The clinical profile, genetic basis and survival of childhood cardiomyopathy: a single-center retrospective study.

Cardiomyopathy (CM) is a heterogeneous group of myocardial diseases in children. This study aimed to identify demographic features, clinical presentation and prognosis of children with CM. Clinical characteristics and prognostic factors associated with mortality were evaluated by Cox proportional hazards regression analyses. Genetic testing was also conducted on a portion of patients. Among the 317 patients, 40.1%, 25.2%, 24.6% and 10.1% were diagnosed with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular noncompaction cardiomyopathy (LVNC) and restrictive cardiomyopathy (RCM), respectively. The most common symptom observed was dyspnea (84.2%). Except for HCM, the majority of patients were classified as NYHA/Ross class III or IV. The five-year survival rates were 75.5%, 67.3%, 74.1% and 51.1% in DCM, HCM, LVNC and RCM, respectively. The ten-year survival rates were 60.1%, 56.1%, 57.2% and 41.3% in DCM, HCM, LVNC and RCM, respectively. Survival was inversely related to NYHA/Ross class III or IV in patients with DCM, HCM and RCM. Out of 42 patients, 32 were reported to carry gene mutations. CONCLUSIONS: This study demonstrates that CM, especially RCM, is related to a high incidence of death. NYHA/Ross class III or IV is a predictor of mortality in the patients and gene mutations may be a common cause. TRIAL REGISTRATION: MR-50-23-011798. WHAT IS KNOWN: • Cardiomyopathy (CM) is a heterogeneous group of myocardial diseases and one of the leading causes of heart failure in children due to the lack of effective treatments. • There remains scarce data on Asian pediatric populations though emerging studies have assessed the clinical characteristics and outcomes of CM. WHAT IS NEW: • A retrospective study was conducted and the follow-up records were established to investigate the clinical characteristics, the profile of gene mutations and prognostic outcomes of children with CM in Western China. • CM, especially RCM, is related to a high incidence of death. NYHA/Ross class III or IV is a predictor of mortality in the patients and gene mutations may be a common cause.

Hyperoside ameliorates cisplatin-induced acute kidney injury by regulating the expression and function of Oat1.

Cisplatin is a widely used chemotherapeutic agent to treat solid tumours in clinics. However, cisplatin-induced acute kidney injury (AKI) limits its clinical application. This study investigated the effect of hyperoside (a flavonol glycoside compound) on regulating AKI.The model of cisplatin-induced AKI was established, and hyperoside was preadministered to investigate its effect on improving kidney injury.Hyperoside ameliorated renal pathological damage, reduced the accumulation of SCr, BUN, Kim-1 and indoxyl sulphate in vivo, increased the excretion of indoxyl sulphate into the urine, and upregulated the expression of renal organic anion transporter 1 (Oat1). Moreover, evaluation of rat kidney slices demonstrated that hyperoside promoted the uptake of PAH (p-aminohippurate, the Oat1 substrate), which was confirmed by transient over-expression of OAT1 in HEK-293T cells. Additionally, hyperoside upregulated the mRNA expression of Oat1 upstream regulators hepatocyte nuclear factor-1α (HNF-1α) and pregnane X receptor (PXR).These findings indicated hyperoside could protect against cisplatin-induced AKI by promoting indoxyl sulphate excretion through regulating the expression and function of Oat1, suggesting hyperoside may offer a potential tactic for cisplatin-induced AKI treatment.

Interfacial Solar Vapour Generation: An Emerging Platform for Sustainable Clean Water Harvesting.

Water is a precious resource of paramount importance on Earth, playing a critical role in the evolution of life [...].

LACTB suppresses migration and invasion of glioblastoma via downregulating RHOC/Cofilin signaling pathway.

Glioblastoma (GBM) is the most malignant tumor in human brain. High invasiveness of this tumor is the main reason causing treatment failure and recurrence. Previous study has found that LACTB is a novel tumor suppressor in breast cancer. Moreover, the function of LACTB in other tumors and mechanisms involving LACTB were also reported. However, the role and relevant mechanisms of LACTB in GBM invasion remains to be revealed. Our aim is to investigate the role LACTB in GBM migration and invasion. We found that LACTB was downregulated in gliomas compared to normal brain tissues. Overexpression of LACTB suppressed migration and invasion of LN229 and U87 cell lines. Mechanistically, LACTB overexpression downregulated the mesenchymal markers. Moreover, LACTB overexpression downregulated the expression of RHOC and inhibited RHOC/Cofilin signaling pathway. The study suggests that LACTB suppresses migration and invasion of GBM cell lines via downregulating RHOC/Cofilin signaling pathway. These findings suggest that LACTB may be a potential treatment target of GBM.

