From single- to multi-omics: future research trends in medicinal plants.

Medicinal plants are the main source of natural metabolites with specialised pharmacological activities and have been widely examined by plant researchers. Numerous omics studies of medicinal plants have been performed to identify molecular markers of species and functional genes controlling key biological traits, as well as to understand biosynthetic pathways of bioactive metabolites and the regulatory mechanisms of environmental responses. Omics technologies have been widely applied to medicinal plants, including as taxonomics, transcriptomics, metabolomics, proteomics, genomics, pangenomics, epigenomics and mutagenomics. However, because of the complex biological regulation network, single omics usually fail to explain the specific biological phenomena. In recent years, reports of integrated multi-omics studies of medicinal plants have increased. Until now, there have few assessments of recent developments and upcoming trends in omics studies of medicinal plants. We highlight recent developments in omics research of medicinal plants, summarise the typical bioinformatics resources available for analysing omics datasets, and discuss related future directions and challenges. This information facilitates further studies of medicinal plants, refinement of current approaches and leads to new ideas.

Cardioprotective effects of asiaticoside against diabetic cardiomyopathy: Activation of the AMPK/Nrf2 pathway.

Diabetic cardiomyopathy (DCM) is a chronic microvascular complication of diabetes that is generally defined as ventricular dysfunction occurring in patients with diabetes and unrelated to known causes. Several mechanisms have been proposed to contribute to the occurrence and persistence of DCM, in which oxidative stress and autophagy play a non-negligible role. Diabetic cardiomyopathy is involved in a variety of physiological and pathological processes. The 5' adenosine monophosphate-activated protein kinase/nuclear factor-erythroid 2-related factor 2 (AMPK/Nrf2) are expressed in the heart, and studies have shown that asiaticoside (ASI) and activated AMPK/Nrf2 have a protective effect on the myocardium. However, the roles of ASI and AMPK/Nrf2 in DCM are unknown. The intraperitoneal injection of streptozotocin (STZ) and high-fat feed were used to establish the DCM models in 100 C57/BL mice. Asiaticoside and inhibitors of AMPK/Nrf2 were used for intervention. Cardiac function, oxidative stress, and autophagy were measured in mice. DCM mice displayed increased levels of oxidative stress while autophagy levels declined. In addition, AMPK/Nrf2 was activated in DCM mice with ASI intervention. Further, we discovered that AMPK/Nrf2 inhibition blocked the protective effect of ASI by compound C and treatment with ML-385. The present study demonstrates that ASI exerts a protective effect against DCM via the potential activation of the AMPK/Nrf2 pathway. Asiaticoside is a potential therapeutic target for DCM.

RIP3 orchestrates oxidative stress and pyroptosis in doxorubicin-induced cardiotoxicity through regulation of AKT/Nrf2 signaling cascade.

This study was designed to explore the role of RIP3 in DOX-induced cardiotoxicity and its underlying molecular mechanisms. Our results demonstrate that RIP3 exacerbates DOX-induced cardiotoxicity through promoting oxidative stress and pyroptosis by regulating the AKT/Nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway. Inhibition of RIP3 using GSK-872 attenuated DOX-induced cardiac remodeling and contractile dysfunction. Moreover, using GSK-872 in vivo, the results revealed that inhibition of RIP3 alleviated DOX-induced cardiotoxicity by the resulting inhibition of oxidative stress and pyroptosis. In addition, inhibition of RIP3 increased the protein levels of AKT and Nrf2 in DOX-treated mouse hearts. Furthermore, the AKT inhibitor LY294002 lessened RIP3 reduction-offered protection against DOX-induced H9c2 cell injury by moderating oxidative stress and pyroptosis. Taken together, these data demonstrate that RIP3 activation orchestrates DOX-induced cardiotoxicity through elevated oxidative stress and pyroptosis in an AKT/Nrf2-dependent manner. Those findings highlight the clinical relevance and therapeutic potential of targeting RIP3 for the treatment of DOX-induced cardiotoxicity.

Follistatin-like protein 1 attenuates doxorubicin-induced cardiomyopathy by inhibiting MsrB2-mediated mitophagy.

