Inhaled nitric oxide: can it serve as a savior for COVID-19 and related respiratory and cardiovascular diseases?

Nitric oxide (NO), as an important gaseous medium, plays a pivotal role in the human body, such as maintaining vascular homeostasis, regulating immune-inflammatory responses, inhibiting platelet aggregation, and inhibiting leukocyte adhesion. In recent years, the rapid prevalence of coronavirus disease 2019 (COVID-19) has greatly affected the daily lives and physical and mental health of people all over the world, and the therapeutic efficacy and resuscitation strategies for critically ill patients need to be further improved and perfected. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator, and some studies have demonstrated its potential therapeutic use for COVID-19, severe respiratory distress syndrome, pulmonary infections, and pulmonary hypertension. In this article, we describe the biochemistry and basic characteristics of NO and discuss whether iNO can act as a "savior" for COVID-19 and related respiratory and cardiovascular disorders to exert a potent clinical protective effect.

COVID-19 and the cardiovascular system: a study of pathophysiology and interpopulation variability.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans can lead to various degrees of tissue and organ damage, of which cardiovascular system diseases are one of the main manifestations, such as myocarditis, myocardial infarction, and arrhythmia, which threaten the infected population worldwide. These diseases threaten the cardiovascular health of infected populations worldwide. Although the prevalence of coronavirus disease 2019 (COVID-19) has slightly improved with virus mutation and population vaccination, chronic infection, post-infection sequelae, and post-infection severe disease patients still exist, and it is still relevant to study the mechanisms linking COVID-19 to cardiovascular disease (CVD). This article introduces the pathophysiological mechanism of COVID-19-mediated cardiovascular disease and analyzes the mechanism and recent progress of the interaction between SARS-CoV-2 and the cardiovascular system from the roles of angiotensin-converting enzyme 2 (ACE2), cellular and molecular mechanisms, endothelial dysfunction, insulin resistance, iron homeostasis imbalance, and psychosocial factors, respectively. We also discussed the differences and mechanisms involved in cardiovascular system diseases combined with neocoronavirus infection in different populations and provided a theoretical basis for better disease prevention and management.

Gender-specific data-driven adiposity subtypes using deep-learning-based abdominal CT segmentation.

OBJECTIVE: The aim of this study was to quantify abdominal adiposity and generate data-driven adiposity subtypes with different diabetes risks. METHODS: A total of 3817 participants from the Pinggu Metabolic Disease Study were recruited. A deep-learning-based recognition model on abdominal computed tomography (CT) images (A-CT model) was developed and validated in 100 randomly selected cases. The volumes and proportions of subcutaneous fat, visceral fat, liver fat, and muscle fat were automatically recognized in all cases. K-means clustering was used to identify subgroups using the proportions of the four fat components. RESULTS: The Dice indices among the measurements assessed by the A-CT model and manual evaluation to detect liver fat, muscle fat, and subcutaneous fat areas were 0.96, 0.95, and 0.92, respectively. Three subtypes were generated separately in men and women: visceral fat dominant type (VFD); subcutaneous fat dominant type (SFD); and intermuscular fat dominant type (MFD). Compared with the SFD group, the MFD group had similar diabetes risk, and the VFD group had a 60% higher diabetes risk when age and BMI were adjusted for in men. The adjusted odds ratio for diabetes was 1.92 (95% CI: 1.32-2.78) in the MFD group and 6.14 (95% CI: 4.18-9.03) in the VFD group in women. CONCLUSIONS: This study identified gender-specific abdominal adiposity subgroups, which may help clinicians to distinguish diabetes risk quickly and automatically.

Does deception involve more cognitive control than truth-telling? Meta-analyses of N2 and MFN ERP studies.

