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Abstract Diabetic cardiomyopathy (DCM) represents a unique myocardial disease originating from diabetic metabolic disturbances that is characterized by myocardial fibrosis and diastolic dysfunction. While recent research regarding the pathogenesis and treatment of DCM has focused primarily on myocardial cells, nonmyocardial cells—including fibroblasts, vascular smooth muscle cells (VSMCs), endothelial cells (ECs), and immune cells—also contribute significantly to the pathogenesis of DCM. Among various therapeutic targets, fibroblast growth factor 21 (FGF21) has been identified as a promising agent because of its cardioprotective effects that extend to nonmyocardial cells. In this review, we aim to elucidate the role of nonmyocardial cells in DCM and underscore the potential of FGF21 as a therapeutic strategy for these cells.

Abstract Sex hormones play a pivotal role as endocrine hormones that exert profound effects on the biological characteristics and vascular function of vascular smooth muscle cells (VSMCs). By modulating intracellular signaling pathways, activating nuclear receptors, and regulating gene expression, sex hormones intricately influence the morphology, function, and physiological state of VSMCs, thereby impacting the biological properties of vascular contraction, relaxation, and growth. Increasing evidence suggests that abnormal phenotypic changes in VSMCs contribute to the initiation of vascular diseases, including atherosclerosis. Therefore, understanding the factors governing phenotypic alterations in VSMCs and elucidating the underlying mechanisms can provide crucial insights for refining interventions targeted at vascular diseases. Additionally, the varying levels of different types of sex hormones in the human body, influenced by sex and age, may also affect the phenotypic conversion of VSMCs. This review aims to explore the influence of sex hormones on the phenotypic switching of VSMCs and the development of associated vascular diseases in the human body. Graphical Abstract

Abstract Background This study investigated the characteristics of Monson’s sphere in Chinese young adult females with individual normal occlusion to provide a reference for oral rehabilitation in prosthodontic and orthodontic treatments. Methods Points at the dental cusps and incisal edges were selected from 51 digital mandibular dental models of Chinese young adult females (aged 18–22 years) with individual normal occlusion. Monson’s spheres were fitted to the selected points based on the least-squares principle and the radii were calculated. The deviation of each selected point from its relative spherical surface was also calculated. The radii and deviations of these points were examined using conventional descriptive statistics and distributions of the most deviated points inside and outside the spheres were analyzed. Results The mean radius of Monson’s sphere in Chinese young adult females was 79.60 ± 14.13 mm. The deviation of each selected point from its relative sphere surface was 0.38 ± 0.30 mm. The maximum deviations inside and outside the sphere were 0.93 ± 0.25 mm and 0.95 ± 0.30 mm, respectively. The most deviated points outside the spheres were mainly distributed at the distolingual cusps of the mandibular second permanent molars (31.37%), while those inside the spheres were mainly distributed at the mesiolingual cusps of the mandibular first permanent molars (45.10%). Conclusions The radius of Monson’s sphere in Chinese young adult females was smaller than the classic four-inch value suggested by Monson. Deviation was observed from all selected points to their Monson’s sphere surface, with the most deviated points distributed primarily in the molar region.

Abstract Diffusion Kurtosis Imaging (DKI)-derived metrics are recognized as indicators of maturation in neonates with low-grade germinal matrix and intraventricular hemorrhage (GMH-IVH). However, it is not yet known if these factors are associated with neurodevelopmental outcomes. The objective of this study was to acquire DKI-derived metrics in neonates with low-grade GMH-IVH, and to demonstrate their association with later neurodevelopmental outcomes. In this prospective study, neonates with low-grade GMH-IVH and control neonates were recruited, and DKI were performed between January 2020 and March 2021. These neonates underwent the Bayley Scales of Infant Development test at 18 months of age. Mean kurtosis (MK), radial kurtosis (RK) and gray matter values were measured. Spearman correlation analyses were conducted for the measured values and neurodevelopmental outcome scores. Forty controls (18 males, average gestational age (GA) 30 weeks ± 1.3, corrected GA at MRI scan 38 weeks ± 1) and thirty neonates with low-grade GMH-IVH (13 males, average GA 30 weeks ± 1.5, corrected GA at MRI scan 38 weeks ± 1). Neonates with low-grade GMH-IVH exhibited lower MK and RK values in the PLIC and the thalamus (P

Cyclin D1 has been recognized as an oncogene due to its abnormal upregulation in different types of cancers. Here, we demonstrated that cyclin D1 is SUMOylated, and we identified Itch as a specific E3 ligase recognizing SUMOylated cyclin D1 and mediating SUMO-induced ubiquitination and proteasome degradation of cyclin D1. We generated cyclin D1 mutant mice with mutations in the SUMOylation site, phosphorylation site, or both sites of cyclin D1, and found that double mutant mice developed a Mantle cell lymphoma (MCL)-like phenotype. We showed that arsenic trioxide (ATO) enhances cyclin D1 SUMOylation-mediated degradation through inhibition of cyclin D1 deSUMOylation enzymes, leading to MCL cell apoptosis. Treatment of severe combined immunodeficiency (SCID) mice grafted with MCL cells with ATO resulted in a significant reduction in tumor growth. In this study, we provide novel insights into the mechanisms of MCL tumor development and cyclin D1 regulation and discover a new strategy for MCL treatment.

Non-coding RNAs have emerged as important regulators of gene expression and contributors to many diseases. LncRNA Morrbid, a long non-coding RNA, has been widely studied in recent years. Current literature reports that lncRNA Morrbid is involved in various diseases such as tumors, cardiovascular diseases, inflammatory diseases and metabolic disorder. However, controversial conclusions exist in current studies. As a potential therapeutic target, it is necessary to comprehensively review the current evidence. In this work, we carefully review the literature on Morrbid and discuss each of the hot topics related to lncRNA Morrbid.

Abstract Background In orthodontics, anterior open bite is a common malocclusion that recurs frequently. Because the causes of anterior open bite are so varied, medical professionals must create customized treatment programs for each patient based on their unique etiology. Through the lowering of the posterior teeth, closure of the anterior teeth gap, and cooperation with intermaxillary traction, the treatment plan outlined in this case study sought to achieve a stable occlusion. Case presentation This case report aims to describe an orthodontic camouflage treatment of a 15-year-old female patient with anterior open bite, arch width discrepancy and a history of temporomandibular joint disorder. The patient was treated with intermaxillary vertical elastics and the multiple edgewise arch wire (MEAW) approach. A satisfactory occlusion with a neutral molar relationship was attained after 29 months of orthodontic therapy. The condylography recording showed that this patient’s occlusion tended to be more stable both before and after our treatment. The purpose of this case study is to provide an overview of an orthodontic camouflage treatment for a female patient, who had a history of temporomandibular joint disease, anterior open bite, and arch width disparity. Conclusions Our results demonstrated that more attention should be paid to levelling the occlusal plane, intrusion of the molars, decompression of temporomandibular joints and the etiology factors of malocclusion during the orthodontic period for those patients with anterior open bite.

