Search

Background: Higher dietary quality, including increased vegetable consumption, was associated with a reduced risk of metabolic syndrome (MetS). However, specific vegetable consumption in the development of MetS remains obscure. Our study aimed to investigate the correlation between starchy and non-starchy vegetables and MetS. Methods: Secondary data analysis from the National Health and Nutrition Examination Survey (NHANES 1999–2018). MetS was defined by National Cholesterol Education Program-Adult treatment Panel III (NCEP ATPIII) and dietary consumption was assessed by trained staff using two 24-h diet recall methods. Weighted logistic regression analysis was carried out to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses and restricted cubic spline (RCS) regression were performed to further investigate specific vegetable subtypes and MetS. Results: This research enrolled 24,646 individuals (11,725 females and 12,921 males), with an average age of 45.84 ± 0.23 years. Approximately 15,828(64.22%) participants were defined to be with non-MetS and 8818(35.78%) were with MetS. Both total starchy vegetables and potatoes were associated with increased MetS risk, with the corresponding OR per standard deviation (SD) (95%CI, p-trend) being 1.06(1.02–1.11, p-trend = 0.028) and 1.08(1.04–1.13, p-trend = 0.011), respectively. However, an inverse correlation was found between dark-green vegetables and MetS, and the OR per SD (95%CI, p-trend) was 0.93(0.90–0.97, p-trend = 0.010). Subgroup analyses showed that the positive associations of starchy vegetables and potatoes on MetS risk were stronger in non-Hispanic White participants (p for interaction < 0.050). Conclusion: Total starchy vegetables and white potatoes were both associated with an increased risk of MetS, while consumption of dark-green vegetables was negatively associated with MetS risk. These findings might provide a promising and healthy dietary strategy for preventing MetS. [ABSTRACT FROM AUTHOR]

Background: Brugada syndrome (BrS) is causing sudden cardiac death (SCD) mainly at young age. Studying the underlying mechanisms associated with BrS type I electrocardiogram (ECG) changes in the presence of fever and roles of autophagy for BrS remains lacking. Objectives: We sought to study the pathogenic role of an SCN5A gene variant for BrS with fever‐induced type 1 ECG phenotype. In addition, we studied the role of inflammation and autophagy in the pathomechanism of BrS. Methods: Human‐induced pluripotent stem cell (hiPSC) lines from a BrS patient harboring a pathogenic variant (c.3148G>A/p. Ala1050Thr) in SCN5A and two healthy donors (non‐BrS) and a CRISPR/Cas9 site‐corrected cell line (BrS‐corr) were differentiated into cardiomyocytes (hiPSC‐CMs) for the study. Results: Reductions of Nav1.5 expression, peak sodium channel current (INa) and upstroke velocity (Vmax) of action potentials with an increase in arrhythmic events were detected in BrS compared to non‐BrS and BrS‐corr cells. Increasing the cell culture temperature from 37 to 40°C (fever‐like state) exacerbated the phenotypic changes in BrS cells. The fever‐effects were enhanced by protein kinase A (PKA) inhibitor but reversed by PKA activator. Lipopolysaccharides (LPS) but not increased temperature up to 40°C enhanced the autophagy level in BrS‐hiPSC‐CMs by increasing reactive oxidative species and inhibiting PI3K/AKT signalling, and hence exacerbated the phenotypic changes. LPS enhanced high temperature‐related effect on peak INa shown in BrS hiPSC‐CMs. Effects of LPS and high temperature were not detected in non‐BrS cells. Conclusions: The study demonstrated that the SCN5A variant (c.3148G>A/p.Ala1050Thr) caused loss‐of‐function of sodium channels and increased the channel sensitivity to high temperature and LPS challenge in hiPSC‐CMs from a BrS cell line with this variant but not in two non‐BrS hiPSC‐CM lines. The results suggest that LPS may exacerbate BrS phenotype via enhancing autophagy, whereas fever may exacerbate BrS phenotype via inhibiting PKA‐signalling in BrS cardiomyocytes with but probably not limited to this variant. [ABSTRACT FROM AUTHOR]

This study introduces an innovative brain-targeted drug delivery system, RVG-Exo/CBD, utilizing rabies virus glycoprotein (RVG)-engineered exosomes for encapsulating cannabidiol (CBD). The novel delivery system was meticulously characterized, confirming the maintenance of exosomal integrity, size, and successful drug encapsulation with a high drug loading rate of 83.0 %. Evaluation of the RVG-Exo/CBD's brain-targeting capability demonstrated superior distribution and retention in brain tissue compared to unmodified exosomes, primarily validated through in vivo fluorescence imaging. The efficacy of this delivery system was assessed using a behavioral sensitization model in mice, where RVG-Exo/CBD notably suppressed methamphetamine-induced hyperactivity more effectively than CBD alone, indicating a reduction in effective dose and enhanced bioavailability. Overall, the RVG-Exo/CBD system emerges as a promising strategy for enhancing the therapeutic efficacy and safety of CBD, particularly for neurological applications, highlighting its potential for addressing the limitations associated with traditional CBD administration in clinical settings. • RVG-Exo/CBD maintained the morphology, structure and particle size of exosomes. • RVG-Exo/CBD exhibited superior brain-targeting efficacy both in vitro and in vivo. • RVG-Exo/CBD improved the bioavailability of CBD. [ABSTRACT FROM AUTHOR]

Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction. Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study. Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (I SK1 – 3) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of I SK1 – 3. H 2 O 2 enhanced I SK1 – 3 and ET-1 production. Enhancing I SK1 – 3 caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways. The study demonstrates that high concentration catecholamine can activate SK1–3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction. Roles of alpha 1 receptor, ROS, and SK1–3 channels in catecholamine induced endothelial dysfunction. In catecholamine excess, alpha 1 receptor in endothelial cells is activated and then NADPH is activated. NADPH increases ROS generation. Increased ROS level leads to 1) increase in ET-1 production and 2) activation of SK1–3 channels. The activation of SK1–3 channels causes membrane hyperpolarization. The hyperpolarization in endothelial cell can enhance the driving force for calcium influx through calcium conducting channel like TRP channel, resulting in an increase in Ca2+-influx. At the same time, the hyperpolarization can also directly hyperpolarize smooth muscle though gap-junctions and in turn may reduce smooth muscle contraction. The increased calcium influx can stimulate generation of ET-1 and ROS, and also SK channels (here is a positive feedback regulation). ET-1 released from endothelial cells stimulates ETA receptors on smooth muscle cells and lead to cell contraction. In catecholamine excess, the effect of ET-1 may overcome the hyperpolarization effect on smooth muscle, leading to vasoconstriction. Epi, epinephrine; alpha-1, alpha-1 adrenoceptor; SK, SK1–3 channels; TRP, TRP channel; HP, hyperpolarization; GJ, gap-junction; ETA, ET-1 receptor; NADPH, NADPH oxidases; ROS, reactive oxygen species. [Display omitted] • Epinephrine can activate SK1–3 channel in endothelial cells via alpha 1 receptor signalling. • SK1–3 channels contribute to alpha 1 receptor activation induced ROS/ET-1 generation. • ROS can enhance ET-1 generation in calcium dependent- and independent ways. • SK1–3 channels are important for catecholamine excess induced endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Fusarium wilt is one of the major biotic factors limiting cucumber (Cucumis sativus L.) growth and yield. The outcomes of cucumber‐Fusarium interactions can be influenced by the form of nitrogen nutrition (nitrate [NO3−] or ammonium [NH4+]); however, the physiological mechanisms of N‐regulated cucumber disease resistance are still largely unclear. Here, we investigated the relationship between nitrogen forms and cucumber resistance to Fusarium infection. Our results showed that on Fusarium infection, NO3− feeding decreased the levels of the fungal toxin, fusaric acid, leaf membrane oxidative, organelle damage and disease‐associated loss in photosynthesis. Metabolomic analysis and gas‐exchange measurements linked NO3− mediated plant defence with enhanced leaf photorespiration rates. Cucumber plants sprayed with the photorespiration inhibitor isoniazid were more susceptible to Fusarium and there was a negative correlation between photorespiration rate and leaf membrane injury. However, there were positive correlations between photorespiration rate, NO3− assimilation and the tricarboxylic acid (TCA) cycle. This provides a potential electron sink or the peroxisomal H2O2 catalysed by glycolate oxidase. We suggest that the NO3− nutrition enhanced cucumber resistance against Fusarium infection was associated with photorespiration. Our findings provide a novel insight into a mechanism involving the interaction of photorespiration with nitrogen forms to drive wider defence. Nitrate‐nitrogen can enhance plant disease resistance by improving photorespiration. This response is related to the potential electron sink or peroxisome hydrogen peroxide signal. [ABSTRACT FROM AUTHOR]