The key role of organic anion transporter 3 in the drug-drug interaction between tranilast and methotrexate.

Tranilast, N-(3',4'-dimethoxycinnamoyl)-anthranilic acid, is an anti-allergic drug and is considered for use in the treatment of rheumatoid arthritis. Methotrexate, an antimetabolite and folate antagonist to treat some cancers, is also a first-line drug for RA. The aim of this study was to understand whether tranilast could inhibit renal uptake transporters (Oat1, Oat3, and Oct2) and whether MTX combined with TL would have drug-drug interactions. The results of kidney slices and HEK293T-OAT3 cell uptake experiments showed that TL (10 µM) could inhibit the uptake of penicillin G and MTX, which are substrates of OAT3. When TL (10 mg/kg) was combined with MTX (5 mg/kg), the area under the curve and peak concentration of MTX increased by 46.46% and 113.51%, respectively, while the pharmacokinetic process of tranilast (10 mg/kg) was not changed by methotrexate (5 mg/kg). TL could increase plasma exposure of MTX by inhibiting Oat3 in vitro and in vivo.

UHPLC-MS/MS-based method for quantification of verinurad in rat plasma and its application in a bioavailability study.

A rapid and sensitive UHPLC-MS/MS method was developed and fully validated for the quantification of verinurad in rat plasma. Lesinurad was used as an internal standard (IS), and simple protein precipitation was utilized to prepare the analytes from the matrix. Chromatographic separation was carried out on a Zorbax SB C18 column. The mobile phase consisted of water with 0.1% formic acid (A) and acetonitrile with 0.1% formic acid (B) at a flow rate of 0.3 mL/min. The short run time of 4 min made it possible to analyze more than 300 samples per day. The ion transitions were quantified in negative mode with multiple reaction monitoring (MRM) transitions of 347.1 â†’ 261.1 for verinurad and 404.2 â†’ 178.9 for the IS. The validated linear ranges of verinurad were 10-5000 ng/mL in rat plasma. The validated UHPLC-MS/MS method was further applied to the pharmacokinetic study of verinurad in rat plasma after intragastric (2 mg/kg) and intravenous (1 mg/kg) administrations. The pharmacokinetic study revealed that verinurad showed high clearance and high bioavailability (78.1%). To the best of our knowledge, this is the first report of the bioavailability study of verinurad.

[Identification of a variant Bw37 allele of the ABO gene].

OBJECTIVE: To explore the molecular basis for an individual with a rare variant of Bw37 phenotype. METHODS: Tube agglutination testing was used to determine the ABO blood groups. Genotyping were carried out using polymerase chain reaction-sequence specific primer (PCR-SSP) and direct sequencing for exons 6 and 7 of the ABO locus. RESULTS: Serologic testing of the proband showed that he was weak B for the positive ABO blood typing and B for the negative blood typing. The genotype of him was determined as B/B by PCR-SSP. DNA sequencing showed that he has harbored c.297A>G, c.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C and c.930G>A variants, which have resulted in p.R176G, p.G235S and p.G268A substitutions. The genotypes of the proband and his mother were identified as ABO*Bw37/B101 and ABO*O.01.02/ABO*O.01.01, respectively. CONCLUSION: Serological identification combined with genotyping should be considered for the verification of ABO subtypes.

[Genetic identification and sequence analysis of three individuals of rare ABO variant Bw subgroup].

OBJECTIVE: To identify and analysis three ABO variant Bw subtypes. METHODS: Serological assays were carried out to identify the ABO blood group of the proband. ABO gene was identified by Sanger sequencing. RESULTS: The genotype of three individuals are ABO*Bw.11/0.01.02, ABO*Bw.12/0.01.01, ABO*Bw.34/A1.02, receptively. Sequencing results showed that there were c.695T>C, c.278C>T, c.889G>A, resulting in variants in Leu232Pro, Pro93Leu and Glu297Lys, receptively. CONCLUSION: Bw11, Bw12 and Bw34 subgroups were identified, and gene testing can be used as a supplement to determine the ABO blood group subtypes.

UPLC-MS/MS Method for the Determination of Hyperoside and Application to Pharmacokinetics Study in Rat After Different Administration Routes.

