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Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor protein expressed on myeloid cells and located downstream of pattern recognition receptors (PRRs), which transduces signals involved in innate immunity. CARD9 deficiency is associated with increased susceptibility to various fungal diseases. Increasing evidence shows that CARD9 mediates the activation of p38 MAPK, NF-κB, and NLRP3 inflammasome in various CVDs and then promotes the production of proinflammatory cytokines and chemokines, which contribute to cardiac remodeling and cardiac dysfunction in certain cardiovascular diseases (CVDs). Moreover, CARD9-mediated anti-apoptosis and autophagy are implicated in the progression of CVDs. Here, we summarize the structure and function of CARD9 in innate immunity and its various roles in inflammation, apoptosis, and autophagy in the pathogenesis of CVDs. Furthermore, we discuss the potential therapies targeting CARD9 to prevent CVDs and raise some issues for further exploring the role of CARD9 in CVDs.

NAFLD is a liver disease that is caused by liver damage or extreme lipid deposition but not alcohol. Nrf2 could mediate resistance to oxidative stress injury. Autophagy can degrade metabolic waste and accumulated toxic endogenous substances. Pterostilbene (PTE) is an active compound extracted from blueberry, and grape, that exhibits many biological effects, such as antiinflammation and antitumor.This study provides a mechanism of PTE affecting on oxidative stress and autophagy in NAFLD mice. Tyloxapol, oil acid (OA) and palmitic acid (PA) were used to induce lipid accumulation in mice and HepG2 cells.Western blotting, CRISPR/Cas 9 and other molecular biological approaches were applied to explore the mechanisms of PTE effected on NAFLD.PTE pretreatment effectively reduced the lipid accumulation in OA and PA induced HepG2 cells and tyloxapol induced mice, and significantly promoted the expression of nNrf2, PPAR-α and HO-1, and AMPK activity, but inhibited the expression of mTORC 1 and SREBP-1c. PTE activated phosphatidylinositide 3-kinase (PI3K) and proteins in the autophagy-related gene (ATG) family, and promoted the transformation of LC3Ⅰ to LC3Ⅱ which indicated the activation of autophagy, however, these effects were abolished after Nrf2 knockout.PTE effectively alleviated oxidative stress damage induced by excessive lipid accumulation in hepatocytes, thus promoting the metabolism and decomposition of fatty acids to improve NAFLD.

Objective. To evaluate the effectiveness of different glucose monitoring methods on blood glucose control and the incidence of adverse events among patients with type 1 diabetes mellitus. Methods. Using the method of literature review, the databases PubMed, Cochrane, and Embase were retrieved to obtain relevant research literature, and the selected studies were analyzed and evaluated. This study used Cochrane software RevMan5.4 to statistically analyze all the data. Results. A total of 15 studies were included in this study, including 10 randomized controlled trials and 5 crossover design trials, with a total of 2071 patients. Meta-analysis results showed that continuous blood glucose monitoring (CGM) could significantly reduce the HbA1c level of patients, weighted mean difference WMD = − 2.69 , 95% confidence interval (CI) (-4.25, -1.14), and P < 0.001 compared with self-monitoring of blood glucose (SMBG). Meanwhile, the incidence of severe hypoglycemia in the CGM group was significantly decreased, risk ratio RR = 0.52 , 95% CI 0.35-0.77, and P = 0.001 . However, there was no statistical difference in the probability of diabetic ketoacidosis between CGM and SMBG groups, RR = 1.34 , 95% CI 0.57-3.15, and P = 0.5 . Conclusion. Continuous blood glucose monitoring is associated with lower blood glucose levels than the traditional blood glucose self-test method.

