Tomato (Solanum lycopersicum) stress resistance and fruit total soluble solid (TSS) content have changed dramatically during selective breeding, and transcriptome variation has played a critical role ...in this rewiring. However, the single tomato reference genome impedes characterization of whole-transcriptome variation during domestication and breeding at the population level. Here, we constructed a pan-transcriptome of orange-stage tomato fruit, and investigated global expression presence/absence variation (ePAV) and differentially expressed genes (DEGs) based on RNA sequencing (RNA-seq) data from 399 tomato accessions. A total of 7 181 genes absent from the reference genome were identified, 6 122 of which were ePAV genes during tomato domestication and breeding including resistance genes such as late blight resistance gene PIM_DN29746_c0_g3_i1 and peroxidase P7-like gene PIM_DN30274_c0_g2_i1. In addition, 3 629 genes were significantly differentially expressed during tomato selection, among which 19 genes were associated with the reduced fruit TSS content of modern tomato cultivars, including LIN5, TIV1, and seven novel sugar transporter genes. Our results indicate that natural and artificial selection greatly shaped the tomato transcriptome, thereby altering the fruit TSS content and resistance to abiotic and biotic stresses.
To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses.
A retrospective observational ...study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B).
Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.500.13-0.94 vs 0.600.26-1.23,
=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031).
Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.
Abstract Objectives The aim of this meta-analysis was to investigate whether an association existed between green tea consumption and the risk for liver cancer in prospective cohort studies in Asian ...populations. Methods Relevant studies were identified by searching PubMed, EMBASE, ISI Web of Science, and the Chinese Bio-medicine Database published before April 2015. Study-specific risk estimates for the highest versus non- or lowest and increment of daily cup of green tea consumption levels were combined based on fixed- or random-effects models. STATA 11.0 (Stata Corporation, College Station, TX, USA) software was used for statistical analysis. Results Nine prospective cohort articles involving 465,274 participants and 3694 cases of liver cancer from China, Japan, and Singapore were included. The summary relative risk (RR) indicated a significant association between the highest green tea consumption and reduced risk for liver cancer (summary RR, 0.88; 95% confidence interval CI, 0.81–0.97). However, no statistically significant association was observed when analyzing daily consumption of one cup (summary RR, 0.97; 95% CI, 0.95–1.00). When stratified by sex, the protective effect of green tea consumption on risk for liver cancer was observed only in the group of women (summary RR, 0.78; 95% CI, 0.64–0.96), but not in men (summary RR, 0.89; 95% CI, 0.79–1.00). Conclusions The present analysis indicated the preventive effects of green tea intake on the risk for liver cancer in female Asian populations. However, additional studies are needed to make a convincing case for this association.
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•The 3D SERS-active substrate, with Ag-dendrites within and on top of AAO membrane has been synthesized.•The Ag dendrite-integrated AAO membrane substrate exhibits high SERS ...sensitivity, excellent reproducibility and tunability.•Without any surface modification, the substrate shows an outstanding SERS response for the molecules with weak affinity for noble metal surfaces.
A novel surface enhanced Raman scattering (SERS)-active substrate has been successfully developed, where Ag-dendrites are assembled on the surface and embedded in the channels of anodic aluminum oxide (AAO) membrane, via electrodeposition in AgNO3/PVP aqueous system. Reaction conditions were systematically investigated to attain the best Raman enhancement. The growth mechanism of Ag dendritic nanostructures has been proposed. The Ag dendrite-integrated AAO membrane with unique hierarchical structures exhibits high SERS activity for detecting rhodamine 6G with a detection limit as low as 1×10−11M. Furthermore, the three-dimensional (3D) substrates display a good reproducibility with the average intensity variations at the major Raman peak less than 12%. Most importantly, the 3D SERS substrates without any surface modification show an outstanding SERS response for the molecules with weak affinity for noble metal surfaces. The potential application for the detection of polycyclic aromatic hydrocarbons (PAHs) was evaluated with fluoranthene as Raman target molecule and a sensitive SERS detection with a limit down to 10−8M was reached. The 3D SERS-active substrate shows promising potential for rapid detection of trace organic pollutants even weak affinity molecules in the environment.
