significant inhibitory effects against various tumors in preclinical and clinical trials. However, the expression levels, gene regulatory networks, prognostic value, and target prediction of BRD2, BRD3, and BRD4 in adrenocortical carcinoma (ACC) have not been fully elucidated. Therefore, this study aimed to systematically analyze the expression, gene regulatory network, prognostic value, and target prediction of BRD2, BRD3, and BRD4 in patients with ACC, and elucidated the association between BET family expression and ACC. We also provided useful information on BRD2, BRD3, and BRD4 and potential new targets for the clinical treatment of ACC.MethodsWe systematically analyzed the expression, prognosis, gene regulatory network, and regulatory targets of BRD2, BRD3, and BRD4 in ACC using multiple online databases, including cBioPortal, TRRUST, GeneMANIA, GEPIA, Metascape, UALCAN, LinkedOmics, and TIMER.ResultsThe expression levels of BRD3 and BRD4 were significantly upregulated in ACC patients at different cancer stages. Moreover, the expression of BRD4 was significantly correlated with the pathological stage of ACC. ACC patients with low BRD2, BRD3, and BRD4 expressions had longer survival than patients with high BRD2, BRD3, and BRD4 expressions. The expression of BRD2, BRD3, and BRD4 was altered by 5%, 5%, and 12% in 75 ACC patients, respectively. The frequency of gene alterations in the 50 most frequently altered BRD2, BRD3, and BRD4 neighboring genes in these ACC patients were ≥25.00%, ≥25.00%, and ≥44.44%, respectively. BRD2, BRD3, and BRD4 and their neighboring genes form a complex network of interactions mainly through co-expression, physical interactions, and shared protein domains. Molecular functions related to BRD2, BRD3, and BRD4 and their neighboring genes mainly include protein-macromolecule adaptor activity, cell adhesion molecule binding, and aromatase activity. Chemokine signaling pathway, thiamine metabolism, and olfactory transduction were found to be enriched as per the KEGG pathway analysis. SP1, NPM1, STAT3, and TP53 are key transcription factors for BRD2, BRD4, and their neighboring genes. MiR-142-3P, miR-484, and miR-519C were the main miRNA targets of BRD2, BRD3, BRD4, and their neighboring genes. We analyzed the mRNA sequencing data from 79 patients with ACC and found that ZSCAN12, DHX16, PRPF4B, EHMT1, CDK5RAP2, POMT1, WIZ, ZNF543, and AKAP8 were the top nine genes whose expression were positively associated with BRD2, BRD3, and BRD4 expression. The expression level of BRD2, BRD3, and BRD4 positively correlated with B cell and dendritic cell infiltration levels. BRD4-targeted drug PFI-1 and (BRD2, BRD3, and BRD4)-targeted drug I-BET-151 may have good inhibitory effects on the SW13 cell line.ConclusionsThe findings of this study provide a partial basis for the role of BRD2, BRD3, and BRD4 in the occurrence and development of ACC. In addition, this study also provides new potential therapeutic targets for ACC, which can serve as a reference for future basic and clinical research.

