Berberine attenuates cognitive dysfunction and hippocampal apoptosis in rats with prediabetes.

The cognitive dysfunction caused by prediabetes causes great difficulties in human life, and the terrible thing is that the means to prevent the occurrence of this disease are very limited at present, Berberine has shown the potential to treat diabetes and cognitive dysfunction, but it still needs to be further explored to clarify the mechanism of its therapeutic effect. Therefore, the aim of this study was to investigate the effects and mechanisms of Berberine on prediabetes-induced cognitive dysfunction. Prediabetes rat model was induced by a high-fat diet and a normal diet was used as a control. They were fed for 20 weeks. At week 13, the model rats were given 100 mg/kg Berberine by gavage for 7 weeks. The cognitive function of rats was observed. At the same time, OGTT, fasting blood glucose, blood lipids, insulin and other metabolic parameters, oxidative stress, and apoptosis levels were measured. The results showed that the model rats showed obvious glucose intolerance, elevated blood lipids, and insulin resistance, and the levels of oxidative stress and apoptosis were significantly increased. However, after the administration of Berberine, the blood glucose and lipid metabolism of prediabetic rats were significantly improved, and the oxidative stress level and apoptosis level of hippocampal tissue were significantly reduced. In conclusion, Berberine can alleviate the further development of diabetes in prediabetic rats, reduce oxidative stress and apoptosis in hippocampal tissue, and improve cognitive impairment in prediabetic rats.

A novel CHD7 variant in a chinese family with CHARGE syndrome.

OBJECTIVE: CHARGE syndrome is a rare autosomal dominant (AD) multi-system disorder with a broad and variable clinical manifestation and occurs in approximately 1/10,000 newborns in the world. Mutations in the CHD7 gene are the genetic cause of over 90% of patients with typical CHARGE syndrome. The present study reported a novel variant in the CHD7 gene in a Chinese family with an abnormal fetus. METHODS: Routine prenatal ultrasound screening showed fetal heart abnormality and left foot varus. Chromosomal microarray analysis (CMA) and fetus-parent whole-exome sequencing (trio-WES) were performed to determine the genetic cause of the fetus. The candidate variant was further verified using Sanger sequencing. RESULTS: CMA analysis revealed normal results. However, WES analysis identified a de novo heterozygous variant of c.2919_2922del (NM_017780.4) on exon 11 of CHD7 gene, resulting in a premature truncation of the CHD7 protein (p.Gly975*). The variant was classified as Pathogenic (PVS1 + PS2_Moderate + PM2_Supporting) based on the ACMG guidelines. Combined with the clinical phenotype of fetal heart abnormalities, it was confirmed CHARGE syndrome. CONCLUSION: We identified a novel heterozygous variant c.2919_2922del in CHD7 of a Chinese fetus with CHARGE syndrome, enriching the genotype-phenotype spectrum of CHD7. These results suggest that genetic testing could help facilitate prenatal diagnosis of CHARGE syndrome, thus promoting the appropriate genetic counseling.

Leukocyte telomere length mediates the association between cadmium exposure and cognitive function in US older adults.

BACKGROUND: Long-term exposure to cadmium-polluted environments may lead to shortened leukocyte telomere length and cognitive decline. This study aims to investigate (1) the associations among blood cadmium levels, leukocyte telomere length, and cognitive function, and (2) the mediating role of leukocyte telomere length between blood cadmium levels and cognitive function among older adults in the United States. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Cadmium exposure level was assessed by measuring cadmium levels in blood samples. Leukocyte telomere length was measured by quantitative polymerase chain reaction, and cognitive function was measured by the digit symbol substitution test (DSST). RESULTS: A total of 2185 older adults aged over 60 were included in this study, comprising 1109 (49.65%) males. Elevated blood cadmium levels were significantly associated with the risk of a decline in cognitive function (ß = - 2.842, p = 0.018). Shorter leukocyte telomere lengths were significantly associated with a higher risk of a decline in cognitive function (ß = 4.144, p = 0.020). The total indirect effect on the blood cadmium level and cognitive function via leukocyte telomere length was - 0.218 (p = 0.012). The mediation effect was estimated to be 0.218/2.084 × 100% = 10.46%. CONCLUSION: The findings suggest that cadmium exposure may increase the risk of cognitive impairment by causing shortened leukocyte telomere length.