A number of psychological theories propose that deception involves more cognitive control than truth-telling. Over the last decades, event-related potentials (ERPs) have been used to unravel this question, but the findings are mixed. To address this controversy, two meta-analyses were conducted to quantify the results of existing studies reporting N2 or medial frontal negativity (MFN) associated with deception. In total, 32 papers consisting of 1091 participants were included, which yielded 32 effect sizes for N2 and 7 effect sizes for MFN. We found that deception was associated with a more negative N2 and MFN than truth-telling with medium and large effect sizes (r = .25 and .51, respectively). We also found that the deception paradigm modulated the results (p = .043), but found no evidence for publication bias. Our findings indicate that deception involves more cognitive control than truth-telling. Our review also identifies gaps in this literature, including a need for more ERP studies using spontaneous deception.

The association between living altitude and serum leptin concentrations in native women.

Background: Lower diabetes prevalence and cardiovascular mortality have been observed in residents at a higher altitude. Leptin is associated with incident diabetes and adverse cardiovascular outcomes, and our aim was to investigate the association of living altitude with serum leptin concentrations. Methods: Two cross-sectional surveys were used in this study, including native populations living at Tibet (high altitude) and Beijing (low altitude). A propensity score was conducted for matching age and body mass index (BMI) between native women at high and low altitude. Pearson's correlation analysis was performed to evaluate the correlation of leptin with other variables. Results: A total of 1414 native women were included in this study, including 594 at high altitude and 820 at low altitude. The serum leptin concentrations of native women living at high altitude were 13.74 ± 11.03 ng/ml, which was significantly lower than that of native women living at low altitude (20.90 ± 12.91 ng/ml). After matching age and BMI, women living at the high altitude still had lower serum leptin concentrations. After adjusting for the potential confounding factors, the correlation coefficient between Ln (leptin) and BMI of women at high altitude was significantly lower than that of women at low altitude (0.228 versus 0.559; P <0.0001). The serum leptin concentrations of each BMI subgroup (<18.5, 18.5 to <25, 25 to <30, ≥ 30 kg/m2) in women at high altitude were lower than that in women at low altitude. Conclusions: Serum leptin concentrations were significantly decreased in native women living at high altitude, and living altitude may alter the correlation of BMI and leptin. The findings of our study support that residents at high altitude have a protective effect with regards to improving cardiovascular and metabolic outcomes.

Effect of low temperature extrusion-modified potato starch addition on properties of whole wheat dough and texture of whole wheat youtiao.

In this study, low temperature extrusion-modified potato starch (MPS) was added to improve properties of whole wheat dough and textural quality of resulted youtiao. Extrusion temperature (60, 90 ℃) and barrel moisture content (30, 42 and 54%) were set as test variables. The results suggested that the low temperature extrusion processing caused moderate gelatinization and improved gel-forming properties of potato starch. MPS addition decreased the setback by up to 46%, and enhanced the viscoelasticity of whole wheat dough significantly. Compared to the whole wheat-based youtiao, the addition of 10% MPS decreased the hardness by up to 72%, and increased the springiness and specific volume by 32% and 22%, respectively. The addition of MPS prepared at lower extrusion temperature (60 ℃) and moderate moisture content (42%) resulted in the optimum textural qualities of whole wheat youtiao. This study will help better understand the role of MPS in whole wheat-based food product.

Potential Involvement of ewsr1-w Gene in Ovarian Development of Chinese Tongue Sole, Cynoglossus semilaevis.

Ewsr1 encodes a protein that acts as a multifunctional molecule in a variety of cellular processes. The full-length of Cs-ewsr1-w and Cs-ewsr1-z were cloned in Chinese tongue sole (Cynoglossus semilaevis). The open reading frame (ORF) of Cs-ewsr1-w was 1,767 bp that encoded 589 amino acids, while Cs-ewsr1-z was 1,794 bp that encoded 598 amino acids. Real-time PCR assays showed that Cs-ewsr1-w exhibited significant female-biased expression and could be hardly detected in male. It has the most abundant expression in ovaries among eight healthy tissues. Its expression in ovary increased gradually from 90 d to 3 y with C. semilaevis ovarian development and reached the peak at 3 y. After Cs-ewsr1-w knockdown with siRNA interference, several genes related to gonadal development including foxl2, sox9b and pou5f1 were down-regulated in ovarian cell line, suggesting the possible participation of Cs-ewsr1-w in C. semilaevis ovarian development. The dual-luciferase reporter assay revealed that the -733/-154 bp Cs-ewsr1-w promoter fragment exhibited strong transcription activity human embryonic kidney (HEK) 293T cell line. The mutation of a MAF BZIP Transcription Factor K (Mafk) binding site located in this fragment suggested that transcription factor Mafk might play an important role in Cs-ewsr1-w basal transcription. Our results will provide clues on the gene expression level, transcriptional regulation and knock-down effect of ewsr1 gene during ovarian development in teleost.