Background: Serine hydroxymethyltransferase (SHMT) is a serine-glycine-one-carbon metabolic enzyme in which SHMT1 and SHMT2 encode the cytoplasmic and mitochondrial isoenzymes, respectively. SHMT1 and SHMT2 are key players in cancer metabolic reprogramming, and thus are attractive targets for cancer therapy. However, the role of SHMT in patients with renal cell carcinoma (RCC) has not been fully elucidated. We aimed to systematically analyze the expression, gene regulatory network, prognostic value, and target prediction of SHMT1 and SHMT2 in patients with kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), and kidney renal papillary cell carcinoma (KIRP); elucidate the association between SHMT expression and RCC; and identify potential new targets for clinical RCC treatment. Methods: Several online databases were used for the analysis, including cBioPortal, TRRUST, GeneMANIA, GEPIA, Metascape, UALCAN, LinkedOmics, and TIMER. Results: SHMT1 and SHMT2 transcript levels were significantly down- and upregulated, respectively, in patients with KICH, KIRC, and KIRP, based on sample type, individual cancer stage, sex, and patient age. Compared to men, women with KIRC and KIRP showed significantly up- and downregulated SHMT1 transcript levels, respectively. However, SHMT2 transcript levels were significantly upregulated in the patients mentioned above. KIRC and KIRP patients with high SHMT1 expression had longer survival periods than those with low SHMT1 expression. In patients with KIRC, the findings were similar to those mentioned above. However, in KICH patients, the findings were the opposite regarding SHMT2 expression. SHMT1 versus SHMT2 were altered by 9% versus 3% (n = 66 KICH patients), 4% versus 4% (n = 446 KIRC patients), and 6% versus 7% (n = 280 KIRP patients). SHMT1 versus SHMT2 promoter methylation levels were significantly up- and downregulated in patients with KIRP versus KIRC and KIRP, respectively. SHMT1, SHMT2, and their neighboring genes (NG) formed a complex network of interactions. The molecular functions of SHMT1 and its NG in patients with KICH, KIRC, and KIRP, included clathrin adaptor, metalloendopeptidase, and GTPase regulator activities; lipid binding, active transmembrane transporter activity, and lipid transporter activity; and type I interferon receptor binding, integrin binding, and protein heterodimerization, respectively. Their respective Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were involved in lysosome activity, human immunodeficiency virus 1 infection, and endocytosis; coronavirus disease 2019 and neurodegeneration pathways (multiple diseases); and RIG-I-like receptor signaling pathway, cell cycle, and actin cytoskeleton regulation. The molecular functions of SHMT2 and its NG in patients with KICH, KIRC, and KIRP included cell adhesion molecule binding and phospholipid binding; protein domain-specific binding, enzyme inhibitor activity, and endopeptidase activity; and hormone activity, integrin binding, and protein kinase regulator activity, respectively. For patients with KIRC versus KIRP, the KEGG pathways were involved in cAMP and calcium signaling pathways versus microRNAs (MiRNAs) in cancer cells and neuroactive ligand-receptor interactions, respectively. We identified the key transcription factors of SHMT1 and its NG. Conclusions: SHMT1 and SHMT2 expression levels were different in patients with RCC. SHMT1 and SHMT2 may be potential therapeutic and prognostic biomarkers in these patients. Transcription factor (MYC, STAT1, PPARG, AR, SREBF2, and SP3) and miRNA (miR-17-5P, miR-422, miR-492, miR-137, miR-30A-3P, and miR-493) regulations may be important strategies for RCC treatment.

Ablation behaviors of laminated carbon fiber reinforced plastics (CFRP) subjected to intense continuous wave laser in the supersonic wind tunnel are investigated experimentally. Comparable laser ablation tests in other environments, i.e., static air, static nitrogen and open airflow, are also carried out. Laser ablation rate in the supersonic wind tunnel is significantly larger than those of the other environments, in particular, at least twice of that in an open tangential airflow condition. The ablation morphology can be classified into two regions, coupled ablation zone (CAZ) and downstream affected zone (DAZ). Coupled thermal-fluid-solid analysis including thermochemical ablation and thermomechanical erosion models reveals that the contribution of each laser mechanisms is distinctive at the different positions of the laser ablation pit.

CRF07_BC is one of the most prevalent HIV-1 strains in China, which contributes over one-third of the virus transmissions in the country. In general, CRF07_BC is associated with slower disease progression, while the underlying mechanisms remain unclear. Our study focused on envelope proteins (Env) and its V3 loop which determine viral binding to co-receptors during infection of cells. We studied a large dataset of 3,937 env sequences in China and found that CRF07_BC had a unique profile of predominantly single CCR5 tropism compared with CCR5 and CXCR4 dual tropisms in other HIV-1 subtypes. The percentages of the CXCR4-tropic virus in B (3.7%) and CRF01_AE (10.4%) infection are much higher than that of CRF07_BC (0.1%), which is supported by median false-positive rates (FPRs) of 69.8%, 25.5%, and 13.4% for CRF07_BC, B, and CRF01_AE respectively, with a cutoff FPR for CXCR4-tropic at 2%. In this study, we identified the first pure CXCR4-tropic virus from one CRF07_BC-infected patient with an extremely low CD4+T cell count (7 cells/mm3). Structural analysis found that the V3 region of this virus has the characteristic 7T and 25R and a substitution of conserved “GPGQ” crown motif for “GPGH”. This study provided compelling evidence that CRF07_BC has the ability to evolve into CXCR4 strains. Our study also lay down the groundwork for studies on tropism switch, which were commonly done for other HIV-1 subtypes, for the long-delayed CRF07_BC.