To assess the influence of lipid-lowering therapy on coronary plaque volume, and to identify the LDL and HDL targets for plaque regression to provide a comprehensive overview. The databases searched (from inception to 15 July 2020) to identify prospective studies investigating the impact of lipid-lowering therapy on coronary plaque volume and including quantitative measurement of plaque volume by intravascular ultrasound after treatment. Thirty-one studies that included 4997 patients were selected in the final analysis. Patients had significantly lower TAV (SMD: 0.123 mm3; 95% CI 0.059, 0.187; P = 0.000) and PAV (SMD: 0.123%; 95% CI 0.035, 0.212; P = 0.006) at follow-up. According to the subgroup analyses, TAV was significantly reduced in the LDL < 80 mg/dL and HDL > 45 mg/dL group (SMD: 0.163 mm3; 95% CI 0.092, 0.234; P = 0.000), and PAV was significantly reduced in the LDL < 90 mg/dL and HDL > 45 mg/dL group (SMD: 0.186%; 95% CI 0.081, 0.291; P = 0.001).Thirty-one studies that included 4997 patients were selected in the final analysis. Patients had significantly lower TAV (SMD: 0.123 mm3; 95% CI 0.059, 0.187; P = 0.000) and PAV (SMD: 0.123%; 95% CI 0.035, 0.212; P = 0.006) at follow-up. According to the subgroup analyses, TAV was significantly reduced in the LDL < 80 mg/dL and HDL > 45 mg/dL group (SMD: 0.163 mm3; 95% CI 0.092, 0.234; P = 0.000), and PAV was significantly reduced in the LDL < 90 mg/dL and HDL > 45 mg/dL group (SMD: 0.186%; 95% CI 0.081, 0.291; P = 0.001). Our meta-analysis suggests that not only should LDL be reduced to a target level of < 80 mg/dL, but HDL should be increased to a target level of > 45 mg/dL to regress coronary plaques. Trial Registration PROSPERO identifier: CRD42019146170. [ABSTRACT FROM AUTHOR]

Galectin-8 gene belongs to the agglutinin family, which can specifically recognize β -galactoside bonds and play essential roles in many biological processes. In this study, we researched the sequence characteristics and immune-related function of Galectin-8 gene in Japanese flounder Paralichthys olivaceus , named PoGalectin-8. The results showed that the open reading frame of PoGalectin-8 was 891 bp, which encoding a protein with 296 amino acid residues and containing typical HXNPR and WGXEE motifs in the N-terminal and C-terminal CRD domains. Sequence alignment showed that PoGalectin-8 was conserved in different aquatic animals and exhibited the highest similarity (95.27%) with Seriola dumerili. PoGalectin-8 expressed in all detected tissues and exhibited the highest expression level in spleen, followed by skin and kidney. After infected by Edwardsiella tarda , the expression of PoGalectin-8 was down-regulated in the spleen and skin tissues of P. olivaceus. Further to study its immune-related functions, the recombinant PoGalectin-8 (rPoGalectin-8) was expressed and purified. The rPoGalectin-8 can specifically bind to lipopolysaccharide and peptidoglycan, the main components of cell walls from Gram-negative and Gram-positive bacteria. Bacteria binding and the microbial agglutinating experiments showed that the rPoGalectin-8 could bind and agglutinate all examined Gram-positive and Gram-negative bacteria. This study implied that PoGalectin-8 , as a pattern recognition receptor, may play important roles during immune responses against bacterial infection, which laid a foundation for further functional identification of Galectin-8 in aquatic animal immunity. • Galectin-8 from Japanese flounder (PoGalectin-8) were identified and characterized. • PoGalectin-8 was ubiquitously expressed in all tested tissues. • PoGalectin-8 was down-regulated after challenged with E. tarda. • The rPoGalectin-8 showed high affinity to lipopolysaccharide and peptidoglycan. • The rPoGalectin-8 could bind and agglutinate Gram-positive and -negative bacteria. [ABSTRACT FROM AUTHOR]

Obesity is a metabolic disease that is accompanied by oxidative stress. Mitochondrial dysfunction is closely associated with the occurrence and development of obesity. However, it is unclear if there are differences in mitochondrial redox homeostasis and energy metabolism between obesity‐prone (OP) and obesity‐resistant (OR) individuals and if these differences account for the different susceptibilities to developing obesity. The present study aimed to compare the regulation of energy metabolism between OP and OR rats during high‐fat diet (HFD)‐induced oxidative stress. Male Sprague Dawley rats were randomly divided into the control group and the HFD group. The HFD group was further divided into the OP and OR groups based on body weight gain (upper 1/3 for OP; lower 1/3 for OR) after eight weeks on HFD. Rats were sacrificed at the 8th and 20th week, and serum and organs were collected. At 8 weeks, HFD decreased mitochondrial antioxidant enzyme activity and increased the production of ROS in the OP rats, which was accompanied by unusual mitochondrial oxidative phosphorylation, reduced mitochondrial membrane potential (MMP), and decreased ATP production. When the feeding period was extended beyond the 8 weeks, the energy expenditure of the OP rats reduced further, resulting in elevated blood lipids and glucose levels and increased body weight. In contrast, the OR rats had higher mitochondrial antioxidant enzyme activity and normal redox homeostasis throughout the period, which was beneficial in energy utilization and ATP production. Thus, the increase in energy expenditure in the OR rats reduced the HFD‐induced weight gain. Mitochondrial function and antioxidant defense might be involved in the different propensities for developing obesity. Consequently, the ability of OR rats to resist obesity may be attributed to their ability to maintain mitochondrial function and redox balance. [ABSTRACT FROM AUTHOR]

Olive flounder (Paralichthys olivaceus) is an important economical flatfish in Japan, Korea and China, but its production has been greatly threatened by various of diseases. Although RNA-seq has provided valuable insights into the host-pathogen interaction, there are still some disadvantages, such as a short sequencing length, the incomplete or inaccurate splicing. Therefore, we generated a full-length transcriptome using mixed immune-related tissues of P. olivaceus with PacBio Sequel platform. In this study, 379,671 full-length non-chimeric (flnc) reads were generated with average length of 2482 bp, which is longer than any previously reported in P. olivaceus. A total of 66,420 isoforms of transcript were identified, 46,850 of which were novel isoforms of known genes accounting for 70.54%. In addition, 7720 novel genes, 12,540 alternative splicing (AS) events, 9296 alternative polyadenylation (APA) events, 2298 transcription factors (TFs), 10,270 lncRNAs and 5400 fusion transcripts were identified. Furthermore, functional annotation showed that most of the full-length transcripts were enriched in immune-related signaling pathways. Otherwise, the mRNA‐miRNA interacting networks confirmed that 28.5% of mRNAs were predicted to be targeted by more than one miRNA. These results facilitate the understanding of gene structure, post-transcriptional regulatory networks, and subsequently proteomic diversity. In conclusion, our study provides the full-length transcriptome from multiple immune-related tissues of P. olivaceus , which is valuable for exploring its immune responses. • A full-length transcriptome was generated by using PacBio Sequel platform. • A total of 379,671 full-length non-chimeric reads with average length of 2482 bp were obtained. • 7720 novel genes, 12,540 alternative splicing events and 9296 alternative polyadenylation events were predicted. • A total of 2298 transcription factors, 10,270 lncRNAs and 5400 fusion genes were identified. • A total of 28,715 mRNA-miRNA pairs were found, including 20,813 mRNA and 291 miRNAs. [ABSTRACT FROM AUTHOR]

Aims: The form of nitrogen (N) supply influences photorespiration in C3 plants, but whether nitrate (NO3−) regulates photorespiration and, if so, the underlying mechanisms for such regulation are still unclear. Methods: Three hydroponic experiments were conducted in a greenhouse to investigate the relationships between leaf NO3− concentrations and photorespiration rates in rice (Oryza sativa L.) genotypes cv. 'Shanyou 63' hybrid indica and 'Zhendao 11' hybrid japonica or using mutants that overexpress NRT2.1 (in cv. 'Nipponbare' inbred japonica). We estimated photorespiratory rate from the CO2 compensation point in the absence of daytime respiration (Γ*) using the biochemical model of photosynthesis. Results: Higher Γ* values under high N level or NO3− were significantly and positively correlated with leaf NO3− concentrations. Further elevating leaf NO3− concentrations by either resuming NO3− nutrition supply after N depletion (in cv. 'Shanyou 63' hybrid indica and 'Zhendao 11' hybrid japonica) or using mutants that overexpress NRT2.1 (in cv. 'Nipponbare' inbred japonica) increased Γ* values. Additionally, the activities of leaf nitrate reductase (Nr) and concentrations of organic acids involving in the tricarboxylic acid (TCA) cycle synchronously changed as environmental conditions were varied. Conclusions: Photorespiration rate is related to the leaf NO3− concentration, and the correlation may links to the photorespiration-TCA derived reductants required for NO3− assimilation. [ABSTRACT FROM AUTHOR]

