•A relatively quantitative targeted method for simultaneous determination of amino acids and neurotransmitters is reported.•The QC-RFSC algorithm was applied to correct for signal drift in the ...large-scale analysis to improve the data quality.•The method was first applied to identify differential levels of serum metabolites between patients with major depression and controls.•Urocanic acid, which promotes glutamate biosynthesis and release, was found to be significantly lowered in major depression.
Targeted metabolomics analysis based on triple quadrupole (QQQ) MS coupled with multiple reaction monitoring mode (MRM) is the gold standard for metabolite quantification and it is widely applied in metabolomics. However, standard compounds for each metabolite and the corresponding analogs are necessary for quantitative measurements. To identify the differentially present metabolites in various groups, determining the relative concentration of metabolites would be more efficient than accurate quantification. In this study, a relatively quantitative targeted method was established for metabonomics research, on the basis of hydrophilic interaction liquid chromatography (HILIC)/QQQ MS operated in MRM mode. The quality control-base random forest signal correction algorithm (QC-RFSC algorithm) was applied for quality control instead of the internal standard method. High quality relative quantification was achieved without internal standards, and integrated peak areas were successfully used for statistical and pathway analyses. Amino acids and neurotransmitters (dopamine, kynurenic acid, urocanic acid, tryptophan, kynurenine, tyrosine, valine, threonine, serine, alanine, glycine, glutamine, citrulline, GABA, glutamate, aspartate, arginine, ornithine and histidine) in serum samples were simultaneously determined with the newly developed method. To demonstrate the applicability of this method in large-scale analyses, we analyzed the above metabolites in serum from patients with major depression. The serum levels of glutamate, aspartate, threonine, glycine and alanine were significantly higher, and those of citrulline, kynurenic acid and urocanic acid were significantly lower, in patients with major depression than in controls. This is the first report of the difference in urocanic acid, a compound reported to improve glutamate biosynthesis and release in the central nervous system, between healthy controls and patients with major depression.
Thoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are mainly caused by variants in the ...MYH11 gene, which encodes the heavy chain of myosin 11. The aim of this study was to evaluate the genotype-phenotype correlation of MYH11 from a distinctive perspective based on a pair of monozygotic twins.
The detailed phenotypic characteristics of the monozygotic twins from the early fetal stage to the infancy stage were traced and compared with each other and with those of previously documented cases. Whole-exome and Sanger sequencing techniques were used to identify and validate the candidate variants, facilitating the analysis of the genotype-phenotype correlation of MYH11.
The monozygotic twins were premature and presented with PDA, pulmonary hypoplasia, and pulmonary hypertension. The proband developed heart and brain abnormalities during the fetal stage and died at 18 days after birth, whereas his sibling was discharged after being cured and developed normally post follow-up. A novel variant c.766 A > G p. (Ile256Val) in MYH11 (NM_002474.2) was identified in the monozygotic twins and classified as a likely pathogenic variant according to the American College of Medical Genetics/Association for Molecular Pathology guidelines. Reviewing the reported cases (n = 102) showed that the penetrance of MYH11 was 82.35%, and the most common feature was TAAD (41.18%), followed by PDA (22.55%), compound TAAD and PDA (9.80%), and other vascular abnormalities (8.82%). The constituent ratios of null variants among the cases with TAAD (8.60%), PDA (43.8%), or compound TAAD and PDA (28.6%) were significantly different (P = 0.01). Further pairwise comparison of the ratios among these groups showed that there were significant differences between the TAAD and PDA groups (P = 0.006).
This study expands the mutational spectrum of MYH11 and provides new insights into the genotype-phenotype correlation of MYH11 based on the monozygotic twins with variable clinical features and outcomes, indicating that cryptic modifiers and complex mechanisms beside the genetic variants may be involved in the condition.
In this work, we have developed an electrochemical sensor for label-free and ultrasensitive detection of DNA (exemplified by breast cancer 1 gene) by using a photocatalytic reaction. Upon recognition ...of target DNA, the ethidium bromide molecules which were embedded in the hybridized double strand DNA (dsDNA, target DNA and capture DNA) could photo-catalytically generate singlet oxygen upon green light emitting diode irradiation, leading to an efficient cleave of the dsDNA. As a result, the voltammetry for the Fe(CN)63−/4− was improved remarkably because of less blocking of electrode and weaker charge repulsion. Such a simple strategy provided an ultrasensitive detection of breast cancer 1 gene down to the attomolar level with a broad linear range (10 aM-100 nM). The sensor is by far the most sensitive electrochemical method for detection of breast cancer 1 gene without an amplification procedure. Also the sensor can discriminate mismatched DNA from perfectly matched target DNA with high selectivity. Therefore, simplicity, high sensitivity and specificity provided by this photocatalytic eletrosensor will make it a promising tool for early diagnosis of gene-related diseases.
•A label-free photocatalytic electrosensor was developed.•The fabricated sensor can be applied for ultrasensitive detection of BRCA1 gene.•The sensor is a potentially appealing tool for early diagnosis of gene-related diseases.