BackgroundOAS1 expression in pancreatic cancer has been confirmed by many studies. However, the prognostic value and mechanism of OAS1 in pancreatic cancer have not been analyzed.MethodsThe RNA-seq in pancreatic cancer were obtained by UCSC XENA and GEO database. In addition, immunohistochemical validation and analysis were performed using samples from the 900th hospital. The prognosis of OAS1 was evaluated by timeROC package, Cox regression analysis, and Kaplan-Meier survival curves. Then, the main functional and biological signaling pathways enrichment and its relationship with the abundance of immune cells were analyzed by bioinformatics.ResultsOAS1 was highly expressed in pancreatic cancer compared with normal pancreatic tissue. High OAS1 expression was associated with poor overall survival (p

The geothermal fields of coal-bearing strata have become a key topic in geological research into coal and coal bed methane (CBM). Based on temperature data from 135 boreholes that penetrate the Upper Permian coal-bearing strata in the Bide-Santang basin, western Guizhou, the precisions of geothermal predictions made using a geothermal gradient model and a gray sequence GM(1,1) model are analyzed and compared. The results indicate that the gray sequence GM(1,1) model is more appropriate for the prediction of geothermal fields. The GM(1,1) model is used to predict the geothermal field at three levels with depths of 500, 1000, and 1500 m, as well as within the No. 6, No. 16, and No. 27 coal seams. The results indicate that the geotemperatures of the 500 m depth level are between 21.0 and 30.0 °C, indicating no heat damage; the geotemperatures of the 1000 m depth level are between 29.4 and 44.7 °C, indicating the first level of heat damage; and the geotemperatures of the 1500 m depth level are between 35.6 and 63.4 °C, indicating the second level of heat damage. The CBM contents are positively correlated with the geotemperatures of the coal seams. The target area for CBM development is identified. Keywords: Geotemperature, Gray sequence, Geothermal gradient, Heat damage, Coal, Coal bed methane

Over the last two decades, Salmonella1, 4, [5], 12:i:-has been frequently detected in many countries or regions around the world, and nowadays it has become one of the major serotypes responsible for human infectious diarrhea. The etiology and genetic features of Salmonella1, 4, [5], 12:i:-is quite similar with Salmonella Typhimurium (1, 4, [5], 12:i:1, 2) but lacking the second phase flagellar antigen. It has evolved from Salmonella Typhimurium through multiple independent events involving different clonal groups or multiple clones. In this study, we reviews the epidemic characteristics including human infections, animal and animal-derived foods of Salmonella1, 4, [5], 12:i:-, providing support for the prevention and control of infection and scientific researches.

Objective To evaluate the association between inflammation-related markers, modified Glasgow Prognostic Score (mGPS) and Glasgow Prognostic Score (GPS), and survival outcome and recurrence risk in patients with hepatocellular carcinoma (HCC) after treatment.Design Systematic reviews and meta-analysis of cohort studies.Date sources Embase, Scopus, Web of Science and PubMed were searched through 10 March 2021.Eligibility criteria We included cohort studies that assessed the effect of pretreatment mGPS/GPS levels on survival outcomes in patients with HCC.Data extraction and synthesis Two researchers independently selected the data and reached a consensus. In case of disagreement, a third researcher was required to assist. The HRs and 95% CIs were used as the effect size indexes. Newcastle-Ottawa Scale was used to assess risk of bias and quality assessment of the included studies.Results The meta-analysis included 23 studies, most of which were retrospective. Participants were grouped according to the score of mGPS/GPS. When analysed into two groups (1/2 vs 0), the results showed that patients with a mGPS/GPS of 1 or 2 had poorer overall survival (OS) than those with a score of 0 (both p

Background: Information on the intention of parents of children with special diseases to vaccinate their children against coronavirus disease 2019 (COVID-19) is scarce.Methods: In this survey, all participants (n = 914) were enrolled from a tertiary children's hospital between September 2020 and April 2021. A face-to-face questionnaire interview was conducted to collect information on the special diseases of children and parental attitudes about the COVID-19 vaccine. We compared the demographic and disease factors between the group of parents who were willing to vaccinate their children against COVID-19 and the group who were unwilling to vaccinate.Results: Among 941 children, 58.1% (n = 547) were boys. The Mean age was 1.4 (SD 1.9) years. If the COVID-19 vaccine becomes available for the child, 470 (49.9%) of parents were willing to provide vaccination for their children. The less the education levels of the father or mother, the more likely they were to vaccinate their children (P = 0.003, P = 0.007). However, more intentions to vaccinate were provided in parents of children with COVID-19 prevention and control education (P < 0.001).Conclusion: Our findings provided evidence that some parents are willing to vaccinate their children with special diseases against COVID-19. Professional knowledge about COVID-19 prevention and control may contribute to increased parental intention.