In Chinese medicine, the Cucurbitaceae family contains many compounds known as cucurbitacins, which have been categorized into 12 classes ranging from A to T and more than 200 derivatives. Cucurbitacins are a class of highly oxidized tetracyclic triterpenoids with potent anticancer properties. The eight components of cucurbitacins with the strongest anticancer activity are cucurbitacins B, D, E, I, IIa, L -glucoside, Q, and R. Cucurbitacins have also been reported to suppress JAK-STAT 3, mTOR, VEGFR, Wnt/β-catenin, and MAPK signaling pathways, all of which are crucial for the survival and demise of cancer cells. In this paper, we review the progress in research on cucurbitacin-induced apoptosis, autophagy, cytoskeleton disruption, cell cycle arrest, inhibition of cell proliferation, inhibition of invasion and migration, inhibition of angiogenesis, epigenetic alterations, and synergistic anticancer effects in tumor cells. Recent studies have identified cucurbitacins as promising molecules for therapeutic innovation with broad versatility in immune response. Thus, cucurbitacin is a promising class of anticancer agents that can be used alone or in combination with chemotherapy and radiotherapy for the treatment of many types of cancer.Therefore, based on the research reports in the past five years at home and abroad, we further summarize and review the structural characteristics, chemical and biological activities, and studies of cucurbitacins based on the previous studies to provide a reference for further development and utilization of cucurbitacins. • Cucurbitacin and its derivatives have a wide range of biological activities. • Cucurbitacin exerts anticancer effects through multiple targets in vivo and in vitro. • Cucurbitacin can greatly enhance the anticancer effect when used in combination with clinical chemotherapy or radiotherapy. • Cucurbitacin has a wide range of multifunctionality in immune response. [ABSTRACT FROM AUTHOR]

Redox-associated events are important in plant development and responses to environmental stresses. In this study, we investigated spatial redox responses of cucumber ( Cucumis sativus L.) leaves to biotic stress ( Fusarium infection) or abiotic stress (water stress). Plants were grown under hydroponic conditions and either treated with polyethylene glycol to simulate drought or infected with Fusarium oxysporum f. sp. cucumerinum. Both water stress and Fusarium infection restricted cucumber growth and were associated with cellular plasma-membrane damage, reactive oxygen species accumulation, and changes in antioxidants; however, the responses to each stress were distinctive. Under water stress, H 2 O 2 generation at the leaf edge increased 29.7% compared with that at the centre but with Fusarium infection there was a relative 10.4% decrease at the edge. These changes correlated with changes in antioxidants and linked enzyme activities. The key sources of variation in oxidative events were defined by principal component analysis of all of the data and redox balance evaluations. We suggest that these spatial differences under water stress and Fusarium infection arise from discrete regulatory mechanisms, reflecting either developmental effect over the leaf regions or systemic anti-oxidative events occurred following infection. [ABSTRACT FROM AUTHOR]

The photosynthetic rate increases under high-N supply, resulting in a large CO2 transport conductance in mesophyll cells. It is less known that water movement is affected by nitrogen supply in leaves. This study investigated whether the expression of aquaporin and water transport were affected by low-N (0.7 mM) and high-N (7 mM) concentrations in the hydroponic culture of four rice varieties: (1) Shanyou 63 (SY63), a hybrid variant of the indica species; (2) Yangdao 6 (YD6), a variant of indica species; (3) Zhendao 11 (ZD11), a hybrid variant of japonica species; and (4) Jiuyou 418 (JY418), another hybrid of the japonica species. Both the photosynthetic and transpiration rate were increased by the high-N supply in the four varieties. The expressions of aquaporins, plasma membrane intrinsic proteins (PIPs), and tonoplast membrane intrinsic protein (TIP) were higher in high-N than low-N leaves, except in SY63. Leaf hydraulic conductance (Kleaf) was lower in high-N than low-N leaves in SY63, while Kleaf increased under high-N supply in the YD6 variant. Negative correlations were observed between the expression of aquaporin and the transpiration rate in different varieties. Moreover, there was a significant negative correlation between transpiration rate and intercellular air space. In conclusion, the change in expression of aquaporins could affect Kleaf and transpiration. A feedback effect of transpiration would regulate aquaporin expression. The present results imply a coordination of gas exchange with leaf hydraulic conductance. [ABSTRACT FROM AUTHOR]

Mass spectrometry technology can realize dynamic detection of many complex matrix samples in a simple, rapid, compassionate, precise, and high-throughput manner and has become an indispensable tool in accurate diagnosis. The mass spectrometry data analysis is mainly to analyze all metabolites in the organism quantitatively and to find the relative relationship between metabolites and physiological and pathological changes. A feature construction of mass spectrometry data (MSFS) method is proposed to construct the features of the original mass spectrometry data, so as to reduce the noise in the mass spectrometry data, reduce the redundancy of the original data and improve the information content of the data. Chi-square test is used to select the optimal non-redundant feature subset from high-dimensional features. And the optimal feature subset is visually analyzed and corresponds to the original mass spectrum interval. Training in 10 kinds of supervised learning models, and evaluating the classification effect of the models through various evaluation indexes. Taking two public mass spectrometry datasets as examples, the feasibility of the method proposed in this paper is verified. In the coronary heart disease dataset, during the identification process of mixed batch samples, the classification accuracy on the test set reached 1.000; During the recognition process, the classification accuracy on the test set advanced to 0.979. On the colorectal liver metastases data set, the classification accuracy on the test set reached 1.000. This paper attempts to use a new raw mass spectrometry data preprocessing method to realize the alignment operation of the raw mass spectrometry data, which significantly improves the classification accuracy and provides another new idea for mass spectrometry data analysis. Compared with MetaboAnalyst software and existing experimental results, the method proposed in this paper has obtained better classification results. [ABSTRACT FROM AUTHOR]

Pathogens infection could induce intestinal inflammatory processes, appropriate intestinal inflammation response had beneficial effects in fish, while excessive inflammation alters enteroendocrine signaling, leading to deregulated immune response. Recently, many researches revealed that microRNAs in teleost serve as vital regulators in innate immunity responses against pathogen infection. However, there are few studies on miRNAs mediated regulatory networks of intestinal inflammatory response in teleost. In our study, miR-144-5p was identified as negative regulators in teleost against bacterial infection. First, we found that the expression of miR-144-5p in flounder both in vivo and in vitro was significantly up-regulated, while the expression of Hsp90α, NLRP3, Caspase1 and IL-1β were significantly down-regulated upon the stimulation of Edwardsiella tarda and lipopolysaccharide (LPS). Furthermore, we confirmed that miR-144-5p modulates intestinal inflammatory responses of flounder by targeting Hsp90α-dependent NLR signaling pathway, in which the miR-144-5p-Hsp90α-NLRP3 signaling pathway was constructed. Besides, the miR-144-5p-Hsp90α-NLRP3 signaling pathway could inhibit antibacterial immune response of flounder and promote the survival of E. tarda. Moreover, the study demonstrated that the miR-144-5p-Hsp90α regulatory network was widely existed in other teleost and human. In conclusion, the expression of miR-144-5p was significantly up-regulated after challenged by E. tarda and LPS, which then down-regulated the expression of inflammation-related cytokines of NLRP3, Caspase1 and IL-1β by targeting Hsp90α, and ultimately promoted bacterial infection. Our findings constructed a novel miR-144-5p-Hsp90α-NLRP3 signaling pathway, which enriched the regulatory network of miRNA on fish intestinal mucosal immunity and would benefit the development of fish disease therapeutic strategies to prevent potentially lethal bacterial infection. • miR-144-5p modulates inflammatory response by targeting Hsp90α-dependent NLR pathway. • A novel inflammation-related miR-144-5p-Hsp90α-NLRP3 pathway was constructed. • The miR-144-5p-Hsp90α-NLRP3 pathway could inhibit antibacterial immune response. • The miR-144-5p-Hsp90α-NLRP3 pathway could promote the survival of bacteria. • The miR-144-5p-Hsp90α regulatory network was existed in other teleost and human. [ABSTRACT FROM AUTHOR]

