The association between systemic inflammation markers and paroxysmal atrial fibrillation.

BACKGROUND: Systemic inflammation markers have recently been identified as being associated with cardiac disorders. However, limited research has been conducted to estimate the pre-diagnostic associations between these markers and paroxysmal atrial fibrillation (PAF). Our aim is to identify potential biomarkers for early detection of PAF. METHODS: 91 participants in the PAF group and 97 participants in the non-PAF group were included in this study. We investigated the correlations between three systemic inflammation markers, namely the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and PAF. RESULTS: The proportion of patients with PAF gradually increased with increasing logSII, logSIRI, and logAISI tertiles. Compared to those in the lowest tertiles, the PAF risks in the highest logSII and logSIRI tertiles were 3.2-fold and 2.9-fold, respectively. Conversely, there was no significant correlation observed between logAISI and PAF risk within the highest tertile of logAISI. The restricted cubic splines (RCS) analysis revealed a non-linear relationship between the elevation of systemic inflammation markers and PAF risk. Specifically, the incidence of PAF is respectively increased by 56%, 95%, and 150% for each standard deviation increase in these variables. The ROC curve analysis of logSII, logSIRI and logAISI showed that they had AUC of 0.6, 0.7 and 0.6, respectively. It also demonstrated favorable sensitivity and specificity of these systemic inflammation markers in detecting the presence of PAF. CONCLUSIONS: In conclusion, our study reveals significant positive correlations between SII, SIRI, and AISI with the incidence of PAF.

Uncovering the crystallography and formation mechanism of nanoscale clusters in Sb-rich SPPs of a p-type (Bi, Sb)2Te3 alloy.

Considering that the crystallographic characteristics of the Sb-rich secondary phase particles (SPPs) greatly affect the thermoelectric properties of Bi2Te3 based materials, it is of great significance to explore the mechanism behind the Sb-rich SPPs in the p-type (Bi, Sb)2Te3 material. Here a conventional TEM technique was used to characterize the composition, size and distribution of Sb-rich SPPs in a spark plasma sintered p-type (Bi, Sb)2Te3 alloy. The results indicated that two different morphologies of Sb-rich SPPs including elongated and circular Sb-rich SPPs were frequently observed. Combined with high-resolution transmission electron microscopy, this work provides atomic-scale evidence for the formation mechanism behind the Sb-rich SPPs in the (Bi, Sb)2Te3 material.

Effect of dapagliflozin on left ventricular structure and function in patients with non-ischemic dilated cardiomyopathy: An observational study.

Non-ischemic dilated cardiomyopathy (NIDCM) is characterized by left ventricular dilatation and contractile dysfunction with severe morbidity and mortality. Sodium glucose cotransporter type 2 (SGLT2) inhibitors significantly reduce cardiovascular events for heart failure patients. We performed to investigate the impact of combined administration of SGLT2 inhibitors on cardiac structure and function in NIDCM patients undergoing conventional therapy. A total of 50 newly diagnosed NIDCM patients received conventional medical therapy, with 23 receiving dapagliflozin 10mg/day in addition (SGLT2i group) and the remaining 27 only receiving conventional therapy (non-SGLT2i group). After 12 months outpatient follow-up, NIDCM patients treated with conventional therapy alone showed a significant reduction of left ventricular end-diastolic dimensions (LVEDd), left ventricular end-systolic dimensions (LVESd), left ventricular end-diastolic volumes (LVEDV), left ventricular end-systolic volumes (LVESV), left ventricular end-diastolic volume index (LVEDVi) and left ventricular end-systolic volume index (LVESVi), while an increase in fractional shortening (FS) and left ventricular ejection fraction (LVEF). Patients receiving dapagliflozin combined with conventional treatment also demonstrated a significant reduction in left ventricular dimensions and volumes, and a marked increase in cardiac function. In non-SGLT2i groups, the % change in LVEDd, LVESd, LVEDV, LVESV, LVEDVi, LVESVi, FS and LVEF was -2.8%, -4.6%, -6.2%, -10.1%, -6.1%, -10.1%, +9.7%, +11%. A greater absolute % fall in left ventricular volume in SGLT2i groups compared to non-SGLT2i groups resulted in a significant improvement in cardiac function. The results showed that SGLT2i combined with conventional therapy has a better beneficial effect on left ventricular volumes and cardiac function in NIDCM patients.