Abstract There is increasing evidence of abnormal neurodevelopmental outcomes in preterm infants with low-grade intraventricular hemorrhage (IVH). The purpose of the study was to explore whether brain microstructure and volume are associated with neuro-behavioral outcomes at 40 weeks corrected gestational age in preterm infants with low-grade IVH. MR imaging at term-equivalent age (TEA) was performed in 25 preterm infants with mild IVH (Papile grading I/II) and 40 control subjects without IVH. These subjects all had neonatal behavioral neurological assessment (NBNA) at 40 weeks’ corrected age. Microstructure and volume evaluation of the brain were performed by using diffusion kurtosis imaging (DKI) and Synthetic MRI. Correlations among microstructure parameters, volume, and developmental outcomes were explored by using Spearman's correlation. In preterm infants with low-grade IVH, the volume of brain parenchymal fraction (BPF) was reduced. In addition, mean kurtosis (MK), fractional anisotropy (FA), radial kurtosis (RK), axial kurtosis (AK) in several major brain regions were reduced, while mean diffusivity (MD) was increased (P

ObjectivesThis study aims to assess the predictive capability of synthetic MRI in assessing neurodevelopmental outcomes for extremely preterm neonates with low-grade Germinal Matrix-Intraventricular Hemorrhage (GMH-IVH). The study also investigates the potential enhancement of predictive performance by combining relaxation times from different brain regions.Materials and methodsIn this prospective study, 80 extremely preterm neonates with GMH-IVH underwent synthetic MRI around 38 weeks, between January 2020 and June 2022. Neurodevelopmental assessments at 18 months of corrected age categorized the infants into two groups: those without disability (n = 40) and those with disability (n = 40), with cognitive and motor outcome scores recorded. T1, T2 relaxation times, and Proton Density (PD) values were measured in different brain regions. Logistic regression analysis was utilized to correlate MRI values with neurodevelopmental outcome scores. Synthetic MRI metrics linked to disability were identified, and combined models with independent predictors were established. The predictability of synthetic MRI metrics in different brain regions and their combinations were evaluated and compared with internal validation using bootstrap resampling.ResultsElevated T1 and T2 relaxation times in the frontal white matter (FWM) and caudate were significantly associated with disability (p

Abstract Long non‐coding RNA RP11‐64B16.4 (myocardial infarction protection‐related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re‐expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta‐8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL‐mediated anti‐apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia‐enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.

Creating top-notch Mashup applications is becoming increasingly difficult with an overwhelming number of Web APIs. Researchers have developed various API recommendation techniques to help developers quickly locate the right API. In particular, deep learning-based solutions have attracted much attention due to their excellent representation learning capabilities. However, existing methods mainly use textual or graphical information, and do not fully consider the two, which may lead to suboptimal representation and damage recommendation performance. In this paper, we propose a Cooperative Mashup Embedding (CME) neural framework that integrates knowledge graph embedding and text encoding, using Node2Vec to convert entities into numerical vectors and BERT to encode text descriptions. A cooperative embedding method was developed to optimize the entire model while capturing graph and text data knowledge. In addition, the representations obtained by the framework of the three recommendation models are derived. Experimental results on the ProgrammableWeb dataset indicate that our proposed method outperforms the SOTA methods in recommendation performance metrics Top@{1,5,10}. Precision and Recall have increased from 3% to 11%, while NDCG and MAP have improved from 3% to 6%.

Abstract Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we constructed a multimodal Ca2+ nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca2+ overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO3) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca2+ nano-regulator SA/Cur@CaCO3-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca2+ at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO3, but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca2+ nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy. Graphical Abstract

Ischemic heart disease (IHD) is a leading cause of disability and death worldwide, with immune regulation playing a crucial role in its pathogenesis. Various immune cells are involved, and as one of the key immune cells residing in the heart, macrophages play an indispensable role in the inflammatory and reparative processes during cardiac ischemia. Exosomes, extracellular vesicles containing lipids, nucleic acids, proteins, and other bioactive molecules, have emerged as important mediators in the regulatory functions of macrophages and hold promise as a novel therapeutic target for IHD. This review summarizes the regulatory mechanisms of different subsets of macrophages and their secreted exosomes during cardiac ischemia over the past five years. It also discusses the current status of clinical research utilizing macrophages and their exosomes, as well as strategies to enhance their therapeutic efficacy through biotechnology. The aim is to provide valuable insights for the treatment of IHD.

Abstract Chronic adipose tissue inflammation accompanied by macrophage accumulation and activation is implicated in the pathogenesis of insulin resistance and type 2 diabetes in humans. The transcriptional coregulator CREBZF is a key factor in hepatic metabolism, yet its role in modulating adipose tissue inflammation and type 2 diabetes remains elusive. The present study demonstrates that overnutrition‐induced CREBZF links adipose tissue macrophage (ATM) proinflammatory activation to insulin resistance. CREBZF deficiency in macrophages, not in neutrophils, attenuates macrophage infiltration in adipose, proinflammatory activation, and hyperglycemia in diet‐induced insulin‐resistant mice. The coculture assays show that macrophage CREBZF deficiency improves insulin sensitivity in primary adipocytes and adipose tissue. Mechanistically, CREBZF competitively inhibits the binding of IκBα to p65, resulting in enhanced NF‐κB activity. In addition, bromocriptine is identified as a small molecule inhibitor of CREBZF in macrophages, which suppresses the proinflammatory phenotype and improves metabolic dysfunction. Furthermore, CREBZF is highly expressed in ATM of obese humans and mice, which is positively correlated with proinflammatory genes and insulin resistance in humans. This study identifies a previously unknown role of CREBZF coupling ATM activation to systemic insulin resistance and type 2 diabetes.