We aimed to explore the associations between the controlling nutritional status (CONUT), the prognostic nutritional index (PNI), and prognostic outcomes in patients with small-cell lung cancer (SCLC) receiving radiotherapy.A total of 93 SCLC patients who received radiotherapy at the hematology department in the First Affiliated Hospital of Hainan Medical University were retrospectively included in this analysis. Patient CONUT and PNI values were calculated. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cut-off, the area under the curve (AUC), sensitivity, and specificity of CONUT and PNI in discriminating patient outcomes. Kaplan-Meier curve analysis was performed, and overall survival (OS) was compared for patients with CONUT3 and ≤3, or those with PNI47.7 and ≤47.7. Univariate and multivariate analysis using the Cox proportional hazard model was performed to identify the risk factors for patient death.The AUCs for CONUT and PNI were 0.95 and 0.82, respectively. The CONUT results indicated that patient OS decreased significantly from normal to mildly malnourished. Meanwhile, the OS for moderately malnourished patient decreased to severely malnourished (P for trend0.001). Patients with CONUT3 or PNI ≤47.7 had significantly shorter OS than those with CONUT ≤3 (median survival time 12 vs. 23 months; P0.001) or with PNI47.7 (median survival time 20 vs. 15 months; P=0.010). Multivariate analysis indicated that the TNM stage [hazard ratio (HR) =1.21; 95% confidence interval (CI): 1.03-1.66], CONUT score (HR =2.33; 95% CI: 1.76-3.91), and PNI ≤47.7 (HR =1.33; 95% CI: 1.09-1.99) were independent prognostic indicators for patient death.The CONUT and PNI were potential indicators for the outcome of patients with SCLC. CONUT3 or PNI ≤47.7 indicated an unfavorable prognosis for SCLC patients.

Context Panax ginseng C.A. Meyer (Araliaceae) has cardioprotective effects. Ginsenosides are responsible for most of the pharmacological activities of ginseng. Objective This study investigates the effect of ginsenoside Rg2 on myocardial fibrosis in myocardial ischaemia rats. Materials and methods Male Wistar rats were divided into control, isoproterenol, ginsenoside Rg2 (5, 20 mg/kg) groups (n = 8). The rats were subcutaneously injected with isoproterenol (5 mg/kg) or normal saline (control group) once daily for 7 days. The animals were intragastrically treated with ginsenoside Rg2 or 0.5% CMC-Na (control and isoproterenol groups) daily for 28 days. At day 28, cardiac function, myocardial fibrosis, and TGF-β1/Smad signalling pathway were evaluated. Results Compared with myocardial ischaemic rats, ginsenoside Rg2 at doses of 5, 20 mg/kg abated partially the augment of LVEDP (8.9 ± 1.3 vs. 7.5 ± 0.7, 7.2 ± 1.0 mmHg) and the decreases of the LVSP (96.75 ± 13.2 vs. 118.3 ± 19.4, 124.3 ± 21.3 mmHg), the + dp/dt (2142.8 ± 309.3 vs. 2598.6 ± 404.0, 2661.5 ± 445.2 mmHg/s), and the -dp/dt (1996.3 ± 306.3 vs. 2476.6 ± 289.7, 2509.6 ± 353.1 mmHg/s). Ginsenoside Rg2 (9.2 ± 0.9%, 8.5 ± 0.8%) alleviated myocardial fibrosis when compared with the isoproterenol group (10.1 ± 1.0%), which was accompanied by suppressed TGF-β1/Smad signalling in heart tissues. Conclusions Ginsenosides from ginseng possess the property of alleviating myocardial fibrosis, improving cardiac function after myocardial ischaemia. Ginsenosides may be promising agents for improving the outcomes of patients with myocardial ischaemia.

M & A was an important means to promote the transformation and upgrading of traditional industries, and also an important way to improve the degree of industrial concentration and speed up the transformation of industrial development mode. As a direct embodiment of the efficiency of M & A, the performance of M & A has been widely concerned by scholars. This paper introduced the concept of M & A performance and motivation of M & A, used Citespace to analyze 749 papers on M & A performance from CNKI core journals from 2000 to 2020,The research focus and frontier of M & A performance a analyzed by keyword clustering and keyword variation, and analyzed the research results of external environment, internal environment, M & A characteristics and external intermediary agencies which affect M & A performance, Finally, the possible direction of future research was proposed.

Recurrent spontaneous abortion affects approximately 1-2% of women of childbearing, and describes a condition in which women suffer from three or more continuous spontaneous miscarriages. However, the origin of recurrent spontaneous abortion (RSA) remains unknown, preventing effective treatment and placing stress upon patients. It has been acknowledged that successful pregnancy necessitates balanced immune responses. Therefore, immunological aberrancy may be considered a root cause of poor pregnancy outcomes. Considerable published studies have investigated the relationship between various immune cells and RSA. Here, we review current knowledge on this area, and discuss the five main categories of immune cells involved in RSA; these include innate lymphocytes (ILC), macrophages, decidual dendritic cells (DCs), and T cells. Furthermore, we sought to summarize the impact of the multiple interactions of various immune cells on the emergence of RSA. A good understanding of pregnancy-induced immunological alterations could reveal new therapeutic strategies for favorable pregnancy outcomes.