As the largest organ of the human body, the skin serves as the primary barrier against external damage. The continuous increase in human activities and environmental pollution has resulted in the ...ongoing depletion of the ozone layer. Excessive exposure to ultraviolet (UV) radiation enhances the impact of external factors on the skin, leading to photoaging. Photoaging causes physical and psychological damage to the human body. The prevention and management of photoaging have attracted increased attention in recent years. Despite significant progress in understanding and mitigating UV-induced photoaging, the precise mechanisms through which autophagy contributes to the prevention of photoaging remain unclear. Given the important role of autophagy in repairing UV-induced DNA damage and scavenging oxidized lipids, autophagy is considered a novel strategy for preventing the occurrence of photoaging and other UV light-induced skin diseases. This review aims to elucidate the biochemical and clinical features of photoaging, the relationship of skin photoaging and chronological aging, the mechanisms underlying skin photoaging and autophagy, and the role of autophagy in skin photoaging.
Bacterial wilt is accompanied by microbial communities shift and soil acidification. However, the relationship between the changes of bacterial communities and bacterial wilt under the influence of ...different acidification levels has not been fully elucidated. Here, we analyzed the abundance of Ralstonia solanacearum, rhizosphere bacterial communities and carbon metabolism at differently acidic levels (pH 6.45, pH 5.60, pH 5.35, pH 4.90 and pH 4.45) and soil amendment treatment (CaO). The results indicated that both the abundance of R. solanacearum and the incidence of bacterial wilt showed a significant trend of first increasing and then decreasing with the increase of soil pH. The Firmicutes phylum and potentially beneficial genera
,
,
and Pseudomonas were significantly enriched at pH 6.45. The metabolic ability in response to the l-arginine and 4-hydroxybenzoic acid was significantly increased at pH 6.45. After using CaO to increase the pH of diseased soil from 5.45 to 6.05, the abundance of R. solanacearum and the incidence of bacterial wilt were significantly reduced, the Firmicutes and potentially beneficial genera
and Pseudomonas were significantly enriched. Overall, alleviating soil acidification to a slightly acidic level (pH 6.0-6.5) could suppress bacterial wilt by suppressing the growth of R. solanacearum and enriching the rhizosphere potentially beneficial bacteria, and further emphasized the importance of increasing soil pH in biological control of bacterial wilt.
The rhizosphere microbiota and soil acidification have been shown to have impacts on bacterial wilt. However, the influence of different acidification levels on the rhizosphere communities and bacterial wilt has not been fully studied. In this study, the potentially beneficial bacteria (
and Pseudomonas) were significantly enriched in the slightly acidic soil (pH 6.45), leading to the increase of the metabolism of 4-hydroxybenzoic acid and the decrease of pathogenic R. solanacearum, thereby alleviating the occurrence of bacterial wilt. The changes of potentially beneficial bacteria and pathogenic R. solanacearum in strongly acidic soil (pH 5.35) with the highest incidence of bacterial wilt were just the opposite. These findings help clarify the mechanisms by which soil bacteria exert influence on bacterial wilt outbreak under different soil acidification levels.
In the field of digital humanities, color research aims to discover explanations for painting history and color usage habits. However, researchers analyzing color relationships is challenging and ...time-consuming, as it requires color extraction and a detailed review of many painting images for reference and comparison of color relationships. In our work, we propose ColorNetVis, an interactive color network analysis tool that enables researchers to explore color relationships through color networks. The core of ColorNetVis is a bipartite network model that establishes a bipartite relationship between colors and Chinese painting within a scope based on color difference measurement. It constructs a one-mode color network through projection algorithms and similarity calculation methods to discover the relationship between colors. We propose a coordinated set of views to demonstrate the combination of determined color networks with painting types and real-world attributes. We use color space view, color attribute distribution view, and single color query components to assist researchers in conducting detailed color analysis and validation. Through case studies, researcher reviews, and user studies, we demonstrate that ColorNetVis can effectively help researchers discover knowledge of color relationships and potential color research directions.
Investigation of electron transfer (ET) between photosensitizers (PSs) and adjacent substrates in hypoxic tumors is integral to highly efficient tumor therapy. Herein, the oxygen-independent ET ...pathway to generate hydrogen free radicals (H˙) was established by the in situ self-assembled phototherapeutic agent d -S T under near-infrared (NIR)-light irradiation, coupled with the oxidation of reduced coenzyme NADPH, which induced ferroptosis and effectively elevated the therapeutic performance in hypoxic tumors. The higher surface energy and longer exciton lifetimes of the fine crystalline d -S T nanofibers were conducive to improving ET efficiency. In hypoxic conditions, the excited d -S T can effectively transfer electrons to water to yield H˙, during which the overexpressed NADPH with rich electrons can power the electron flow to facilitate the generation of H˙, accompanied by NADP + formation, disrupting cellular homeostasis and triggering ferroptosis. Tumor-bearing mouse models further showed that d -S T accomplished excellent phototherapy efficacy. This work sheds light onto the versatile electron pathways between PSs and biological substrates.
