Effects of light qualities on growth and physiological-biochemical traits of Scutellaria baicalensis.

Canopy spectral composition significantly affects growth and functional traits of understory plants. In this study, we explored the optimal light condition suitable for enhancing Scutellaria baicalensis's yield and quality, aiming to provide scientific reference for the exploitation and utilization of medicinal plant resources in the understory of forests. We measured the responses of growth, morphology, biomass allocation, physiological traits, and secon-dary metabolites of S. baicalensis to different light qualities. S. baicalensis was cultured under five LED-light treatments including full spectrum light (control), ultraviolet-A (UV-A) radiation, blue, green, and red light. Results showed that UV-A significantly reduced plant height, base diameter, leaf thickness, leaf area ratio, and biomass of each organ. Red light significantly reduced base diameter, biomass, effective quantum yield of photosystem Ⅱ (ФPSⅡ), and total flavonoid concentration. Under blue light, root length and total biomass of S. baicalensis significantly increased by 48.0% and 10.8%, respectively, while leaf number and chlorophyll content significantly decreased by 20.0% and 31.6%, respectively. The other physiological and biochemical traits were consistent with their responses in control. Our results suggested that blue light promoted photosynthesis, biomass accumulation, and secondary metabolite synthesis of S. baicalensis, while red light and UV-A radiation negatively affected physiological and biochemical metabolic processes. Therefore, the ratio of blue light could be appropriately increased to improve the yield and quality of S. baicalensis.

Modeling alternative translation initiation sites in plants reveals evolutionarily conserved cis-regulatory codes in eukaryotes.

mRNA translation relies on identifying translation initiation sites (TISs) in mRNAs. Alternative TISs are prevalent across plant transcriptomes, but the mechanisms for their recognition are unclear. Using ribosome profiling and machine learning, we developed models for predicting alternative TISs in the tomato (Solanum lycopersicum). Distinct feature sets were predictive of AUG and nonAUG TISs in 5' untranslated regions and coding sequences, including a novel CU-rich sequence that promoted plant TIS activity, a translational enhancer found across dicots and monocots, and humans and viruses. Our results elucidate the mechanistic and evolutionary basis of TIS recognition, whereby cis-regulatory RNA signatures affect start site selection. The TIS prediction model provides global estimates of TISs to discover neglected protein-coding genes across plant genomes. The prevalence of cis-regulatory signatures across plant species, humans, and viruses suggests their broad and critical roles in reprogramming the translational landscape.

Licochalcone A Induces Ferroptosis in Hepatocellular Carcinoma via Reactive Oxygen Species Activated by the SLC7A11/GPX4 Pathway.

Liver cancer is a common malignant tumor, and its incidence is increasing yearly. Millions of people suffer from liver cancer annually, which has a serious impact on global public health security. Licochalcone A (Lico A), an important component of the traditional Chinese herb licorice, is a natural small molecule drug with multiple pharmacological activities. In this study, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma cell lines (HepG2 and Huh-7), and explored the inhibitory mechanism of Lico A on hepatocellular carcinoma. First, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma, and showed that Lico A significantly inhibited and killed HepG2 and Huh-7 cells in vivo and in vitro. Transcriptomic analysis showed that Lico A inhibited the expression of solute carrier family 7 member 11 (SLC7A11), which induced ferroptosis. We confirmed through in vivo and in vitro experiments that Lico A promoted ferroptosis in hepatocellular carcinoma cells by downregulating SLC7A11 expression, thereby inhibiting the glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway and inducing activation of reactive oxygen species (ROS). In this study, we suggest that Lico A is a potential SLC7A11 inhibitor that induces ferroptotic death in hepatocellular carcinoma cells, thereby providing a theoretical basis for the development of natural small molecule drugs against hepatocellular carcinoma.

A systematic review and network meta-analysis comparing various non-pharmacological treatments for older people with mild cognitive impairment.