Identification of Characteristic Genes and Immune Cell Infiltration Signatures in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a lung disease caused by limited airflow that leads to difficulty breathing. It is a major chronic disease that affects human quality of life and even endangers life. However, the exact cause of COPD is still unclear. The present study aimed to identify characteristic genes in COPD, assess the level of immune cell infiltration in COPD samples, and explore the association between characteristic genes and infiltrating immune cells. In this paper, we used dataset GSE76925 to identify 452 differentially expressed genes (DEGs) (including 407 downregulated and 45 upregulated DEGs). Gene Ontology (GO) enrichment analysis showed that the functions mainly include leukocyte migration, protein folding, negative regulation of cell activation, transcription regulator complex, collagen-containing extracellular matrix, RNA polymerase II transcription regulator complex, guanyl nucleotide binding, guanyl ribonucleotide binding, ubiquitin protein ligase binding, etc. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, pathways identified by DEGs mainly focused on Basal transcription factors, Arachidonic acid metabolism, Nucleocytoplasmic transport, Glutamatergic synapse, Ether lipid metabolism, alpha-Linolenic acid metabolism, etc. Next, we constructed a weighted gene co-expression network, identified six gene modules, found that the module with the highest correlation was the MEturquoise, and obtained 51 hub module genes. Further, 43 overlapping genes were obtained after the intersection of 452 DEGs and 51 hub genes in MEturquoise module, and seven characteristic DEGs (C-DEGs) (LOC649214, LOC440563, LOC643431, LOC642585, KRT18P17, LOC648057 and UBASH3B) were identified by the Least absolute shrinkage and selection operator (LASSO) regression method. In addition, we assessed the infiltration of 28 immune cells in 111 COPD samples and 40 NC samples, calculated and visualized the correlation between the expression of 7 C-DEGs and the infiltration level of 28 immune cells. These results will contribute to our further understanding of the molecular immunopathogenesis of COPD and have potential reference value for the development of molecular drug targets in the future.

Novel inner filter effect-based near-infrared electrochemiluminescence sensor mediated by well-matched AgBr-nitrogen-doped Ti3C2 MXene and nonmetallic plasmon WO3•H2O.

The development of innovative and efficient strategy is of paramount importance for near-infrared (NIR) electrochemiluminescence (ECL) sensing, which can substantially promote ECL detection in a wide range of situations. Herein, the inner filter effect (IFE) strategy was designed to construct an ultrasensitive NIR ECL biosensor based on the well-matched AgBr nanocrystals (NCs) decorated nitrogen-doped Ti3C2 MXene nanocomposites (AgBr-N-Ti3C2) and hydrated defective tungsten oxide nanosheets (dWO3•H2O). Specifically, the AgBr-N-Ti3C2 nanocomposites displayed extremely effective NIR ECL emission because N-doping could accelerate electron transfer and boost the red-shift of the ECL spectrum. The nonmetallic plasmon dWO3•H2O was used as an absorber due to its facile tuning of the spectra overlap and higher molar extinction coefficients. Time-resolved emission decay curves proved that the decreased ECL intensity was ascribed to the IFE-based steady quenching mechanism. With the support of tetracycline (TC) aptamer and the complementary DNA chain, the fabricated NIR ECL-IFE biosensor performed a wide linear range of 100 nM âˆ¼ 10 fM with a low detection limit of 2.2 fM (S/N = 3), and it exhibited excellent stability, sensitivity, and reproducibility, so as to be applied to real samples. This strategy opens a new avenue to constructing an efficient NIR ECL-IFE system and shows excellent practical potential in actual sample analysis.