Doxorubicin (DOX) is a potent chemotherapeutic drug; however, its clinical use is limited due to its cardiotoxicity. Mitochondrial dysfunction plays a vital role in the pathogenesis of DOX-induced cardiomyopathy. Follistatin-like protein 1 (FSTL1) is a potent cardiokine that protects the heart from diverse cardiac diseases, such as myocardial infarction, cardiac ischemia/reperfusion injury, and heart failure. However, its role in DOX-induced cardiomyopathy is unclear. Therefore, the present study investigated whether administering recombinant FSTL1 could mitigate DOX-induced cardiomyopathy and clarified the underlying molecular mechanisms. FSTL1 treatment attenuated DOX-induced cardiac dysfunction, cardiac fibrosis, and cellular apoptosis by inhibiting excess mitochondrial matrix protein methionine sulfoxide reductase B2 (MsrB2)-mediated mitophagy. Furthermore, FSTL1 administration reduced the expression of apoptotic proteins, including MsrB2, Bax, caspase 3, mitochondrial Parkin, and LC3-II, increased myocardial ATP content, and decreased cardiac malondialdehyde levels, thus protecting mitochondrial function against DOX-induced cardiac injury. Furthermore, FSTL1 treatment protected the contractile properties of adult cardiomyocytes against DOX-induced injury in vitro. Furthermore, carbonyl cyanide m-chlorophenylhydrazone, a mitophagy inducer, impaired the protective effects of FSTL1 in DOX-treated H9c2 cardiomyocytes. In conclusion, these results show that FSTL1 is a novel therapeutic agent against DOX-induced cardiotoxicity that improves mitochondrial function and decreases mitophagy.

Echocardiographic assessment for cardiopulmonary function in patients with congenital heart disease-related pulmonary arterial hypertension.

BACKGROUND: For patients with congenital heart disease-related pulmonary arterial hypertension (CHD-PAH), cardiopulmonary exercise testing (CPET) can reflect cardiopulmonary reserve function. However, CPET may not be readily accessible for patients with high-risk conditions or limited mobility due to disability. Echocardiography, on the other hand, serves as a widely available diagnostic tool for all CHD-PAH patients. This study was aimed to identify the parameters of echocardiography that could serve as indicators of cardiopulmonary function and exercise capacity. METHODS: A cohort of 70 patients contributed a total of 110 paired echocardiogram and CPET results to this study, with 1 year interval for repeated examinations. Echocardiography and exercise testing were conducted following standardized procedures, and the data were collected together with clinically relevant indicators for subsequent statistical analysis. Demographic comparisons were performed using t-tests and chi-square tests. Univariate and multivariate analyses were conducted to identify potential predictors of peak oxygen uptake (peak VO2) and the carbon dioxide ventilation equivalent slope (VE/VCO2 slope). Receiver operating characteristic (ROC) analysis was used to assess the performance of the parameters. RESULTS: The ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) was found to be the only independent indicator significantly associated with both peak VO2 and VE/VCO2 slope (both p < 0.05). Additionally, left ventricular ejection fraction (LVEF) and right ventricular fractional area change (FAC) were independently correlated with the VE/VCO2 slope (both p < 0.05). TAPSE/PASP showed the highest area under the ROC curve (AUC) for predicting both a peak VO2 ≤ 15 mL/kg/min and a VE/VCO2 slope ≥ 36 (AUC = 0.91, AUC = 0.90, respectively). The sensitivity and specificity of TAPSE/PASP at the optimal threshold exceeded 0.85 for both parameters. CONCLUSIONS: TAPSE/PASP may be a feasible echocardiographic indicator for evaluating exercise tolerance.

New risk model by right ventricle - pulmonary arterial coupling and inferior vena cava from echocardiography in patients with conventional low-intermediate risk pulmonary artery hypertension under targeted treatment.