Mass spectrometry technology can realize dynamic detection of many complex matrix samples in a simple, rapid, compassionate, precise, and high-throughput manner and has become an indispensable tool in accurate diagnosis. The mass spectrometry data analysis is mainly to analyze all metabolites in the organism quantitatively and to find the relative relationship between metabolites and physiological and pathological changes. A feature construction of mass spectrometry data (MSFS) method is proposed to construct the features of the original mass spectrometry data, so as to reduce the noise in the mass spectrometry data, reduce the redundancy of the original data and improve the information content of the data. Chi-square test is used to select the optimal non-redundant feature subset from high-dimensional features. And the optimal feature subset is visually analyzed and corresponds to the original mass spectrum interval. Training in 10 kinds of supervised learning models, and evaluating the classification effect of the models through various evaluation indexes. Taking two public mass spectrometry datasets as examples, the feasibility of the method proposed in this paper is verified. In the coronary heart disease dataset, during the identification process of mixed batch samples, the classification accuracy on the test set reached 1.000; During the recognition process, the classification accuracy on the test set advanced to 0.979. On the colorectal liver metastases data set, the classification accuracy on the test set reached 1.000. This paper attempts to use a new raw mass spectrometry data preprocessing method to realize the alignment operation of the raw mass spectrometry data, which significantly improves the classification accuracy and provides another new idea for mass spectrometry data analysis. Compared with MetaboAnalyst software and existing experimental results, the method proposed in this paper has obtained better classification results. [ABSTRACT FROM AUTHOR]

Mass spectrometry technology can realize dynamic detection of many complex matrix samples in a simple, rapid, compassionate, precise, and high-throughput manner and has become an indispensable tool in accurate diagnosis. The mass spectrometry data analysis is mainly to analyze all metabolites in the organism quantitatively and to find the relative relationship between metabolites and physiological and pathological changes. A feature construction of mass spectrometry data (MSFS) method is proposed to construct the features of the original mass spectrometry data, so as to reduce the noise in the mass spectrometry data, reduce the redundancy of the original data and improve the information content of the data. Chi-square test is used to select the optimal non-redundant feature subset from high-dimensional features. And the optimal feature subset is visually analyzed and corresponds to the original mass spectrum interval. Training in 10 kinds of supervised learning models, and evaluating the classification effect of the models through various evaluation indexes. Taking two public mass spectrometry datasets as examples, the feasibility of the method proposed in this paper is verified. In the coronary heart disease dataset, during the identification process of mixed batch samples, the classification accuracy on the test set reached 1.000; During the recognition process, the classification accuracy on the test set advanced to 0.979. On the colorectal liver metastases data set, the classification accuracy on the test set reached 1.000. This paper attempts to use a new raw mass spectrometry data preprocessing method to realize the alignment operation of the raw mass spectrometry data, which significantly improves the classification accuracy and provides another new idea for mass spectrometry data analysis. Compared with MetaboAnalyst software and existing experimental results, the method proposed in this paper has obtained better classification results. [ABSTRACT FROM AUTHOR]

The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus. Further, we show how the duck's defense mechanisms against influenza infection have been optimized through the diversification of its β-defensin and butyrophilin-like repertoires. These analyses, in combination with the genomic and transcriptomic data, provide a resource for characterizing the interaction between host and influenza viruses. [ABSTRACT FROM AUTHOR]

Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes. [ABSTRACT FROM AUTHOR]

Here we use whole-genome de novo assembly of second-generation sequencing reads to map structural variation (SV) in an Asian genome and an African genome. Our approach identifies small- and intermediate-size homozygous variants (1-50 kb) including insertions, deletions, inversions and their precise breakpoints, and in contrast to other methods, can resolve complex rearrangements. In total, we identified 277,243 SVs ranging in length from 1-23 kb. Validation using computational and experimental methods suggests that we achieve overall <6% false-positive rate and <10% false-negative rate in genomic regions that can be assembled, which outperforms other methods. Analysis of the SVs in the genomes of 106 individuals sequenced as part of the 1000 Genomes Project suggests that SVs account for a greater fraction of the diversity between individuals than do single-nucleotide polymorphisms (SNPs). These findings demonstrate that whole-genome de novo assembly is a feasible approach to deriving more comprehensive maps of genetic variation. [ABSTRACT FROM AUTHOR]

Polarization effect has become one of the main factors that limit the application of CdZnTe X-ray photon-counting detectors. In this study, we systematically investigate the impact of deep-level traps on the carrier transport properties and explore its underlying correlation with the polarization effect. Besides, the critical deep-level traps affecting photon counting performance are identified. Two types of CdZnTe detectors with significant differences in counting performance are explicitly selected for comparative research. The carrier transport characteristics are discussed by analyzing X-ray and γ-ray energy spectrum responses. The data shows the detectors with larger (μτ) h and smaller (μτ) e have better photon counting performance. This type of detectors can withstand higher X-ray doses without polarization. However, their relatively poor electron transport performance will reduce the detection efficiency. We comprehensively analyzed the TSC and i-DLTS results to obtain deep-level trap characteristics of the two types of CdZnTe detectors. The results indicate that CdZnTe detectors with good hole transport properties and photon counting performance have fewer Te i , Te secondary phases and Te precipitates related defects identified as deep hole traps with large capture cross-sections. Their larger Te cd 2 + concentration, which acts as a deep electron trap, should be responsible for poor electron transport properties and consequently reduced detection efficiency. • The effects of deep-level traps on the transport properties of high-flux X-ray CdZnTe detectors are investigated. • The CdZnTe detectors with good photon counting performance exhibit large (μτ) h and small (μτ) e. • The relationships of transport properties, photon counting performance and deep-level trap characteristics are discussed. • The T e i , Te secondary phases and Te precipitates related defects and T e c d 2 + are the main traps affecting the counting performance. [ABSTRACT FROM AUTHOR]

The motor parameters of permanent magnet synchronous motor (PMSM) can be mismatched in operation due to temperature variations and magnetic saturation. The parameter mismatch leads to a significant decrease in the robustness of traditional deadbeat predictive current control (DPCC), which leads to issues such as current static error and motor vibration noise. In this paper, a model-free predictive current control (MFPCC) method based on an improved sliding mode disturbance observer (SMDO) was proposed. The method estimated the total disturbance of the system using the improved SMDO, which could effectively suppress sliding mode chattering and accelerate the convergence speed of current errors. Subsequently, the predicted control voltage was calculated using a hyper-local model and compensated for the time delay. The experimental results demonstrated that the improved MFPCC-SMDO method generated lower motor noise compared to the traditional DPCC method when the controller's inductance parameters are mismatched. [ABSTRACT FROM AUTHOR]

Sodium butyrate (NaB), obtained by fermenting dietary fiber via intestinal microflora, was recently shown to improve the activity of some antioxidant enzymes in vivo. This study aims to investigate the term changes of mitochondrial energy metabolism and redox homeostasis in skeletal muscles and clarify the regulatory mechanism and dose effect of NaB on skeletal muscle. Male Sprague–Dawley rats were divided into the control group, obesity‐prone (OP) group and obesity‐resistant (OR) group based on the gain of body weight after 8 weeks' of feeding high‐fat diet (HFD), followed by sacrificing rats at the end of 20th week. NaB intervention (12 weeks) could effectively reduce the body weight of rats in the OP and OR groups. NaB also mediated upregulation of antioxidant enzyme activity and GSH/GSSG ratio, while reducing reactive oxygen species (ROS) levels and malondialdehyde (MDA) content. At the molecular level, NaB upregulated Pi3k, Nrf2, Nqo‐1, and Ho‐1, but downregulated Gsk‐3β mRNA expression by regulating the Nrf2 antioxidant pathway to enhance tissue antioxidant capacity. At the same time, NaB intervention significantly upregulated Glut4, Irs‐1, Pdx1, and MafA, expression in gastrocnemius muscles of OP and OR rats, and elevated insulin secretion and muscle insulin sensitivity. Thus, NaB activates antioxidant pathway, improves the antioxidant capacity of obese rat tissues and promotes glucose metabolism. Practical applications: This study found that obesity‐prone and obesity‐resistant rats have differences in mitochondrial redox homeostasis and energy metabolism in tissues. Meanwhile, sodium butyrate can effectively promote muscle protein synthesis, increase insulin sensitivity, and promote glucose metabolism in obesity rats. Thus, sodium butyrate supplementation or increasing intestinal butyrate production (e.g., by consuming foods rich in dietary fiber) is a potential means of improving the body's glucose metabolism and obesity profile. [ABSTRACT FROM AUTHOR]

