The current in-depth proteomics makes use of long chromatography gradient to get access to more peptides for protein identification, resulting in covering of as many as 8000 mammalian gene products ...in 3 days of mass spectrometer running time. Here we report a fast sequencing (Fast-seq) workflow of the use of dual reverse phase high performance liquid chromatography - mass spectrometry (HPLC-MS) with a short gradient to achieve the same proteome coverage in 0.5 day. We adapted this workflow to a quantitative version (Fast quantification, Fast-quan) that was compatible to large-scale protein quantification. We subjected two identical samples to the Fast-quan workflow, which allowed us to systematically evaluate different parameters that impact the sensitivity and accuracy of the workflow. Using the statistics of significant test, we unraveled the existence of substantial falsely quantified differential proteins and estimated correlation of false quantification rate and parameters that are applied in label-free quantification. We optimized the setting of parameters that may substantially minimize the rate of falsely quantified differential proteins, and further applied them on a real biological process. With improved efficiency and throughput, we expect that the Fast-seq/Fast-quan workflow, allowing pair wise comparison of two proteomes in 1 day may make MS available to the masses and impact biomedical research in a positive way.
Summary
Starch is the most abundant storage carbohydrate in maize kernels and provides calories for humans and other animals as well as raw materials for various industrial applications. Decoding the ...genetic basis of natural variation in kernel starch content is needed to manipulate starch quantity and quality via molecular breeding to meet future needs. Here, we identified 50 unique single quantitative trait loci (QTLs) for starch content with 18 novel QTLs via single linkage mapping, joint linkage mapping and a genome‐wide association study in a multi‐parent population containing six recombinant inbred line populations. Only five QTLs explained over 10% of phenotypic variation in single populations. In addition to a few large‐effect and many small‐effect additive QTLs, limited pairs of epistatic QTLs also contributed to the genetic basis of the variation in kernel starch content. A regional association study identified five non‐starch‐pathway genes that were the causal candidate genes underlying the identified QTLs for starch content. The pathway‐driven analysis identified ZmTPS9, which encodes a trehalose‐6‐phosphate synthase in the trehalose pathway, as the causal gene for the QTL qSTA4−2, which was detected by all three statistical analyses. Knockout of ZmTPS9 increased kernel starch content and, in turn, kernel weight in maize, suggesting potential applications for ZmTPS9 in maize starch and yield improvement. These findings extend our knowledge about the genetic basis of starch content in maize kernels and provide valuable information for maize genetic improvement of starch quantity and quality.
The rennin-angiotensin-aldosterone system (RAAS) plays a critical role in the pathogenesis of diabetic cardiomyopathy, but the role of a member of RAAS, angiotensin IV (Ang IV), in this disease and ...its underlying mechanism are unclear. This study was aimed to clarify the effects of Ang IV and its downstream mediator forkhead box protein O1 (FoxO1) on diabetic cardiomyopathy.
, diabetic mice were treated with low-, medium- and high-dose Ang IV, AT
R antagonist divalinal, FoxO1 inhibitor AS1842856 (AS), or their combinations.
, H9C2 cardiomyocytes and cardiac fibroblasts were treated with different concentrations of glucose, low-, medium- and high-dose Ang IV, divalinal, FoxO1-overexpression plasmid (FoxO1-OE), AS, or their combinations.
Ang IV treatment dose-dependently attenuated left ventricular dysfunction, fibrosis, and myocyte apoptosis in diabetic mice. Besides, enhanced autophagy and FoxO1 protein expression by diabetes were dose-dependently suppressed by Ang IV treatment. However, these cardioprotective effects of Ang IV were completely abolished by divalinal administration. Bioinformatics analysis revealed that the differentially expressed genes were enriched in autophagy, apoptosis, and FoxO signaling pathways among control, diabetes, and diabetes+high-dose Ang IV groups. Similar to Ang IV, AS treatment ameliorated diabetic cardiomyopathy in mice.
, high glucose stimulation increased collagen expression, apoptosis, overactive autophagy flux and FoxO1 nuclear translocation in cardiomyocytes, and upregulated collagen and FoxO1 expression in cardiac fibroblasts, which were substantially attenuated by Ang IV treatment. However, these protective effects of Ang IV were completely blocked by the use of divalinal or FoxO1-OE, and these detrimental effects were reversed by the additional administration of AS.
Ang IV treatment dose-dependently attenuated left ventricular dysfunction and remodeling in a mouse model of diabetic cardiomyopathy, and the mechanisms involved stimulation of AT
R and suppression of FoxO1-mediated fibrosis, apoptosis, and overactive autophagy.