The association between systemic inflammation markers and the prevalence of hypertension.

BACKGROUND: We conducted a large-scale epidemiological analysis to investigate the associations between systemic inflammation markers and hypertension prevalence. Our aim is to identify potential biomarkers for early detection of hypertension. METHODS: A cross-sectional study with 119664 individuals from the National Health and Nutrition Examination Survey was performed. We investigated the associations between three systemic inflammation markers, namely the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and the prevalence of hypertension. RESULTS: The prevalence rates of hypertension gradually increased with increasing logSII, logSIRI, and logAISI quartiles. In continuous analyses, each unit increase in logSII, logSIRI, and logAISI was associated with a 20.3%, 20.1%, and 23.7% increased risk of hypertension. Compared to those in the lowest quartiles, the hypertension risks for subjects in the highest logSII, logSIRI, and logAISI quartiles were 1.114-fold,1.143-fold, and 1.186-fold. The restricted cubic splines (RCS) analysis revealed a non-linear relationship between the elevation of systemic inflammation markers and hypertension prevalence. Specifically, a per standard deviation increase in any of these variables is associated with a respective 9%, 16%, and 11% increase in hypertension prevalence. CONCLUSION: Our cross-sectional study reveals significant positive correlations between SII, SIRI, and AISI with the prevalence of hypertension.

Hypobaric hypoxia induces iron mobilization from liver and spleen and increases serum iron via activation of ghrelin/GHSR1a/MAPK signalling pathway in mice.

Hypobaric hypoxia (HH) exposure affects appetite and serum iron levels in both humans and animals. Thus, whether appetite-regulating ghrelin is involved in iron regulation under HH needs to be elucidated. In vivo, C57BL/6J mice were placed in a hypobaric chamber to establish a 6000-m-high altitude exposure animal model. In vitro, mouse primary hepatocytes and peritoneal macrophages were exposed to hypoxia (1% O2) to examine the effects of ghrelin on iron-regulating proteins. HH obviously reduced the body weight of mice and significantly increased the levels of erythrocytes, and also significantly enhanced the levels of serum iron and plasma ghrelin. However, iron content in the liver and spleen was decreased, while ferroportin (Fpn) expression was increased. Moreover, ghrelin significantly induced Fpn and pERK expression in both hepatocytes and macrophages under hypoxia, which were reversed by pretreatment with growth hormone secretagogue receptor 1a (GHSR1a) antagonist or pERK inhibitor. Our findings indicated that HH leads to decreased appetite and insufficient dietary intake, which may negatively regulate the levels of ghrelin. Furthermore, GHSR1a/ERK signalling pathway is further activated to upregulate the expression of Fpn, and then promoting iron mobilization both in the liver/hepatocytes and spleen/macrophages in mice. Thus, these results revealed that ghrelin may be a potential iron regulatory hormone, and raised the possibility of ghrelin as a promising therapeutic target against iron disorders under HH.

Transitional structure of {0001} twin in a deformed p-type (Bi,Sb)2Te3 alloy: a direct experimental basis for understanding the twinning mechanism.

Twin boundaries provide a strong phonon scattering center to hinder the lattice thermal conductivity in thermoelectric materials, but the underlying evolution process of deformation twinning remains to be figured out. By applying atomic resolution transmission electron microscope (TEM) observations, a novel type of transitional structure of {0001} twin was observed, for the first time, in the p-type (Bi,Sb)2Te3 alloy subjected to three-point bending deformation. The transformation from matrix to (0001) twin can be realized by the following path: matrix → transitional twin → (0001) twin, and this process was completed by the gliding of a total of four partial dislocations (b1 = 1/3[011̄0]) extended in the different (0001) planes. This new finding here will shed light on the nucleation and growth of deformation twins in the p-type (Bi, Sb)2Te3 alloy.