A rapid and sensitive UPLC-MS/MS method was developed and fully validated for the quantification of hyperoside in rat plasma after intragastric, intraperitoneal and intravenous administration. Geniposide was used as an internal standard, and simple liquid-liquid extraction by ethyl acetate was utilized for to extracting the analytes from the rat plasma samples. Chromatographic separation was carried out on an InfinityLab Poroshell 120EC-C18column (2.1 mm × 50 mm, 1.9-Micro, Agilent technologies, USA). The mobile phase consisted of methanol (A) and water (B) (containing 0.1% acetic acid) at a flow rate of 0.4 mL/min. A run time of 3 min for each sample made it possible to analyze more than 300 plasma samples per day. The validated linear ranges of hyperoside were 2-1000 ng/mL in rat plasma. The intra-day and inter-day precision were within 2.6-9.3%, and accuracy were ± 8.6%. And the results of recovery and matrix interference studies were well within the accepted variability limits. Finally, this method was fully validated and successfully applied to the pharmacokinetic studies of hyperoside via different administration routes in rats.

Changes in serum inflammatory factors in acute gouty arthritis patients treated using ultrashort wave combined with loxoprofen sodium.

OBJECTIVES: To study the effect of ultrashort wave combined with loxoprofen sodium on serum inflammatory factors in patients with acute gouty arthritis. METHODS: Records of patients with acute gouty arthritis who were treated in The Fourth Hospital of Changsha from May 2018 to September 2020, were reviewed. Of them, 77 cases were selected and divided into two groups based on the received treatment. The control group (n=39) was treated with loxoprofen sodium, and the treatment group (n=38) was treated with an ultrashort wave combined with loxoprofen sodium, for 10 continuous days. The clinical efficacy of the treatment in two groups was analyzed. RESULTS: After treatment, the quality of life of patients in both groups was improved (P < 0.05), but there was no significant difference in the degree of improvement between the two groups (P > 0.05). After treatment, the VAS score of the treatment group was lower than that of the control group (P < 0.05), the improvement of symptoms and signs of the treatment group was better than that of the control group (P < 0.05). Serum CRP and ESR levels in the treatment group were lower than those in the control group (P < 0.05), and the serum IL-1 ß, IL-8, TNF-a and MMP-3 levels of the treatment group were lower than those of the control group (P < 0.05). The total effective rate of the treatment group (94.87%) was higher than that of the control group (87.18%), the difference was statistically significant (P < 0.05). No adverse reactions occurred in all patients during the treatment. CONCLUSION: An ultrashort wave combined with loxoprofen sodium in the treatment of acute gouty arthritis can reduce the inflammatory reaction, improve the degree of joint pain and swelling, improve the curative effect, and do not increase the adverse reactions. The results may be related to the regulation of IL-1 ß, IL-8, TNF-a and MMP-3.

Microarray analysis of preterm preeclampsia.

Premature preeclampsia is the second cause of maternal mortalities around the world. To investigate its potential driving mechanism(s), we constructed a multi-regulatory-mediated preeclampsia dysfunction module. Through combining differential expression analysis, co-expression analysis, and enrichment analysis, we obtained 23 sets of preeclampsia expression disorder modules in the disease, which involve the modular aggregations of 3016 genes. The modules were subjected to be analyzed for GO and KEGG paths for enrichment analysis. Based on these pivotal regulators, it is possible to manipulate the essential parts of the modular subnetwork and study their cooperative acts to mediate the driving mechanism of the preeclampsia. Simultaneously, they mainly cause the onset of the disease through the regulation of the apoptotic signaling pathway, down-regulation of an inflammatory response and retinol metabolism. This may present a potential driving mechanism for the disease. The predictor analysis of the regulators showed a series of non-coding RNAs that have potentially significant regulatory effects on the disease, including miR-182-5p, miR-200b-3p, miR-23a-3p, miR -429, miR-590-3p, and transcription factors. These pivotal regulators might mediate the potential driving processes. Based on a comprehensive multivariate analysis, we found a possible driving mechanism in which significant pivotal regulators were used as distinct functional segments in the preterm preeclampsia-driven process.

B, N Co-Doped Three-Dimensional Carbon Aerogels with Excellent Electrochemical Performance for the Oxygen Reduction Reaction.