The quantitative identification of water sources is an important prerequisite for objectively evaluating the degree of aquifer interference and predicting the production potential of coalbed methane (CBM) wells. However, this issue has not been solved yet, and water sources are far from being completely understood. Stable water isotopes are important carriers of water source information, which can be used to identify the water sources for CBM wells. Taking the Zhijin block in the Western Guizhou Province as an example, the produced water samples were collected from CBM wells. The relationships between the stable isotopic compositions of the produced water samples and the production data were quantitatively analyzed. The following main conclusions were obtained. (1) The δD and δ18O values of the produced water samples were between −73.37‰ and −27.56‰ (average −56.30‰) and between −11.04‰ and −5.93‰ (average −9.23‰), respectively. The water samples have D-drift characteristics, showing the dual properties of atmospheric precipitation genesis and water–rock interaction modification of the produced water. An index d was constructed to enable the quantitative characterization of the degree of D-drift of the produced water. (2) The stable isotopic compositions of produced water showed the control of the water sources on the CBM productivity. The probability of being susceptible to aquifer interference increased with the increasing span of the producing seam combination, reflected in the lowering δD and δ18O values and the decreasing gas productivity. (3) Three types of water, namely, static water, dynamic water, and mixed water, were identified. The characteristic values of the isotopic compositions of the static and dynamic water were determined. Accordingly, a quantitative identification method for the produced water sources was constructed, based on their stable isotopic compositions. The identification results have a clear correlation with the gas production, and the output of the static water contributes to the efficient CBM production. The method for the quantitative identification of the water sources proposed in this study, can help to improve the CBM development efficiency and optimize the drainage technology.

Background: Pyrroline-5-carboxylate reductase (PYCR) includes three human genes encoding three isozymes, PYCR1, PYCR2, and PYCR3 (or PYCRL), which facilitate the final step in the conversion of glutamine to proline. These genes play important roles in regulating the cell cycle and redox homeostasis as well as promoting growth signaling pathways. Proline is abnormally upregulated in a variety of cancers, and as the last key enzyme in proline production, PYCR plays an integral role in promoting tumorigenesis and cancer progression. However, its role in patients with kidney renal papillary cell carcinoma (KIRP) has not been fully elucidated. In this study, we aimed to systematically analyze the expression, gene regulatory network, prognostic value, and target prediction of PYCR in patients with KIRP, elucidate the association between PYCR expression and KIRP, and identify potential new targets for the clinical treatment of KIRP. Methods: We systematically analyzed the expression, prognosis, gene regulatory network, and regulatory targets of PYCR1, PYCR2, and PYCRL in KIRP using multiple online databases including cBioPortal, STRING, MethSurv, GeneMANIA, Gene Expression Profiling Interactive Analysis (GEPIA), Metascape, UALCAN, LinkedOmics, and TIMER. Results: The expression levels of PYCR1, PYCR2, and PYCRL were considerably upregulated in patients with KIRP based on sample type, sex, age, and individual cancer stage. PYCR1 and PYCR2 transcript levels were markedly upregulated in females than in males, and patients aged 21–40 years had higher PYCR1 and PYCR2 transcript levels than those in other age groups. Interestingly, PYCR2 transcript levels gradually decreased with age. In addition, the expressions of PYCR1 and PYCR2 were notably correlated with the pathological stage of KIRP. Patients with KIRP with low PYCR1 and PYCR2 expression had longer survival than those with high PYCR1 and PYCR2 expression. PYCR1, PYCR2, and PYCRL were altered by 4%, 7%, and 6%, respectively, in 280 patients with KIRP. The methylation levels of cytosine-phosphate-guanine (CpG) sites in PYCR were markedly correlated with the prognosis of patients with KIRP. PYCR1, PYCR2, PYCRL, and their neighboring genes form a complex network of interactions. The molecular functions of the genes, as demonstrated by their corresponding Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, included calcium channel activity, phospholipid binding, RNA polymerase II-specificity, and kinase and GTPase-regulatory activities. PYCR1, PYCR2, and PYCRL targeted miR-21, miR-221, and miR-222, resulting in a better prognosis of KIRP. We analyzed mRNA sequencing data from 290 patients with KIRP and found that ADA, NPM3, and TKT were positively associated with PYCR1 expression; PFDN2, JTB, and HAX1 were positively correlated with PYCR2 expression; SHARPIN, YDJC, and NUBP2 were positively correlated with PYCRL expression; PYCR1 was positively correlated with B cell and CD8+ T-cell infiltration levels; macrophage infiltration was negatively correlated with PYCR2 expression; and PYCRL expression was negatively correlated with B-cell, CD8+ T cell, and dendritic cell infiltration levels. Conclusions: PYCR1, PYCR2, and PYCRL may be potential therapeutic and prognostic biomarkers for patients with KIRP. The regulation of microRNAs (miRNAs), including miR-21, miR-221, and miR-222, may prove an important strategy for KIRP treatment.