BACKGROUND: Accurately stratifying patients with pulmonary arterial hypertension (PAH) is very important, and traditional risk scores still have internal heterogeneity. This study aimed to construct a risk stratification model that can accurately identify clinical worsening (CW) events in conventional low-intermediate risk patients with pulmonary hypertension under targeted drug treatment by using echocardiographic parameters. METHODS: This study is a single-center, prospective study, including 105 PAH patients who underwent regular follow-up at Guangdong Provincial People's Hospital from October 2021 to April 2023. The primary endpoint was the occurrence of CW, including death, hospitalization due to pulmonary hypertension, escalation of targeted drug therapy, and worsening of PAH. The predictive value of the echocardiography-based three-strata risk model was assessed using Kaplan-Meier curves and COX regression analysis. RESULTS: A total of 98 PAH patients were ultimately included in this study. The median follow-up duration was 26 months (range 7-28 months). The echocardiography-based three-strata model included the ratio of tricuspid annular plane systolic excursion and pulmonary artery systolic pressure (TAPSE/PASP) and inferior vena cava (IVC). The echocardiography-based three-strata model had higher diagnostic value (C-index = .76) compared to the 2022 ESC/ERS three-strata model and four-strata model (C-index = .66 and C-index = .61, respectively). PAH patients with lower TAPSE/PASP and wider IVC showed a higher CW rate compared to patients with higher TAPSE/PASP and normal IVC (HR = 15.1, 95%CI:4.4-51.9, p < .001). CONCLUSION: The echocardiography-based three-strata model based on TAPSE/PASP and IVC can effectively improve the stratification of low-intermediate risk PAH patients under targeted treatment.

Decoding Typical Flight States Based on Neural Signals from the Midbrain Motor Nuclei of Pigeons.

BACKGROUND: Exploring the neural encoding mechanism and decoding of motion state switching during flight can advance our knowledge of avian behavior control and contribute to the development of avian robots. However, limited acquisition equipment and neural signal quality have posed challenges, thus we understand little about the neural mechanisms of avian flight. METHODS: We used chronically implanted micro-electrode arrays to record the local field potentials (LFPs) in the formation reticularis medialis mesencephali (FRM) of pigeons during various motion states in their natural outdoor flight. Subsequently, coherence-based functional connectivity networks under different bands were constructed and the topological features were extracted. Finally, we used a support vector machine model to decode different flight states. RESULTS: Our findings indicate that the gamma band (80-150 Hz) in the FRM exhibits significant power for identifying different states in pigeons. Specifically, the avian brain transmitted flight related information more efficiently during the accelerated take-off or decelerated landing states, compared with the uniform flight and baseline states. Finally, we achieved a best average accuracy of 0.86 using the connectivity features in the 80-150 Hz band and 0.89 using the fused features for state decoding. CONCLUSIONS: Our results open up possibilities for further research into the neural mechanism of avian flight and contribute to the understanding of flight behavior control in birds.

First Report of Diaporthe hongkongensis Causing Leaf Blight on Macadamia in China.