BACKGROUND Alzheimer's disease (AD) results in cognitive impairment. The calcium voltage-gated channel subunit alpha-1 C CACNA1C gene encodes an alpha-1 C subunit of L-type calcium channel (LTCC). ...The aim of this study was to investigate the role of micro-RNA-137 (miR-137) and the CACNA1C gene in APPswe/PS1ΔE9 (APP/PS1) double-transgenic AD mice and in human neuroblastoma SH-SY5Y cells. MATERIAL AND METHODS Six-month-old APP/PS1 double-transgenic AD mice (N=6) and age-matched normal C57BL/6 mice (N=6) underwent a Morris water maze (MWM) test, expression levels of amyloid-β (Aβ), LTCC, the CACNA1C gene, and miR-137 were measured in the rat hippocampus and cerebral cortex in both groups of mice. A luciferase assay was used to evaluate the effect of miR-137 on the expression of CACNA1C in SH-SY5Y human neuroblastoma SH-SY5Y cells. Western blotting was used to detect the CACNA1C, phosphorylated-tau (p-tau), and Aβ proteins. RESULTS In APP/PS1 transgenic AD mice, spatial learning and memory was significantly reduced, levels of Aβ1-40 and Aβ1-42 were increased in the serum, hippocampus, and cerebral cortex, expression levels of miR-137 were reduced, expression of CACNA1C protein was increased in the hippocampus and cerebral cortex, compared with normal control mice. miR-137 regulated the expression of the CACNA1C gene. Increased expression levels of p-tau (Ser202, Ser396, and Ser404) induced by Aβ1-42 were inhibited by miR-137 mimics in SH-SY5Y human neuroblastoma cells in vitro. CONCLUSIONS In a transgenic mouse model of AD, miR-137 and expression of the CACNA1C gene inhibited the hyperphosphorylation of tau protein.
Chronic obstructive pulmonary disease (COPD) is an illness characterized by progressive aggravation of airflow limitation, which seriously affects patients' quality of life, and even ...life-threatening. The lung function of COPD patients is chronically and progressively deteriorated. Among them, the lung function of early COPD patients deteriorates rapidly, and forced expiratory volume in 1 second (FEV1) declines faster than other stages. If diagnosed early and effectively treated in time, it can greatly affect the prognosis. As a traditional exercise regimen, Baduanjin can improve lung function, exercise capacity, and quality of life of COPD patients. However, high-quality evidence-based medical evidence is so far be lacking to confirm the effectiveness of Baduanjin in reducing or preventing mild COPD lung function decline.
This study is a randomized controlled trial, 192 patients with mild COPD were randomly divided into experimental group and control group. Both of them will receive basic treatment (health education and Tiotropium bromide), the experimental group will receive Baduanjin exercise training, and the control group will be told to maintain the original lifestyle and control the exercise. The Baduanjin exercise will last for 24 weeks and will be followed up for 72 weeks. The primary outcome is the change in lung function, including FEV1, FEV1/forced vital capacity (FVC), and FEV1/predicted. The secondary results included COPD assessment test, 6-minute walk test, St. George Respiratory Questionnaire, and Dyspnea Scale. Safety will also serve as assessing during the test.
The results of this trial will provide that traditional Baduanjin exercises can prevent COPD lung function deterioration, and provide a simple, inexpensive, and daily pulmonary rehabilitation measure for the patients with mild COPD.
•The highly selective and stable mixed potential type YSZ-based gas sensor using Cd2V2O7-SE was fabricated for effective detection of NH3 at 650 °C.•The sensor attached with Cd2V2O7-SE displayed the ...response value of −68 mV and rapid response rate of 5 s to 100 ppm NH3 at 650 °C.•The fabricated device showed good repeatability, excellent selectivity, humidity resistance and long-term stability.•The sensitivities of the sensor decreased by 1 mV/decade to 1–10 ppm NH3 and 2.5 mV/decade to 10–200 ppm NH3 after 30 days measurement of 650 °C.
In this work, the highly selective and stable mixed potential type stabilized zirconia (YSZ) based gas sensor using Cd2V2O7 sensing electrode (SE) synthesized via simple coprecipitation method was fabricated and developed for effective detection of NH3 at 650 °C. The as-prepared Cd2V2O7 sensing material was characterized by X-ray diffraction (XRD), Raman spectrum, X-ray photoelectron spectroscopy (XPS) and Field-emission scanning electron microscopy (FESEM). The results of gas sensing measurement indicated that the sensor attached with Cd2V2O7- SE displayed the response value of −68 mV and rapid response rate of 5 s to 100 ppm NH3 at 650 °C. The present device also exhibited the low detection limit of 1 ppm and the piecewise sensitivities of −6 and −66 mV/decade to NH3 in the concentration ranges of 1–10 ppm and 10–200 ppm, respectively. Moreover, the fabricated sensor showed good reproducibility, excellent selectivity, stability to oxygen concentration, relative humidity and 30 days continuous aging of high temperature at 650 °C. And the complex impedance and polarization curves were performed to explain the selectivity and verify the sensing mechanism involving mixed potential model.
