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Abstract People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. −10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed. Clinical Trials.gov registration: NCT03743636.

Abstract Background Asthma is widely recognized as an inflammatory disorder. In the context of this inflammatory microenvironment, the involvement of hypoxia and its impact on related pathways have drawn considerable attention. However, the exact role of hypoxia, a prevalent environmental factor, in the development and progression of asthma remains poorly understood. Methods Mice were treated with house dust mite (HDM) extracts for 23 days to induce asthma. Mice were divided into room air (RA) group and intermittent hypoxic (IH) group by exposing to different conditions and IH preconditioning (IHP) were underwent to the above groups before the hypoxic regimen. Airway inflammation in mice was evaluated by airway hyperresponsiveness, excessive mucus secretion, and recruitment of inflammatory cells. Immunohistochemistry was employed to quantify the expression levels of NF‐κB. Subsequently, the dose of allergen was modified to investigate whether the impact of hypoxia on asthma is affected by different doses of allergens. Result Compared to the RA and IH groups, HDM‐treated mice in the IHP group exhibited aggravated inflammatory cell infiltration and airway hyperresponsiveness (p＜.05). Moreover, there was an increased release of inflammatory mediators and higher expression levels of NF‐κB (p＜.05). Importantly, the impact ia on asthma was found to be influenced by high dose of allergen (p＜.05). Conclusion IHP treatment potentially exacerbates HDM‐induced airway inflammation in asthma, with the involvement of NF‐κB, particularly under high‐dose allergen stimulation.

Objective Vascular calcification is a common chronic kidney disease complication. This study aimed to investigate the function of long non-coding RNA (LncRNA) H19 in vascular calcification to explore new therapeutic strategies. Methods We induced osteogenic differentiation and calcification of vascular smooth muscle cells (VSMCs) using β-glycerophosphate. Then, we detected the LncRNA H19 promoter methylation status and Erk1/2 pathways using methylation-specific polymerase chain reaction and western blotting, respectively. Results Compared with the control group, high phosphorus levels induced VSMC calcification, accompanied by increases in LncRNA H19 and the osteogenic marker Runx2 and reduction of the contractile phenotype marker SM22a. LncRNA H19 knockdown inhibited osteogenic differentiation and calcification of VSMCs. However, the suppressed role of VSMC calcification caused by shRNA H19 was partially reversed by simultaneous activation of the Erk1/2 pathways. Mechanically, we found that the methylation rate of CpG islands in the LncRNA H19 promoter region was significantly lower in the high-phosphorus group, and the hypomethylation state elevated LncRNA H19 levels, which in turn regulated phosphorylated Erk1/2 expression. Conclusions LncRNA H19 promoted osteogenic differentiation and calcification of VSMCs by regulating the Erk1/2 pathways. Additionally, hypomethylation of LncRNA H19 promoter CpG islands upregulated LncRNA H19 levels and subsequently activated Erk1/2 phosphorylation.

Very long chain fatty acids (VLCFAs) are fatty acids with chain lengths of 20 or more carbon atoms, which are the building blocks of various lipids that regulate developmental processes and plant stress responses. 3-ketoacyl-CoA synthase encoded by the KCS gene is the key rate-limiting enzyme in VLCFA biosynthesis, but the KCS gene family in soybean (Glycine max) has not been adequately studied thus far. In this study, 31 KCS genes (namely GmKCS1 - GmKCS31) were identified in the soybean genome, which are unevenly distributed on 14 chromosomes. These GmKCS genes could be phylogenetically classified into seven groups. A total of 27 paralogous GmKCS gene pairs were identified with their Ka/Ks ratios indicating that they had undergone purifying selection during soybean genome expansion. Cis-acting element analysis revealed that GmKCS promoters contained multiple hormone- and stress-responsive elements, indicating that GmKCS gene expression levels may be regulated by various developmental and environmental stimuli. Expression profiles derived from RNA-seq data and qRT-PCR experiments indicated that GmKCS genes were diversely expressed in different organs/tissues, and many GmKCS genes were found to be differentially expressed in the leaves under cold, heat, salt, and drought stresses, suggesting their critical role in soybean resistance to abiotic stress. These results provide fundamental information about the soybean KCS genes and will aid in their further functional elucidation and exploitation.