Effects of Jet Milling on the Physicochemical Properties of Buckwheat Flour and the Quality Characteristics of Extruded Whole Buckwheat Noodles.

The effects of jet milling on the physicochemical properties of buckwheat flour and the quality characteristics of extruded whole buckwheat noodles (WBN) were investigated in this study. The results reveal that the application of jet milling significantly reduced the particle size of buckwheat flour. As a result, the damaged starch content, water solubility index, water absorption index and swelling power of buckwheat flour all increased. It was worth noting that moderately ground buckwheat flour powder (D50 = 65.86 µm) had the highest pasting viscosity and gel hardness. The breaking rate and cooking loss of extruded whole buckwheat noodles made from the above powder were reduced by 33% and 16%, respectively. Meanwhile, they possessed the highest lightness and firmest network structure. Jet milling increased the soluble dietary fiber (SDF) content from 3.45% to 4.39%, and SDF further increased to 5.28% after noodle extrusion. This study was expected to provide a reference for exploiting high-quality gluten-free noodles from the perspective of milling.

Belief or disbelief in feedback influences the detection efficiency of the feedback concealed information test.

The feedback concealed information test (fCIT) is a new variant of the CIT that added feedback about participants' concealing performances in the classical CIT. The advantage of the fCIT is that the resulting feedback related event-related potentials (ERPs) can be used to detect concealed information. However, the detection efficiency of feedback-based ERPs varies across studies. The present experiment examined whether the extent participants believed the feedback influenced their detection efficiency. Specifically, participants did a mock crime and were then tested in a fCIT. Following the fCIT, participants were asked to report how much they believed the feedback was accurate. Results showed that there were no significant correlations between the amplitude of the feedback related negativity (FRN), feedback P300, and participants' self-report at the group level. However, individual analyses showed that the detection efficiency of both the FRN and feedback P300 were influenced by participants' belief about the presented feedback. The detection efficiency of the FRN and the feedback P300 was higher among participants who believed the feedback. These findings suggest that the fCIT is dependent to some extent on the participants' level of belief in the feedback.

Sex- and body mass index-specific reference intervals for serum leptin: a population based study in China.

BACKGROUND: Leptin is a peptide hormone secreted by adipose tissue and is an important determinant of obesity and its complications. The purpose of this study was to establish sex- and body mass index (BMI)-specific reference intervals for serum leptin in a Chinese population and investigate the factors influencing leptin concentrations. METHODS: Fasting serum leptin levels were assayed in 469 men and 773 women from randomly sampled Chinese residents. Blood glucose, insulin, hemoglobin A1c (HbA1c), liver enzymes, blood lipid profiles, creatinine, and uric acid (UA) levels were measured. Pearson's correlation coefficient and multiple linear regression analyses were used to estimate the relationship between serum leptin level and other variables. The reference intervals were determined by the 2.5th and 97.5th percentiles. RESULTS: The mean ± standard deviation serum leptin level was much higher in women (20.92 ± 12.96 ng/mL) than in men (6.45 ± 5.53 ng/mL). The reference interval of serum leptin was 0.33-19.85 ng/mL in men and 3.60-54.86 ng/mL in women. The specific reference intervals of serum leptin in men with BMI of 20 to < 25 and 25 to < 27.5 kg/m2 were 0.42-12.32 and 2.17-20.22 ng/ml, respectively. The specific reference intervals of serum leptin in women with BMI of 20 to < 25 and 25 to < 27.5 kg/m2 were 4.11-38.09 and 8.27-48.66 ng/ml, respectively. BMI was significantly correlated with Ln (leptin) both in men (r = 0.698, P < 0.001) and women (r = 0.626, P < 0.001). In multivariate linear regression analysis, serum leptin was correlated with BMI, homeostasis model assessment of insulin resistance (HOMA-IR), UA in women, and plus triglyceride (TG) in men. The variance in serum leptin levels could be partially explained by these variables in both women (adjusted R2 = 0.447) and men (adjusted R2 = 0.552). In participants with leptin levels higher than the reference intervals, significantly higher levels of HOMA-IR, low-density lipoprotein cholesterol (LDL-C), UA, a higher proportion of central obesity (waist circumference [WC] > 90 cm), and metabolic syndrome were found in men, and significantly higher levels of HOMA-IR, UA and a higher proportion of central obesity (WC > 85 cm) were found in women. CONCLUSION: This is the first study to establish sex- and BMI-specific reference intervals of leptin for both sexes in a large Chinese population. Serum concentration of leptin was predicted by BMI, HOMA-IR, UA in women, and TG in men.