Introduction: The characteristics of the tumor immune microenvironment (TIME) are closely related to immunotherapy. Breast cancer can benefit from immunotherapy, and its TIME is still unclear. Methods: We utilized mass cytometry to explore the immune cell heterogeneity in breast cancer. Double‐negative T cells (DNTs) from healthy volunteers (HBs) were enriched in vitro. Flow cytometry was used to detect the cell surface receptors of cancer cells and DNT cells. The correlation between immune checkpoints and the abundance of immune cells or prognosis of breast cancer was analyzed by the TCGA database. The messenger RNA (mRNA) expression of functional genes was performed by quantitative real‐time PCR. Results: We found that the frequencies of Granzyme B (GZMB)+CD8+T and GZMB+DNT cells in cancer tissues (CA) of breast cancer were lower than those in blood samples of patients (PB), and the frequencies of programmed cell death protein 1 (PD1)+CD8+T and PD1+DNT cells in CA were higher than those in PB. DNTs from HBs had a cytotoxic effect on MDA‐MB‐231. LAG3Ab could upregulate the mRNA expression of interferon gamma and perforin by increasing T‐BET transcription to enhance the cytotoxicity of DNT cells in vitro. Conclusion: Our study revealed the suppressive status of TIME in breast cancer and supported DNT cells had the potential to be applied as a novel adoptive cell therapy for TNBC either alone or combined with LAG3Ab. [ABSTRACT FROM AUTHOR]

The effect of deep-level defects is a key issue for the applications of CdZnTe high-flux photon counting devices of X-ray irradiations. However, the major trap energy levels and their quantitive relationship with the device's performance are not yet clearly understood. In this study, a 16-pixel CdZnTe X-ray photon counting detector with a non-uniform counting performance is investigated. The deep-level defect characteristics of each pixel region are analyzed by the current–voltage curves (I–V), infrared (IR) optical microscope photography, photoluminescence (PL) and thermally stimulated current (TSC) measurements, which indicate that the difference in counting performance is caused by the non-uniformly distributed deep-level defects in the CdZnTe crystals. Based on these results, we conclude that the CdZnTe detectors with a good photon counting performance should have a larger Te cd 2 + and Cd vacancy-related defect concentration and a lower A-center and Tei concentration. We consider the deep hole trap Tei, with the activation energy of 0.638–0.642 eV, to be the key deep-level trap affecting the photon counting performance. In addition, a theoretical model of the native defect reaction is proposed to understand the underlying relationships of resistivity, deep-level defect characteristics and photon counting performance. [ABSTRACT FROM AUTHOR]

Background: Epicardial fat tissue (EFT) is the visceral fat distributed along the coronary arteries between the pericardium and the myocardium. Increases in EFT are closely related to the occurrence of diabetes mellitus (DM) and cardiovascular disease. To further understand the link between EFT and DM, we conducted a meta-analysis of the relevant literature. Methods: We systematically searched electronic databases for studies on EFT performed in DM patients and published up to 30 September 2018. We included data on EFT in a DM patient group and a non-DM control group. We then assessed the effect of DM on EFT by meta-analysis and trial sequential analysis (TSA). All statistical analyses were performed using Stata 12.0 and TSA software. Results: A total of 13 studies (n = 1102 patients) were included in the final analysis. Compared with the control group, DM patients had significantly higher EFT (SMD: 1.23; 95% CI 0.98, 1.48; P = 0.000; TSA-adjusted 95% CI 0.91, 2.13; P < 0.0001). The TSA indicated that the available samples were sufficient and confirmed that firm evidence was reached. According to the regression analysis and subgroup analyses, DM typing, EFT ultrasound measurements, total cholesterol (TC) and triglyceride (TG) levels were confounding factors that significantly affected our results. Conclusions: Our meta-analysis suggests that the amount of EFT is significantly higher in DM patients than in non-DM patients. [ABSTRACT FROM AUTHOR]

Background: Albuminuria, the presence of excess of protein in urine, is a well-known risk factor for early kidney damage among diabetic/prediabetic patients. There is a complex interaction between physical activity (PA) and albuminuria. However, the relationship of specific-domain PA and albuminuria remained obscure. Methods: Albuminuria was defined as urinary albumin/creatinine ratio (ACR) > 30 mg/g. PA was self-reported by participants and classified into transportation-related PA (TPA), occupation-related PA (OPA), and leisure-time PA (LTPA). Weighted logistic regression was conducted to compute the odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic spline (RCS) was used to evaluate the dose–response of PA domains with the risk of albuminuria. Results: A total of 6739 diabetic/prediabetic patients (mean age: 56.52 ± 0.29 years) were enrolled in our study, including 3181 (47.20%) females and 3558 (52.80%) males. Of them, 1578 (23.42%) were identified with albuminuria, and 5161(76.58%) were without albuminuria. Diabetic/prediabetic patients who adhered the PA guidelines for total PA had a 22% decreased risk of albuminuria (OR = 0.78, 95%CI 0.64–0.95), and those met the PA guidelines for LTPA had a 28% decreased of albuminuria (OR = 0.72, 95%CI 0.57–0.92). However, OPA and TPA were both not associated with decreased risk of albuminuria. RCS showed linear relationship between the risk of albuminuria with LTPA. Conclusions: Meeting the PA guideline for LTPA, but not OPA and TPA, was inversely related to the risk of albuminuria among diabetic/prediabetic patients. Additionally, achieving more than 300 min/week of LTPA conferred the positive effects in reducing albuminuria among diabetic/prediabetic patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: The gangue content in coal seriously affects the calorific value produced by its combustion. In practical applications, gangue in coal needs to be completely separated. The pseudo-dual-energy X-ray method does not have high sorting accuracy. OBJECTIVE: This study aims to propose a novel multi-dimensional coal and gangue X-ray sorting algorithm based on CdZnTe photon counting detectors to solve the problem of coal and gangue sorting by X-ray. METHODS: This complete algorithm includes five steps: (1) Preferred energy bins, (2) transmittance sorting, (3) one-dimensional R-value sorting, (4) two-dimensional R-value sorting, and (5) three-dimensional R-value sorting. The output range of each step is determined by prior information from 65 groups of coal and gangue. An additional 110 groups of coal and gangue are employed experimentally to validate the algorithm's accuracy. RESULTS: Compared with the 60% sorting accuracy of the Pseudo-dual-energy method, the new algorithm reached a sorting accuracy of 99%. CONCLUSIONS: Study results demonstrate the superiority of this novel algorithm and its feasibility in practical applications. This novel algorithm can guide other two-substance X-ray sorting applications based on photon counting detectors. [ABSTRACT FROM AUTHOR]

ZnSe films with a sphalerite structure and about 100nm grain size were deposited on ITO substrate. 200 stable bipolar resistive switching (RS) cycles were obtained in Au/ZnSe/ITO chalcogenide-based memory cells and it shows an ON/OFF ratio of 10 and retention time of 104 seconds. The conduction mechanism is Ohmic in both low resistance state (LRS) and low voltage region in high resistance state (HRS) while thermionic emission limited conduction (TELC) at high voltage region in HRS. The top electrode (TE) size independence of low resistance implies a filamentary resistive switching mechanism. Photoluminescence (PL) spectroscopy shows a double difference of relative intensity between shallow zinc vacancy state and deep zinc vacancy complex state in HRS and LRS. The explanation for HRS is the dissociation of zinc vacancy complex and the formation of zinc vacancy. Then the shallow acceptor zinc vacancy compensates for the shallow donor contributing the HRS. It is deduced from linear relation of reset voltage and reset power versus temperature that the thermal activation energy of ZnSe film is 0.19 eV, which indicates an over 20nm intertrap distance and the critical temperature for conductive filament (CF) rupture is 305.6K with 0.2mV/s sweep rate, respectively. The component of CF is metal-like shallow donor such as Al or Ga with the help of deep zinc vacancy complex to depress the compensation of shallow zinc vacancy acceptor. [ABSTRACT FROM AUTHOR]

BACKGROUND: In fan beam X-ray imaging applications, several X-ray images sometimes need to be stitched together into a panoramic image because of the size limitations of the detector. OBJECTIVE: This study aims to propose a novel multi-view X-ray digital imaging stitching algorithm (MVS) based on the CdZnTe photon counting linear array detectors to solve the problem of fan beam X-ray stitching deformation. METHODS: The panoramic image is generated in four steps including (1) multi-view projection data acquisition, (2) overlapping positioning, (3) weighted fusion and (4) projected pixel value calculation. Images of a globe and foot are scanned by fan beam X-rays and a CdZnTe detector. The proposed method is applied to stitch together the scanned images of the globe. Three other methods are also used for comparison. Finally, this MVS algorithm is also used in the stitching of scanned images of the foot. RESULTS: Compared with the 50% stitching accuracy of other methods, the new MVS algorithm reached a stitching accuracy of 94.4%. Image distortion on the globe and feet is also eliminated and thus image quality is significantly improved. CONCLUSIONS: This study proposes a new multi-view X-ray digital imaging stitching algorithm. Study results demonstrate the superiority of this new algorithm and its feasibility in practical applications. [ABSTRACT FROM AUTHOR]