Background Mitochondrial abnormalities exist in gastrocnemius muscle of people with peripheral artery disease (PAD). Whether abnormalities in mitochondrial biogenesis and autophagy are associated with greater ischemia or walking impairment in PAD is unknown. Methods and Results Protein markers of mitochondrial biogenesis and autophagy and the abundance of mitochondrial electron transport chain complexes were quantified in gastrocnemius muscle biopsies from people with and without PAD. Their 6‐minute walk distance and 4‐m gait speed were measured. Sixty‐seven participants (mean age 65.0 years [±6.8], 16 [23.9%] women, 48 [71.6%] Black) were enrolled, including 15 with moderate to severe PAD (ankle brachial index [ABI]

Flower type is the most valuable ornamental trait in floricultural plants, for which the ABCDE model was proposed to explain the identity of each floral organ in flowering plants. The C-class gene AGAMOUS (AG) is responsible for stamen formation and plays an essential role in the double flower phenotype. A previous study in carnation revealed that the mutation in the miR172 binding site of the A-class gene APETALA2 (AP2) leads to petal accumulation. And the expression level of AG was reduced significantly in the double flowers compared with that in the single flowers. However, there was no sequence polymorphism detected between AGs isolated from the double flowers and single flowers. Here, we performed AG analysis using single and semi-double flower carnations, and detected several mutations located in the crucial position like the MADS-box domain in the AGs of semi-double flower carnations while no changes were found at the miR172 binding site of AP2. As a result, the expression levels of AGs are reduced in the semi-double flower carnation, which could be caught by the loss function of AGs. Our data proves that AGs mutations are also associated with the semi-double flower formation in carnation, complementing the lack of research about AG-mutation-associated double flower formation in carnation.

Abstract Background To investigate the difference in the structural composition of salivary flora between chronic periodontitis patients with and without diabetic nephropathy (DN). Methods Thirty salivary samples of 15 chronic periodontitis patients with DN (DN group) and 15 chronic periodontitis patients with diabetes but without DN (DM group) were subjected to pyrosequencing of polymerase chain reaction-amplified 16 s ribosomal RNA genes. After diversity testing, the differential flora were analyzed. The sequencing results were compared with GenBank database to determine the type of differential flora using species composition analysis, hierarchical cluster analysis, principal co-ordinate analysis, and species difference analysis. Results There were significant between-group differences with respect to Gemella, Selenomonas spp, Lactobacillales_unclassified, Bacteria-unclassified and Abiotrophia (p

Abstract Intestinal diseases seriously affect the quality of life. The assays for intestinal disease study based on two‐dimensional in vitro cell culture and animal models fail to model human physiology and pathophysiology accurately. As a bridge between in vitro cell culture and clinical pathological specimens, intestine‐on‐a‐chip lined with living cells under dynamic flow can recapitulate the human intestinal microenvironment with high precision. Here, we summarize important elements for reconstructing the intestinal microenvironment and the mostly used intestine‐on‐a‐chip models that simulate the basic intestinal microenvironment, and the intestinal microenvironment with pathogenic bacteria, probiotic bacteria, viruses, tumor cells, and parasites. We also introduce the commonly used analytical techniques, including immunofluorescence imaging, mass spectrometry, DNA/RNA‐based analysis, and electrochemistry, which can be integrated with intestine chips for intestinal microenvironment characterization. We further review the application of intestine‐on‐a‐chip for intestinal disease study and pharmacological research. Finally, we discuss the application prospects and challenges of intestine chips in biomedical and clinical research.

Background Supervised exercise therapy (SET) is the first‐line therapy for walking impairment in peripheral artery disease (PAD). This study evaluated the association between attendance at SET and improved walking performance, compared with a control group, in PAD. Methods and Results Data from 2 randomized clinical trials of SET for PAD were combined. In each trial, participants were randomized to 3 times weekly supervised treadmill exercise or an attention control group for 6 months (maximum, 77 exercise sessions). Participants randomized to SET were categorized into tertiles, according to the proportion of exercise sessions they attended. Results adjusted for age, sex, race, baseline walking performance, comorbidities, and other potential confounders. A total of 272 participants with PAD (mean age, 67.9±9.3 years; 44% women; 61% Black race) were included. For participants randomized to SET, tertiles of attendance rates at exercise sessions were as follows: 11% to 68% (N=45), 69% to