Miniaturized mass spectrometers have become increasingly prevalent for real-time detection and analysis, owing to their compact size and portability. The pursuit of performance enhancement in these ...instruments is a pivotal objective within the domain of mass spectrometry miniaturization. This study introduces a novel miniature mass spectrometer featuring a discontinuous atmospheric pressure interface and a dual pressure chamber. Compared to conventional single-chamber, discontinuous sampling interface mass spectrometers, the newly developed instrument demonstrates a more than tenfold improvement in detection efficiency. This significant enhancement is achieved without the need for complex control of switch coupling time series, thereby streamlining the circuit design and improving the instrument's fault tolerance. Furthermore, by capitalizing on the benefits of discontinuous sampling, the instrument reduces the operational pressure relative to traditional continuous sampling in differential pressure vacuum chambers. It accommodates larger inlet capillary (0.38 mm) and skimmer (0.5 mm) diameters, leading to a ninefold increase in response strength for risperidone and lowering the detection limit to 0.5 ppb. The instrument's capacity for rapid drug detection, along with enhanced resolution and detection limits, underscores its potential utility. Additionally, it facilitates the use of smaller mechanical pumps, significantly diminishing both the instrument's volume and power consumption. This presents a promising avenue for further miniaturization of mass spectrometers.
The unit uses a pinch valve for discontinuous atmospheric pressure interface and a skimmer is used to isolate the two chambers and ultimately achieve vacuum differential pressure After ions pass through the sample enter tube, they are focused on the axis through the ion funnel and passed through the skimmer. Entrance lens is used to reduce the effect of air impact on ions. The linear ion trap finally captures ions and completes the analysis. Display omitted
•The new instrument outperforms the discontinuous atmospheric pressure interface mass spectrometer in detection efficiency.•The new instrument has better resolution than the continuous atmospheric pressure interface mass spectrometer.•The new instrument has a better detection limit than the continuous atmospheric pressure interface mass spectrometer.•The newly developed instrument has a more relaxed choice of pump.
Homocysteine (Hcy) is a sulfur‐containing amino acid that originated in methionine metabolism and the elevated level of Hcy in plasma is considered to be an independent risk factor for cardiovascular ...diseases (CVD). Endothelial dysfunction plays a major role in the development of CVD, while the potential mechanism of Hcy‐induced endothelial dysfunction is still unclear. Here, in Hcy‐treated endothelial cells, we observed the destruction of mitochondrial morphology and the decline of mitochondrial membrane potential. Meanwhile, the level of ATP was reduced and the reactive oxygen species was increased. The expressions of dynamin‐related protein 1 (Drp1) and phosphate‐Drp1 (Ser616) were upregulated, whereas the expression of mitofusin 2 was inhibited by Hcy treatment. These findings suggested that Hcy not only triggered mitochondrial dysfunction but also incurred an imbalance of mitochondrial dynamics in endothelial cells. The expression of mitochondrial calcium uniporter (MCU) was activated by Hcy, contributing to calcium transferring into mitochondria. Interestingly, the formation of mitochondria‐associated membranes (MAMs) was increased in endothelial cells after Hcy administration. The inositol 1,4,5‐triphosphate receptor (IP3R)–glucose‐regulated protein 75 (Grp75)–voltage‐dependent anion channel (VDAC) complex, which was enriched in MAMs, was also increased. The accumulation of mitochondrial calcium could be blocked by inhibiting with the IP3R inhibitor Xestospongin C (XeC) in Hcy‐treated cells. Then, we confirmed that the mitochondrial dysfunction and the increased mitochondrial fission induced by Hcy could be attenuated after Hcy and XeC co‐treatment. In conclusion, Hcy‐induced mitochondrial dysfunction and dynamics disorder in endothelial cells were mainly related to the increase of calcium as a result of the upregulated expressions of the MCU and the IP3R–Grp75–VDAC complex in MAMs.
Saxagliptin is a dipeptidyl peptidase 4 (DPP‐4) inhibitor widely used in patients with type 2 diabetes. It can increase the amount of insulin after meals and lower blood sugar. CYP450 3A4 (CYP3A4) ...can metabolize about 30%–40% of therapeutic drugs. Individual differences caused by CYP3A4 genetic polymorphisms can lead to treatment failure, unpredictable side effects, or severe drug toxicity. The aim of this study was to evaluate the catalytic activities of 27 CYP3A4 variants on saxagliptin metabolism in vitro, which were identified in human CYP alleles. We successfully constructed 27 kinds of wild‐type and variant vectors of pFast‐dual‐OR‐3A4 by overlap extension PCR and prepared 27 kinds of CYP3A4 highly expressed cell microsomes by baculovirus insect cell expression system. The ultra‐performance liquid chromatography tandem mass spectrometry (UPLC‐MS/MS) was used to detect the concentrations of the metabolite of saxagliptin (5‐hydroxysaxagliptin) and the internal standard. Compared with the wild‐type CYP3A4.1, the intrinsic clearance values of most varieties decreased to 1.91%–77.08%. Most of these varieties showed a decrease in Vmax and an increase in Km values compared with wild type. We are the first to report the vitro metabolic data of 27 CYP3A4 variants of the metabolism of saxagliptin which can deepen our understanding of individualized drug use by combining previous studies about the effects of CYP3A4 variants of drug metabolism. With further in vivo studies, we hope it can guide individualized drug use in the clinic when the variants with low metabolic activity to saxagliptin were sequenced in the human body.