Effect of colchicine on inflammatory markers in patients with coronary artery disease: A meta-analysis of clinical trials.

Whether colchicine reduces the levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) remains uncertain. Therefore, this systematic review and meta-analysis were conducted to evaluate the overall effect of colchicine treatment on hs-CRP and IL-6 levels in patients with coronary artery disease (CAD). PubMed/Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies published before October 2021. Clinical trials in patients with CAD with reports of hs-CRP and IL-6 level changes before and after colchicine intervention were included. In total, 11 trials on hs-CRP and two trials on IL-6 were included in this meta-analysis. Compared with that in the control group, colchicine treatment was significantly associated with decreased hs-CRP levels (weighted mean differences [WMDs], -0.81 mg/L; 95% confidence interval [CI], -1.34 to -0.28 mg/L; P = 0.003) in patients with CAD. Besides, the levels of IL-6 were significantly reduced in colchicine users compared to that of placebo (WMD, -1.28 pg/mL; 95% CI, -2.35 to -0.21 pg/mL; P = 0.02). In a subgroup analysis, colchicine led to a significant reduction in hs-CRP levels in studies with duration of intervention >7 days (WMD, -0.65 mg/L; 95% CI, -1.08 to -0.21 mg/L; P = 0.004) and studies with baseline hs-CRP levels ≥3.0 mg/L (WMD, -0.99 mg/L; 95% CI, -1.92 to -0.06 mg/L; P = 0.04). Colchicine intervention was associated with a reduction in hs-CRP and IL-6 levels in patients with CAD. Future investigations are required to verify the effect of colchicine on inflammatory markers and clarify the potential mechanisms of the cross talk between colchicine, inflammation, and cardiovascular outcomes.

The effect of mental countermeasures on a novel brain-based feedback concealed information test.

The feedback concealed information test (fCIT) is a novel form of the CIT, providing participants with feedback regarding their memory concealment performance. The fCIT utilizes event-related potentials (recognition-P300 and feedback-related event-related potentials) and has been shown to provide high efficiency in detecting information concealment. However, it is unclear how well the fCIT performs in the presence of mental countermeasures. To address this question, participants were trained to use countermeasures during fCIT. Results showed that the recognition-P300 efficiency decreased when participants used countermeasures. However, the efficiencies of feedback-related negativity and feedback-P300 were unchanged, with feedback-P300 still showing a high detection efficiency (AUC = 0.86) during countermeasures. These findings demonstrate the potential of fCIT for subverting countermeasures.

The Determination of Step Frequency in 3-min Incremental Step-in-Place Tests for Predicting Maximal Oxygen Uptake from Heart Rate Response in Taiwanese Adults.