Abstract Background Dysregulated lncRNA score and PVT1 expression may be involved in cancer. However, relationships of lncRNAs with hyperparathyroidism and parathyroid cancer (PC) diagnosis remain mysterious. Methods Using quantitative real-time polymerase chain reaction (RT-qPCR), expression profile of PVT1 was evaluated in 57 patients with primary hyperparathyroidism, including 11 with parathyroid cancer (PC) and 46 with parathyroid adenoma (PA). Results Higher levels of lncRNA score and PVT1 expression were associated with increased serum calcium level after water ingestion and PC risk (P

Abstract In this article, a powerful method to synthesize uniform CaCO3 rod bundles with a high mass fraction of aragonite from carbide slag in large‐scale production via a two‐step leaching‐precipitation process is reported. The effects of the addition of ethylene glycol and reaction temperature on the structure and morphology of the prepared CaCO3 samples were investigated and then demonstrated by the experimental results. It is beneficial to increase the mass fraction of aragonite in CaCO3 samples and ensure the formation of regular rod bundles in morphology when the addition of ethylene glycol is 30 mL and the reaction temperature is 80 °C. The formation mechanism of the CaCO3 rod bundles was preliminarily discussed according to the Muffins–Sekerka theory.

Radiative cooling is an approach that maximizes the thermal emission through the atmospheric window in order to dissipate heat, while minimizing the absorption of incoming atmospheric radiation, to realize a net cooling effect without consuming energy. Electrospun membranes are made of ultra-thin fibers with high porosity and surface area, which makes them suitable for radiative cooling applications. Many studies have investigated the use of electrospun membranes for radiative cooling, but a comprehensive review that summarizes the research progress in this area is still lacking. In this review, we first summarize the basic principles of radiative cooling and its significance in achieving sustainable cooling. We then introduce the concept of radiative cooling of electrospun membranes and discuss the selection criteria for materials. Furthermore, we examine recent advancements in the structural design of electrospun membranes for improved cooling performance, including optimization of geometric parameters, incorporation of highly reflective nanoparticles, and designing multilayer structure. Additionally, we discuss dual-mode temperature regulation, which aims to adapt to a wider range of temperature conditions. Finally, we provide perspectives for the development of electrospun membranes for efficient radiative cooling. This review will provide a valuable resource for researchers working in the field of radiative cooling, as well as for engineers and designers interested in commercializing and developing new applications for these materials.

Background Associations of 1‐year change in functional performance measures with subsequent mobility loss and mortality in people with lower extremity peripheral artery disease are unknown. Methods and Results Six‐minute walk and 4‐meter walking velocity (usual and fastest pace) were measured at baseline and 1 year later in 612 people with peripheral artery disease (mean age 71±9 years, 37% women). Participants were categorized into tertiles, based on 1‐year changes in walking measures. Cox proportional hazards models were used to examine associations between 1‐year change in each walking measure and subsequent mobility loss and mortality, respectively, adjusting for potential confounders. Compared with the best tertile, the worst tertile (ie, greatest decline) in 1‐year change in each performance measure was associated with higher rates of mobility loss: 6‐minute walk (Tertile 1 [T1] cumulative incidence rate [IR], 72/160; Tertile 3 [T3] IR, 47/160; hazard ratio [HR], 2.35; 95% CI, 1.47–3.74), usual‐paced 4‐meter walking velocity (T1 IR, 54/162; T3 IR, 57/162; HR, 2.21; 95% CI, 1.41–3.47), and fast‐paced 4‐meter walking velocity (T1 IR, 61/162; T3 IR, 58/162; HR, 1.81; 95% CI, 1.16–2.84). Compared with the best tertile, the worst tertiles in 1‐year change in 6‐minute walk (T1 IR, 66/163; T3 IR, 54/163; HR, 1.61; 95% CI, 1.07–2.43) and fast‐paced 4‐meter walking velocity (T1 IR, 63/166; T3 IR, 44/166; HR, 1.75; 95% CI, 1.16, 2.64) were associated with higher mortality. Conclusions In people with peripheral artery disease, greater 1‐year decline in 6‐minute walk or 4‐meter walking velocity may help identify people with peripheral artery disease at highest risk for mobility loss and mortality.