Macadamia (Macadamia ternifolia Maiden and Betche) belongs to the Proteaceae family (Li et al. 2022). In the hilly areas of Guangxi (southern China), macadamia trees are an important source of revenue. The planting area in Guangxi has increased in recent years, exceeding 53,333 hectares by the end of 2022, but this increase is also associated with emergency of, macadamia diseases. Leaf blight symptoms were observed in 37/241 macadamia trees (15% incidence) in a plantation in Nanning, Guangxi province in China, during June, 2022. Disease severity on infected trees ranged from 5% to 60%. The disease developed from the tips or margins of leaves, causing the leaves to turn brown, and later gradually withered (Fig. 1 A). Ten leaves with lesions were collected from five macadamia trees (two leaves per tree. Thereafter, small segments (3 to 4 mm²) excised from the margins of ten lesions were surface sterilized in 75% ethanol for 30 s and 1% hypochlorite for 90 s and Page 1 of 6 2 rinsed in sterile water, before plating onto potato dextrose agar (PDA) medium. Plates were incubated under lighting during the daytime, and darkness at night-time for 5 days at 25℃. Twenty-two purified colonies were generated by subculturing hyphal tips, of which eight exhibited similar morphology and were further characterized. The colonies on PDA were gray with a white outer ring and flat lawn on the surface (Fig. 1 B). The pycnidia were superficial to semi-immersed on PDA, solitary to aggregated, globose to sub-globose, brown to black and oozed yellow mucilaginous masses (Fig.1 C). The α-conidia were unicellular, hyaline elliptical or fusiform, and measuring 4-8 × 1.9-4 µm (n=30) ， whereas the ß-conidia were hyaline, long, straight or curved, measuring 20-23 × 0.9-2 µm (n=30) (Fig. 1 D-E). The morphological features were similar to Diaporthe hongkongensis (Dissanayake et al. 2015). The eight morphologically similar isolates were identified as D. hongkongensis using the internal transcribed spacer (ITS) region, but only one isolate, JG11, was selected for further molecular identification. Five target genes, including the ITS region, translation elongation factor 1 alpha (EF1-α), beta-tubulin genes (TUB2), calmodulin (CAL), and histone H3 (HIS) were amplified and sequenced using primers ITS1/ITS4, EF1-728F/EF1-986R, Bt2a/Bt2b, CAL-228F/CAL-737R, and CYLH3F/H3-1b, respectively (Carbone and Kohn 1999). The sequences were deposited in GenBank under accession numbers OQ932790 (ITS) and OR147955-58 for EF1-α, TUB, CAL and HIS genes, respectively. BLAST search of GenBank showed that ITS, EF1-α, TUB, CAL, and HIS sequences of JG11 were similar to Page 2 of 6 3 those of D. hongkongensis NR111848 (99.22% identity), KY433566 (99.72%), MW208603 (99.42%), MW221740 (99.80%), and MW221661 (99.79%), respectively. Phylogenetic analysis of concatenated sequences was performed with IQ-TREE software. JG11 was grouped in the same clade as other Diaporthe hongkongensis isolates (Fig. 2). Pathogenicity experiments were carried out on healthy macadamia trees in a greenhouse. Three macadamia trees were used as negative controls where five uninjured leaves per tree were sprayed with sterile distilled water. Uninjured five leaves per tree of three other macadamia trees were sprayed with conidia suspension of the isolate JG11 at a concentration of 1×106. Each treatment was repeated 3 times independently, with 5 leaves per tree (Liu et al. 2023; Havill et al. 2023; Zhang et al. 2022). Plastic bags were placed over all inoculated leaves. The average daily temperature and relative humidity in the greenhouse were 32°C and 65%, respectively. Two days later, browning appeared on the leaves inoculated with the spore suspension and expanded outward. After 5 days, all macadamia leaves inoculated with the fungal spores began to wither, while controls remained asymptomatic (Fig. 1 H-I). D. hongkongensis was consistently re-isolated and purified from inoculated leaves and the identity was confirmed by morphological identification and molecular analysis, completed Koch's postulates. D. hongkongensis has been reported on peach (Zhang et al. 2021), grapevine trunk (Dissanayake et al. 2015) and Cunninghamia lanceolata (Liao et al. 2022). To our knowledge, this is the first report of D. hongkongensis causing leaf blight on macadamia in China. These findings provide a foundation for future research on the epidemiology and control of this newly emerging disease of macadamia.

UBE2T promotes glioblastoma malignancy through ubiquitination-mediated degradation of RPL6.

Glioblastoma (GBM) is the most frequent and aggressive malignant glioma. Due to patients' poor prognosis, it is of great clinical significance to determine new targets that may improve GBM treatment. In the present study, we showed that ubiquitin (Ub)-conjugating enzyme E2T (UBE2T) was significantly overexpressed in GBM and could promote proliferation, invasion, and inhibit apoptosis of GBM cells. Mechanistically, UBE2T functioned as the Ub enzyme of ribosomal protein L6 (RPL6) and induced the ubiquitination and degradation of RPL6 in an E3 ligase-independent manner through direct modification by K48-linked polyubiquitination, thus contributing to the malignant progression of GBM cells. Furthermore, inhibiting the expression of RPL6 by UBE2T could not only reduce the expression of wild-type p53, but also enhance the gain-of-function of mutant p53. Moreover, knockdown of UBE2T in LN229 cells obviously suppressed tumor growth in LN229 xenograft mouse models. Collectively, our study demonstrated that UBE2T promotes GBM malignancy through ubiquitination-mediated degradation of RPL6 regardless of the p53 mutation status. It will provide new candidates for molecular biomarkers and therapeutic targets for clinical application in GBM.

NR2C2 of macrophages promotes inflammation via NF-κB in LPS-induced orchitis in mice.