The rapidly increasing prevalence of Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing bacteria has become a serious challenge to public health. Currently, the blaKPC–2 gene is mainly disseminated through plasmids of different sizes and replicon types. However, the plasmids carrying the blaKPC–2 gene have not been fully characterized. In this study, we report the complete genome sequences of two novel blaKPC–2-harboring incompatibility group U (IncU) plasmids, pEC2341-KPC and pEC2547-KPC, from international high-risk clones of Escherichia coli isolated from Zhejiang, China. Two KPC-2-producing E. coli isolates (EC2341 and EC2547) were collected from clinical samples. Whole-genome sequencing (WGS) analysis indicated that EC2341 and EC2547 belonged to the ST410 and ST131 clones, respectively. S1-nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blot and conjugation experiments confirmed the presence of the blaKPC–2 gene on the pEC2341-KPC plasmid and that this was a conjugative plasmid, while the blaKPC–2 gene on the pEC2547-KPC plasmid was a non-conjugative plasmid. In addition, plasmid analysis further revealed that the two blaKPC–2-harboring plasmids have a close evolutionary relationship. To the best of our knowledge, this is the first report of E. coli strains carrying the blaKPC–2 gene on IncU plasmids. The emergence of the IncU-type blaKPC–2-positive plasmid highlights further dissemination of blaKPC–2 in Enterobacteriaceae. Therefore, effective measures should be taken immediately to prevent the spread of these blaKPC–2–positive plasmids.

For sandwich panels with truss core, the weakest part is the low-density core; therefore, some effective damage identification methods have been previously proposed for sandwich panels. However, these studies have mainly focused on damage location identification and only a few studies have discussed detection of the extent of the damage. In this study, a damage identification method integrating a deep learning technique with dynamic properties is proposed to identify both the location and extent of internal damage in sandwich panels with truss core. An analytical model verified by experiments based on a laser vibrometer is used to obtain raw data, which can generate various levels of damage inside the two face sheets. Instead of using surface photographs or raw data as the deep learning training dataset, the dataset is constructed using damage indices. By combining this with an analytical model, a dataset of specimens with various defects was collected and used as the input for the neural networks. The ability to identify the locations of damage and the extent of damage was used to evaluate the effectiveness of the proposed technique. The results show that the proposed method could be used to identify the location and extent of internal damage accurately.

C-C chemokine receptor type 5 (CCR5) is the main co-receptor for HIV entry into the target CD4+ cells, and homozygous CCR5Δ32/Δ32 cells are resistant to CCR5-tropic HIV infection. However, the CCR5Δ32/Δ32 homozygous donors in populations are rare. Here we developed a simple approach to induce CCR5Δ32/Δ32 homozygotes through CRISPR-Cas9 genome-editing technology. Designing a pair of single-guide RNA targeting the flank region of the CCR5Δ32 mutation locus, we applied the CRISPR-Cas9 and lentiviral packaging system to successfully convert wild-type CCR5 into CCR5Δ32/Δ32 homozygotes in the human Jurkat CD4+ cell line and primary CD4+ cells, exactly the same as the naturally occurring CCR5Δ32/Δ32 mutation. The successful rate is up to 20% in Jurkat cells but less in primary CD4+ cells. The modified CCR5Δ32/Δ32 CD4+ cells are resistant to CCR5-tropic HIV infection. Whole-genome sequencing revealed no apparent off-target sites. This approach has the promise to promote HIV/AIDS therapy from the only cured unique Berlin patient to a routine autologous cell-based therapy. Keywords: HIV, AIDS, CCR5Δ, 32, CRISPR-Cas9, CD4+ cells