BACKGROUND AND OBJECTIVE: Non-pharmacological therapy appeared to alleviate Mild Cognitive Impairment (MCI) symptoms and signs, according to systematic studies. This network meta-analysis aimed to assess the impact of non-pharmacological therapies on improving cognition in individuals with MCI and identified the most effective intervention. METHODS: We reviewed six databases in search of potentially relevant studies of non-pharmacological therapies such as Physical exercise (PE), Multidisciplinary intervention (MI), Musical therapy (MT), Cognitive training (CT), Cognitive stimulation (CS), Cognitive rehabilitation (CR)，Art therapy (AT), general psychotherapy or interpersonal therapy (IPT), and Traditional Chinese Medicine (TCM) (such as acupuncture therapy, massage, auricular-plaster and other related systems) and others. Excluded the literature such as missing full text, missing search results, or no reporting specific values and combined with the inclusion criteria and exclusion criteria in this article, the literature ultimately included in the analysis addressed the following seven non-drug therapies PE, MI, MT, CT, CS, CR, AT. Mini-mental state evaluation paired meta-analyses were undertaken by taking weighted average mean differences with confidence intervals (CI) of 95%. The network meta-analysis was conducted to compare various therapies. RESULTS: A total of 39 randomized controlled trials, including two three-arm studies, with 3157 participants were included. PE was most likely to be the most effective intervention to slow down the cognitive ability of patients (SMD = 1.34, 95%CI: 0.80, 1.89). CS and CR had no significant effect on cognitive ability. CONCLUSIONS: The non-pharmacological therapy had the potential to greatly promote the cognitive ability of the adult population with MCI. PE had the best chance of being the best non-pharmacological therapy. Due to the limited sample size, substantial variability among different study designs, and the potential for bias, the results should be regarded with caution. Our findings should be confirmed by future multi-center randomized controlled, high-quality large-scale studies.

Comparison of protective effects of alprostadil with Salvia miltiorrhiza against myocardial ischemia-reperfusion injury in rats.

OBJECTIVES: Our study aimed to investigate the effects of alprostadil and Salvia miltiorrhiza extract on myocardial ischemia-reperfusion injury (IRI) and related underlying molecular mechanisms. METHODS: A myocardial IRI model was established in Wistar rats via surgical ligation of the left anterior descending coronary artery followed by loosening of the occlusion. The rats were divided into four groups: saline, sham, alprostadil, and S. miltiorrhiza. Rats in the saline and sham groups were injected with normal saline by tail vein once daily for 10 consecutive days. Rats in the S. miltiorrhiza and alprostadil groups were injected with S. miltiorrhiza extract (20 µg/kg) or alprostadil. Histological differences in myocardial tissues between rats in the sham group and in the myocardial IRI model were observed by hematoxylin and eosin staining. India ink perfusion was used to quantify the number of capillary microvessels. Real-time quantitative reverse transcription polymerase chain reaction was used to determine serum expression levels of soluble intercellular adhesion molecule (sICAM), soluble vascular adhesion molecule (sVCAM), CD11b and CD18. RESULTS: The alprostadil and S. miltiorrhiza groups had significantly higher numbers of microvessels than the saline group. Serum sICAM and sVCAM expression was significantly reduced in the alprostadil and S. miltiorrhiza groups. Meanwhile, sICAM and sVCAM in the alprostadil group were markedly lower than in the S. miltiorrhiza group. Moreover, the alprostadil group had markedly lower mRNA expression of CD11b and CD18, which were clearly lower than in the S. miltiorrhiza group. CONCLUSION: Alprostadil may have cardioprotective effects for myocardial IRI, with down-regulated expression of sICAM, sVCAM, CD11b, and CD18.

[Analysis and Treatment Experience of 25 Cases of Primary Gastric Lymphoma with Acute Upper Gastrointestinal Bleeding as the Primary Manifestation].

Objective: To summarize the clinical characteristics and treatment experience of gastric primary lymphoma with acute upper gastrointestinal bleeding as the primary manifestation, and to provide support for clinical treatment. Methods: Information on gastric primary lymphoma patients admitted to the Department of Gastroenterology, West China Hospital of Sichuan University between January 2010 and March 2021 for acute upper gastrointestinal bleeding was retrospectively collected. Data on endoscopic morphology, tumor staging, pathology typing, severity of bleeding, risks of rebleeding, treatment and inhospital prognosis were documented and analyzed. Results: A total of 25 patients with a mean age of 57.2 years were included in the study, all of whom presented clinically with melena (100%), 9 (36%) had hematemesis, and 6 (24%) was accompanied with abdominal pain. Twenty, or 80%, of the gastric lymphoma patients with bleeding as the primary manifestation showed endoscopically a tumor-forming phenotype (Yao Classification), mostly involving the middle and lower parts of the gastric body (44% and 32%, respectively). After conservative treatment with medication, rebleeding occurred in 4 patients during hospitalization. One of them required endoscopic hemostasis, two required surgical resection to stop the bleeding, and one decided not to undergo any further treatment. Only one patient died from infection and no death resulted directly from severe bleeding. Conclusion: Gastric primary lymphoma presenting acute upper gastrointestinal bleeding as the sole clinical manifestation rarely occurs, but when the condition does occur, it shows a wide range of endoscopic involvement. It has a higher risk of rebleeding, and endoscopic or surgical treatment may be attempted when conservative medication treatment for acute upper gastrointestinal bleeding fails.