Two new polyacylated germacrane sesquiterpenoids, named as salvianols A (1) and B (2), were isolated from the aerial parts of Salvia chinensis. Their structures were established by extensive analysis of HR-ESI-MS and NMR spectra. The polyacylated germacrane sesquiterpenoids are rare in natural products.

Perturbations to acoustic speech feedback have been typically localized to specific phonetic characteristics, for example, fundamental frequency (F0) or the first two formants (F1/F2), or affect all aspects of the speech signal equally, for example, via the addition of background noise. This paper examines the consequences of a more selective global perturbation: real-time cochlear implant (CI) simulation of acoustic speech feedback. Specifically, we examine the potential similarity between speakers’ response to noise vocoding and the characteristics of Lombard speech. An acoustic analysis of supra-segmental characteristics in speaking rate, F0 production, and voice amplitude revealed changes that paralleled the Lombard effect in some domains but not others. Two studies of speech intelligibility complemented the acoustic analysis, finding that intelligibility significantly decreased as a result of CI simulation of speaker feedback. Together, the results point to differences in speakers’ responses to these two superficially similar feedback manipulations. In both cases we see a complex, multi-faceted behavior on the part of talkers. We argue that more instances of global perturbation and broader response assessment are needed to determine whether such complexity is present in other feedback manipulations or if it represents a relatively rare exception to the typical compensatory feedback response.

Additional file 1. The details spectra for the identification of compound 1â 3. This file includes 1D-NMR, 2D-NMR, HR-MS, IR and UV spectra of compound 1â 3.

The medicinal plant Tirpitzia sinensis has been used by the Zhuang ethnic people in mountainous areas of Southwest China to stop bleeding, invigorate blood circulation, and treat inflammation and wounds. In order to further explore its traditional medicinal uses, the phytochemical constituents of this species were examined. Three new compounds, the lignan tirpitzin (1), the flavonoid tirpitzoside (2), and the furan-glycoside tirpitziol (3), along with five known compounds were isolated from the aerial part of T. sinensis for the first time. The structures of these compounds were elucidated by 1D and 2D NMR, LC/MS, IR spectrometric methods and compared with published data. The results of an in silico pharmacophore-based analysis showed potential targets of the new compounds, including ERBB2, IRAK4, LCK, JAK2, MAPK14, and MMP-12. These targets suggested that 1–3 may be involved with wound-healing and/or inflammation, leading to an in vitro assay of nitric oxide (NO) inhibition assays with lipopolysaccharide-induced BV-2 cells. All three new compounds displayed moderate NO inhibitory activity with the IC50 values of 14.97 ± 0.87, 26.63 ± 1.32, and 17.09 ± 2.3 μM, respectively. Electronic supplementary material The online version of this article (10.1186/s13065-019-0568-9) contains supplementary material, which is available to authorized users.

Rationale Dual atrioventricular nodal non-reentrant tachycardia (DAVNNT) is an uncommon arrhythmia. Because of the different refractory periods of fast and slow pathways, a single atrial depolarization gives rise to 2 ventricular activationsthrough fast and slow pathways separately. Patient concerns A 45-year-old woman was referred to our Cardiology Center with symptoms of recurrent palpitations and fatigue persisting for the previous 3 years. On echocardiography, the ejection fraction of the left ventricle was 45%. Diagnoses Electrophysiological study findings and 12-lead electrocardiogram led to a diagnosis of DAVNNT. Interventions Our case responded very well to the ablation of the slow pathway, and her tachycardia completely disappeared. Outcome Her left ventricle ejection fraction also improved to52% after 3 months of follow-up. The patient remained asymptomatic throughout the follow-up period of 1 year, without any recurrence or complications. Lessons DAVNNT is a rare arrhythmia which can induce tachycardia-induced cardiomyopathy. Ablation of the slow pathway isconsidered a curative treatment.

A new triterpenoid, 2α, 3β, 20β, 23-tetrahydroxy-urs-12, 19 (29)-dien-28-oic acid, together with eight known triterpenoids, was isolated from the aerial parts of Salvia chinensis . Their structures were identified by spectroscopic analyses. The antiproliferative effects and differentiation induction abilities of these compounds were determined in human leukemia HL-60 cells.

Two new germacrane sesquiterpenes, called salviadienol A (1) and salviadienol B (2), together with five known compounds, methyl-ent-4-epi-agath-18-oate (3), angelicoidenol (4), clovane-2beta,9alpha-diol (5), dehydrovomifoliol (6) and blumenol A (7), were isolated from Salvia chinensis. Their structures were identified on the basis of spectral characteristics.