Cercospora apii is an important seedborne pathogenic fungus causing severe Cercospora leaf spot of celery worldwide. Here, we first present a complete genome assembly of C. apii QCYBC from celery, based on Illumina paired-end and PacBio long-read sequencing data. The high-quality genome assembly contains 34 scaffolds with a 34.81 Mb genome size, 330 interspersed repeat genes, 114 noncoding RNAs, and 12,631 protein-coding genes. The benchmarking universal single-copy ortholog (BUSCO) analysis indicated that 98.2% of the BUSCOs were complete, whereas 0.3, 0.7, and 1.1% were duplicated, fragmented, and missing, respectively. Based on annotation, 508 carbohydrate-active enzymes, 243 cytochromes P450 enzymes, 1,639 translocators, 1,358 transmembrane proteins, and 1,146 virulence genes were identified. This genome sequence provides a valuable reference for future studies to improve understanding of the C. apii–celery pathosystem. [Graphic: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Esketamine provides an immediate and noticeable antidepressant effect, although the underlying molecular processes are yet unclear. Irisin induced by aerobic exercise has been implicated in the alleviation of depressive symptoms, whether irisin expression responds to the administration of esketamine remains unknown. In this study, we found that irisin was reduced in the hippocampus and peripheral blood of chronic unpredictable mild stress (CUMS) mice, whereas the irisin level was rescued by esketamine treatment. The reduction of PGC-1α expression (transcriptional regulator of irisin gene expression) in the CUMS mice was rescued by esketamine treatment, PGC-1α knockdown significantly reduced the irisin level induced by esketamine. Additionally, FNDC5/irisin-knockout mice developed more severe depressant-like behaviors than wild-type mice under CUMS stimulation, with an attenuated the antidepressant effect of esketamine. Further research indicated that irisin-mediated modulation of esketamine on depressive-like behaviors in CUMS mice involved the ERK1/2 pathway. Overall, the PGC-1α/irisin/ERK1/2 signaling activation may be a new mechanism underlying the antidepressant activity of esketamine, denoting that irisin may be a promising therapeutic target for the treatment of depression.

Abstract Acute myocardial infarction has long been the leading cause of death in coronary heart disease, which is characterized by irreversible cardiomyocyte death and restricted blood supply. Conventional reperfusion therapy can further aggravate myocardial injury. Stem cell therapy, especially with mesenchymal stem cells (MSCs), has emerged as a promising approach to promote cardiac repair and improve cardiac function. MSCs may induce these effects by secreting exosomes containing therapeutically active RNA, proteins and lipids. Notably, normal cardiac function depends on intracardiac paracrine signaling via exosomes, and exosomes secreted by cardiac cells can partially reflect changes in the heart during disease, so analyzing these vesicles may provide valuable insights into the pathology of myocardial infarction as well as guide the development of new treatments. The present review examines how exosomes produced by MSCs and cardiac cells may influence injury after myocardial infarction and serve as therapies against such injury. Graphical Abstract Video Abstract

Abstract Background Clinicians agree that obtaining and retaining good treatment results for missing maxillary central incisors owing to trauma is not easy. Management of adult patients with permanent maxillary central incisor loss who visit the clinic with high expectations for aesthetics and function pose a significant diagnostic dilemma. Therefore, esthetic and functional outcomes should be taken into consideration when deciding the proper treatment method. The treatment described in this study aimed to reestablish smile esthetics by proposing an effective multidisciplinary clinical approach that includes orthodontic-prosthetic-periodontal procedures, optimally reduced lip protrusion, center dental midlines, and establishment of stable occlusion. Case presentation The patient was a 19-year-old adult female with bimaxillary arch protrusion who had been wearing removable dentures for several years since the loss of her maxillary central permanent incisors. A multidisciplinary treatment including the extraction of two mandibular primary premolars was adopted. The treatment plan consisted of orthodontic space closure by shifting the adjacent teeth towards the central incisor spaces combined with appropriate morphologic remodeling and gingival reshaping to obtain good aesthetic and functional results. The duration to complete the orthodontic treatment was 35 months. Clinical and radiographic results after treatment suggested smile harmony with an improvement in the facial profile, good function of the occlusion, and a positive effect on bone remodeling in the area of the missing incisors during orthodontic tooth movement. Conclusions This clinical case illustrated the necessity for using multidisciplinary methods involving orthodontic, prosthodontic, and periodontic procedures to treat an adult female patient with bimaxillary arch protrusion and long-term absence of anterior teeth due to severe trauma.

Abstract Background Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in women of reproductive age that still lacks effective treatment. Inflammation is one of the important features of PCOS. Asparagus (ASP) has anti-inflammatory, antioxidant, and anti-aging pharmacological effects, and its anti-tumor effects have been demonstrated in a variety of tumors. However, the role and mechanism of ASP in PCOS remain unclear. Methods The active components of ASP and the key therapeutic targets for PCOS were obtained by network pharmacology. Molecular docking was used to simulate the binding of PRKCA to the active components of ASP. The effects of ASP on inflammatory and oxidative stress pathways in PCOS, and the regulation of PRKCA were examined by KGN, a human derived granulosa cell line. PCOS mouse model validated the results of in vivo experiments. Results Network pharmacology identified 9 major active ingredients of ASP with 73 therapeutic targets for PCOS. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment yielded 101 PCOS-related signaling pathways. The hub gene PRKCA was obtained after taking the gene intersection of the top 4 pathways. Molecular docking showed the binding of PRKCA to the 7 active components in ASP. In vitro and in vivo experiments showed that ASP alleviated the course of PCOS through antioxidant, anti-inflammatory effects. ASP can partially restore the low expression of PRKCA in the PCOS models. Conclusion The therapeutic effect of ASP on PCOS is mainly achieved by targeting PRKCA through the 7 active components of ASP. Mechanistically, ASP alleviated the course of PCOS through antioxidant, anti-inflammatory effects, and PRKCA was its potential target.

Background. Acute pancreatitis (AP) is a clinically frequent acute abdominal condition, which refers to an inflammatory response syndrome of edema, bleeding, and even necrosis caused by abnormal activation of the pancreas’s own digestive enzymes. Intestinal damage can occur early in the course of AP and is manifested by impaired intestinal mucosal barrier function, and inflammatory reactions of the intestinal mucosa, among other factors. It can cause translocation of intestinal bacteria and endotoxins, further aggravating the condition of AP. Therefore, actively protecting the intestinal mucosal barrier, controlling the progression of intestinal inflammation, and improving intestinal dynamics in the early stages of AP play an important role in enhancing the prognosis of AP. Methods. The viability and apoptosis of RAW264.7 cells treated with Esculentoside A (EsA) and/or lipopolysaccharide were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry, respectively. The expression of apoptosis-related proteins and NF-κB signaling pathway-related proteins were detected by western blot (WB). An enzyme-linked immunosorbent assay was used to measure TNF-α and IL-6 secretion. Results. In vitro experiments demonstrated that EsA not only promoted the apoptosis of inflammatory cells but also reduced the secretion of TNF-α and IL-6 in a dose-dependent manner. Additionally, it inhibited the activation of the NF-κB signaling pathway by decreasing the expression of phosphorylated-p65(p-p65) and elevating the expression of IκBα. Similarly, in vivo experiments using a rat AP model showed that EsA inhibited the expression of p-p65 elevating the expression of IκBα in the intestinal tissues of the rat AP model and promoting the apoptosis of inflammatory cells in the intestinal mucosa in vivo experiments, while improving the pathological outcome of the pancreatic and intestinal tissues. Conclusion. Our results suggest that EsA can reduce intestinal inflammation in the rat AP model and that EsA may be a candidate for treating intestinal inflammation in AP and further arresting AP progression.