Herein, an ordinary and mass-production approach is reported to synthesize boron (B) and nitrogen (N) co-doped three-dimensional (3D) carbon aerogels (CA) by using glucose and borax as the raw materials by a simple hydrothermal method and then carbonization in NH3 atmosphere. The porous material (BN-CA-900) possesses a large specific surface area (1032 m2 g-1 ) and high contents of doped pyridinic N and graphitic N. The onset potential (0.91 V vs. reversible hydrogen electrode, RHE), half-wave potential (0.77 V vs. RHE), and current density (5.70 mA cm-2 at 0.2 V vs. RHE) of BN-CA-900 for ORR are similar to those of commercial Pt/C, indicating that BN-CA-900 has a comparable catalytic activity with Pt/C in alkaline media. The number of electron transfer is 3.86-3.99 and the yield of hydrogen peroxide is less than 6.8 %. BN-CA-900 also presents decent catalytic performance in acidic medium. Moreover, the stability and methanol tolerance of BN-CA-900 are superior to commercial Pt/C in both alkaline and acidic media. The prepared BN-CA-900 is a promising candidate that may be applied in other areas, such as the adsorption of pollution, porous conductive electrodes, and lithium-ion batteries.

The effect of Heweijiangni-decoction on esophageal morphology in a rat model of OVA-induced visceral hypersensitivity followed by acid exposure.

Heweijiangni decoction (HWJND) is an effective traditional Chinese medicine prescription in clinical treatment of nonerosive reflux disease (NERD). Esophageal hypersensitivity and acid contribute to the disease. However, the exact underlying mechanism of action remains unclear. In this study, we observed the effect of HWJND on esophageal morphology in a rat model of ovalbumin (OVA)-induced visceral hypersensitivity followed by acid exposure. Esophageal morphology was assessed by measuring the extent of dilated intercellular spaces (DIS), desmosome disruption, and mitochondrial fragmentation. HWJND in low, moderate, and high doses relieved DIS and desmosome disruption in esophageal epithelium compared with model group (P<0.05 for all doses). In addition, HWJND in high dose protected mitochondria from fragmentation (P<0.05). Other findings suggest that DIS and mitochondrial fragmentation are independent events, and that omeprazole protects mitochondria. Overall, HWJND significantly resists esophageal morphology changes in OVA-induced and acid exposure rat model.

Expression and purification of recombinant puroindoline A protein in Escherichia coli and its antifungal effect against Aspergillus flavus.

Aspergillus flavus is the main cause of postharvest agricultural commodity loss. In this study, puroindoline A (PINA) protein was expressed in Escherichia coli, purified, and its antifungal properties against A. flavus were characterized. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that the molecular weight of the recombinant PINA protein was approximately 44 kDa. PINA exerted a powerful antifungal effect against A. flavus at 42.42 µg/mL on potato dextrose agar culture medium. Flow cytometry and scanning electron microscopy revealed that the spore morphology was damaged by PINA exposure; spores were depressed and broken, suggesting that the cell wall was impaired. Transmission electron microscopy and propidium iodide staining illustrated significant changes in intracellular spore structure, indicating cell membrane damage. 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine iodide staining indicated decreased mitochondrial membrane potential. Large nuclear condensation and DNA fragmentation were detected by 4',6-diamidino-2-phenylindole staining. The expression of genes related to the cell wall, cell membrane, and spore germination significantly changed in PINA-treated cells; this illustrated the probable mode of PINA action on A. flavus through cell wall destruction and triggered cell membrane, mitochondrial, and DNA damage leading to cell death. The antifungal mechanism of wheat PINA protein on A. flavus has been demonstrated in this study, and has potential application in preventing postharvest loss in the agricultural industry.

Isolation of Tricin as a Xanthine Oxidase Inhibitor from Sweet White Clover (Melilotus albus) and Its Distribution in Selected Gramineae Species.

Xanthine oxidase, an enzyme present in significant levels in the intestine and liver, metabolizes hypoxanthine to xanthine and xanthine to uric acid in the purine catabolic pathway. An inhibitory compound acting against xanthine oxidase was isolated from sweet white clover (Melilotus albus) by bioassay and high-performance liquid chromatography guided separation. It was identified as tricin by spectroscopic analysis. Tricin possessed a potent xanthine oxidase inhibitory activity with an IC50 value of 4.13 µM. Further inhibition kinetics data indicated it to be a mixed-type inhibitor and Ki and KI values were determined to be 0.47 µM and 4.41 µM. To find a rich source of tricin, the distribution of tricin in seven different tissues from four Gramineae species was investigated by high-performance liquid chromatography analysis. The highest amount (1925.05 mg/kg dry materials) was found in the straw of wheat, which is considered as a potentially valuable source of natural tricin.

High-performance gas sensors based on a thiocyanate ion-doped organometal halide perovskite.