Hydrovoltaic Effect Coupling with Capacitor Amplification: A Mode for Sensitive Self-Powered Electrochemical Sensing.

Self-powered electrochemical sensors, which can function without external electricity, are incredibly valuable in the realm of sensing. However, most of the present testing methods are normally confined to high environmental requirements, restricted lighting conditions, and temperature differences. Herein, an innovative self-powered electrochemical sensor was successfully developed based on hydrovoltaic effect coupling with capacitor amplification. Due to the combined merits from the two-dimensional transition metal carbides and nitrides (MXene)-polyaniline (PANI) with high surface potential and good hydrophilicity, and the capacitor amplification strategy, the device could harvest electric energy from water evaporation and displayed a high short circuit current value. Under optimal conditions, the proposed self-powered electrochemical sensor presented excellent sensitivity and high specificity for enrofloxacin (ENR) detection in the concentration range from 1 fM to 1 nM with a detection limit of 0.585 fM. Such a proposed sensor also has the advantages of environmental friendliness and ease of use, which is an ideal choice for accurately and precisely detecting ENR in real samples. The mode of such electrochemical detection outlined in this technical note implements a breakthrough in designing self-powered electrochemical sensors, providing a rational basis for development of a diversified sensing platform.

Ultrasensitive self-powered photoelectrochemical sensing for enrofloxacin detection by coupling piezoelectric effect with nonmetallic surface plasmon resonance based on ZnO nanorod arrays/WO3-x.

Exploring efficient strategy for high-efficiency photoelectric conversion is quite important to design sensitive self-powered photoelectrochemical (PEC) sensing platform. This work designed a high performance self-powered PEC sensing platform by the integration of piezoelectric effect with localized surface plasmon resonance (LSPR) effect based on ZnO-WO3-x heterostructures. Due to the fluid eddy induced piezoelectric effect by magnetic stirring, the piezoelectric semiconductor ZnO nanorod arrays (ZnO NRs) can facilitate the transfer of electrons and holes by generating piezoelectric potentials under external forces, thereby contributing to the performance of self-powered PEC platforms. Such working mechanism of the piezoelectric effect was studied by using the COMSOL software. Moreover, the introduction of defect engineered WO3 (WO3-x) can further broaden the light absorption and promote the charge transfer owing to the nonmetallic surface plasmon resonance effect. Remarkably, due to the synergizing piezoelectric and plasmonic effect, the photocurrent and maximum power output of ZnO-WO3-x heterostructures were enhanced by 3.3-fold and 5.5-fold than that of bare ZnO, respectively. After the immobilization of the enrofloxacin (ENR) aptamer, the self-powered sensor demonstrated an excellent linearity (1 × 10-14 M to 1 × 10-9 M) with a low detection limit of 1.8 × 10-15 M (S/N = 3). This work undoubtedly holds great promise to provide the innovative inspiration for the formation of high-performance self-powered sensing platform, which opens up a new horizon of potential in food safety and environmental monitoring.

A novel molecular mechanism mediated by circCCDC134 regulates non-small cell lung cancer progression.

BACKGROUND: Circular RNA (circRNA) plays a crucial role in non-small cell lung cancer (NSCLC) progression. However, the role of circCCDC134 in NSCLC is still largely unknown. METHODS: Quantitative real-time PCR was utilized for measuring circCCDC134, microRNA (miR)-625-5p and nuclear factor of activated T cell 5 (NFAT5) expression. Cell functions were evaluated by colony formation, EdU, transwell, and wound healing assays and flow cytometry. Glucose consumption, lactate production, and ATP level were determined to analyze cell glycolysis. Western blot analysis was used to detect protein expression. Animal experiments were performed to assess the effect of circCCDC134 on NSCLC tumor growth. RNA interaction was evaluated by dual-luciferase reporter assay and RIP assay. Exosomes were isolated from the serum of NSCLC patients and healthy normal controls. RESULTS: Highly expressed circCCDC134 was found in NSCLC tissues and cells, as well as in the serum exosomes of NSCLC patients. Downregulated circCCDC134 restrained NSCLC cell growth, metastasis and glycolysis. CircCCDC134 sponged miR-625-5p to regulate NFAT5. MiR-625-5p inhibitor abolished the regulation of circCCDC134 knockdown on NSCLC progression, and NFAT5 overexpression eliminated the effects of miR-625-5p on NSCLC cell behaviors. CircCCDC134 knockdown also inhibited NSCLC tumor growth. CONCLUSION: Our study revealed that circCCDC134 was involved in regulating NSCLC progression through the miR-625-5p/NFAT5 pathway, confirming that circCCDC134 might function as the diagnostic and therapeutic target for NSCLC.