The Hancheng area is a hot spot for coalbed methane exploration and exploitation in China. Structure is a key factor affecting coalbed methane accumulation and production in the Hancheng area. For a better understanding of the coalbed methane accumulation conditions and high-yield potential, this study investigates the structural patterns and evolution, the hydrogeological conditions, and the geothermal field in the coal-bearing strata in the Hancheng area. Then, the spatial distribution of the coalbed methane content and the tectonic deformation of the coal seam are evaluated. Finally, the critical depth for coalbed methane enrichment and a high-yield potential are revealed, and the favorable areas for coalbed methane development are predicted. The following conclusions are obtained: (1) Under the Yanshanian SE–NW trending maximum principle stress, the Hancheng overturned anticline was formed and subsequently subjected to uplift and erosion along its axis, which led to the NW limb of the anticline forming the current uniclinal structure of the Hancheng area; (2) Four degrees of tectonic deformation in the coal seam are identified based on structural curvature analysis. The moderately deformed area shallower than 800 m would benefit coalbed methane production with higher permeability. Most of the locations of coal and gas outburst events that occur during coal mining were distributed along the highly and very highly deformed areas; (3) The gas content gradually increases along the NW-trending inclination of the coal seam. 400 m and 800 m are discriminated as the critical depth levels for controlling coalbed methane accumulation and a high yield. Secondary biogenic methane was generated in the shallow formations; and (4) The Hancheng area is divided into four ranks for determining coalbed methane development potential. From high to low, they are ranked A, B-1, B-2, and C. Most of the high-yield wells are located in the areas ranked A and B-1.

Tactile sensing is paramount for robots operating in human-centered environments to help in understanding interaction with objects. To enable robots to have sophisticated tactile sensing capability, researchers have developed different kinds of electronic skins for robotic hands and arms in order to realize the ‘sense of touch’. Recently, Stanford Structures and Composites Laboratory developed a robotic electronic skin based on a network of multi-modal micro-sensors. This skin was able to identify temperature profiles and detect arm strikes through embedded sensors. However, sensing for the static pressure load is yet to be investigated. In this work, an electromechanical impedance-based method is proposed to investigate the response of piezoelectric sensors under static normal pressure loads. The smart skin sample was firstly fabricated by embedding a piezoelectric sensor into the soft silicone. Then, a series of static pressure tests to the skin were conducted. Test results showed that the first peak of the real part impedance signal was sensitive to static pressure load, and by using the proposed diagnostic method, this test setup could detect a resolution of 0.5 N force. Numerical simulation methods were then performed to validate the experimental results. The results of the numerical simulation prove the validity of the experiments, as well as the robustness of the proposed method in detecting static pressure loads using the smart skin.

Geothermal fields in coal-bearing strata significantly influence coal mining and coalbed methane accumulation and development. Based on temperature data from 135 coalfield exploration boreholes and thermophysical tests of 43 rock and coal samples from the Upper Permian coal-bearing strata of the Bide-Santang basin in western Guizhou, South China, the distribution of terrestrial heat flow and the geothermal gradient in the study area are revealed, and the geological controls are analysed. The results show that the thermal conductivity of the coal-bearing strata ranges from 0.357 to 3.878 W (m K) −1 and averages 1.962 W (m K) −1 . Thermal conductivity is controlled by lithology and burial depth. Thermal conductivity progressively increases for the following lithologies: coal, mudstone, siltstone, fine sandstone, and limestone. For the same lithology, the thermal conductivity increases with the burial depth. The present geothermal gradient ranges from 15.5 to 30.3°C km −1 and averages 23.5°C km −1 ; the terrestrial heat flow ranges from 46.94 to 69.44 mW m −2 and averages 57.55 mW m −2 . These values are lower than the averages for South China, indicating the relative tectonic stability of the study area. The spatial distribution of the terrestrial heat flow and geothermal gradient is consistent with the main structural orientation, indicating that the geothermal field distribution is tectonically controlled at the macro-scale. This distribution is also controlled by active groundwater, which reduces the terrestrial heat flow and geotemperature. The high geothermal gradient in the shallow strata (