Objectives: To investigate the role played by sperm damnification in reproduction and correlation with sperm motility and sperm malformation rate. Method: We chosed 186 clinical samples for assaying their semen parameters by Computer Assisted Semen Analysis (CASA), meanwhile, we investigated sperm DNA damnification by Single cell gel electrophoresis(SCGE). Our work highlight that the correlation analysis of DNA damnification with the sperm deformity and motility. Then, we randomly selected some datas made statistics analysis by SPSS13.0. Result: The results showed that the SCGE method is very accurate for detected sperm DNA damnification. Statistics analysis showed that compared with the control group (male fertility), sperm viability, DNA damnification and morphology are significant difference of the group low sperm motility (P

Excess cardiac iron levels are associated with cardiac damage and can result in increased morbidity and mortality. Here, we hypothesize that elevations in tissue iron can activate caspase-dependent signaling, which leads to increased cardiac apoptosis and fibrosis, and that these alterations can be attenuated by iron chelation. Using an iron-overloaded gerbil model, we show that increased cardiac iron is associated with reduced activation of Akt (Ser473 and Thr308), diminished phosphorylation of the proapoptotic regulator Bad (Ser136), and an increased Bax/Bcl-2 ratio. These iron-overload-induced alterations in Akt/Bad phosphorylation and Bax/Bcl-2 ratio were coupled with increased activation of the downstream caspase-9 (40/38- and 17-kDa fragments) and apoptosis executioner caspase-3 (19- and 17-kDa fragments), which were accompanied by evidence of elevated cytoskeletal α-fodrin cleavage (150- and 120-kDa fragments), discontinuity of myocardial membrane dystrophin immunoreactivity, increases in the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells (nucleic DNA fragmentation), and cardiac fibrosis. We demonstrate that the administration of deferasirox, a tridentate iron chelator, is associated with diminished tissue iron deposition, attenuated activation of caspases, reduced α-fodrin cleavage, improved membrane integrity, decreased TUNEL reactivity, and attenuated cardiac fibrosis. These results suggest that the activation of caspase-dependent signaling may play a role in the development of iron-induced cardiac apoptosis and fibrosis, and deferasirox, via a reduction in cardiac tissue iron levels, may be useful for decreasing the extent of iron-induced cardiac damage.

Age-related muscle atrophy is characterized by increased oxidative stress, diminished Akt enzymatic function, and reduced phosphorylation of the mammalian target of rapamycin (mTOR), which can be attenuated by chronic acetaminophen ingestion. Here we hypothesize that age-related impairments in Akt/mTOR function are associated with reduced protein translational signaling, and that these changes, if present, can be attenuated by acetaminophen treatment.Compared to 6- and 27-month old animals, the expression of the mTOR-complex proteins raptor and GβL and the phosphorylation of tuberin/TSC2 (Thr1462) were reduced in the soleus muscles of very aged rats (33 months old). These changes in Akt/mTOR pathway signaling proteins were in turn associated with decreased phosphorylation of S6 kinase p85S6K (Thr412) and eukaryotic translation initiation factor-4E (eIF4E) binding protein-1 (4EBP1, Thr37/46), reduced phosphorylation of S6 ribosomal protein (Ser235/236), and increased inhibition of eIF4E by binding to 4EBP1. Age-associated alterations in the Akt/mTOR pathway signaling and in the phosphorylation of the stress-responsive eIF2α protein were attenuated by chronic acetaminophen treatment (30 mg/kg body weight per day). Ex vivo incubation of adult muscles with hydrogen peroxide mimicked the age-related decreases seen in eIF4E and 4EBP1 phosphorylation, whereas the inclusion of acetaminophen in the muscle bath attenuated this effect.Aging is associated with impairments in the regulation of proteins thought to be important in controlling mRNA translation, and acetaminophen may be useful for the treatment of age-related muscle atrophy by reducing oxidative stress.

Two new germacrane sesquiterpenes, called salviadienol A (1) and salviadienol B (2), together with five known compounds, methyl-ent-4-epi-agath-18-oate (3), angelicoidenol (4), clovane-2β,9α-diol (5), dehydrovomifoliol (6) and blumenol A (7), were isolated from Salvia chinensis. Their structures were identified on the basis of spectral characteristics.

A new aromatic alkine was isolated from the tuber of Sparganium stoloniferum . Its structure was assigned to be methyl 3,6-dihydroxy-2-[2-(2-hydroxyphenyl)-ethynyl]benzoate (1) by spectroscopic methods.