A novel mutation in ryanodine receptor 2 (RYR2) genes at c.12670G>T associated with focal epilepsy in a 3-year-old child.

Background: Ryanodine receptor 2 (RYR2) encodes a component of a calcium channel. RYR2 variants were well-reported to be associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), but rarely reported in epilepsy cases. Here, we present a novel heterozygous mutation of RYR2 in a child with focal epilepsy. Methods: At the age of 2 years and 7 months, the patient experienced seizures, such as eye closure, tooth clenching, clonic jerking and hemifacial spasm, as well as abnormal electroencephalogram (EEG). Then, he was analyzed by whole-exome sequencing (WES). The mutations of both the proband and his parents were further confirmed by Sanger sequencing. The pathogenicity of the variant was further assessed by population-based variant frequency screening, evolutionary conservation comparison, and American Association for Medical Genetics and Genomics (ACMG) scoring. Results: WES sequencing revealed a novel heterozygous truncating mutation [c.12670G > T, p.(Glu4224*), NM_001035.3] in RYR2 gene of the proband. Sanger sequencing confirmed that this mutation was inherited from his mother. This novel variant was predicted to be damaging by different bioinformatics methods. Cardiac investigation showed that the proband had no structural abnormalities, but sinus tachycardia. Conclusion: We proposed that RYR2 is a potential candidate gene for focal epilepsy, and epilepsy patients carried with RYR2 variants should be given more attention, even if they do not show cardiac abnormalities.

Ginsenoside Rg1 suppresses paraquat-induced epithelial cell senescence by enhancing autophagy in an ATG12-dependent manner.

Paraquat (PQ), as a widely used herbicide, is highly toxic to human. PQ-induced pulmonary fibrosis is the main reason for respiratory failure and death. In PQ-poisoned mice, we find abundant senescent epithelial cells in the lung tissues, which can contribute to the activation of pulmonary fibroblasts. Ginsenoside Rg1 (Rg1), the main active component of ginseng, possess beneficial properties against aging. In our work, we aimed to investigate the potential protective effects of Rg1 on PQ-induced pulmonary fibrosis and the underlying mechanism. In vivo, the treatment of Rg1 can attenuate PQ-induced pulmonary fibrosis and decrease senescence and senescence associated secretory phenotype (SASP) expression. In vitro, Rg1 can effectively eliminate senescent cells via apoptosis, but not normal cells. In addition, we demonstrate that Rg1 can enhance autophagy activity via inducing the expression of ATG12. Inhibition of autophagy via 3-MA or transfection of the siRNA targeting ATG12 can impair the antiaging effect of Rg1. Taken together, our data implicates that Rg1 can protect pulmonary epithelial cells from PQ-induced cellular senescence in an ATG12 dependent manner, which may provide a preventive and therapeutic strategy for PQ poisoning-induced pulmonary fibrosis.

Identification of a Novel Salt Tolerance-Related Locus in Wild Soybean (Glycine soja Sieb. & Zucc.).