Abstract In this study, we identified that a conserved circular RNA (circRNA) DICAR, which was downregulated in diabetic mouse hearts. DICAR had an inhibitory effect on diabetic cardiomyopathy (DCM), as the spontaneous cardiac dysfunction, cardiac cell hypertrophy, and cardiac fibrosis occurred in DICAR deficiency (DICAR +/− ) mice, whereas the DCM was alleviated in DICAR-overexpressed DICAR Tg mice. At the cellular level, we found that overexpression of DICAR inhibited, but knockdown of DICAR enhanced the diabetic cardiomyocyte pyroptosis. At the molecular level, we identified that DICAR-VCP-Med12 degradation could be the underlying molecular mechanism in DICAR-mediated effects. The synthesized DICAR junction part (DICAR-JP) exhibited a similar effect to the entire DICAR. In addition, the expression of DICAR in circulating blood cells and plasma from diabetic patients was lower than that from health controls, which was consistent with the decreased DICAR expression in diabetic hearts. DICAR and the synthesized DICAR-JP may be drug candidates for DCM.

The objective of this study was to investigate age-related changes in cashmere production and the population of active secondary hair follicles in cashmere goats across different age groups as well as to explore the association between secondary hair follicle activity and oxidative stress. A total of 104 adult Inner Mongolian ewe goats, aged between 2 and 7 years old, were randomly selected as experimental subjects. Skin samples were collected in August 2020 and cashmere samples were collected in April 2021. The cashmere fiber yield, staple length, and diameter showed age-related variations in cashmere goats aged 2 to 7 years (p < 0.05). Cashmere production was higher in goats aged 2–4 years compared to those aged 5–7 years (p < 0.05). There were no significant differences in the population of primary and secondary hair follicles among goats aged 2 to 7 years. However, the population of active secondary hair follicles varied significantly with age, with the younger group (aged 2–4 years) having a higher population than those aged 5–7 years (p < 0.05). A moderate negative correlation was observed between cashmere fiber diameter and the population of active secondary hair follicles (p < 0.05). Age-related variations in skin antioxidant capacity and oxidative damage were observed among cashmere goats aged 2 to 7 years old (p < 0.05). Goats aged 2 to 4 years exhibited higher antioxidant capacity and lower oxidative damage (p < 0.05). Interestingly, the skin’s antioxidant capacity and oxidative damage exhibited significant positive and negative correlations with the population of active secondary hair follicles (p < 0.05). This study presents a novel approach to enhance the activity of secondary hair follicles and improve cashmere production performance through the regulation of oxidative stress.

The aim of this study was to investigate if the supplementation of folic acid and taurine can relieve the adverse effects of different levels of heat stress (HS) on growth performance, physiological indices, antioxidative capacity, immunity, rumen fermentation and microbiota. A total of 24 Dorper × Hu crossbred lambs (27.51 ± 0.96 kg) were divided into four groups: control group (C, 25 °C), moderate HS group (MHS, 35 °C), severe HS group (SHS, 40 °C), and the treatment group, under severe HS (RHS, 40 °C, 4 and 40 mg/kg BW/d coated folic acid and taurine, respectively). Results showed that, compared with Group C, HS significantly decreased the ADG of lambs (p < 0.05), and the ADG in the RHS group was markedly higher than in the MHS and SHS group (p < 0.05). HS had significant detrimental effects on physiological indices, antioxidative indices and immune status on the 4th day (p < 0.05). The physiological indices, such as RR and ST, increased significantly (p < 0.05) with the HS level and were significantly decreased in the RHS group, compared to the SHS group (p < 0.05). HS induced the significant increase of MDA, TNF-α, and IL-β, and the decrease of T-AOC, SOD, GPx, IL-10, IL-13, IgA, IgG, and IgM (p < 0.05). However, there was a significant improvement in these indices after the supplementation of folic acid and taurine under HS. Moreover, there were a significant increase in Quinella and Succinivibrio, and an evident decrease of the genera Rikenellaceae_RC9_gut_group and Asteroleplasma under HS (p < 0.05). The LEfSe analysis showed that the genera Butyrivibrio, Eubacterium_ventriosum_group, and f_Bifidobacteriaceae were enriched in the MHS, SHS and RHS groups, respectively. Correlated analysis indicated that the genus Rikenellaceae_RC9_gut_group was positively associated with MDA, while it was negatively involved in IL-10, IgA, IgM, and SOD (p < 0.05); The genus Anaeroplasma was positively associated with the propionate and valerate, while the genus Succinivibrio was negatively involved in TNF-α (p < 0.05). In conclusion, folic acid and taurine may alleviate the adverse effects of HS on antioxidant capacity, immunomodulation, and rumen fermentation of lambs by inducing changes in the microbiome that improve animal growth performance.

Abstract Background Kawasaki disease (KD) is a kind of vasculitis with unidentified etiology. Given that the current diagnosis and therapeutic strategy of KD are mainly dependent on clinical experiences, further research to explore its pathological mechanisms is warranted. Methods Enzyme linked immunosorbent assay (ELISA) was used to measure the serum levels of SIGIRR, TLR4 and caspase-8. Western blotting was applied to determine protein levels, and flow cytometry was utilized to analyze cell apoptosis. Hematoxylin eosin (HE) staining and TUNEL staining were respectively used to observe coronary artery inflammation and DNA fragmentation. Results In this study, we found the level of SIGIRR was downregulated in KD serum and KD serum-treated endothelial cells. However, the level of caspase-8 was increased in serum from KD patients compared with healthy control (HC). Therefore, we hypothesized that SIGIRR-caspase-8 signaling may play an essential role in KD pathophysiology. In vitro experiments demonstrated that endothelial cell apoptosis in the setting of KD was associated with caspase-8 activation, and SIGIRR overexpression alleviated endothelial cell apoptosis via inhibiting caspase-8 activation. These findings were also recapitulated in the Candida albicans cell wall extracts (CAWS)-induced KD mouse model. Conclusion Our data suggest that endothelial cell apoptosis mediated by SIGIRR-caspase-8 signaling plays a crucial role in coronary endothelial damage, providing potential targets to treat KD.

Abstract Synthetic nanoparticles with surface bioconjugation are promising platforms for targeted therapy, but their simple biological functionalization is still a challenging task against the complex intercellular environment. Once synthetic nanoparticles enter the body, they are phagocytosed by immune cells by the immune system. Recently, the cell membrane camouflage strategy has emerged as a novel therapeutic tactic to overcome these issues by utilizing the fundamental properties of natural cells. Macrophage, a type of immune system cells, plays critical roles in various diseases, including cancer, atherosclerosis, rheumatoid arthritis, infection and inflammation, due to the recognition and engulfment function of removing substances and pathogens. Macrophage membranes inherit the surface protein profiles and biointerfacing properties of source cells. Therefore, the macrophage membrane cloaking can protect synthetic nanoparticles from phagocytosis by the immune cells. Meanwhile, the macrophage membrane can make use of the natural correspondence to accurately recognize antigens and target inflamed tissue or tumor sites. In this review, we have summarized the advances in the fabrication, characterization and homing capacity of macrophage membrane cloaking nanoparticles in various diseases, including cancers, immune diseases, cardiovascular diseases, central nervous system diseases, and microbial infections. Although macrophage membrane-camouflaged nanoparticles are currently in the fetal stage of development, there is huge potential and challenge to explore the conversion mode in the clinic.