In brief: Bacterial infection can induce testicular inflammation and damage male fertility. This paper reveals the role of nuclear receptor subfamily 2 group C member 2 (NR2C2) in macrophage cells in orchitis caused by bacterial endotoxin lipopolysaccharide (LPS) infection. Abstract: Bacterial infection and induced inflammation are important causes of male infertility. Here, we described the characteristics of expression and the regulatory role of NR2C2 in testicular inflammatory injury induced by infection with the bacterial endotoxin LPS. We found that NR2C2 was highly expressed in the testes and the expression of NR2C2 was upregulated in testicular macrophages in the LPS-induced mouse orchitis model in vivo. In primary testicular macrophages and RAW264.7 cells in vitro, RNA interference with the Nr2c2 gene downregulated the expression of inflammatory factors such as IL-1ß and IL-6. In addition, the knockdown of NR2C2 in macrophages alleviated the inhibitory effect of the inflammatory supernatant secreted by the macrophages on the proliferation of spermatogonia GC-1 SPG cells. Mechanistically, NR2C2 activated NF-κB signaling by binding with DR elements in the promotor of the Nfκb gene and promoted the development of inflammation. These data are the first to confirm that during LPS-induced bacterial infection, NR2C2 plays a proinflammatory role by activating IL-1ß and IL-6 via the NF-κB pathway in macrophages, consequently inhibiting the proliferation of spermatogonia and damaging the quality of sperm. Our findings reveal the important role of NR2C2 in testicular inflammatory injury induced via LPS and provide a new potential target and a molecular basis for the treatment of male infertility caused by bacterial infection.

Design, synthesis and biological evaluation of novel 3,4-dihydro-2H-[1,4]oxazino [2,3-f]quinazolin derivatives as EGFR-TKIs.

Starting with our previously reported work, a novel series of 3,4-dihydro-2H-[1,4]oxazino[2,3-f]quinazolin-derivatives were designed, synthesized and evaluated as potent EGFR tyrosine kinase inhibitors. All of the compounds showed significant inhibitory activities against EGFRwt kinase (IC50 ≤ 937.7 nM). Among them, compound 7j demonstrated the most potent inhibitory activity toward EGFRwt tyrosine kinase with IC50 value of 25.69 nM and showed good antiproliferative activities against NCI-H1563 and H1975 cells. The median cytotoxic concentration (CC50) showed that most of the tested compounds displayed almost no cytotoxicity in vitro against 16HBE cells. In view of the reported compounds activity, the structure deserves further optimization as cancer treatment agents.

Advances of nanomedicine in treatment of atherosclerosis and thrombosis.

Atherosclerosis (AS) is a chronic inflammatory vascular disease. Myocardial ischemia originated from AS is the main cause of cardiovascular diseases, one of the major factors contributing to the global disease burden. AS is typically quiescent until occurrence of plaque rupture and thrombosis, leading to acute coronary syndrome and sudden death. Currently, clinical diagnostic techniques suffer from major pitfalls including lack of accuracy and specificity, which makes it rather difficult for drugs to directly target plaques to achieve therapeutic effect. Therefore, how to accurately diagnose and effectively intervene vulnerable AS plaques to achieve accurate delivery of drugs has become an urgent and evolving clinical problem. With the rapid development of nanomedicine and nanomaterials, nanotechnology has shown unique advantages in monitoring vulnerable plaques and thrombus and improving drug efficacy. Recent studies have shown that application of nanoparticle drug delivery system can booster the safety and effectiveness of drug therapy, and molecular imaging technology and nanomedicine also exhibit high clinical application potentials in disease diagnosis. Therefore, nanotechnology provides another promising avenue for diagnosis and treatment of AS and thrombosis, and has shown excellent performance in the development of targeted drug therapy and biomaterials. In this review, the research progress, challenges and prospects of nanotechnology in AS and thrombosis are discussed, expecting to provide new ideas for the prevention, diagnosis and treatment of AS and thrombosis.

Nanoparticles in the New Era of Cardiovascular Therapeutics: Challenges and Opportunities.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Although a cadre of therapeutic strategies have been made available for CVDs in the clinical setting, predominantly through medication and surgery, these do not fully address the clinical needs of patients with CVD. As a new technique for CVD treatment, nanocarriers are employed to modify and package medications to ease the targeting of tissues, cells and molecules within the cardiovascular system. Nanocarriers are made of biomaterials, metals, or a combination of these materials, with sizes similar to bioactive molecules such as proteins and DNA. Cardiovascular nanomedicine (CVN) has only surfaced in recent years and is still in its infancy. Ample studies have displayed promise for the clinical utility of nanomedicine techniques, courtesy of continued perfection in nanocarrier design to optimize drug delivery and treatment outcomes. Here in this review, we will summarize the research advances in the literature on nanoparticles in the management of CVDs, including ischemic and coronary heart disease (e.g., atherosclerosis, angina pectoris and myocardial infarction), myocardial ischemia-reperfusion injury, aortic aneurysm, myocarditis, hypertension, and pulmonary artery hypertension and thrombosis.