Salinity is an important abiotic stress factor that affects growth and yield of soybean. NY36-87 is a wild soybean germplasm with high salt tolerance. In this study, two F2:3 mapping populations derived from NY36-87 and two salt-sensitive soybean cultivars, Zhonghuang39 and Peking, were used to map salt tolerance-related genes. The two populations segregated as 1 (tolerant):2 (heterozygous):1 (sensitive), indicating a Mendelian segregation model. Using simple sequence repeat (SSR) markers together with the bulked segregant analysis (BSA) mapping strategy, we mapped a salt tolerance locus on chromosome 03 in F2:3 population Zhonghuang39×NY36-87 to a 98-kb interval, in which the known gene GmSALT3 co-segregated with the salt tolerance locus. In the F2:3 population of Peking×NY36-87, the dominant salt tolerance-associated gene was detected and mapped on chromosome 18. We named this gene GmSALT18 and fine mapped it to a 241-kb region. Time course analysis and a grafting experiment confirmed that Peking accumulated more Na+ in the shoot via a root-based mechanism. These findings reveal that the tolerant wild soybean line NY36-87 contains salt tolerance-related genes GmSALT3 and GmSALT18, providing genetic material and a novel locus for breeding salt-tolerant soybean.

Improvement of Cerebral Ischemia-Reperfusion Injury via Regulation of Apoptosis by Exosomes Derived from BDNF-Overexpressing HEK293.

Brain-derived neurotrophic factor (BDNF) provides neuroprotective effects towards therapeutic cerebral ischemia-reperfusion (I/R) injury. This view has been proposed by more and more evidence. However, due to the lack of permeability of the blood-brain barrier (BBB) as well as the brief half-life in serum, clinical application is not widespread. To study the participation of exosomes containing BDNF in I/R, we isolated exosomes from BDNF-overexpressing HEK293. The protective outcomes of exosomes in hypoxia/reoxygenation (H/R) experiments were determined by the use of SY-5Y cells. Exosome-BDNF therapy restrained H/R-induced apoptosis by inhibition of the reducing levels of oxidative stress and calcium ions in the cells while maintaining stable levels of mitochondrial membrane potential in brain cells damaged by I/R. We then constructed a cerebral I/R injury model using SD rats to find the function of BDNF in exosome-mediated neuroprotection. The in vivo experiments conducted established that exosomes from BDNF-overexpressing HEK293 cells improved cerebral I/R injury by concealing neuronal apoptosis. Findings gained demonstrated that BDNF is a part of preventing cerebral I/R injury due to exosome mediation by regulating the cellular internal environment and inhibiting apoptosis.

A Retrospective Analysis of Crayfish-Related Rhabdomyolysis (Haff Disease).

OBJECTIVE: To investigate the epidemiologic and etiologic factors, clinical features, therapeutic regimen, and prognosis of crayfish-related rhabdomyolysis (Haff disease). METHODS: Retrospectively analyzed the clinical data of 29 patients with crayfish-related rhabdomyolysis (Haff disease) from July to August 2016, summarized the clinical characteristics, and evaluated the prognosis. RESULTS: Clinical data of a total of 29 cases of Haff disease were retrospectively analyzed. The disease onset occurred after consumption of cooked crayfish with the incubation period ranging from 1 h to 48 h. There were no gender differences and significantly elevated CK in the duration with peak value of 41575.0U/L; the median value was 2445.0U/L (range: from 1187.0 U/L to 4722.0 U/L) and there was coincident elevated CK-MB. There was also no hepatorenal damage and transient urinalysis was abnormal. The most common presenting symptoms were myalgia (100%), weakness and numbness (51.7%), chest tightness and chest pain (41.4%), back pain (41.4%), and extremities pain (37.9%). All the patients recovered and no patients died. CONCLUSIONS: Crayfish-related rhabdomyolysis (Haff disease) is a kind of a case or cluster of patients present with severe myalgia or weakness of unknown etiology and mechanism disease; however, the clinical signs and symptoms are relatively mild with favorable outcome.

Salinity tolerance in soybean is modulated by natural variation in GmSALT3.