Abstract Background Taxillus chinensis (DC.) Danser (T. chinensis), known as “Sangjisheng” in Chinese, is a member of the family Loranthaceae, with the traditional functions of “dispelling wind dampness, strengthening bones and muscles, and preventing miscarriage”. Since Eastern Han dynasty, it has been used for the treatment of rheumatoid arthritis, arthralgia, threatened abortion, and hypertension. Nowadays, T. chinensis is included in the 2020 Edition of the Chinese Pharmacopoeia as Taxilli Herba. The purpose of this review is to summarize the latest research on T. chinensis in recent years, and make critical comments, so as to provide reference for the clinical application and modern research of T. chinensis. Main body In this review, we summarize the botany, traditional uses, and research advances in the phytochemistry and pharmacological effects of T. chinensis. Its toxicity has also been discussed. The published literature on current pharmacological and toxicological data has also been assessed. To date, approximately 110 compounds, including flavonoids, phenolic acids, phenylpropanoids, tannins, glycosides, amino acids, and nucleosides, have been identified in T. chinensis. Flavonoids are considered the most vital bioactive ingredients in T. chinensis. Pharmacological studies have demonstrated that T. chinensis possesses anti-inflammatory, antioxidant, anticancer, antimicrobial, antiviral, diuretic, antihypertensive, antihyperglycemic, and other properties. Conclusion Currently, research on T. chinensis is in the preliminary stages, and further research is required to understand the active compounds present and mechanisms of action. We hope that this comprehensive review of T. chinensis will serve as a background for further research.

Myeloid RNA regulator of Bim-induced death (Morrbid) is a newly identified leukocyte-specific long noncoding RNA (lncRNA). However, the expression and biological functions of Morrbid in cardiomyocytes and heart disease are currently unclear. This study was meant to determine the role of cardiac Morrbid in acute myocardial infarction (AMI) and to identify the potential cellular and molecular mechanisms involved. We found that both human and mouse cardiomyocytes could express a significant amount of Morrbid and that its expression was increased in cardiomyocytes with hypoxia or oxidative stress as well as in mouse hearts with AMI. Overexpression of Morrbid reduced the myocardial infarct size and cardiac dysfunction, whereas the infarct size and cardiac dysfunction deteriorated in cardiomyocyte-specific Morrbid-KO (Morrbidfl/fl/Myh6-Cre) mice. We identified that Morrbid had a protective effect against hypoxia- or H2O2-induced apoptosis; this was also confirmed in vivo in mouse hearts after AMI. We further discovered that serpine1 was a direct target gene of Morrbid that was involved in the Morrbid-mediated protective effect on cardiomyocytes. In summary, we have found, for the first time to our knowledge, that the cardiac Morrbid is a stress-enhanced lncRNA that protects hearts from AMI via antiapoptosis through its target gene serpine1. Morrbid may be a novel promising therapeutic target for ischemic heart diseases such as AMI.

Marigold can protect crops against soil-borne diseases. However, the effects of intercropping with marigold on apple rhizosphere soils are not known. In this study, we investigated the metabolite profiles and bacterial community structures in rhizosphere soils of the apple-marigold intercropping system by high-throughput sequencing and soil metabolomics. The results show that intercropping marigold could significantly enhance soil moisture, nitrogen, and enzyme activities compared with clean tillage. The soil metabolite profiles and the soil bacterial community structures in the rhizosphere soils were different between the inter-and mono-cropping systems. Among nine metabolites, carbohydrates were more increased in the intercropping system than in the monocropping system. Pathway enrichment analysis revealed that the greatest differential, in terms of metabolic pathway, was starch and sucrose metabolism. Moreover, intercropping marigold significantly increased the relative abundance of plant growth promoting bacteria in rhizosphere soils, such as Rhizobiales, Pseudomonadales, and Bacillales. These results indicate that marigold intercropping positively affected the apple orchard’s soil quality and may provide a new intercropping technique to improve soil fertility in orchards and promote plant growth.

Recently, the relationship between the goat host and its gastrointestinal microbiome has emerged as a hallmark of host-microbiota symbiosis, which was indispensable for the proper physiological function that convert the plant biomass to livestock products. However, little integrative information about the establishment of gastrointestinal microflora in goats exists. Herein, we characterized the colonizing process of the bacterial community in the digesta and mucosa of the rumen, cecum, and colon of the cashmere goat from birth to adulthood to compare its spatiotemporal difference via 16S rRNA gene sequencing. A total of 1,003 genera belonging to 43 phyla were identified. Principal coordinate analysis unveiled the similarity of microbial community between or within each age group increased and gradually developed toward mature whatever in digesta or mucosa. In the rumen, the composition of the bacterial community in digesta differed significantly from in mucosa across age groups; whereas in the hindgut, there was a high similarity of bacterial composition between the in digesta and mucosa in each age group before weaning, while the bacterial community structure differed markedly between these two types of samples after weaning. Taxonomic analysis indicated that 25 and 21 core genera coexisted in digesta and mucosa of the rumen and hindgut, respectively; but their abundances differed considerably by GIT region and/or age. In digesta, as goats aged, a lower abundance of Bacillus was observed with higher abundances of Prevotella 1 and Rikenellaceae RC9 in the rumen; while in the hindgut, the genera Escherichia-Shigella, Variovorax, and Stenotrophomonas decreased and Ruminococcaceae UCG-005, Ruminococcaceae UCG-010, and Alistipes increased with age increased. In mucosa, the rumen showed microbial dynamics with increases of Butyrivibrio 2 and Prevotellaceae UCG-001 and decreases of unclassified_f_Pasteurellaceae; while the genera Treponema 2 and Ruminococcaceae UCG-010 increased and Escherichia-Shigella decreased in the hindgut as goats aged. These results shed light on the colonization process of microbiota in the rumen and hindgut, which mainly include the initial, transit, and mature phases. Furthermore, there is a significant difference in the microbial composition between in digesta and mucosa, and both these exhibit a considerable spatiotemporal specificity.