Translation initiation landscape profiling reveals hidden open-reading frames required for the pathogenesis of tomato yellow leaf curl Thailand virus.

Plant viruses with densely packed genomes employ noncanonical translational strategies to increase the coding capacity for viral function. However, the diverse translational strategies used make it challenging to define the full set of viral genes. Here, using tomato yellow leaf curl Thailand virus (TYLCTHV, genus Begomovirus) as a model system, we identified genes beyond the annotated gene sets by experimentally profiling in vivo translation initiation sites (TISs). We found that unanticipated AUG TISs were prevalent and determined that their usage involves alternative transcriptional and/or translational start sites and is associated with flanking mRNA sequences. Specifically, two downstream in-frame TISs were identified in the viral gene AV2. These TISs were conserved in the begomovirus lineage and led to the translation of different protein isoforms localized to cytoplasmic puncta and at the cell periphery, respectively. In addition, we found translational evidence of an unexplored gene, BV2. BV2 is conserved among TYLCTHV isolates and localizes to the endoplasmic reticulum and plasmodesmata. Mutations of AV2 isoforms and BV2 significantly attenuated disease symptoms in tomato (Solanum lycopersicum). In conclusion, our study pinpointing in vivo TISs untangles the coding complexity of a plant viral genome and, more importantly, illustrates the biological significance of the hidden open-reading frames encoding viral factors for pathogenicity.

Disrupting cannabinoid receptor interacting protein 1 rescues cognitive flexibility in long-term estrogen-deprived female mice.

Hormone therapy (HT) has failed to improve learning and memory in postmenopausal women according to recent clinical studies; however, the reason for failure of HT in improving cognitive performance is unknown. In our research, we found cognitive flexibility was improved by 17ß-Estradiol (E2) in mice 1 week after ovariectomy (OVXST), but not in mice 3 months after ovariectomy (OVXLT). Isobaric tags for relative and absolute quantitation (iTRAQ) revealed increased cannabinoid receptor interacting protein 1 (CNRIP1) in E2-treated OVXLT mice compared with E2-treated OVXST mice. Adeno-associated virus 2/9 (AAV2/9) delivery of Cnrip1 short-hairpin small interfering RNA (Cnrip1-shRNA) rescued the impaired cognitive flexibility in E2 treated OVXLT mice. This effect is dependent on CB1 function, which could be blocked by AM251-a CB1 antagonist. Our results indicated a new method to increasing cognitive flexibility in women receiving HT by disrupting CNRIP1.

Prevalence of alternative AUG and non-AUG translation initiators and their regulatory effects across plants.

Translation initiation is a key step determining protein synthesis. Studies have uncovered a number of alternative translation initiation sites (TISs) in mammalian mRNAs and showed their roles in reshaping the proteome. However, the extent to which alternative TISs affect gene expression across plants remains largely unclear. Here, by profiling initiating ribosome positions, we globally identified in vivo TISs in tomato and Arabidopsis and found thousands of genes with more than one TIS. Of the identified TISs, >19% and >20% were located at unannotated AUG and non-AUG sites, respectively. CUG and ACG were the most frequently observed codons at non-AUG TISs, a phenomenon also found in mammals. In addition, although alternative TISs were usually found in both orthologous genes, the TIS sequences were not conserved, suggesting the conservation of alternative initiation mechanisms but flexibility in using TISs. Unlike upstream AUG TISs, the presence of upstream non-AUG TISs was not correlated with the translational repression of main open reading frames, a pattern observed across plants. Also, the generation of proteins with diverse N-terminal regions through the use of alternative TISs contributes to differential subcellular localization, as mutating alternative TISs resulted in the loss of organelle localization. Our findings uncovered the hidden coding potential of plant genomes and, importantly, the constraint and flexibility of translational initiation mechanisms in the regulation of gene expression across plant species.

[Efficacy of Transcatheter Embolization for Gastrointestinal Stromal Tumor with Gastrointestinal Hemorrhage in 17 Cases].