Sedum plumbizincicola is an herbaceous species tolerant of excessive cadmium accumulation in above-ground tissues. The implications of membrane proteins, especially integrative membrane proteins, in ...Cd detoxification of plants have received attention in recent years, but a comprehensive profiling of Cd-responsive membrane proteins from Cd hyperaccumulator plants is lacking. In this study, the membrane proteins of root, stem, and leaf tissues of S. plumbizincicola seedlings treated with Cd solution for 0, 1 or 4 days were analyzed by Tandem Mass Tag (TMT) labeling-based proteome quantification (Data are available via ProteomeXchange with identifier PXD025302). Total 3353 proteins with predicted transmembrane helices were identified and quantified in at least one tissue group. 1667 proteins were defined as DAPs (differentially abundant proteins) using fold change >1.5 with p-values <0.05. The number of DAPs involved in metabolism, transport protein, and signal transduction was significantly increased after exposure to Cd, suggesting that the synthesis and decomposition of organic compounds and the transport of ions were actively involved in the Cd tolerance process. The number of up-regulated transport proteins increased significantly from 1-day exposure to 4-day exposure, from 5 to 112, 16 to 42, 18 to 44, in root, stem, and leaf, respectively. Total 352 Cd-regulated transport proteins were identified, including ABC transporters, ion transport proteins, aquaporins, proton pumps, and organic transport proteins. Heterologous expression of SpABCB28, SpMTP5, SpNRAMP5, and SpHMA2 in yeast and subcellular localization showed the Cd-specific transport activity. The results will enhance our understanding of the molecular mechanism of Cd hypertolerance and hyperaccumulation in S. plumbizincicola and will be benefit for future genetic engineering in phytoremediation.
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•A total of 3353 membrane proteins are first identified from Sedum plumbizincicola.•Cd up-regulates lots of proteins related to metabolism, signal transduction, and protein transport.•SpABCB28, SpMTP5, SpNRAMP5, and SpHMA2 influence Cd sensitivity and accumulation.
Photocatalytic degradation of MB (a) and Tc (b) over different photocatalysts.
•Phosphorous-doped anatase P-TiO2 was prepared by rapid microwave hydrothermal method.•Steps-controlling model was ...applied for preparing catalysts.•P-TiO2-2 exhibited highest degradation efficiency for MB and Tc.
Phosphorous-doped anatase TiO2 powders (P-TiO2) were prepared by rapid microwave hydrothermal method. The resulting materials were characterized by XRD, SEM, XPS, DRS and N2 adsorption. P-doping decreased the band gap and enlarged the surface area of P-doped samples than that of undoped TiO2 samples. Therefore, the photocatalytic degradation of methyl blue (MB) and tetracycline hydrochloride (Tc) experiments showed that the P-TiO2 catalysts, especially the two-steps-controlling products P-TiO2-2, exhibited higher degradation efficiency than the undoped TiO2 and commercial P25 under visible-light irradiation. Hydroxyl radicals (OH) have been confirmed to be the active species during the photocatalytic oxidation reaction. The microwave hydrothermal method confirms to be very suitable for the synthesis of superior visible-light activity P-doped samples.
The intricate relationship between hypertension and chronic kidney disease (CKD) presents a global challenge for prevention of hypertension-related CKD. This study's objective is to analyze age, ...gender, regional disparities, and evolving trends in the disease burden of hypertension-related CKD. We aim to estimate changing spatial and temporal trends in incidence and mortality rates, considering the socio-demographic index (SDI), to inform health strategies effectively.
Age-standardized incidence rates (ASIR) and death rates (ASDR) were collected from the GBD 2019. Trend analysis was conducted by Joinpoint regression of ASRs from 1990 to 2019. Spatial autocorrelation analysis was performed to obtain spatial patterns. The association between SDI and burden of CKD due to hypertension was estimated using a Pearson correlation analysis.
The global ASIR and ASDR due to hypertension-related CKD were 19.45 (95% CI, 17.85 to 21.09) and 5.88 (95% CI, 4.95 to 6.82) per 100 K population in 2019, representing increases of 17.89% and 13.29% compared to 1990, respectively. The elderly population and males were found the highest ASIR and ASDR. The high SDI region had the highest ASIRs, while low SDI regions experienced the highest ASDRs. Joinpoint regression found both global ASIR and ASDR showed increasing trends, with the highest increases observed in middle- and high-SDI regions, respectively. The SDI exhibited a positive association with ASIRs but displayed an inverse V-shaped correlation with the average annual percentage change (AAPC) of ASIRs. Spatial autocorrelation analysis revel significant positive spatial autocorrelation for the AAPC of ASDRs and ASIRs, from 1990 to 2019.
Results met the objectives, and demonstrated a rising global burden of hypertension-related CKD. Factors such as aging, gender, and regional variations should be considered when designing control measures and developing healthcare systems to effectively address the burden of this complex condition.