Abstract Micelle Encapsulation Zinc‐doped copper oxide nanocomposites (MEnZn‐CuO NPs) is a novel doped metal nanomaterial prepared by our group based on Zinc doped copper oxide nanocomposites (Zn‐CuO NPs) using non‐micellar beam. Compared with Zn‐CuO NPs, MEnZn‐CuO NPs have uniform nanoproperties and high stability. In this study, we explored the anticancer effects of MEnZn‐CuO NPs on human ovarian cancer cells. In addition to affecting cell proliferation, migration, apoptosis and autophagy, MEnZn‐CuO NPs have a greater potential for clinical application by inducing HR repair defects in ovarian cancer cells in combination with poly (ADP‐ribose) polymerase inhibitors for lethal effects.

The electron re-injection effect has revealed the great probability rate of photon generation due to the head-on collision between relativistic electrons and laser. We study the electron re-injection dynamics when the ultra-intense laser irradiates the near-critical-density plasma and successfully controls the photon radiation by means of the transversely tailored plasma. Starting from the relativistic corrected ponderomotive force, the critical strength of the laser field required by the refluxing effect is theoretically obtained. Then, the theoretical description of the wavefront formed by electron refluxing is given via plugging in the difference in the transverse phase velocity of the plasma wave. Simulation results display a curved surface of the refluxing electrons, which are in good agreement with the calculation results stemming from the physics model. The re-built phase space of the refluxing electrons illustrates that they gain energy mainly from the longitudinal electrostatic field on the re-injection path. Despite the energy of the refluxing electron being relatively low, it could radiate more photons via more efficient non-linear Compton scattering than the electron being accelerated in the positive direction. Furthermore, we employ a transverse density profile in the plasma and successfully achieve control of the electron re-injection effect and the properties of the resultant photons as well. Simulation results exhibit that overcritical electron beams are successively re-injected from the plasma density peaks. These backward electrons emit photons along the two maximal plasma densities as they collide with the laser pulse. Although the quality of the photons is not improved, their spatial distribution is changed, which is a big step toward manipulating light sources.

The objective of this study was to investigate the effects of fasted live-weight gain during the cashmere non-growing period on cashmere production performance and secondary hair follicle activity, to provide a theoretical basis for appropriate supplementary feeding of cashmere goats. Fifty Inner Mongolian cashmere goats aged 2–4 years old were randomly selected and weighed in May and September 2019, respectively. Based on fasted live-weight gain between the two weights, the experimental ewe goats were divided into two groups: 0–5.0 kg group (n = 30) and 5.0–10.0 kg group (n = 20). Skin samples and cashmere samples were collected. Results of a Pearson correlation analysis showed that fasted live-weight gain during the cashmere non-growing period had a moderate and strong positive correlation with cashmere yield (p = 0.021) and cashmere staple length (p = 0.002), respectively, but did not correlate with cashmere diameter (p = 0.254). Compared with cashmere goats with a fasted live-weight gain of 0–5.0 kg, cashmere goats with a fasted live-weight gain of 5.0–10.0 kg had a 17.10% increase in cashmere yield (p = 0.037) and an 8.09% increase in cashmere staple length (p = 0.045), but had no significant difference in cashmere diameter (p = 0.324). Results of a Pearson correlation analysis showed that there was a strong positive correlation between fasted live-weight gain and the population of active secondary hair follicles in the skin of cashmere goats (p < 0.01). Compared with cashmere goats with a fasted live-weight gain of 0–5.0 kg, cashmere goats with a fasted live-weight gain of 5.0–10.0 kg had an increase in the population of active secondary hair follicles (p < 0.05). In conclusion, the fasted live-weight gain during the cashmere non-growing period had a significant effect on secondary hair follicle activity and cashmere production performance in cashmere goats. Since fasted live-weight gain reflects nutritional level to a certain extent, this study suggests that nutritional manipulations such as supplementary feeding during cashmere non-growing periods can increase cashmere production performance. However, specific nutritional manipulations during the cashmere non-growing period need further research to increase cashmere production performance.

Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis. Long non-coding RNAs (lncRNAs) are a group of protein expression regulators; however, the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear. The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis. We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis. In cultured monocytes, Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation. The differentiation stimuli-induced monocyte–macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown. Moreover, overexpression of Morrbid alone was sufficient to elicit the monocyte–macrophage differentiation. The role of Morrbid in monocyte–macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice. We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression, whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation. To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease, we applied an acute atherosclerosis model in mice. The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice. The results suggest that Morrbid is a novel biomarker and a modulator of monocyte–macrophage phenotypes, which is involved in atherogenesis.

Platelets, generated from precursor megakaryocytes (MKs), are central mediators of hemostasis and thrombosis. The process of thrombopoiesis is extremely complex, regulated by multiple factors, and related to many cellular events including apoptosis. However, the role of apoptosis in thrombopoiesis has been controversial for many years. Some researchers believe that apoptosis is an ally of thrombopoiesis and platelets production is apoptosis-dependent, while others have suggested that apoptosis is dispensable for thrombopoiesis, and is even inhibited during this process. In this review, we will focus on this conflict, discuss the relationship between megakaryocytopoiesis, thrombopoiesis and apoptosis. In addition, we also consider why such a vast number of studies draw opposite conclusions of the role of apoptosis in thrombopoiesis, and try to figure out the truth behind the mystery. This review provides more comprehensive insights into the relationship between megakaryocytopoiesis, thrombopoiesis, and apoptosis and finds some clues for the possible pathological mechanisms of platelet disorders caused by abnormal apoptosis.

Thrombocytopenia is a thrombopoietin (TPO)-related disorder with very limited treatment options, and can be lifethreatening. There are major problems with typical thrombopoietic agents targeting TPO signaling, so it is urgent to discover a novel TPO-independent mechanism involving thrombopoiesis and potential druggable targets. We developed a drug screening model by the multi-grained cascade forest (gcForest) algorithm and found that 3,8-di-O-methylellagic acid 2- O-glucoside (DMAG) (10, 20 and 40 μM) promoted megakaryocyte differentiation in vitro. Subsequent investigations revealed that DMAG (40 mM) activated ERK1/2, HIF-1b and NF-E2. Inhibition of ERK1/2 blocked megakaryocyte differentiation and attenuated the upregulation of HIF-1b and NF-E2 induced by DMAG. Megakaryocyte differentiation induced by DMAG was inhibited via knockdown of NF-E2. In vivo studies showed that DMAG (5 mg/kg) accelerated platelet recovery and megakaryocyte differentiation in mice with thrombocytopenia. The platelet count of the DMAG-treated group recovered to almost 72% and 96% of the count in the control group at day 10 and 14, respectively. The platelet counts in the DMAG-treated group were almost 1.5- and 1.3-fold higher compared with those of the irradiated group at day 10 and 14, respectively. Moreover, DMAG (10, 25 and 50 mM) stimulated thrombopoiesis in zebrafish. DMAG (5 mg/kg) could also increase platelet levels in c-MPL knockout (c-MPL-/-) mice. In summary, we established a drug screening model through gcForest and demonstrated that DMAG promotes megakaryocyte differentiation via the ERK/HIF1/NF-E2 pathway which, importantly, is independent of the classical TPO/c-MPL pathway. The present study may provide new insights into drug discovery for thrombopoiesis and TPO-independent regulation of thrombopoiesis, as well as a promising avenue for thrombocytopenia treatment.