Gamma-ray coded-aperture imaging technology plays an important role in nuclear security, decommissioning of nuclear facilities, and nuclear medicine diagnosis. However, under near-field imaging condition, artifacts in the reconstructed image can interfere with identifying the shape and position of the radioactive source. In this paper, a gamma-ray coded-aperture imaging method based on mask and anti-mask functions was proposed to suppress imaging artifacts and speed up the acquisition of low-noise reconstructed images. Through simulation, the effects of the number of iterations and the thickness of the coded-aperture collimator on the imaging quality were studied, and the range of the optimal correction factor in the method was determined. Imaging experiments were conducted using a compact coded-aperture gamma camera based on CdZnTe detector to verify the applicability of the optimal correction factor range. The limitations of the proposed method were analyzed through complex-shaped source imaging simulations and multi-source imaging experiments. This method has an insufficient suppression effect on random artifacts and requires further improvement in imaging irregular radioactive sources. However, it has good imaging performance for single-point source and multi-point sources, effectively reducing regular cross-shaped and stripe-like artifacts. In the non-uniform radioactive background, it can eliminate a part of artifacts, significantly improving imaging quality. Therefore, this method has potential applications in complex radioactive environments. • Improvement of a coded-aperture imaging method. • Suppress the artifacts of coded-aperture imaging. • Artifact suppression is better than the MLEM method. • Simulation and experimental validation. [ABSTRACT FROM AUTHOR]

Aims: Some gene variants in the sodium channels, as well as calcium channels, have been associated with Brugada syndrome (BrS). However, the investigation of the human cellular phenotype and the use of drugs for BrS in presence of variant in the calcium channel subunit is still lacking. Objectives: The objective of this study was to establish a cellular model of BrS in the presence of a CACNB2 variant of uncertain significance (c.425C > T/p.S142F) using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and test drug effects using this model. Methods and results: This study recruited cells from a patient with Brugada syndrome (BrS) and recurrent ventricular fibrillation carrying a missense variant in CACNB2 as well as from three healthy independent persons. These cells (hiPSC-CMs) generated from skin biopsies of healthy persons and the BrS patient (BrS-hiPSC-CMs) as well as CRISPR/Cas9 corrected cells (isogenic control, site-variant corrected) were used for this study. The hiPSC-CMs from the BrS patient showed a significantly reduced L-type calcium channel current (ICa-L) compared with the healthy control hiPSC-CMs. The inactivation curve was shifted to a more positive potential and the recovery from inactivation was accelerated. The protein expression of CACNB2 of the hiPSC-CMs from the BrS-patient was significantly decreased compared with healthy hiPSC-CMs. Moreover, the correction of the CACNB2 site-variant rescued the changes seen in the hiPSC-CMs of the BrS patient to the normal state. These data indicate that the CACNB2 gene variant led to loss-of-function of L-type calcium channels in hiPSC-CMs from the BrS patient. Strikingly, arrhythmia events were more frequently detected in BrS-hiPSC-CMs. Bisoprolol (beta-blockers) at low concentration and quinidine decreased arrhythmic events. Conclusions: The CACNB2 variant (c.425C > T/p.S142F) causes a loss-of-function of L-type calcium channels and is pathogenic for this type of BrS. Bisoprolol and quinidine may be effective for treating BrS with this variant. [ABSTRACT FROM AUTHOR]

Previously, we demonstrated that drought resistance in rice seedlings was increased by ammonium (NH 4 + ) treatment, but not by nitrate (NO 3 − ) treatment, and that the change was associated with root development. To study the effects of different forms of nitrogen on water uptake and root growth under drought conditions, we subjected two rice cultivars (cv. ‘Shanyou 63’ hybrid indica and cv. ‘Yangdao 6’ indica , China) to polyethylene glycol-induced drought stress in a glasshouse using hydroponic culture. Under drought conditions, NH 4 + significantly stimulated root growth compared to NO 3 − , as indicated by the root length, surface area, volume, and numbers of lateral roots and root tips. Drought stress decreased the root elongation rate in both cultivars when they were supplied with NO 3 − , while the rate was unaffected in the presence of NH 4 + . Drought stress significantly increased root protoplast water permeability, root hydraulic conductivity, and the expression of root aquaporin (AQP) plasma intrinsic protein (PIP) genes in rice plants supplied with NH 4 + ; these changes were not observed in plants supplied with NO 3 − . Additionally, ethylene, which is involved in the regulation of root growth, accumulated in rice roots supplied with NO 3 − under conditions of drought stress. We conclude that the increase in AQP expression and/or activity enhanced the root water uptake ability and the drought tolerance of rice plants supplied with NH 4 + . [ABSTRACT FROM AUTHOR]

An experimental method was described to calibrate the depth of interaction (DOI) of high-energy $\gamma $ -ray in large-size thick pixel CdZnTe detector. The experimental results indicated that the ratio of the cathode and anode amplitude strongly showed linear relationship with the DOI of incidence $\gamma $ -rays and the detector. The correlation coefficients were optimized. Based on the experimental calibration of DOI, the photoelectric effect signals from the depth range where the energy resolution and the photopeak location are high were screened out to draw the energy spectrum. In this way, the energy resolution of the CdZnTe pixel detector was improved to 0.707% for 137Cs@662 keV. Further combined with the anode rise time, the electron mobility of CdZnTe in 2-D (1 mm accuracy) and 3-D (2 mm $\times $ 2 mm $\times $ 1 mm accuracy) scales was calculated. At different pixel positions and depths in CdZnTe detector, the electron mobility varies between 1000 and 1150 cm2/($\text{V}\cdot \text{s}$). [ABSTRACT FROM AUTHOR]

In this paper, we mine full mtDNA sequences from an exome capture data set of 2000 Danes, showing that it is possible to get high-quality full-genome sequences of the mitochondrion from this resource. The sample includes 1000 individuals with type 2 diabetes and 1000 controls. We characterise the variation found in the mtDNA sequence in Danes and relate the variation to diabetes risk as well as to several blood phenotypes of the controls but find no significant associations. We report 2025 polymorphisms, of which 393 have not been reported previously. These 393 mutations are both very rare and estimated to be caused by very recent mutations but individuals with type 2 diabetes do not possess more of these variants. Population genetics analysis using Bayesian skyline plot shows a recent history of rapid population growth in the Danish population in accordance with the fact that >40% of variable sites are observed as singletons. [ABSTRACT FROM AUTHOR]

The radiation detection performance of CZT epitaxial single crystal grown by the Close Space Sublimation (CSS) method is hindered by inherent defects. However, significant improvement in this work is achieved through annealing in a Te 2 atmosphere. The saturation channel value of the total energy peak of the detector for 241Am α-particles has shown a substantial increase from 1900 to 6000, resulting in a notable enhancement of the carrier collection efficiency. After annealing, the detector's energy resolution to 241Am gamma-rays can reach 8.3%, representing the highest energy resolution achieved by CSS growth of CZT materials. This remarkable achievement holds great promise for its potential application in the field of low-energy detection. Analysis of the laser-beam-induced current (LBIC) curve results reveals that the surface recombination of the detector is more pronounced prior to annealing, adversely affecting the transport process of photogenerated carriers. The low-temperature photoluminescence (PL) results and I–V curve demonstrate a significant compensation effect on the shallow acceptor level V Cd after annealing, leading to a reduced concentration of free carriers and subsequently leading to lower leakage current and improved signal-to-noise ratio for the detector. The concurrent reduction in leakage current and surface recombination contributes collectively to improving the radiation detection performance of the CZT detector. These findings underscore the importance of annealing in a Te 2 atmosphere as a viable method for mitigating defects and optimizing the performance of CZT epitaxial single crystals, showcasing the potential for broader applications in the field of low-energy detection. • The leakage current is reduced from 1.3 nA to 0.59 nA under the applied bias voltage of 0.5 V, which makes the detector obtain a good signal-to-noise ratio. • The surface recombination rate decreased from 13.78 × 106 cm s−1 to 3.82 × 105 cm s−1, significantly improving the carrier collection efficiency. • The energy resolution to 241Am@59.5 KeV gamma-rays of the detector reached 8.3% for the first time, which is expected to be applied in the field of low energy detection. [ABSTRACT FROM AUTHOR]