OBJECTIVE: To evaluate the clinical efficacy of transcatheter embolization for patients with gastrointestinal stromal tumor and gastrointestinal hemorrhage. METHODS: From June 2006 to June 2019, 17 patients with gastrointestinal stromal tumor and who were gastrointestinal bleeding treated with transcatheter embolization due to gastrointestinal hemorrhage in our hospital were included in this study. The technical and clinical success rates and clinical success rate were analyzed retrospectively. RESULTS: Among 17 patients who underwent angiography before embolotherapy, 5 patients (29.4%) showed tumor staining and contrast extravasation, 9 patients (52.9%) showed tumor staining but no significant contrast extravasation, and 3 patients (17.6%) were negative. 14 patients had with positive angiographic findings and then underwent transcatheter embolization. Technical success was achieved in 13 patients (76.5%). Of the 13 technically successful patients, 12 patients (70.6%) achieved clinical success, one patient (5.9%) suffered from repeated gastrointestinal bleeding, which was improved after conservative treatment. No embolization-related complication occurred. The 30-day mortality rate was 0%. CONCLUSION: Transcatheter embolization for gastrointestinal stromal tumor with gastrointestinal hemorrhage is a safe and effective minimally invasive technique.

Regulatory cascade involving transcriptional and N-end rule pathways in rice under submergence.

The rice SUB1A-1 gene, which encodes a group VII ethylene response factor (ERFVII), plays a pivotal role in rice survival under flooding stress, as well as other abiotic stresses. In Arabidopsis, five ERFVII factors play roles in regulating hypoxic responses. A characteristic feature of Arabidopsis ERFVIIs is a destabilizing N terminus, which functions as an N-degron that targets them for degradation via the oxygen-dependent N-end rule pathway of proteolysis, but permits their stabilization during hypoxia for hypoxia-responsive signaling. Despite having the canonical N-degron sequence, SUB1A-1 is not under N-end rule regulation, suggesting a distinct hypoxia signaling pathway in rice during submergence. Herein we show that two other rice ERFVIIs gene, ERF66 and ERF67, are directly transcriptionally up-regulated by SUB1A-1 under submergence. In contrast to SUB1A-1, ERF66 and ERF67 are substrates of the N-end rule pathway that are stabilized under hypoxia and may be responsible for triggering a stronger transcriptional response to promote submergence survival. In support of this, overexpression of ERF66 or ERF67 leads to activation of anaerobic survival genes and enhanced submergence tolerance. Furthermore, by using structural and protein-interaction analyses, we show that the C terminus of SUB1A-1 prevents its degradation via the N-end rule and directly interacts with the SUB1A-1 N terminus, which may explain the enhanced stability of SUB1A-1 despite bearing an N-degron sequence. In summary, our results suggest that SUB1A-1, ERF66, and ERF67 form a regulatory cascade involving transcriptional and N-end rule control, which allows rice to distinguish flooding from other SUB1A-1-regulated stresses.

Mitochondrial Ferritin Is a Hypoxia-Inducible Factor 1α-Inducible Gene That Protects from Hypoxia-Induced Cell Death in Brain.

Aims: Mitochondrial ferritin (protein [FtMt]) is preferentially expressed in cell types of high metabolic activity and oxygen consumption, which is consistent with its role of sequestering iron and preventing oxygen-derived redox damage. As of yet, the mechanisms of FtMt regulation and the protection FtMt affords remain largely unknown. Results: Here, we report that hypoxia-inducible factor 1α (HIF-1α) can upregulate FtMt expression. We verify one functional hypoxia-response element (HRE) in the positive regulatory region and two HREs possessing HIF-1α binding activity in the minimal promoter region of the human FTMT gene. We also demonstrate that FtMt can alleviate hypoxia-induced brain cell death by sequestering uncommitted iron, whose levels increase with hypoxia in these cells. Innovation: In the absence of FtMt, this catalytic metal excess catalyzes the production of cytotoxic reactive oxygen species. Conclusion: Thus, the cell ability to increase expression of FtMt during hypoxia may be a skill to avoid tissue damage derived from oxygen limitation.

[Effect of Lentiviral Vector-Mediated CXCR4 Gene Overexpression on Mesenchymal Stem Cell Homing Capacity].