In this study, 1-methylhydantoin cinnamic imides were synthesized from 1-methylhydantoin and trans-cinnamic acid, and their anti-inflammatory activity was investigated. The anti-inflammatory activity in vitro was evaluated by measuring the contents of NO, TNF-α and IL-1β in the supernatant of RAW264.7 cells stimulated by LPS. The cytotoxicity of 1-methylhydantoin cinnamoyl imides on RAW264.7 cells was detected using the CCK-8 method. The results showed that compounds 2 and 4 can significantly inhibit the release of NO and reduce the secretion of TNF-α and IL-1β. Compound 3 inhibited the production of TNF-α. The inhibition rate of COX was evaluated in vitro. The in vivo anti-inflammatory activities of the five compounds were evaluated by establishing an animal model of xylene ear swelling. The results showed that 1-methylhydantoin cinnamic imides could alleviate xylene-induced ear edema in mice in a dose-dependent manner. Among them, the effect of compound 5 was the most significant. Under the action of high dosage, its ear swelling inhibition rate was as high as 52.08%.

ObjectivesTo evaluate the value of synthetic magnetic resonance imaging (syMRI), diffusion-weighted imaging (DWI), DCE-MRI, and clinical features in breast imaging–reporting and data system (BI-RADS) 4 lesions, and develop an efficient method to help patients avoid unnecessary biopsy.MethodsA total of 75 patients with breast diseases classified as BI-RADS 4 (45 with malignant lesions and 30 with benign lesions) were prospectively enrolled in this study. T1-weighted imaging (T1WI), T2WI, DWI, and syMRI were performed at 3.0 T. Relaxation time (T1 and T2), apparent diffusion coefficient (ADC), conventional MRI features, and clinical features were assessed. “T” represents the relaxation time value of the region of interest pre-contrast scanning, and “T+” represents the value post-contrast scanning. The rate of change in the T value between pre- and post-contrast scanning was represented by ΔT%.ResultsΔT1%, T2, ADC, age, body mass index (BMI), menopause, irregular margins, and heterogeneous internal enhancement pattern were significantly associated with a breast cancer diagnosis in the multivariable logistic regression analysis. Based on the above parameters, four models were established: model 1 (BI-RADS model, including all conventional MRI features recommended by BI-RADS lexicon), model 2 (relaxation time model, including ΔT1% and T2), model 3 [multi-parameter (mp)MRI model, including ΔT1%, T2, ADC, margin, and internal enhancement pattern], and model 4 (combined image and clinical model, including ΔT1%, T2, ADC, margin, internal enhancement pattern, age, BMI, and menopausal state). Among these, model 4 has the best diagnostic performance, followed by models 3, 2, and 1.ConclusionsThe mpMRI model with DCE-MRI, DWI, and syMRI is a robust tool for evaluating the malignancies in BI-RADS 4 lesions. The clinical features could further improve the diagnostic performance of the model.

Objective To identify serum microRNAs (miRNAs) as potential non-invasive biomarkers for patients with chronic kidney disease (CKD). Methods We collected serum samples from healthy controls, CKD stage 1 (CKD1), and stage 5 (CKD5) patients with primary glomerulonephritis (GN), screened differentially expressed miRNAs (DEMs) using next-generation sequencing (NGS), and confirmed the sequencing data using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results We identified 20 and 42 DEMs in the CKD1 and CKD5 patients compared with the controls, respectively, and 70 DEMs in the CKD5 compared with the CKD1 patients. The qRT-PCR results showed that miR-483-5p was up-regulated in the CKD1 and CKD5 patients compared with controls (fold change = 2.56 and 18.77, respectively). miR-363-3p was down-regulated in the CKD5 patients compared with the controls and CKD1 patients (fold change = 0.27 and 0.48, respectively). Conclusion We identified a genome-wide serum miRNA expression profile in CKD patients, and serum miR-483-5p and miR-363-3p may act as potential diagnostic biomarkers for CKD.