Phenolic compound SG-1 from Balanophora harlandii and its derivatives exert anti-influenza A virus activity via activation of the Nrf2/HO-1 pathway.

Influenza A virus (IAV) is one of the leading causes of respiratory illness and continues to cause pandemics around the world. Against this backdrop, drug resistance poses a challenge to existing antiviral drugs, and hence, there is an urgent need for developing new antiviral drugs. In this study, we obtained a phenolic compound SG-7, a derivative of natural compound 2-hydroxymethyl-1,4-hydroquinone, which exhibits inhibitory activity toward a panel of influenza viruses and has low cellular toxicity. Mechanistic studies have shown that SG-7 exerts its anti-IAV properties by acting on the virus itself and modulating host signaling pathways. Namely, SG-7 targets the HA2 subunit of hemagglutinin (HA) to block the fusion of viral-cellular membranes and inhibits IAV-induced oxidative stress and overexpression of pro-inflammatory factors by activating the Nrf2/HO-1 pathway and reducing NF-κB activation. In addition, SG-7 can enhance type I IFN antiviral response by inducing Nrf2 expression. Importantly, SG-7 showed the ability to inhibit viral replication in the lungs of IAV-infected mice and reduce their mortality. Therefore, SG-7 may be a promising lead compound for anti-influenza drug development.

5-Lipoxygenase Contributes to Benzo[a]pyrene-Induced Cytotoxicity and DNA Damage in Human Bronchial Epithelial Cells.

Metabolic activation of indirect-acting carcinogens in target organs is a recognized mechanism of carcinogenesis. This study aimed to determine the role of benzo[a]pyrene (BaP) metabolism enzymes lipoxygenase (LOX), cytochrome P4501A1 (CYP1A1), and prostaglandin synthetase (PGS) in the cytotoxicity and DNA damage induced by BaP in the human tracheobronchial epithelial cells (HBECs) using RNA interference strategy and metabolic enzyme inhibitors. Our results showed that in three epithelial cell lines (HBE, HTR-8/SVneo, and HaCat), BaP significantly upregulated 5-LOX protein expression. 15-LOX-2 expression also increased with increasing BaP concentration, but the change was less pronounced than that of 5-LOX. BaP caused significant cytotoxicity, DNA strand breaks, and 8-hydroxy-2'-deoxyguanosine formation in HBE, which was inhibited by 5-LOXshRNA, a specific inhibitor of 5-LOX (AA861), the CYP1A1 inhibitor α-naphthoflavone, and the PGS inhibitor naproxen. The protective effects of 5-LOXshRNA were stronger than AA861, naproxen and α-naphthoflavone. We conclude that BaP may be activated more by 5-LOX than by CYP1A1 and PGS to produce cytotoxicity and DNA damage in HBE.

A novel elicitor protein phosphopentomutase from Bacillus velezensis LJ02 enhances tomato resistance to Botrytis cinerea.

The loss of tomatoes caused by Botrytis cinerea (B. cinerea) is one of the crucial issues restricting the tomato yield. This study screened the elicitor protein phosphopentomutase from Bacillus velezensis LJ02 (BvEP) which improves the tomato resistance to B. cinerea. Phosphatemutase was reported to play a crucial role in the nucleoside synthesis of various microorganisms. However, there is no report on improving plant resistance by phosphopentomutase, and the related signaling pathway in the immune response has not been elucidated. High purity recombinant BvEP protein have no direct inhibitory effect on B. cinerea in vitro,and but induce the hypersensitivity response (HR) in Nicotiana tabacum. Tomato leaves overexpressing BvEP were found to be significantly more resistant to B. cinerea by Agrobacterium-mediated genetic transformation. Several defense genes, including WRKY28 and PTI5 of PAMP-triggered immunity (PTI), UDP and UDP1 of effector-triggered immunity (ETI), Hin1 and HSR203J of HR, PR1a of systemic acquired resistance (SAR) and the SAR related gene NPR1 were all up-regulated in transgenic tomato leaves overexpressing BvEP. In addition, it was found that transient overexpression of BvEP reduced the rotting rate and lesion diameter of tomato fruits caused by B. cinerea, and increased the expression of PTI, ETI, SAR-related genes, ROS content, SOD and POD activities in tomato fruits, while there was no significant effect on the weight loss and TSS, TA and Vc contents of tomato fruits. This study provides new insights into innovative breeding of tomato disease resistance and has great significance for loss reduction and income enhancement in the tomato industry.