CaMKII orchestrates endoplasmic reticulum stress and apoptosis in doxorubicin-induced cardiotoxicity by regulating the IRE1α/XBP1s pathway.

Doxorubicin (Dox), an anthracycline antibiotic with potent antitumor effects, has limited clinical applications due to cumulative cardiotoxicity. Ca2+ /calmodulin-dependent protein kinase II (CaMKII) is implicated in the pathological progression of Dox-induced cardiotoxicity. This study examined the hypothesis that CaMKII exacerbates Dox-induced cardiotoxicity by promoting endoplasmic reticulum stress and apoptosis through regulation of the inositol-requiring enzyme 1α (IRE1α)/spliced X-box binding protein 1 (XBP1s) pathway. Our results demonstrated that CaMKII activation and IRE1α/XBP1s pathway were involved in Dox-treated hearts. CaMKII inhibition with KN-93 ameliorated Dox-induced cardiac dysfunction and pathological myocardial changes. In addition, CaMKII inhibition prevented Dox-induced endoplasmic reticulum stress and apoptosis. Moreover, CaMKII inhibition increased the expression of IRE1α and XBP1s in Dox-treated hearts. The IRE1α inhibitor 4µ8C blocked the protective effect of CaMKII inhibition against Dox-induced cardiotoxicity. Mechanistically, 4µ8C prevented the effects of CaMKII inhibition on Dox-induced endoplasmic reticulum stress and apoptosis by inhibiting the expression of IRE1α and XBP1s. Additionally, treatment with rhADAMTS13 decreased the protein level of thrombospondin 1 (TSP1) and the phosphorylation of CaMKII in Dox-treated human AC16 cardiomyocytes. Taken together, these results demonstrate that the ADAMTS13-TSP1 axis regulates CaMKII activation and exacerbates Dox-induced cardiotoxicity by triggering endoplasmic reticulum stress and apoptosis by inhibiting the IRE1α/XBP1s pathway.

De novo and comparative transcriptomic analysis explain morphological differences in Panax notoginseng taproots.

BACKGROUND: Panax notoginseng (Burk.) F. H. Chen (PN) belonging to the genus Panax of family Araliaceae is widely used in traditional Chinese medicine to treat various diseases. PN taproot, as the most vital organ for the accumulation of bioactive components, presents a variable morphology (oval or long), even within the same environment. However, no related studies have yet explained the molecular mechanism of phenotypic differences. To investigate the cause of differences in the taproot phenotype, de novo and comparative transcriptomic analysis on PN taproot was performed. RESULTS: A total of 133,730,886 and 114,761,595 paired-end clean reads were obtained based on high-throughput sequencing from oval and long taproot samples, respectively. 121,955 unigenes with contig N50 = 1,774 bp were generated by using the de novo assembly transcriptome, 63,133 annotations were obtained with the BLAST. And then, 42 genes belong to class III peroxidase (PRX) gene family, 8 genes belong to L-Ascorbate peroxidase (APX) gene family, and 55 genes belong to a series of mitogen-activated protein kinase (MAPK) gene family were identified based on integrated annotation results. Differentially expressed genes analysis indicated substantial up-regulation of PnAPX3 and PnPRX45, which are related to reactive oxygen species metabolism, and the PnMPK3 gene, which is related to cell proliferation and plant root development, in long taproots compared with that in oval taproots. Furthermore, the determination results of real-time quantitative PCR, enzyme activity, and H2O2 content verified transcriptomic analysis results. CONCLUSION: These results collectively demonstrate that reactive oxygen species (ROS) metabolism and the PnMPK3 gene may play vital roles in regulating the taproot phenotype of PN. This study provides further insights into the genetic mechanisms of phenotypic differences in other species of the genus Panax.

Pontibacter qinzhouensis sp. nov., isolated from rhizosphere soil of a mangrove plant Rhizophora stylosa.