The maximal oxygen uptake (VO2max) prediction models established by step tests are often used for evaluating cardiorespiratory fitness (CRF). However, it is unclear which type of stepping frequency sequence is more suitable for the public to assess the CRF. Therefore, the main purpose of this study was to test the effectiveness of two 3-min incremental step-in-place (3MISP) tests (i.e., 3MISP30s and 3MISP60s) with the same total number of steps but different step-frequency sequences in predicting VO2max. In this cross-sectional study, a total of 200 healthy adults in Taiwan completed 3MISP30s and 3MISP60s tests, as well as cardiopulmonary exercise testing. The 3MISP30s and 3MISP60s models were established through multiple stepwise regression analysis by gender, age, percent body fat, and 3MISP-heart rate. The statistical analysis included Pearson's correlations, the standard errors of estimate, the predicted residual error sum of squares, and the Bland-Altman plot to compare the measured VO2max values and those estimated. The results of the study showed that the exercise intensity of the 3MISP30s test was higher than that of the 3MISP60s test (% heart rate reserve (HRR) during 3MISP30s vs. %HRR during 3MISP60s = 81.00% vs. 76.81%, p < 0.001). Both the 3MISP30s model and the 3MISP60s model explained 64.4% of VO2max, and the standard errors of the estimates were 4.2043 and 4.2090 mL·kg-1·min-1, respectively. The cross-validation results also indicated that the measured VO2max values and those predicted by the 3MISP30s and 3MISP60s models were highly correlated (3MISP30s model: r = 0.804, 3MISP60s model: r = 0.807, both p < 0.001). There was no significant difference between the measured VO2max values and those predicted by the 3MISP30s and 3MISP60s models in the testing group (p > 0.05). The results of the study showed that when the 3MISP60s test was used, the exercise intensity was significantly reduced, but the predictive effectiveness of VO2max did not change. We concluded that the 3MISP60s test was physiologically less stressful than the 3MISP30s test, and it could be a better choice for CRF evaluation.

Association Between Non-Alcoholic Fatty Liver Disease and Diabetes-Related Microvascular Complications: A Retrospective Cross-Sectional Study of Hospitalized Patients.

OBJECTIVE: Owing to limited research, the effect of nonalcoholic fatty liver disease (NAFLD) on type 2 diabetes outcomes remains unclear. This study aimed to investigate the association between NAFLD and microvascular complications in hospitalized patients with type 2 diabetes. METHODS: We included 1982 patients with type 2 diabetes. NAFLD was defined as hepatic steatosis detected by ultrasound without secondary causes of fat accumulation. The diagnosis of diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy was based on clinical medical records. Risk for advanced liver fibrosis was categorized as "low risk," "indeterminate risk," and "high risk," based on the NAFLD fibrosis score (NAFLD-FS). Logistic regression was used to test the association between NAFLD, risk for advanced fibrosis, and the presence of DR, DKD, and diabetic neuropathy. RESULTS: The prevalence of NAFLD was 61.3%. The presence of DR and DKD was inversely associated with NAFLD, after adjusting for covariates. The presence of DR and DKD was higher in the "indeterminate risk" and "high risk" groups than in the "low risk" group, after adjusting for the same covariates. Only the presence of DKD significantly increased with high NAFLD-FS. CONCLUSION: The presence of DR and DKD was inversely associated with NAFLD among hospitalized patients with type 2 diabetes. DKD was closely associated with high NAFLD-FS among patients with NAFLD.

The BZR1-EDS1 module regulates plant growth-defense coordination.

Plants have developed sophisticated strategies to coordinate growth and immunity, but our understanding of the underlying mechanism remains limited. In this study, we identified a novel molecular module that regulates plant growth and defense in both compatible and incompatible infections. This module consisted of BZR1, a key transcription factor in brassinosteroid (BR) signaling, and EDS1, an essential positive regulator of plant innate immunity. We found that EDS1 interacts with BZR1 and suppresses its transcriptional activities. Consistently, upregulation of EDS1 function by a virulent Pseudomonas syringae strain or salicylic acid treatment inhibited BZR1-regulated expression of BR-responsive genes and BR-promoted growth. Furthermore, we showed that the cytoplasmic fraction of BZR1 positively regulates effector-triggered immunity (ETI) controlled by the TIR-NB-LRR protein RPS4, which is attenuated by BZR1's nuclear translocation. Mechanistically, cytoplasmic BZR1 facilitated AvrRps4-triggered dissociation of EDS1 and RPS4 by binding to EDS1, thus leading to efficient activation of RPS4-controlled ETI. Notably, transgenic expression of a mutant BZR1 that accumulates exclusively in the cytoplasm improved pathogen resistance without compromising plant growth. Collectively, these results shed new light on plant growth-defense coordination and reveal a previously unknown function for the cytoplasmic fraction of BZR1. The BZR1-EDS1 module may be harnessed for the simultaneous improvement of crop productivity and pathogen resistance.