Abstract: There are numerous approaches to decipher a whole genome DNA methylation profile (“methylome”), each varying in cost, throughput and resolution. The gold standard of these methods, whole genome bisulfite-sequencing (BS-seq), involves treatment of DNA with sodium bisulfite combined with subsequent high throughput sequencing. Using BS-seq, we generated a single-base-resolution methylome in human peripheral blood mononuclear cells (in press). This BS-seq map was then used as the reference methylome to compare two alternative sequencing-based methylome assays (performed on the same donor of PBMCs): methylated DNA immunoprecipitation (MeDIP-seq) and methyl-binding protein (MBD-seq). In our analysis, we found that MeDIP-seq and MBD-seq are complementary strategies, with MeDIP-seq more sensitive to highly methylated, high-CpG densities and MDB-seq more sensitive to highly methylated, moderate-CpG densities. Taking into account the size of a mammalian genome and the current expense of sequencing, we feel 3gigabases (Gbp) 45bp paired-end MeDIP-seq or MBD-seq uniquely mapped reads is the minimum requirement and cost-effective strategy for methylome pattern analysis. [ABSTRACT FROM AUTHOR]

The bias-induced temporal behavior of the dark current in CdZnTe radiation detectors essentially determines the detector's performance, but the traditional electric field dependent Schottky barrier height model cannot explain the complicated current transient behavior observed in experiments. In this work, dark current temporal response in CdZnTe detectors as a function of temperature is investigated both experimentally and numerically. After biasing, the transient current increases for detectors with small barrier heights, while decreases for those with large barrier heights before reaching the steady state. This current saturation process is attributed to the de-trapping of deep level defects. The evolution of the electric potential, electric field and trap occupancy in the detector is simulated, which shows an agreement with the measurement results. Schottky barrier height dependent electric potential distribution between bulk material and depletion layer at the blocking contact is responsible for different dark current temporal behavior in CdZnTe detectors. [ABSTRACT FROM AUTHOR]

In the practical application of CdZnTe photon counting detectors, severe detector counting distortion can be caused by pulse pileup. A count rate correction method in this paper is proposed to solve this problem. In this method, the case where multi-photons are recorded by higher energy regions due to pulse pileup crossing the energy threshold is considered to calculate the true count rates under all energy bins. A verification method based on Poisson distribution is also proposed to evaluate the accuracy of the correction method. A 16-pixel linear array CdZnTe photon counting detector was used for verification. Taking the dual-energy bin as an example, this method was introduced, and the true count rates of the high- and low-energy bins are successfully calculated. The result was highly consistent with the verification result, which proves the reliability of the proposed method. [ABSTRACT FROM AUTHOR]

Phenolic compounds constitute probably the largest group of plant secondary metabolites and have key roles in plant metabolism. Simulated nitrogen (N) deposition is important to agriculture and has considerable impacts on plant phenolic metabolism but a systematic understanding of such effects is lacking. We here synthesized results from 123 articles and evaluated the responses of plant biomass, in vivo N status, soluble sugar concentrations, carbon (C)/N ratios and multiple phenolic compounds to the simulated N deposition. This meta-analysis showed that the simulated N deposition significantly increased plant biomass and N content but reduced the concentrations of phenolic compounds in a dose-depended manner. This was linked to the suppression of phenolic generating phenylalanine ammonia_lyase activity and key associated gene expression by the simulated N deposition. Total phenolic concentrations were negatively related to biomass but were positively correlated with C/N and soluble sugar contents. Overall, our results indicated adverse effects of simulated N deposition on phenolic metabolism which could compromise key aspects of crop quality and are apparently hidden by positive effects on plant biomass. Our findings have significant ecological and biological implications for plant phenolic metabolism facing global N deposition. Unlabelled Image • Simulated N deposition decreased plant phenolic compounds concentrations. • Phenolic changes are positively correlated to plant C/N ratio and soluble sugar concentrations. • Simulated N deposition inhibits phenolic synthesis related genes expressions. [ABSTRACT FROM AUTHOR]

The plant stress hormone salicylic acid (SA) participates in local and systemic acquired resistance, which eventually leads to whole-plant resistance to bacterial pathogens. However, if SA-mediated signaling is not appropriately controlled, plants incur defense-associated fitness costs such as growth inhibition and cell death. Despite its importance, to date only a few components counteracting the SA-primed stress responses have been identified in Arabidopsis (Arabidopsis thaliana). These include other plant hormones such as jasmonic acid and abscisic acid, and proteins such as LESION SIMULATING DISEASE1, a transcription coregulator. Here, we describe PLANT NATRIURETIC PEPTIDE A (PNP-A), a functional analog to vertebrate atrial natriuretic peptides, that appears to antagonize the SA-mediated plant stress responses. While loss of PNP-A potentiates SA-mediated signaling, exogenous application of synthetic PNP-A or overexpression of PNP-A significantly compromises the SA-primed immune responses. Moreover, we identify a plasma membrane–localized receptor-like protein, PNP-R2, that interacts with PNP-A and is required to initiate the PNP-A–mediated intracellular signaling. In summary, our work identifies a peptide and its putative cognate receptor as counteracting both SA-mediated signaling and SA-primed cell death in Arabidopsis. [ABSTRACT FROM AUTHOR]

Influenza remains a global health concern due to its potential to cause pandemics as a result of rapidly mutating influenza virus strains. Existing vaccines often struggle to keep up with these rapidly mutating flu viruses. Therefore, the development of a broad-spectrum peptide vaccine that can stimulate an optimal antibody response has emerged as an innovative approach to addressing the influenza threat. In this study, an immunoinformatic approach was employed to rapidly predict immunodominant epitopes from different antigens, aiming to develop an effective multiepitope influenza vaccine (MEV). The immunodominant B-cell linear epitopes of seasonal influenza strains hemagglutinin (HA) and neuraminidase (NA) were predicted using an antibody-peptide microarray, involving a human cohort including vaccinees and infected patients. On the other hand, bioinformatics tools were used to predict immunodominant cytotoxic T-cell (CTL) and helper T-cell (HTL) epitopes. Subsequently, these epitopes were evaluated by various immunoinformatic tools. Epitopes with high antigenicity, high immunogenicity, non-allergenicity, non-toxicity, as well as exemplary conservation were then connected in series with appropriate linkers and adjuvants to construct a broad-spectrum MEV. Moreover, the structural analysis revealed that the MEV candidates exhibited good stability, and the docking results demonstrated their strong affinity to Toll-like receptors 4 (TLR4). In addition, molecular dynamics simulation confirmed the stable interaction between TLR4 and MEVs. Three injections with MEVs showed a high level of B-cell and T-cell immune responses according to the immunological simulations in silico. Furthermore, in-silico cloning was performed, and the results indicated that the MEVs could be produced in considerable quantities in Escherichia coli (E. coli). Based on these findings, it is reasonable to create a broad-spectrum MEV against different subtypes of influenza A and B viruses in silico. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a highly heterogeneous genetic disorder with strong evidence of ASD‐association currently available only for a small number of genes. This makes it challenging to identify the underlying genetic cause in many cases of ASD, and there is a continuing need for further discovery efforts. We sequenced whole genomes of 119 deeply phenotyped ASD probands in order to identify likely pathogenic variants. We prioritized variants found in each subject by predicted damage, population frequency, literature evidence, and phenotype concordance. We used Sanger sequencing to determine the inheritance status of high‐priority variants where possible. We report five novel de novo damaging variants as well as several likely damaging variants of unknown inheritance; these include two novel de novo variants in the well‐established ASD gene SCN2A. The availability of rich phenotypic information and its concordance with the literature allowed us to increase our confidence in pathogenicity of discovered variants, especially in probands without parental DNA. Our results contribute to the documentation of potential pathogenic variants and their associated phenotypes in individuals with ASD. [ABSTRACT FROM AUTHOR]

The survivability of γ-ray detector in radiation environment of energetic neutrons is a key issue for its application in spacecraft, accelerator, nuclear reactor, etc., especially for the case of CdZnTe detectors. Nevertheless, very little attention has been paid to the radiation damage mechanism of detectors and the evolution of radiation-induced defects in the detector medium, i.e. Cd 0.9 Zn 0.1 Te:In crystals. We proposed and simulated the radiation defects type and amount of Cd 0.9 Zn 0.1 Te:In crystals after neutron irradiation with the Monte-Carlo software SRIM. The calculated data are also compared with experimental results of detector performance and the crystal defects obtained using thermally stimulated current (TSC) measurement. We also discuss the influence of defect concentrations on crystal resistivity and detector energy resolution. It was shown that the concentration of vacancies, interstitials, and their related defects increased after neutron irradiation, which could be the reason for the worsening of Cd 0.9 Zn 0.1 Te:In γ-ray detector performance after the neutron irradiation. [ABSTRACT FROM AUTHOR]