OBJECTIVE: To explore the effects of lentiviral-mediated CXC chemokine receptor-4（CXCR-4）gene over-expression on the homing capacity of mesenchymal stem cells（MSC）in vivo. METHODS: The MSC overexpressing CXCR-4 were constructed by using the lentiviral vector-mediated mouse MSC overexpressing the CXCR-4 gene. The BALB/c mice were divided into 3 group: simple radiation group（TBI）in which mice exposed to total body irradiation, then were infused with normal saline; EGFP-MSC group in which mice were infused with MSC（5×105）transducted by EGFP via tail vein after TBI; and CXCR-4-MSC group in which mice were infused with MSC (5×105) simultaneously carraying EGFP and CXCR-4 gene via tail vein after TBI. The mice were sacrified at 24 hours after infusion, the frozen sections were prepared to detect the distribution of infused MSC. Furthermore, the numbers of MSC homing into spleen and bone marrow was detected by flow cytometry, and the level of stromal cell-derived factor-1(SDF-1) was detected by ELISA. RESULTS: The frozen section showed that the CXCR-4 over-expression could significantly enhance the efficacy of MSC homing into lung, liver and spleen; the flow cytonetry detection slowed that the number of over-expressed CXCR-4 MSC homing into spleen and bone matrow was sigmificantly higher than that in EGFP-MSC group（P<0.05）, the ELISA showed that the SDF-1 level in peripheral blood and bone marrow after 24 hours of irradiation significantly incrtaoed （P<0.05）, moreover, the SDF-1 level increase was associcted with horming efficacy of MSC with CXCR-4 overexpression. CONCLUSION: overexpression CXCR-4 gene mediated by lentiviral vector can prmote the efficacy of MSC homing into spleen and bone marrow.

Synthesis and Antimicrobial Evaluation of (Z)-5-((3-phenyl-1H-pyrazol-4- yl)methylene)-2-thioxothiazolidin-4-one Derivatives.

BACKGROUND: An alarming increment in pathogenic resistance to existing anti-microbial agents is a serious problem and the treatment of these bacterial infections is becoming increasingly challenging. Therefore, there is an urgent need to develop novel antimicrobial agents. OBJECTIVE: As a part of our ongoing studies toward the development of novel antibacterial agents, the synthesis and antibacterial activity of a series of (Z)-5-((3-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one derivatives will be discussed in this study. METHOD: (Z)-5-((3-phenyl-1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one derivatives were designed, synthesized and evaluated for antibacterial activity. The structures were confirmed by IR, 1H NMR, 13C NMR and mass spectrometry. All of the synthesized compounds were evaluated in vitro using a 96-well microtiter plate and a serial dilution method to obtain their minimum inhibitory concentration (MIC) values against a variety of different strains, including multidrug-resistant clinical isolates. RESULTS: The antibacterial test in-vitro showed that most compounds in series 7 and 9 exhibited significant inhibitory activities against anaerobic bacteria (Streptococcus mutans) strains with a MIC value of 1 µg/mL. Compounds 7c and 9c showed the most potent activity against MRSA (3167 and 3506) with a minimum inhibitory concentration (MIC) value of 1 µg/mL, which is equivalent to moxifloxacin and greater than gatifloxacin, oxacillin and norfloxacin. Additionally, compound 9c showed potent antibacterial activity against Bacillus subtilis (aerobic bacteria) with a MIC value of 2 µg/mL. CONCLUSION: The work suggests that these type of rhodanine compounds had a better potent activity against MRSA compared with other perviously reported rhodanine derivatives, which might provide a valuable information for the development of new antibacterial agents against multidrug-resistant clinical isolates MRSA.

Association of short-term exposure to fine particulate matter and nitrogen dioxide with acute cardiovascular effects.

This study evaluated whether exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) is associated with cardiovascular effects by examining a panel of 89 healthy subjects in Taipei, Taiwan. The subjects received two health examinations approximately 8months apart in 2013. Brachial-ankle pulse wave velocity (baPWV), a physiological indicator of arterial stiffness, and high-sensitivity C-reactive protein (hsCRP), a biomarker of vascular inflammations, were measured during each examination. Two exposure assessment methods were used for estimating the subjects' exposure to PM2.5 and NO2. The first method involved constructing daily land use regression (LUR) models according to measurements collected at ambient air quality monitoring stations. The second method required combining the LUR estimates with indoor monitoring data at the workplace of the subjects. Linear mixed models were used to examine the association between the exposure estimates and health outcomes. The results showed that a 10-µg/m(3) increase in PM2.5 concentration at a 1-day lag was associated with 2.1% (95% confidence interval: 0.7%-3.6%) and 2.4% (0.8%-4.0%) increases in baPWV based on the two exposure assessment methods, whereas no significant association was observed for NO2. The significant effects of PM2.5 remained in the two-pollutant models. By contrast, NO2, but not PM2.5, was significantly associated with increased hsCRP levels (16.0%-37.3% in single-pollutant models and 26.4%-44.6% in two-pollutant models, per 10-ppb increase in NO2). In conclusion, arterial stiffness might be more sensitive to short-term PM2.5 exposure than is inflammation.