The pathology of Parkinson’s disease (PD) is characterized by intracellular neurofibrillary tangles of phosphorylated α-synuclein (α-syn). Protein phosphatase 2A (PP2A) is responsible for α-syn dephosphorylation. Previous work has demonstrated that α-syn can regulate PP2A activity. However, the mechanisms underlying α-syn regulation of PP2A activity are not well understood. In this study, we found that α-syn overexpression induced increased α-syn phosphorylation at serine 129 (Ser129), and PP2A inhibition, in vitro and in vivo. α-syn overexpression resulted in PP2A demethylation. This demethylation was mediated via downregulated leucine carboxyl methyltransferase (LCMT-1) expression, and upregulated protein phosphatase methylesterase (PME-1) expression. Furthermore, LCMT-1 overexpression, or PME-1 inhibition, reversed α-syn-induced increases in α-syn phosphorylation and apoptosis. In addition to post-translational modifications of the catalytic subunit, regulatory subunits are involved in the regulation of PP2A activity. We found that the levels of regulatory subunits which belong to the PPP2R2 subfamily, not the PPP2R5 subfamily, were downregulated in the examined brain regions of transgenic mice. Our work identifies a novel mechanism to explain how α-syn regulates PP2A activity, and provides the optimization of PP2A methylation as a new target for PD treatment.

Fluid–structure interaction is an important issue for non-rigid airships with inflated envelopes. In this study, a wind tunnel test is conducted, and a loosely coupled procedure is correspondingly established for numerical simulation based on computational fluid dynamics and nonlinear finite element analysis methods. The typical results of the numerical simulation and wind tunnel experiment, including the overall lift and deformation, are in good agreement with each other. The results obtained indicate that the effect of fluid–structure interaction is noticeable and should be considered for non-rigid airships. Flow-induced deformation can further intensify the upward lift force and pitching moment, which can lead to a large deformation. Under a wind speed of 15 m/s, the lift force of the non-rigid model is increased to approximately 60% compared with that of the rigid model under a high angle of attack.

Background/Aims: IGF1 is a key regulator in cell proliferation and apoptosis, and the 3' un-translated region (3'UTR) of the gene plays an important role in gene expression. For the first time, we explored the relationship between polymorphisms in the IGF1 3'UTR region and the risk of childhood acute lymphoblastic leukemia (ALL). Methods: Questionnaires were applied to collect epidemiological data. The genotypes of IGF1 polymorphisms were tested in a population of 744 ALL patients and 1088 cancer-free controls utilizing Taqman. Cell functional studies included real-time PCR, cell culture and transfection and luciferase assays. Results: We found that rs6214 homozygous AA genotype and rs6218 homozygous CC genotype were significantly associated with increased risk of childhood ALL. In addition, rs6218 CC genotype was associated with increased level of IGF1 mRNA in bone marrow, and the mutation in rs6218 led to aberrant binding capacity of hsa-miR-603 and hsa-miR-3941 in the 3'UTR of IGF1. Conclusion: Polymorphisms of rs6214 and rs6218 in the 3'UTR of IGF1 are associated with childhood ALL susceptibility, and the polymorphism of rs6218 is related with IGF1 expression at mRNA level.

Quench polish quench (QPQ) is a specialized type of nitrocarburizing case hardening that increases corrosion resistance. In recent years, QPQ technology has attracted the attention of other industries, such as piston rod, oil and other industries. The workpiece treated with QPQ has good abrasion resistance and high corrosion resistance. The surface of the oil pipe is prone to rust, which inevitably affects its performance in the well. Aiming at the problems in practical application, the test method was used to evaluate the corrosion resistance of the treated samples in the atmosphere. By using API standard tensile test and electrochemical corrosion test, the mechanical properties and corrosion resistance of N80 treated with QPQ were studied.

C-C chemokine receptor 5 (CCR5) is a receptor for chemokines and a co-receptor for HIV-1 entry into the target CD4+ cells. CCR5 delta 32 deletion is a loss-of-function mutation, resistant to HIV-1 infection. We tried to induce the CCR5 delta 32 mutation harnessing the genome editing technique, CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR and CRISPR associated protein 9, Cas9) in the commonly used cell line human embryonic kidney HEK 293T cells. Surprisingly, we found that HEK293T cells are heterozygous for CCR5 delta 32 mutation, in contrast to the wild type CCR5 cells, human acute T cell leukemia cell line Jurkat and human breast adenocarcinoma cell line MDA-MB-231 cells. This finding indicates that at least one human cell line is heterozygous for the CCR5 delta 32 mutation. We also found that in PCR amplification, wild type CCR5 DNA and mutant delta 32 DNA can form mismatched heteroduplex and move slowly in gel electrophoresis.