The metal/semiconductor interface plays an important role in semiconductor detectors for high energy radiation, such as that in CdZnTe detectors. Nevertheless, very little attention has been paid to radiation damage effects on the metal/semiconductor interface, especially the Schottky barrier interface. The influence of 2 MeV neutron irradiation on current-voltage (I–V) and direct current photoconductivity properties of Au/CdZnTe/Au structure with a Schottky barrier on the interface as a function of neutron fluences are investigated. The irradiation fluences were 1 × 1010 and 1 × 1011 neutron/cm2, respectively. The current transport across the Au/CdZnTe junction is described by the diffusion process. Several mechanisms for the effects such as Pool-Frankel effect, surface recombination and electron tunnelling are suggested, which may account for the variations of I–V curves and photoconductivity properties of CdZnTe detectors after irradiation. Various interface Schottky barrier parameters, such as Schottky barrier height and the donor concentration, have been discussed as a function of neutron irradiation fluences. The observed variation of Au/CdZnTe interface states are mainly attributed to the defects and electron active traps induced by the neutron irradiation. • Au/CdZnTe/Au devices are fabricated and characterized. • Electrical and photoconductivity properties of the devices are presented. • Irradiation effect on Au/CdZnTe interface was examined. [ABSTRACT FROM AUTHOR]

Fish fillet is heavily influenced by swimming exercise and other factors leading to a great change in fish physiology. During the present study, muscle cellularity, texture and composition, antioxidant activities and flavor characteristics were assessed and compared between non-exercised (N-EXF) and long-term exercised Largemouth bass. Exercised fish (EXF) showed improve in muscle cellularity and texture with high protein, hydroxyproline, collagen and low crude lipid compared to N-EXF. In addition, EXF showed Higher INOS, T-AOC, CAT and lower MDA, indicating high antioxidant activities in EXF compared to N-EXF. Furthermore, EXF showed lower hydrocarbons and alcohols content but higher in carboxylic acid, esters and aromatic compounds content compared N-EXF. EXF also showed lower TMAO, TMA, HX and high IMP content, indicating better freshness. Generally, EXF largemouth bass should be preferred depends on its high nutrition value, better flesh and freshness quality; and pleasant flavor. • Exercised fish (EXF) in raw muscle showed better muscle quality than non-exercise fish. • EXF showed good muscle cellularity and texture, and high antioxidant activities. • Both raw and cooked in EXF presented high quality in volatile compounds. • EXF (raw and cooked) showed better muscle freshness. [ABSTRACT FROM AUTHOR]

• Combination strategies enlarge the clinical utility of immunotherapy. • The latest researches about combination immunotherapy are involved in our analysis. • Combination immunotherapy can achieve synergistic effects. • Combination immunotherapy could bring more benefits compared to monotherapy. • Combination immunotherapy was associated with increased AEs but it was manageable. Combination immunotherapy has become an actively growing field of clinical investigation. We searched for clinical trials of combination immunotherapy and calculated the pooled hazard ratio (HR), odds ratio (OR) of clinical outcomes and safety by subgroups of different combination regimens. Totally 28 clinical trials were analyzed. The study showed that the pooled HRs of overall survival and progression-free survival for combination therapy were 0.77 (95% CI: 0.70−0.84, p < 0.001) and 0.72 (95% CI: 0.66−0.79, p < 0.001) while the pooled OR of high-grade adverse effects was 1.45 (p = 0.004). Subgroup analysis showed that the HR of overal survival were 0.74 (p = 0.005), 0.79 (p < 0.001), 0.70 (p = 0.003) and 0.85 (p = 0.052) for immunotherapy combined with immunotherapy, chemotherapy, targeted therapy and radiotherapy group, respectively. The meta-analysis indicated that combination immunotherapy could bring more clinical benefits with increased high-grade adverse effects. [ABSTRACT FROM AUTHOR]

Abstract Most coronary smooth muscle cells(CoSMCs) are differentiated from epicardial progenitor cells(EPCs), but the specific mechanism is not fully investigated. Previous studies have shown that autophagy plays an important role for smooth muscle cells(SMCs) differentiation, yet whether autophagy is involved in the differentiation of EPCs into CoSMCs remains unclear. In the present study, We first isolated and cultured EPCs and continuously cultured them for 72 h. Then the autophagy induction and inhibition experiment was established by using the autophagy inducer Rapamycin(RAPA) and the inhibitor 3-Methyladenine(3-MA). And further animal experiments were conducted to observe the effects of autophagy on the development of coronary arteries. Our data showed that autophagy occurred in the differentiation of EPCs into SMCs. Over activation of autophagy may lead to early transient differentiation of EPCs, enhanced migration ability and weakened systolic function, but overall, CoSMC development is still inhibited. However, inhibition of autophagy may delay the differentiation of EPCs, thus reducing the number of coronary arteries. Together, all these processes indicate that autophagy may regulate the differentiation of EPCs into CoSMCs by affecting the time point of differentiation, and appropriate autophagy intensity is required during the development of CoSMCs. [ABSTRACT FROM AUTHOR]

Background: Adjuvant endocrine therapy undoubtedly prolongs the time to recurrence for patients with hormone-positive early breast cancer. Extended endocrine therapy to 10 years or longer has been expected to bring a greater clinical advantage. However, the related research conclusions are controversial.Methods: Tamoxifen (TAM), Aromatase Inhibitor (AI), Exemestane, letrozole (LET) and anastrozole were used as key words in the literature search. After the patients completed 5 years of adjuvant endocrine treatment, they were allocated to continue endocrine treatment for 5 years or receive placebo/observation for 5 years. Disease-free survival (DFS) and overall survival (OS) were the end points. Systematic assessment was performed using Stata 12.0.Results: Twelve trials including 30,848 cases were involved. The overall analysis demonstrated that extended endocrine therapy to 10 years significantly prolonged DFS compared with 5 years of endocrine therapy [hazard ratio (HR) = 0.84, 95% CI: 0.73-0.97]. Subgroup analysis showed that DFS was significant prolonged with TAM 5y - AI 5y treatment versus TAM 5y treatment and with (AI and/or TAM) 5y - LET 5y treatment versus (AI and/or TAM) 5y treatment [(HR = 0.61, 95% CI: 0.50-0.76) and (HR = 0.81, 95% CI: 0.71-0.93), respectively]. However, no significant difference was found in the DFS with TAM 5y - TAM 5y treatment versus TAM 5y treatment (HR = 0.97, 95% CI: 0.81-1.17). Overall and subgroup analysis did not demonstrate an OS benefit of therapy extended to 10 years. A DFS benefit of extended endocrine therapy to 10 years was verified in the lymph node-positive subgroup, postmenopausal subgroup and ER+ and/or PR+ subgroup (HR = 058, 95% CI: 0.45-0.75; HR = 0.70, 95% CI: 0.58-0.80; HR = 0.80, 95% CI: 0.67-0.96).Conclusions: An extended 10 years of endocrine treatment yields a DFS benefit for patients with early breast cancer; (AI and/or TAM) 5y - AI 5y treatment is the optimal choice. ER+ and/or PR+, postmenopausal and lymph node-positive patients are the most suitable groups. [ABSTRACT FROM AUTHOR]

The early stages of close spaced sublimation growth of CdZnTe(0 0 1)/GaAs(0 0 1) epilayer were experimentally studied under different substrate temperatures and ambient pressures. SEM, AFM, XRD, EBSD and EDS were used for the characterization of morphology, structure and composition of the films. The films were found to be (0 0 1) oriented and epitaxial in nature with zinc blende cubic structure. Deposition models were used to explain the correlation between growth condition and CdZnTe island morphology. Films grown at 350 °C and 1 × 10 2  Pa show the best uniform and smooth surface. When increasing substrate temperature to 430 °C or ambient pressure to 1 × 10 4  Pa or 3 × 10 4  Pa, islands are less compact and exhibit preferential growth along one of 〈1 1 0〉 directions, which could be resulted from the big lattice mismatch (14.0%) of Cd 0.9 Zn 0.1 Te(0 0 1)/GaAs(0 0 1) heterojunction. For the growth at 430 °C in 3 × 10 4  Pa, prior nucleation at defect site was found, and the appearance of regular 〈0 1 0〉 oriented island edges proposes that steps 〈0 1 0〉{1 0 0} are more stable for CdZnTe(0 0 1)/GaAs(0 0 1) epilayer than steps 〈1 1 0〉{1 1 1}. [ABSTRACT FROM AUTHOR]