The identification of genes that improve the salt tolerance of crops is essential for the effective utilization of saline soils for agriculture. Here, we use fine mapping in a soybean (Glycine max (L.) Merr.) population derived from the commercial cultivars Tiefeng 8 and 85-140 to identify GmSALT3 (salt tolerance-associated gene on chromosome 3), a dominant gene associated with limiting the accumulation of sodium ions (Na+) in shoots and a substantial enhancement in salt tolerance in soybean. GmSALT3 encodes a protein from the cation/H+ exchanger family that we localized to the endoplasmic reticulum and which is preferentially expressed in the salt-tolerant parent Tiefeng 8 within root cells associated with phloem and xylem. We identified in the salt-sensitive parent, 85-140, a 3.78-kb copia retrotransposon insertion in exon 3 of Gmsalt3 that truncates the transcript. By sequencing 31 soybean landraces and 22 wild soybean (Glycine soja) a total of nine haplotypes including two salt-tolerant haplotypes and seven salt-sensitive haplotypes were identified. By analysing the distribution of haplotypes among 172 Chinese soybean landraces and 57 wild soybean we found that haplotype 1 (H1, found in Tiefeng 8) was strongly associated with salt tolerance and is likely to be the ancestral allele. Alleles H2-H6, H8 and H9, which do not confer salinity tolerance, were acquired more recently. H1, unlike other alleles, has a wide geographical range including saline areas, which indicates it is maintained when required but its potent stress tolerance can be lost during natural selection and domestication. GmSALT3 is a gene associated with salt tolerance with great potential for soybean improvement.

[Nicotine regulates large conductance ca2+ activated K+ channels in rat coronary arterial smooth muscle cells].

OBJECTIVE: The present study was to explore signaling mechanisms underlying nicotine-induced inhibition of large-conductance calcium-activated potassium channels (BK(Ca)). METHODS: 8 week male Wistar rats were divided randomly into saline group and nicotine group and received respectively injection with saline or nicotine (Sigma, Shanghai, China) at 2 mg/(kg x d) for 21 days. Coronary vascular smooth muscle cells were dissociated enzymatically. Dissociated smooth muscle cells were interfered with CPT-cAMP (100 micromol/L) or forskolin (10 micromol/L). The signal channel open dwell-time (To), close dwell-time (Tc) and open probability (Po) were recorded. RESULTS: CPT-cAMP or forskolin significantly prolonged To, shorten Tc and increased Po in saline group (P < 0.01). But in nicotine group To, Tc and Po did not been changed. CONCLUSION: This phenomenon may serve as a physiological mechanism that nicotine inhibits BK(Ca) channel activity to increase via cAMP/PKA-dependent pathway.

[Correlation of plasma endothelin and multiple organ dysfunction syndrome caused by acute paraquat poisoning].

OBJECTIVE: To investigate the relationship between endothelin (ET) and multiple organ dysfunction syndrome (MODS) caused by acute paraquat poisoning (APP). METHODS: The levels of plasma ET were measured by radioimmunoassay in 24 patients with MODS caused by APP and 19 healthy persons as controls. The levels of plasma ET patients in MODS caused by APP were correlatively analysed with acute physiology and chronic health evaluation II (APACHE II) score, partial pressure of oxygen in artery (PaO2), troponin I (cTnI) level, blood enzymology and biochemistry indexes. RESULTS: The levels of plasma ET in patients with MODS caused by APP were much higher than controls (P<0.01), the level of plasma ET in death group was much higher than that of survivor group (P<0.01). Plasma ET was positively correlated with APACHE II score, cTnI, MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and serum creatinine (SCr, P<0.05 or P<0.01), where there was a negative correlation with PaO2 (P<0.01). CONCLUSION: Endothelin may be involved in the pathogenesis of MODS caused by APP, plasma ET may be one of a clinical index for evaluating the degree of multiple organ function damage, for guiding treatment, and judging the prognosis of MODS caused by APP.