A novel bacterium of the genus Pontibacter, designated GY10130T, was isolated from rhizosphere soil of a mangrove plant Rhizophora stylosa collected from Guangxi province, China. Strain GY10130T was Gram-stain negative, positive for oxidase activities, aerobic, short rod-shaped cells without flagella. Growth was observed at 10-40 °C (optimum, 28 °C), pH 6.0-9.0 (optimum, 7.0) and NaCl concentrations of 0-4% (optimum, 1%). Strain GY10130T is closely related to members of the genus Pontibacter, namely P. beigongshangensis CGMCC 1.17104T (97.8%) and P. amylolyticus CGMCC 1.12749T (95.0%), P. humi SWU8T (94.7%), and less than 94.0% with other currently described type strains of Pontibacter. The strain GY10130T showed an ANI value of 80.6% and dDDH value of 23.2% with P. beigongshangensis CGMCC 1.17104T, followed by P. amylolyticus CGMCC 1.12749T with ANI and dDDH values of 72.9 and 13.8%, respectively. Strain GY10130T contains carotenoid-like pigments, but flexirubin-type pigments were absent. The cellular fatty acids (> 10%) consist of summed feature 4 (17:1 iso I/anteiso B) and iso-C15:0. The predominant menaquinone is MK-7. The polar lipids comprise phosphatidylethanolamine, two unidentified glycolipids, two unidentified aminolipids and six unidentified phospholipids. The genome length of strain GY10130T was 6.2 Mbp with a DNA G + C content of 47.1 mol% and 4727 protein-coding genes. The result of polyphasic taxonomic study show strain GY10130T represents one novel species of Pontibacter, Pontibacter qinzhouensis sp. nov., with the type strain GY10130T (=NBRC 113901T = CGMCC 1.16772T).

Metabacillus kandeliae sp. nov., isolated from the rhizosphere soil of a decayed mangrove plant Kandelia candel.

In this study, we isolated a novel Gram-stain-positive, aerobic, motile, rod-shaped bacterium, named GX 13764T, from the rhizosphere soil of a decayed mangrove plant Kandelia candel collected from Beihai, Guangxi, PR China, and characterized using a polyphasic taxonomic approach. The strain exhibited yellow-orange, round, convex, shiny, smooth, opaque and 2-3 mm diameter colonies on marine agar 2216 media after 3 days of incubation at 30 °C and was capable of growth at 4-45 °C (optimum, 30 °C), pH 5.0-9.0 (optimum, pH 7.0) and 0-4 % NaCl (w/v; optimum, 2 %). The strain was positive for catalase and negative for the oxidase. The main cellular fatty acid was anteiso-C15:0, iso-C15:0, iso-C16:0 and iso-C14:0. The cell-wall peptidoglycan comprised meso-diaminopimelic acid and the main menaquinone was MK-7. The polar lipids included one diphosphatidylglycerol, one phosphatidylglycerol, two glycolipids, two unidentified phospholipids and three unidentified lipids. Based on 16S rRNA gene analysis, GX 13764T presented the highest sequence similarity to Metabacillus mangrovi KCTC 33872T (97.04 %). The DNA G+C content of the type strain was 44.2 mol%. The average nucleotide identity values between GX 13764T and M. mangrovi KCTC 33872T, Metabacillus idriensis DSM 19097T and Metabacillus indicus LMG 22858T were 69.39, 68.87 and 68.95 %, respectively, with digital DNA-DNA hybridization values of 19.9, 19.5 and 19.5 %, respectively. Based on the polyphasic data, strain GX 13764T should be nominated as a novel species of the genus Metabacillus, for which the name Metabacillus kandeliae sp. nov. is proposed. The type strain is GX 13764T (=MCCC 1K06654T=KCTC 43366T).

Bacillus pinisoli sp. nov., Isolated from Soil of a Decayed Pine Tree.