Abstract Pancreatic cancer is one of the most lethal malignant tumors with a low survival rate, partly because the tumor microenvironment (TME), which consists of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), immune cells, and vascular systems, prevents effective drug delivery and chemoradiotherapy. Thus, modulating the microenvironment of pancreatic cancer is considered a promising therapeutic approach. Since nanoparticles are one of the most effective cancer treatment strategies, several nano-delivery platforms have been developed to regulate the TME and enhance treatment. Here, we summarize the latest advances in nano-delivery systems that alter the TME in pancreatic cancer by depleting ECM, inhibiting CAFs, reversing immunosuppression, promoting angiogenesis, or improving the hypoxic environment. We also discuss promising new targets for such systems. This review is expected to improve our understanding of how to modulate the pancreatic cancer microenvironment and guide the development of new therapies. Graphical Abstract

Rubia cordifolia (family: Rubiaceae) L (R. cordifolia) is a perennial botanical drug climbing vine. As the main part of the traditional Chinese medicine, the rhizome has a long history. A great number of literary studies have reported that it can be used for the improvement of blood circulation, hemostasis, activation of collaterals, etc. When it comes to the wide application of R. cordifolia in traditional medicine, we systematically review its traditional uses, phytochemistry and pharmacological effects. Literatures were systematically searched using several scientific databases, including China National Knowledge Infrastructure (CNKI), Baidu Scholar, PubMed, Web of Science, and other professional websites. Kew Botanical Garden and the iPlant were used for obtaining the scientific names and plant images of R. cordifolia. In addition, other information was also gathered from books including traditional Chinese herbal medicine, the Chinese Pharmacopoeia, and Chinese Materia Medica. So far, many prescriptions containing R. cordifolia have been widely used in the clinical treatment of abnormal uterine bleeding, primary dysmenorrhea and other gynecological diseases, allergic purpura, renal hemorrhage and other diseases. The phytochemistry studies have reported that more than 100 compounds are found in R. cordifolia, such as bicyclic peptides, terpenes, polysaccharides, trace elements, flavonoids, and quinones. Among them, quinones and peptides are the types of components with the highest contents in R. cordifolia. The modern pharmacological studies have revealed that R. cordifolia and its derived components have anti-tumor, anti-oxidative, anti-platelet aggregation, and anti-inflammatory effects. However, most studies are preclinical. The pharmacological mechanism of R. cordifolia has not been thoroughly studied. In addition, there are few pharmacokinetic and toxicity studies of R. cordifolia, therefore the clinical safety data for R. cordifolia is lacking. To sum up, this review for the first time summarizes a systemic and integrated traditional uses, chemical compositions, pharmacological actions and clinical applications of R. cordifolia, which provides the novel and full-scale insight for the drug development, medicinal value, and application of R. cordifolia in the future.

In this study, the constitutive equation of the high-strength Mg-Gd-Y-Zn-Zr alloy sheet was established by tensile tests at different temperatures and different tensile rates. The U-shape bending forming process of the sheet was simulated under different process conditions by the DEFORM software. The variation rules of the stress field, strain field and free bending force of the formed parts were analyzed, and the accuracy of the finite element simulation was verified by the U-shaped bending test. Studies have shown that the equivalent stress, equivalent strain and free bending force decreased with the increase in forming temperature. With an increase in the stamping speed, the equivalent stress and free bending force increased, while the equivalent strain did not change significantly. Notably, the maximum difference in the free bending force between the test and simulation was less than 10%. The results of this study can provide guidance for the stamping forming of high-strength Mg-Gd-Y-Zn-Zr alloy sheets.

Hepatic gluconeogenesis is important for glucose homeostasis and a therapeutic target for type 2 diabetes. Here, the authors show that the RNA-binding adaptor protein Sam68 promotes the expression level of gluconeogenic genes and increases blood glucose levels by stabilizing the transcriptional coactivator CRTC2, while hepatic Sam68 deletion alleviates hyperglycemia in mice.

Although it is generally very difficult to supplement flow energy into the tight oil reservoir, there is still good prospect for enhanced oil and gas recovery in this area due to its large proportion of hydrocarbon reserves. However, due to the sensitivity of tight oil reservoir to formation pressure, the porosity and permeability of the reservoir will change greatly with the change of formation pressure in the process oil development, which has a complex impact on dynamic analysis, productivity evaluation and later adjustment of potential stimulation measures. This study mainly focus on the characterization of tight formation rock in the Northwest part of China. In order to get a visual impression of the reservoir core, some routine tests were firstly carried out. After that, porosity and permeability are tested under overburden pressure conditions. Studies show that overburden porosity and permeability will decrease but total decrease percentage will increase with the increase of net effective overburden pressure. The decrease percentage of permeability is much higher compared with that of porosity decrease percentage under overburden pressures. When the net effective overburden pressure is larger than 10 MPa, the decrease of overburden porosity will become relatively small. At the same time, when the net effective overburden pressure is larger than 15 MPa, the decrease of overburden permeability will become relatively small. Taking the pressure-increasing process and the pressure-decreasing process as a whole: the permeability cannot recover to the initial level when overburden pressure is the same as previous round because certain permeability is permanently damaged in the process. At the same time, when the net effective overburden pressure increased to a higher level, the permeability damaged will become relatively smaller. These experiments compose of a comprehensive characterization of formation rock and are of great significance to accurately understand the reservoir damage in the process of tight oil development and reasonably evaluate the productivity of oil producers.

BackgroundKawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that occurs during early childhood, commonly involving the coronary artery, and can lead to coronary artery aneurysms (CAAs).MethodsThe demographic, clinical, and laboratory data of KD patients without coronary artery lesions (N-CAL) and with CAA were collected during 2005–2020 at the Second Affiliated Hospital of Wenzhou Medical University. The patients were divided into the development cohort and the validation cohort. First, we compared the general information, symptoms, and laboratory data of N-CAL and CAA patients in the development cohort and the total cohort and screened out the different indices by logistic regression analysis. Then, we established three models and compared the area under the curve (AUC) values of the receiver operating characteristic (ROC) curves to identify meaningful models for CAA, which were further verified by decision curve analysis (DCA). Second, taking into account previous reports on the importance of gender to CAA, gender stratification was conducted.ResultsThe analysis of clinical and blood indices revealed the following novel features: (i) Many factors were found to be related to CAA, including IVIG resistance and the symptoms of rash, oral changes, and cervical lymphadenopathy. (ii) The development cohort was analyzed by logistic regression, and three models were established. The ROC curves showed that Model 2, composed of IVIG resistance, rash, oral changes, and cervical lymphadenopathy, had a better AUC value and easily to evaluate in the prediction of CAA. (iii) The selected model for predicting CAA in the development cohort was further confirmed in the validation cohort through DCAs. (iv)We further compared the items enrolled in the three models above between the N-CAL and CAA groups by sex, and the results indicated that female KD patients without rash, oral changes, and cervical lymphadenopathy were more likely to develop CAA.ConclusionThe absence of rash, oral changes, and cervical lymphadenopathy are risk factors for CAA, especially in female KD patients. Accurately recognizing symptoms, early diagnosis, and standard treatment for KD are key to reducing the incidence of CAA.