Thin films of a thiocyanate ion (SCN-)-doped organometal halide perovskite, CH3NH3PbI3-x(SCN)x, were used as a sensing material for developing high-performance gas sensors. The CH3NH3PbI3-x(SCN)x-based chemiresistor-type sensor can sensitively and selectively detect acetone and nitrogen dioxide (NO2) at room temperature with high sensitivities of 5.6 × 10-3 and 5.3 × 10-1 ppm-1. The limits of detection for acetone and NO2 were measured to be 20 ppm and 200 ppb. This sensor also exhibited excellent repeatability, and its environmental stability was greatly improved by doping the perovskite with SCN- ions.

Genetic variant near TERC influencing the risk of gliomas with older age at diagnosis in a Chinese population.

A recent genome-wide association study has identified an association between rs1920116 near TERC and high-grade glioma in populations of European ancestry. In order to evaluate the effect of the SNP rs1920116 near TERC in the Chinese population, we examined associations of this candidate SNP with glioma in a sample of 1970 Chinese Han individuals. SNP genotype data were available for 980 Chinese glioma patients and 990 healthy controls. Logistic regression analyses were performed to evaluate the association between rs1920116 and glioma risk adjusted for age, gender and stratified by tumor grade where appropriate. The allele G at TERC rs1920116 are risk factors for gliomas, and its association with glioma risk was consistent across tumor subgroups in the Chinese Han population (OR = 1.18-1.21). In order to assess variation in SNP effect size at different patient ages, glioma cases and controls were divided into 3 age strata, in years: <50, 50-59, and 60+. The results of multiple logistic regression analyses indicate that the SNP has age-specific effects on the risk of developing glioma. Our report confirmed the effects of rs1920116 near TERC on glioma occurring in older peoples in the Chinese Han population for the first time. As TERC is a candidate for inter-individual variation in telomere length, our study supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life.

Picomolar detection of mercury (II) using a three-dimensional porous graphene/polypyrrole composite electrode.

A polypyrrole (PPy)-functionalized three-dimensional (3D) porous electrode of electrochemically reduced graphene oxide (ErGO) has been prepared by electrochemical deposition. This PPy-modified 3D-ErGO electrode was used for the electrochemical detection of Hg(2+) ions, and it exhibited high sensitivity and selectivity. Furthermore, the limit of detection (LOD) was measured to be as low as 0.03 nM (30 ppt), and this value is much lower than the guideline value of 2 ppb for drinking water given by the World Health Organization.

Factors Affecting Sustainability-Related Career Expectations among Engineering Undergraduates in China: An Empirical Study Based on a Modified College Impact Model.

The international engineering education community has reached a consensus regarding the need to enhance engineering students' awareness of and capability to provide sustainable services in their future careers. Based on a modified college impact model, this study analyzed the impacts of curricular emphasis, curricular instruction, and sustainability-related career self-efficacy on the sustainability-related career expectations of engineering students and investigated the moderating effects of gender on the relationships among the research variables. The results show that both curricular emphasis and curricular instruction have direct positive effects on the sustainability-related career expectations of engineering students; sustainability-related career self-efficacy plays a partial mediating role in this process; and gender significantly moderates the influence of curricular emphasis and curricular instruction on sustainability-related career expectations. The findings of this study provide empirical evidence that can be used by higher education institutions and engineering educators to enhance the belief of engineering students in their ability to solve sustainability-related issues in their future careers and promote the diversification of engineering education.

Limiting Temperature Rise in Cochlear Implantation Bone Drilling: A Novel Approach.

OBJECTIVE: In the process of cochlear implantation surgery, it is crucial to develop a method to control the temperature during the drilling of the implant channel since high temperatures can result in damage to bone and nerve tissue. METHODS: This paper simplified the traditional point heat source temperature rise model and proposed a novel extreme peck drilling model to quantitatively calculate the maximum temperature rise value. It is also innovatively introduced a new method for calculating the best peck drilling duty cycle to strictly control the maximum temperature rise value. Besides, the neural network is trained with virtual data to identify two important thermal parameters in the temperature rise model. RESULTS: In the experiment of epoxy resin and temporal bone, the difference between predicted maximum temperature and actual maximum temperature was less than 1.5 °C, and the error rate was less than 10%. And the error source was analyzed by variational mode decomposition, along with discussion of potential solutions. In the temperature control experiment, the model successfully controlled the maximum temperature rise within 10 °C.For cochlear implantation surgery, we also divide the implantation channel into different stages based on the bone density in CT images to identify thermal parameters and calculate drilling strategies. CONCLUSION: This method provides a new strategy for accurate and effective control of borehole heat generation. SIGNIFICANCE: These achievements provide new ideas and directions for research in cochlear implantation surgery and related fields, and are expected to have extensive application in medical practice.