A Gram-stain-positive, rod-shaped, facultatively anaerobic, motile and spore-forming bacterium with multiple flagella designated GXH0341T was isolated from the soil associated with decayed pine tree samples collected from Weizhou Island, Beihai, Guangxi, China. Growth occurred at 4-37 °C (optimum 30 °C), at pH 5.0-11.0 (optimum 8.0) and in the presence of 0-7% (w/v) NaCl (optimum 2%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain GXH0341T was most closely related to Bacillus mesophilus DSM 101000 T (98.9%), followed by Bacillus salitolerans KC1T (96.95%) and Margalitia shackletonii DSM 18435 T (96.67%). Phylogenetic analysis revealed that strain GXH0341T represented a separate lineage within the genus Bacillus. Peroxidase is positive. The predominant quinone was MK-7 and the cell-wall diagnostic diamino acid was meso-diaminopimelic acid. The predominant polar lipids are diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, and two unidentified phospholipids. The major fatty acids are iso-C14:0, iso-C15:0, anteiso-C15:0 and iso-C16:0. The genome of GXH0341T comprises the biosynthetic gene cluster for T3PKS, terpene, lassopeptide and RRE-containing element as secondary metabolites. The average nucleotide identity values and the digital DNA-DNA hybridization values between GXH0341T and B. mesophilus DSM 101000 T were 78.22% and 21.00%, respectively, which were in the range of the recommended level for interspecies identity. The results of phenotypic, chemotaxonomic and genotypic analyses clearly indicated strain GXH0341T represents a novel species of the genus Bacillus, for which the name Bacillus pinisoli sp. nov. is proposed. The type strain is GXH0341T (= MCCC 1K07157T = JCM 35212 T).

Cardioprotective effects of melatonin against myocardial ischaemia/reperfusion injury: Activation of AMPK/Nrf2 pathway.

Although reperfusion is the most effective therapy for patients with acute myocardial infarction, reperfusion injury limits the therapeutic effects of early reperfusion. Oxidative stress plays a crucial role in myocardial ischaemia/reperfusion (I/R) injury. Melatonin, a circulating hormone, is well-known as an antioxidant in cardiovascular diseases. In this short communication, we show that melatonin significantly improves post-ischaemic cardiac function, reduces infarct size and decreases oxidative stress. Furthermore, melatonin markedly increases AMPK activation and Nrf2 nuclear translocation. Nevertheless, these melatonin-induced changes are abrogated by compound C. In addition, ML-385, an Nrf2 inhibitor, also withdraws the antioxidative effects of melatonin but has little effect on AMPK activation. In conclusion, our results demonstrate that melatonin alleviates myocardial I/R injury by inhibiting oxidative stress via the AMPK/Nrf2 signalling pathway.

Flavimobilis rhizosphaerae sp. nov., isolated from rhizosphere soil of Spartina alterniflora.

A novel Gram-stain positive, facultatively anaerobic, motile, irregularly rod-shaped bacterium, designated GY 10621T, was isolated from rhizosphere soil of Spartina alterniflora in Beihai City, Guangxi Province, PR China, and characterized using a polyphasic taxonomic approach. GY 10621T was positive for catalase and oxidase. Growth occurred at 4-42 °C (optimum 30-37 °C), at pH 5.0-9.0 (optimum pH 7.0) and in the presence of 0-5% NaCl (w/v) (optimum 1-3%). The main menaquinones were MK-9 (H4) (92.2 %) and MK-10 (7.8 %). The major cellular fatty acids were anteiso-C15 : 0 and C14 : 0. The peptidoglycan was the type A4α (l-Lys-Ser-d-Glu). The polar lipids included four phosphoglycolipids, four glycolipids, an unidentified lipid and six unidentified phospholipids. The DNA G+C content of the type strain was 71.7 mol%. On the basis of the results of 16S rRNA gene analysis, the type strain of a species with a validly published name with the highest similarity to GY 10621T was Flavimobilis soli KCTC 13155T (97.16 %), followed by Sanguibacter suarezii NBRC 16159T (96.39 %). The calculated results indicated that compared with GY 10621T, the average nucleotide identity (ANI) values of three strains closely related to GY 10621T (the two aforementioned type strains and 'S. massiliensis' Marseille-P3815) were 74.18-94.97 %, and the digital DNA-DNA hybridization (dDDH) values were 20.3-60.6 %. The results of 16S rRNA-based and genome-based phylogenetic tree analysis indicated that GY 10621T should be assigned to the genus Flavimobilis. On the basis of evidence from polyphasic studies, GY 10621T should be designated as representing a novel species of the genus Flavimobilis, for which the name Flavimobilis rhizosphaerae sp. nov. is proposed. The type strain is GY 10621T (=CGMCC 1.17411T=KCTC 49515T).