Distinctive characteristics of land reclamation have formed strong attractions, which inspired people’s curiosity and tourist motives. As a unique and essential resource of tourism activities, land reclamation with its highly patriotic spirit and eclectic heritages presents tremendous value in the Chinese tourism industry. However, there is no comprehensive evaluation system of land reclamation tourism (LRT). To solve this research problem, in this study, we delimit the connotation of land reclamation and propose the classification and resources evaluation system of LRT based on the combination of resource characteristics and tourism mode. The classification, balancing the concerns of unit tourist resources, and comprehensively integrated resources while highlighting the principles of universality and practicality, can be classified into two main types, 10 sub-types, and 46 base types. On this basis, the tourism resource evaluation indicator system of land reclamation resources has been built from the aspects of the value of land reclamation culture and tourism resources, natural and social environment, regional development conditions by the methods of Delphi, and analytical hierarchy process (AHP). The empirical research results of Xinjiang Production and Construction Corps (XPCC) provide us with a specific weight distribution prospect of the classification and evaluation system. The conclusions proposed a new way and method to evaluate LRT resources and provided a necessary reference basis for LRT development.

Coronavirus disease 2019 (COVID-19) has become a global public health catastrophe. Vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is proven to be the most effective measure to suppress the pandemic. With the widespread application of the four vaccines, namely, ChAdOx1, Ad26.COV2.S, BNT162b2, and mRNA-1273.2, several adverse effects have been reported. The most serious type of complication is cardiovascularly related, including myocarditis, immune thrombocytopenia (ITP), cerebral sinus venous thrombosis, among others. All these adverse events undermine the health of the vaccinees and affect the administration of the vaccines. As the distribution of COVID-19 vaccines is surrounded by suspicion and rumors, it is essential to provide the public with accurate reports from trusted experts and journals. Monitoring the safety of COVID-19 vaccines is an important and ongoing process that is also urgent. Thus, we summarized the cardiovascular complications of the major types of COVID-19 vaccines, including mRNA vaccines, which are now generally considered to be innovative vaccines, and the future for vaccination against COVID-19, in addition to the underlying pathogenesis and potential therapeutics.

Objective Astragalus membranaceus root is a well-known traditional Chinese herbal medicine with many biological active constituents. This study was conducted to examine the effects of Astragalus membranaceus root powder (AMP) on growth performance, serum antioxidant and immune response in finishing lambs. Methods A total of thirty-six Guangling fat-tailed ram lambs (body weight = 19±2 kg, mean ±standard deviation) were randomly assigned to one of six treatments for a 40 d feeding period, with the first 10 d for adaptation. Treatments consisted of the lambs’ basal diets with addition of 0, 5, 10, 15, 20, and 30 g/kg of diet of AMP. Results Response to supplementation level of AMP was quadratic (p≤0.032) for final weight and ADG with the greatest at 10 g/kg of diet, but dry matter intake was not affected (p≥ 0.227) by treatments. The increase of AMP supplementation resulted in a quadratic response in contents of triglyceride and creatinine (p

Abstract Background Recent studies have shown that circular RNA (circRNA) is rich in microRNA (miRNA) binding sites. We have previously demonstrated that the antidepressant effect of ketamine is related to the abnormal expression of various miRNAs in the brain. This study determined the expression profile of circRNAs in the hippocampus of rats treated with ketamine. Methods The aberrantly expressed circRNAs in rat hippocampus after ketamine injection were analyzed by microarray chip, and we further validated these circRNAs by quantitative reverse-transcription PCR (qRT-PCR). The target genes of the different circRNAs were predicted using bioinformatic analyses, and the functions and signal pathways of these target genes were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Results Microarray analysis showed that five circRNAs were aberrantly expressed in rat hippocampus after ketamine injection (fold change > 2.0, p

In this paper, the effects of three modifiers, such as PEG, ATBC, and DOP, on the modification of PBAT/PLA-based fully degradable brush monofilaments were studied. The microstructure and the mechanical properties of the PBAT/PLA brush wire before and after modification were characterized by Fourier-transform infrared spectroscopy, scanning electron microscope, and universal material testing machine. The effect of modifiers on bending recovery was discussed in detail and was analyzed combined with the results of differential scanning calorimetry and low-field nuclear magnetic resonance spectroscopy. The results showed that with an increase in the content of modifiers, the tensile strength and the impact strength of the PBAT/PLA brush wire would decrease, and the bending recovery rate would increase. The effect of PEG and ATBC on bending recovery is weaker than that of DOP, and the bending recovery rate of the PBAT/PLA brush wire modified by DOP is close to 80%. With an increase in the content of modifiers, the melting enthalpy and transverse relaxation time T2 of PBAT/PLA would increase. This research has guiding significance for the preparation of fully degradable brush wires.

Objective: Preterm infants are at high risk of the adverse neurodevelopmental outcomes. Our aim is to explore the value of diffusion kurtosis imaging (DKI) in diagnosing brain developmental disorders in premature infants.Materials and Methods: A total of 52 subjects were included in this study, including 26 premature infants as the preterm group, and 26 full-term infants as the control group. Routine MRI and DKI examinations were performed. Mean kurtosis (MK), radial kurtosis (RK), fractional anisotropy (FA), and mean diffusivity (MD) values were measured in the brain regions including posterior limbs of the internal capsule (PLIC), anterior limb of internal capsule (ALIC), parietal white matter (PWM), frontal white matter (FWM), thalamus (TH), caudate nucleus (CN), and genu of the corpus callosum (GCC). The chi-squared test, t-test, Spearman's correlation analysis, and receiver operating characteristic curve were used for data analyses.Results: In the premature infant group, the MK and RK values of PLIA, ALIC, and PWM were lower than those in the control group (p < 0.05). The FA values of PWM, FWM, and TH were also lower than those of the control group (p < 0.05). The area under curves of MK in PLIC and ALIC, MD in PWM, and FA in FWM were 0.813, 0.802, 0.842, and 0.867 (p < 0.05). In the thalamus and CN, the correlations between MK, RK values, and postmenstrual age (PMA) were higher than those between FA, MD values, and PMA.Conclusion: Diffusion kurtosis imaging can be used as an effective tool in detecting brain developmental disorders in premature infants.