Effect of live and inactivated Chlamydomonas reinhardtii on the removal of tetracycline in aquatic environments.

With the development of medical drugs, the widely used tetracycline has brought many adverse effects on the ecosystem and human health. Tetracycline pollution of water environment is becoming more and more serious, and has become an emerging environmental problem. As single celled organisms, microalgae are not only model organisms for risk assessment of aquatic ecosystems, but also can efficiently purify sewage. Microalgae-mediated pollutant remediation has attracted more and more attention from researchers. In this paper, Chlamydomonas reinhardtii (C. reinhardtii) was used to remove tetracycline in aqueous solution, and the removal efficiency and mechanism of microalgae on tetracycline were studied. The results showed that the removal rates of tetracycline by active and inactivated microalgae at a density of 5 × 106 cells·mL-1 were 81.9% and 89.8%, respectively. C. reinhardtii removed tetracycline through biosorption and nonmetabolic processes. Microalgal cell supernatant and hydroxyl radicals could significantly promote the removal of tetracycline. The positively charged tetracycline was electrostatically adsorbed on the microalgae surface and extracellular polymeric substances. Microalgae biomass can promote the production of ROS and enhance the ability of microalgae to remove tetracycline.

Identification of Key Residues Essential for the Activation of Plant Immunity by Subtilisin From Bacillus velezensis LJ02.

Subtilisin, a serine protease, can trigger defense responses in a wide variety of plants, both locally and systemically, to protect against pathogens. However, key residues of subtilisin to improve resistance to plant diseases remain unknown. In this study, Nicotiana benthamiana (N. benthamiana) leaves expressing subtilisin from Bacillus velezensis LJ02 were shown to improve protection against Botrytis cinerea (B. cinerea). Furthermore, the underlying mechanism that LJ02 subtilisin improved the protective effect was explored, and the direct inhibitory effect of subtilisin on B. cinerea was excluded in vitro. Subsequently, reactive oxygen species (ROS) burst and upregulation of resistance-related genes in systemic leaves of N. benthamiana further verified that subtilisin could induce systemic protection against B. cinerea. G307A/T308A and S213A/L214A/G215A subtilisin significantly reduced the ability to resist B. cinerea infection in N. benthamiana. Furthermore, the ROS content and expression levels of resistance-related genes of both mutants were significantly decreased compared with that of wild-type subtilisin. This work identified key residues essential for the activation function of subtilisin plant immunity and was crucial in inducing plant defense responses against B. cinerea.

Sesquiterpenoids isolated from feces-residing Streptomyces sp. inhibit the cellular entry of influenza a viruses.

Five metabolites (1-5), including two new sesquiterpenoids, designated ganodermanol L (1) and 4α,15-epoxyeudesmane-1ß,6α,11-triol (2), together with three known structurally related compounds (3-5), have been isolated from the cultures of Streptomyces sp. XM17, a bacteria residing in the fresh feces of the giant panda Ailuropoda melanoleuca. The structures of 1-2 were established on the basis of extensive spectroscopic analyses, including 1D- and 2D-NMR (1H-1H COSY, HMQC, HMBC and NOESY) experiments. Furthermore, the absolute configuration of 1 was established by single-crystal X-ray crystallographic analyses. Of noted, these compounds were found to possessed antiviral activities using the 'pretreatment of virus' approach with IC50 values ranging from 4 to 30 nM, indicating that these sesquiterpenoids were potent in inhibiting the entry of influenza A virus.

New anti-influenza A viral norsesquiterpenoids isolated from feces-residing Streptomyces sp.