Roxarsone (3-nitro-4-hydroxyphenylarsonic acid, Rox(V)), an extensively used organoarsenical feed additive, enters soils through the application of Rox(V)-containing manure and further degrades to ...highly toxic arsenicals. Microplastics, as emerging contaminants, are also frequently detected in soils. However, the effects of microplastics on soil Rox(V) degradation are unknown. A microcosm experiment was conducted to investigate soil Rox(V) degradation responses to polyethylene (PE) microplastics and the underlying mechanisms. PE microplastics inhibited soil Rox(V) degradation, with the main products being 3-amino-4-hydroxyphenylarsonic acid 3-AHPAA(V), N-acetyl-4-hydroxy-m-arsanilic acid N-AHPAA(V), arsenate As(V), and arsenite As(III). This inhibition was likely driven by the decline in soil pH by PE microplastic addition, which may directly enhance Rox(V) sorption in soils. The decreased soil pH further suppressed the nfnB gene related to nitroreduction of Rox(V) to 3-AHPAA(V) and nhoA gene associated with acetylation of 3-AHPAA(V) to N-AHPAA(V), accompanied by a decrease in the relative abundance of possible Rox(V)-degrading bacteria (e.g., Pseudomonadales), although the diversity, composition, network complexity, and assembly of soil bacterial communities were largely influenced by Rox(V) rather than PE microplastics. Our study emphasizes microplastic-induced inhibition of Rox(V) degradation in soils and the need to consider the role of microplastics in better risk assessment and remediation of Rox(V)-contaminated soils.
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•Rox(V) mainly degraded to 3-AHPAA(V), N-AHPAA(V), and inorganic arsenic in soils.•PE microplastic addition inhibited Rox(V) degradation in soils.•PE microplastic-induced decline in soil pH affected Rox(V) degradation.•PE microplastics suppressed the nfnB and nhoA genes involved in Rox(V) degradation.•PE microplastics shifted soil bacterial communities much less than Rox(V).
ABSTRACT
Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) is a dedicated mission, launched in December 2020, for gamma-ray transients, including gamma-ray bursts ...(GRBs) and soft gamma repeater (SGR) bursts in the multimessenger and multiwavelength astronomy era. Since GECAM consists of two independent spacecrafts (or say instruments), and the framework of data analysis for multiple spacecrafts is distinctive from that for only one spacecraft, which is the case for most GRB missions, we developed a dedicated pipeline called Energetic Transients Joint Analysis System for Multi-INstrument (ETJASMIN) for GECAM mission. This pipeline has been naturally extended to incorporate data from other gamma-ray instruments, including the operating missions, such as Insight-HXMT/HE, Fermi/GBM, Swift/BAT, INTEGRAL/SPI-ACS, Konus-Wind, and GRID, as well as the forthcoming missions, such as SVOM/GRM and HEBS. In this paper, we present this pipeline with a focus on the data analysis procedures, methodology, and results in terms of the localization, verification (classification), spectral, and temporal analyses of gamma-ray transients. We show that this pipeline could provide more accurate, reliable, and comprehensive results than that of individual spacecraft, which is beneficial for gamma-ray transients observation.
A 8‐week feeding trial was conducted to evaluate the effects of combined oral administration of the yeast Rhodotorula sp. H26 and bacterium Bacillus sp. BC26 on growth, digestive enzyme activity, ...body composition, immunity, and intestinal microbiota in the juvenile sea cucumber, Apostichopus japonicus. Sea cucumbers were divided into four groups and received one of the following diets: BD) basal diet; H) H26; B) BC26; HB) H26 + BC26. After feeding for 4 and/or 8 weeks, sea cucumbers fed the HB diet showed a significant increase in specific growth rate, pepsin, trypsin, amylase, and lipase activities, and body wall crude protein, carbohydrate, arachidonic and adrenic acids contents compared with the BD and/or single probiont (H26 and/or BC26) groups. Feeding the mixture significantly improved phagocytic activity and respiratory burst of the coelomocytes, and lysozyme activity and phenoloxidase activity of the coelomic fluid supernatant and coelomocyte lysate supernatant compared with the BD and and/or single probiont (H26 and/or BC26) groups. Gel electrophoresis revealed that the mixture of H26 and BC26 did not significantly affect the composition of intestinal microbiota. These data suggest that a mixture of H26 and BC26 supplementation can improve the growth, enhance digestive enzyme activity, add nutritional value, and stimulate the innate immune system of sea cucumber juveniles.
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