To investigate injury pattern during intense exercises in hot and humid environment particularly on liver in a rat exertional heat stroke model.We randomly divided 30 rats into a control group (CG), a normal temperature (25±2°C, 60%±5% humidity) exercise group (NTEG) and a high temperature and high humidity (35±2°C, 80%±10% humidity) exercising group (HTEG), each comprising 10 animals. The NTEG and HTEG rats were forced to run in a treadmill for 1 hour maximum at 20 rpm. We analyzed liver cells of all three groups with JC-1 dye and flow cytometry for apoptosis rates in addition to liver tissue 8 - hydroxy deoxyguanosine (8 - OhdG) and blood serum IL-6, tumor necrosis factor alpha (TNF-α), alanine aminotransferase ALT, aspartate amino transferase (AST), serum creatinine (CREA), blood urea nitrogen (BUN), lactate dehydrogenase (LDH), creatine phosphate kinase (CK) concentrations.Compared with NTEG rats, beside reduced exercise tolerance (60±5 vs. 15±3 minutes) (p = 0.002) the 8-OhdG liver tissue concentrations were significantly higher (p = 0.040) in the HTEG rats. The HTEG developed more organ tissue damage and cellular fragmentations of liver cells. In both exercise groups TNF-α and IL-6 serum concentrations were enhanced significantly (p

Renal tubular injury is considered as the main pathological feature of acute kidney injury (AKI), and mitochondrial dysfunction in renal tubular cells is implicated in the pathogenesis of AKI. The estrogen-related receptor γ (ERRγ) is a member of orphan nuclear receptors which plays a regulatory role in mitochondrial biosynthesis, energy metabolism and many metabolic pathways. Online datasets showed a dominant expression of ERRγ in renal tubules, but the role of ERRγ in AKI is still unknown. In the present study, we investigated the role of ERRγ in the pathogenesis of AKI and the therapeutic efficacy of ERRy agonist DY131 in several murine models of AKI. ERRγ expression was reduced in kidneys of AKI patients and AKI murine models along with a negative correlation to the severity of AKI. Consistently, silencing ERRγ in vitro enhanced cisplatin-induced tubular cells apoptosis, while ERRγ overexpression in vivo utilizing hydrodynamic-based tail vein plasmid delivery approach alleviated cisplatin-induced AKI. ERRγ agonist DY131 could enhance the transcriptional activity of ERRγ and ameliorate AKI in various murine models. Moreover, DY131 attenuated the mitochondrial dysfunction of renal tubular cells and metabolic disorders of kidneys in AKI, and promoted the expression of the mitochondrial transcriptional factor A (TFAM). Further investigation showed that TFAM could be a target gene of ERRγ and DY131 might ameliorate AKI by enhancing ERRγ-mediated TFAM expression protecting mitochondria. These findings highlighted the protective effect of DY131 on AKI, thus providing a promising therapeutic strategy for AKI. [ABSTRACT FROM AUTHOR]

Recently, many authors have studied degenerate Bernoulli and degenerate Euler polynomials. Let [Formula: see text] be a random variable whose moment generating function exists in a neighbourhood of the origin. The aim of this paper is to introduce and study the probabilistic extension of degenerate Bernoulli and degenerate Euler polynomials, namely the probabilistic degenerate Bernoulli polynomials associated with [Formula: see text] and the probabilistic degenerate Euler polynomials associated with [Formula: see text]. Also, we intoduce the probabilistic degenerate [Formula: see text]-Stirling numbers of the second associated with [Formula: see text] and the probabilistic degenerate two variable Fubini polynomials associated with [Formula: see text]. We obtain some properties, explicit expressions, recurrence relations and certain identities for those polynomials and numbers. As special cases of [Formula: see text], we treat the gamma random variable with parameters [Formula: see text], the Poisson random variable with parameter [Formula: see text], and the Bernoulli random variable with probability of success [Formula: see text].