Myopia is an increasingly serious health issue among children and adolescents worldwide. This study investigated the situation related to myopia among students in Chengdu, a city in western China, ...and analyzed the prevalence of myopia spectacle wear and myopia full-correction and their influencing factors to understand the current status of myopia prevention. This school-based cross-sectional study investigated 1582 schools in seven districts of Chengdu City, China, enrolling a total of 417,337 students aged 6–18 years (elementary, middle, and high school) from 2020 to 2022. Examination items included uncorrected visual acuity (UCVA), slit lamp examination and non-cycloplegic autorefraction. Myopia was defined as non-cycloplegic SE ≤ −0.50 D + UCVA> 0 log MAR (age ≥6). The prevalence of myopia spectacle wear is defined as the number of people wearing glasses for myopia/the number of people with myopia (%) within the study population, and myopia full-correction is defined as normal vision after wearing glasses for myopia (≤0 log MAR for 6 years and above). With the support of the government, this programme is conducted 1–2 times a year. Statistical analyses are conducted to determine the association between myopia and various parameters.
The average age of the entire survey population was 10.96 ± 3.5 years, and the overall prevalence of myopia was 48.7%, myopia spectacle wear was 65.7%, and myopia full-correction was 50.5%. With increasing age and educational levels, the prevalence of moderate to high myopia, the prevalence of myopia spectacle wear, and the prevalence of myopia full-correction all rise. The prevalence of mild myopia full-correction (46.5%) was higher than that for moderate myopia (47.1%) and even higher than that for high myopia (39.6%). The correct utilization rate of myopic spectacles was 33.17%, increasing with age and education levels, with the highest correct utilization rate of 40.7% among those with moderate myopia. The prevalence of myopia among children and adolescents in Chengdu is relatively low, and the prevalence of myopia spectacle wear and myopia full-correction need to be improved, and it was found that with the increase of myopia, the prevalence of myopia full-correction among adolescents decreased instead.
β-amylase proteins (BAM) are important to many aspects of physiological process such as starch degradation. However, little information was available about the BAM genes in Annona atemoya, an ...important tropical fruit. Seven BAM genes containing the conservative domain of glycoside hydrolase family 14 (PF01373) were identified with Annona atemoya genome, and these BAM genes can be divided into four groups. Subcellular localization analysis revealed that AaBAM3 and AaBAM9 were located in the chloroplast, and AaBAM1.2 was located in the cell membrane and the chloroplast. The AaBAMs belonging to Subfamily I contribute to starch degradation have the higher expression than those belonging to Subfamily II. The analysis of the expression showed that AaBAM3 may function in the whole fruit ripening process, and AaBAM1.2 may be important to starch degradation in other organs. Temperature and ethylene affect the expression of major AaBAM genes in Subfamily I during fruit ripening. These expressions and subcellular localization results indicating β-amylase play an important role in starch degradation.
JOURNAL/nrgr/04.03/01300535-202419110-00027/figure1/v/2024-03-08T184507Z/r/image-tiff Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer's disease. Citri ...Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases, including Parkinson's and Huntington's diseases, however, the effect of Citri Reticulatae Semen on Alzheimer's disease remains unelucidated. In the current study, the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated. Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy. In addition, Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro, and suppress amyloid-beta-induced pathology such as paralysis, in a transgenic Caenorhabditis elegans in vivo model. Moreover, genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent. Most importantly, Citri Reticulatae Semen extract was confirmed to improve cognitive impairment, neuronal injury and amyloid-beta burden in 3×Tg Alzheimer's disease mice. As revealed by both in vitro and in vivo models, these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer's disease via its neuroprotective autophagic effects.
Genome-wide association study (GWAS) has identified thousands of single nucleotide polymorphisms (SNPs) associated with complex diseases and traits. However, deciphering the functions of these SNPs ...still faces challenges. Recent studies have shown that SNPs could alter chromatin accessibility and result in differences in tumor susceptibility between individuals. Therefore, systematically analyzing the effects of SNPs on chromatin accessibility could help decipher the functions of SNPs, especially those in non-coding regions. Using data from The Cancer Genome Atlas (TCGA), chromatin accessibility quantitative trait locus (caQTL) analysis was conducted to estimate the associations between genetic variants and chromatin accessibility. We analyzed caQTLs in 23 human cancer types and identified 9,478 caQTLs in breast carcinoma (BRCA). In BRCA, these caQTLs tend to alter the binding affinity of transcription factors, and open chromatin regions regulated by these caQTLs are enriched in regulatory elements. By integrating with eQTL data, we identified 141 caQTLs showing a strong signal for colocalization with eQTLs. We also identified 173 caQTLs in genome-wide association studies (GWAS) loci and inferred several possible target genes of these caQTLs. By performing survival analysis, we found that ~10% caQTLs potentially influence the prognosis of patients. To facilitate access to relevant data, we developed a user-friendly data portal, BCaQTL (
http://gong_lab.hzau.edu.cn/caqtl_database
), for data searching and downloading. Our work may facilitate fine-map regulatory mechanisms underlying risk loci of cancer and discover the biomarkers or therapeutic targets for cancer prognosis. The BCaQTL database will be an important resource for genetic and epigenetic studies.
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