Three novel norsesquiterpenoids, (2R,4S,8aR)-8,8a,1,2,3,4-hexahydro-2-hydroxy-4,8a-dimethyl-2(2H)-naphthalenone (1), (1S,3S,4S,4aS,8aR)-4,8a-dimethyloctahydronaphthalene-1,3,4a(3H)-triol(2), (4S,4aS,8aS)-octahydro-4a-hydroxy-4, 8a-dimethyl-1(2H)-naphthalenone (3), as well as six other known analogues (4-9), were isolated from the culture broth of Streptomyces sp. XM17, an actinobacterial strain inhabiting the fresh feces of the giant panda Ailuropoda melanoleuca. The chemical structures of 1-3 were elucidated comprehensively by NMR spectroscopic and MS analyses, furthermore, the stereochemical configurations were resolved by NOESY experiments, along with ECD spectral and single-crystal X-ray crystallographic analyses. These compounds were then tested for their antiviral activities using the "pretreatment of virus" approach, which showed that most of these compounds were potent in inhibiting the entry of influenza A virus, with IC50 values ranging from 5 to 49 nM and selectivity indices all above 500.

Secondary Metabolites with Cytotoxic Activities from Streptomyces sp. BM-8 Isolated from the Feces of Equusquagga.

A new aliphatic acid, compound 1, together with six known metabolites, including nonactic acid (2), homononactic acid (3), ethyl homononactate (4), homononactylhomononactate (5), valinomycin (6), and cyclo-(Pro-Leu) (7), was isolated from the culture broth of Streptomyces sp. BM-8, an actinobacterial strain isolated from the feces of Equus quagga. The structures of these compounds were established by analyses of spectroscopic data, including 1D and 2D nuclear magnetic resonance spectra (NMR), as well as by HR-ESI-MS spectrometry and chemical derivative analyses. Additionally, a serial analogue of nonactic acid and homononacticacid (8-21) was synthesized. The cytotoxicity of 1-21 wastested against a panel of cancer cell lines, such as HT-29, MCF-7, A375 and K562, with MTT assay. In addition, the cytotoxicity tests revealed that 1 was less cytotoxic toward a panel of cancerous cells, as compared with valinomycin (6).

Elevated homocysteine levels in patients with heart failure: A systematic review and meta-analysis.

BACKGROUND: Elevated homocysteine (Hcy) levels showed increasing significance as the predisposing factor for the pathogenesis of atherosclerotic sequelae, including cardiovascular mortality, coronary artery disease, and stroke. There is increasing evidence linking plasma Hcy levels and heart failure (HF). The association between the elevated level of plasma Hcy and HF was examined by meta-analysis and systematic review in this study. METHODS: The PubMed and ScienceDirect databases until April 2020 were utilized to collect previous literature on plasma Hcy levels and the potential relation to HF. The pooled effects were evaluated depending on standardized mean differences (SMDs) with 95% confidence intervals (CIs), and the calculation was performed using Stata 12 software. Potential sources of heterogeneity were assessed with subgroup analysis and sensitivity analysis. RESULTS: A total of 12 research projects including 5506 subjects were selected. For pooled effect, the results confirmed that patients with HF had higher Hcy levels than the control subjects (SMD,1.148 and 95%CI, [0.715, 1.581]). Based on the classification of New York Heart Association (NYHA), the Hcy levels for the group of NYHA I or II (SMD, 1.484 and 95% CI, [0.442, 2.527]) and the group of NYHA III or IV (SMD, 3.361 and 95% CI, [1.902, 4.820]) were significantly increased compared to controls, while the increase was more intensive for the group of NYHA III or IV. Subgroup analyses revealed similar results. CONCLUSION: Our meta-analysis identified that plasma Hcy levels were significantly elevated in HF patients compared to control subjects, which is positively related to the advancement of NYHA class.

Structures, Synthesis and Biological Activities of Nonactic Acid and Its Derivatives.

Nonactic acid, which is a macrocyclic nonactin subunit, contains four asymmetric centers and has the molecular formula of C10H18O3. Due to their various biological activities and challenging structural characteristics, nonactic acid and its derivatives have attracted much attention from scientists since 1955. These compounds possess significant antibacterial, insecticidal and acaricidal activities, as well as a promoting effect on plant growth. However, the studies in the anticancer activities of these compounds are limited. It is noticed that some derivatives of nonactic acid show significant cytotoxicity toward different human cancer cells, from which, a basic structure-activity relationship might be able to obtain. On the basis of these progresses, we believe that this review may provide new ideas for generating potent anticancer compounds bearing the same pharmacophores derived from those macrocyclic molecules.