WRINKLED1 (WRI1), an APETALA2 (AP2) transcription factor (TF), critically regulates the processes related to fatty acid synthesis, storage oil accumulation, and seed development in plants. However, the WRI1 genes remain unknown in allohexaploid bread wheat (Triticum aestivum L.). In this study, based on the sequence of Arabidopsis AtWRI1, two TaWRI1Ls genes of bread wheat, TaWRI1L1 and TaWRI1L2, were cloned. TaWRI1L2 was closely related to monocotyledons and clustered in one subgroup with AtWRI1, while TaWRI1L1 was clustered in another subgroup with AtWRI3 and AtWRI4. Both were expressed highly in the developmental grain, subcellular localized in the nucleus, and showed transcriptional activation activity. TaWRI1L2, rather than TaWRI1L1, promoted oil body accumulation and significantly increased triglyceride (TAG) content in tobacco leaves. Overexpression of TaWRI1L2 compensated for the functional loss of AtWRI1 in an Arabidopsis mutant and restored the wild-type phenotypes of seed shape, generation, and fatty acid synthesis and accumulation. Knockout of TaWRI1L2 reduced grain size, 1000 grain weight, and grain fatty acid synthesis in bread wheat. Conclusively, TaWRI1L2, rather than TaWRI1L1, was the key transcriptional factor in the regulation of grain fatty acid synthesis in bread wheat. This study lays a foundation for gene regulation and genetic manipulation of fatty acid synthesis in wheat genetic breeding programs.

Background Among people with lower extremity peripheral artery disease, obesity is associated with faster functional decline than normal weight. The association of weight loss with functional decline in peripheral artery disease is unknown. Methods and Results Adults with an ankle‐brachial index

Background. Long noncoding RNAs (lncRNAs) were recently shown to have potential in the diagnosis and prognosis for numerous cancers. lncRNA GAS8-AS1 is decreased in papillary thyroid cancer (PTC) tissue, but its plasma expression and clinical value in patients with PTC remain unknown. Materials and Methods. We investigated the expression profile of plasma GAS8-AS1 in 97 patients with PTC and 39 patients with nodular goiter by quantitative real-time polymerase chain reaction. Results. GAS8-AS1 expression in plasma was downregulated in patients with PTC in comparison with those in nodular goiters (P

The title compound, C21H19ClN2O5, is a tetrasubstituted hydantoin derivative which contains an imidazolidine-2,4-dione core. The dihedral angle between the aromatic rings is 64.53 (14)°. In the crystal, weak intermolecular C—H...O hydrogen bonding is found. An intramolecular C—H...O interaction also occurs.

In the thioglycoluril system of the title compound, C32H30N8S2·CHCl3, the two pyridine rings are roughly parallel, forming a dihedral angle of 7.2 (1)°, and the distance between the centroids of the two phenyl rings is 3.951 (5) Å. The chloroform solvent molecule is linked to the main molecule via a weak C—H...N hydrogen bond.

The pathophysiology of muscle damage in peripheral artery disease (PAD) includes increased oxidant production and impaired antioxidant defenses. Epicatechin (EPI), a naturally occurring flavanol, has antioxidant properties that may mediate the beneficial effects of natural products such as cocoa. In a phase II randomized trial, a cocoa-flavanol-rich beverage significantly improved walking performance compared with a placebo in people with PAD. In the present work, the molecular mechanisms underlying the therapeutic effect of cocoa flavanols were investigated by analyzing baseline and follow-up muscle biopsies from participants. Increases in nuclear factor erythroid 2-related factor 2 (Nrf2) target antioxidants heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) in the cocoa group were significantly associated with reduced accumulation of central nuclei, a myopathy indicator, in type II muscle fibers (P ¼ 0.017 and P ¼ 0.023, respectively). Protein levels of the mitochondrial respiratory complex III subunit, cytochrome b-c1 complex subunit 2 (UQCRC2), were significantly higher in the cocoa group than in the placebo group (P ¼ 0.032), and increases in UQCRC2 were significantly associated with increased levels of Nrf2 target antioxidants HO-1 and NQO1 (P ¼ 0.001 and P ¼ 0.035, respectively). Exposure of non-PAD human myotubes to ex vivo serum from patients with PAD reduced Nrf2 phosphorylation, an indicator of activation, increased hydrogen peroxide production and oxidative stress, and reduced mitochondrial respiration. Treatment of myotubes with EPI in the presence of serum from patients with PAD increased Nrf2 phosphorylation and protected against PAD serum-induced oxidative stress and mitochondrial dysfunction. Overall, these findings suggest that cocoa flavanols may enhance antioxidant capacity in PAD via Nrf2 activation. NEW & NOTEWORTHY The current study supports the hypothesis that in people with PAD, cocoa flavanols activate Nrf2, thereby increasing antioxidant protein levels, protecting against skeletal muscle damage, and increasing mitochondrial protein abundance. These results suggest that Nrf2 activation may be an important therapeutic target for improving walking performance in people with PAD. [ABSTRACT FROM AUTHOR]