Dietary bile acid supplementation reveals beneficial effects on intestinal healthy status of tongue sole (Cynoglossus semiliaevis).

The aim of this study was to investigate the effects of dietary bile acids (BAs) on intestinal healthy status of tongue sole in terms of immunity, antioxidant status, digestive ability, mucosal barrier-related genes expression and microbiota. Three experimental diets were prepared with BA levels at 0 mg/kg (CT), 300 mg/kg (BA1) and 900 mg/kg (BA2) in a commercial basal diet. Each diet was fed to three replicates with 120 fish (10.87 ± 0.32 g) in each tank. After an 8-week feeding trial, growth parameters were significantly enhanced in both BAs supplementary groups (P < 0.05), and compared with CT group, survival rate in BA2 group was significantly improved (P < 0.05). Intestinal lysozyme activity and contents of immunoglobulin M and complement 3 were significantly increased in both BAs supplementary groups (P < 0.05), suggesting an enhancement effect on the non-specific immune response. BAs inclusion also significantly improved intestinal antioxidant capabilities by increasing antioxidase activities and decreasing malondialdehyde levels. In addition, compared with CT group, intestinal digestive ability was substantially enhanced as indicated by the significantly increased lipase activity in BA2 group (P < 0.05) and significantly increased amylase activity in BA1 and BA2 groups (P < 0.05). Coincidentally, BAs inclusion significantly upregulated the relative expression of intestinal mucosal barrier-related genes (P < 0.05). Further, dietary BAs distinctly remodeled intestinal microbiota by decreased the abundance of some potential pathogenic bacteria. In conclusion, dietary BAs supplementation is an effective way to improve the intestinal healthy status of tongue sole.

Comparative transcriptome profiling of immune response against Vibrio harveyi infection in Chinese tongue sole.

Vibrio harveyi is a major bacterial pathogen that causes fatal vibriosis in Chinese tongue sole (Cynoglossus semilaevis), resulting in massive mortality in the farming industry. However, the molecular mechanisms of C. semilaevis response to V. harveyi infection are poorly understood. Here, we performed transcriptomic analysis of C. semilaevis, comparing resistant and susceptible families in response to V. harveyi challenge (CsRC and CsSC) and control conditions (CsRU and CsSU). RNA libraries were constructed using 12 RNA samples isolated from three biological replicates of the four groups. We performed transcriptome sequencing on an Illumina HiSeq platform, and generating a total of 1,095 million paired-end reads, with the number of clean reads per library ranging from 75.27 M to 99.97 M. Through pairwise comparisons among the four groups, we identified 713 genes exhibiting significant differences at the transcript level. Furthermore, the expression levels were validated by real-time qPCR. Our results provide a valuable resource and new insights into the immune response to V. harveyi infection.

Gene expression profile-based drug screen identifies SAHA as a novel treatment for NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Being part of the metabolic syndrome, NAFLD is characterized by the deposition of triglycerides (TGs) as lipid droplets in the cytoplasm of hepatic cells. Recently, the rapid development of high-throughput genome analysis technologies provided opportunities to screen for new drugs for NAFLD. In this study, we screened for potential drugs based on the gene expression profiles of 73 compounds and identified histone deacetylase (HDAC) inhibitors as a novel treatment for the accumulation of lipids in hepatocytes. In the subsequent analysis and experiments, we discovered that SAHA inhibited the fatty acid and lipid metabolism pathways in hepatic cells and induced a significant deficiency of lipid accumulation in HepG2 and SMMC-7721 cells. Furthermore, SAHA inhibited lipid synthesis in hepatic cells by directly suppressing the expression of DGAT2. Hence, our study provides a novel method to screen for effective drugs for liver diseases and identifies SAHA as a potent treatment for NAFLD.