Antiviral Bafilomycins from a Feces-Inhabiting Streptomyces sp.

A new bafilomycin derivative (1) and another seven known bafilomycins (2-8) were isolated from feces-derived Streptomyces sp. HTL16. The structure of 1 was elucidated by 1D and 2D NMR spectroscopic analysis. Biological testing demonstrated that these bafilomycins exhibited potent antiviral activities against the influenza A and SARS-CoV-2 viruses, with IC50 values in the nanomolar range, by inhibiting the activity of endosomal ATP-driven proton pumps.

Fasting Increases Iron Export by Modulating Ferroportin 1 Expression Through the Ghrelin/GHSR1α/MAPK Pathway in the Liver.

The liver is contributed to maintaining body iron homeostasis and controlling of body adaptation to fasting. Although previous studies implied a negative relationship between iron and ghrelin in both mice and humans, it remains to be explored whether fasting or ghrelin has a functional effect on iron homeostasis in the liver. In this study, we examined the roles of fasting and ghrelin in modulating the protein expression of Fpn1, transferrin receptor 1 (TfR1), and ferritin light chain (Ft-L), as well as the mRNA expression of ghrelin, hepcidin, ghrelin O-acyltransferase (GOAT), and growth hormone secretagogue receptor 1 alpha (GHSR1α) in mouse liver and cultured hepatocytes. Our in vivo results suggested that fasting significantly upregulated the mRNA expression of ghrelin, GOAT, and GHSR1α, as well as the protein levels of ghrelin, Fpn1, and Ft-L, but not TfR1, in mouse liver. Interestingly, mRNA expression of hepcidin did not change significantly after fasting. Meanwhile, in cultured hepatocytes, ghrelin significantly increased the protein expression of Fpn1 but not Ft-L and TfR1 and significantly enhanced ERK phosphorylation. Furthermore, the pretreatment of cultured hepatocytes with either a pERK inhibitor or a GHSR1α antagonist abolished the effects of ghrelin on Fpn1 expression and ERK phosphorylation. Our findings confirmed that fasting increases iron export in the liver by upregulating Fpn1 expression through the ghrelin/GHSR1α/MAPK signaling pathway.

Hepcidin Decreases Rotenone-Induced α-Synuclein Accumulation via Autophagy in SH-SY5Y Cells.

Parkinson's disease (PD) is a neurodegenerative disorder, and the hallmarks of this disease include iron deposition and α-synuclein (α-syn) aggregation. Hepcidin could reduce iron in the central and peripheral nervous systems. Here, we hypothesized that hepcidin could further decrease α-syn accumulation via reducing iron. Therefore, rotenone or α-syn was introduced into human neuroblastoma SH-SY5Y cells to imitate the pathological progress of PD in vitro. This study investigated the clearance effects of hepcidin on α-syn induced by a relatively low concentration of rotenone exposure or α-syn overexpression to elucidate the potential clearance pathway involved in this process. We demonstrated that SH-SY5Y cell viability was impaired after rotenone treatment in a dose-dependent manner. α-syn expression and iron content increased under a low concentration rotenone (25 nM for 3 days) treatment in SH-SY5Y cells. Pre-treatment with hepcidin peptide suppressed the abovementioned effects of rotenone. However, hepcidin did not affect treatment with rotenone under high iron conditions. Hepcidin also played a role in reducing α-syn accumulation in rotenone and α-syn overexpression conditions. We identified that the probable clearance effect of hepcidin on α-syn was mediated by the autophagy pathway using pretreatment with autophagy inhibitors (3-MA and CQ) and detection of autophagy protein markers (LC3II/I and p62). In conclusion, hepcidin eliminated α-syn expression via the autophagy pathway in rotenone-treated and α-syn overexpression SH-SY5Y cells. This study highlights that hepcidin may offer a potential therapeutic perspective in α-syn accumulation diseases.