Association of urban particle numbers and sources with lung function among children with asthma or allergies.

Previous studies have reported sources of particle number pollution in urban air, but have not evaluated relationships between respiratory health and these sources. We compared, among children with asthma or allergies, the associations of spirometric lung functions with increased exposure to source-specific versus size-segregated particle number concentrations (PNC). Hourly measurements of PNC were acquired from the aerosol Supersite in New Taipei, Taiwan. Spirometry (FVC, FEV1, and FEF) was recorded monthly for 59 children with asthma or allergies at five schools during 2007-2008. After co-pollutant adjustment for ozone, we found a 0.21 and 0.17 L decrease in FVC [95% confidence interval (CI): -0.35, -0.06 L] and FEV1 (95% CI: -0.32, -0.03 L), respectively, with an interquartile range increase (1879.7#/cm(3)) in secondary aerosol contribution observed on the previous day. In addition, we found no significant associations of FVC with accumulation mode (0.1 µm

Synthesis and biological evaluation of 1,3-diaryl pyrazole derivatives as potential antibacterial and anti-inflammatory agents.

Three series of 1,3-diaryl pyrazole derivatives bearing aminoguanidine or furan-2-carbohydrazide moieties have been synthesized, characterized and evaluated for antibacterial and anti-inflammatory activities. Most of the synthesized compounds showed potent inhibition of several Gram-positive bacterial strains (including multidrug-resistant clinical isolates) and Gram-negative bacterial strains with minimum inhibitory concentration values in the range of 1-64 µg/mL. Compounds 6g, 6l and 7l presented the most potent inhibitory activity against Gram-positive bacteria (e.g. Staphylococcus aureus 4220), Gram-negative bacteria (e.g. Escherichia coli 1924) and the fungus, Candida albicans 7535, with minimum inhibitory concentration values of 1 or 2 µg/mL. Compared with previous studies, these compounds exhibited a broad spectrum of inhibitory activity. Furthermore, compound 7l showed the greatest anti-inflammatory activity (93.59% inhibition, 30 min after intraperitoneal administration), which was more potent than the reference drugs ibuprofen and indomethacin.

[Qangxin Granule Intervened Chronic Heart Failure Rats with Xin-qi Deficiency Complicated Blood Stasis and Edema Syndrome: an Experimental Study].

OBJECTIVE: To study and evaluate the curative effect and mechanism of Qiangxin Granule (QXG) in intervening chronic heart failure (CHF) rats with Xin-qi deficiency complicated blood stasis and edema syndrome (XQD-BS-ES). METHODS: Totally 72 SD rats of clean grade were randomly divided to the normal control group (n =10) and the model group (n = 62). The XQD-BS-ES rat model was established by adriamycin plus propylthiouracil method. Survived modeled rats were then randomly divided to 5 groups i.e., the model group (n = 11, administered with normal saline by gastrogavage), the Western medicine (WM) group (n =11 , administered with perindopril and hydrochlorothiazide by gastrogavage), the low dose QXG (QXG(L)) group (n = 11, administered with 9.26 g/kg QXG by gastrogavage), the middle dose QXG (QXG(M)) group (n = 11, administered with 18.52 g/kg QXG by gastrogavage), the high dose QXG (QXG(H)) group (n = 11, administered with 37.04 g/kg QXG by gastrogavage). After 4 weeks of treatment, left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), brain natriuretic peptide (BNP), heart rate (HR), respiratory rate (RR), urine output, ear temperature, exhaustive swimming test (EST), tri-iodothyronine (T3), tetra-iodothyronine (T4), thyroid stimulating hormone (TSH), as well as heart, lung, liver weight index and their pathological sections, and high sensitivity C-reactive protein (HS-CRP), angiotensin II (Ang II), carbohydrate antigen 125 (CA125) were detected and compared. RESULTS: Compared with the normal control group, LVEF, LVFS, BNP, HR, RR, urine output, ear temperature, EST, T3, T4, TSH, HS-CRP, Ang II, and CA125 changed significantly in the model group (P < 0.01). Compared with the model group after treatment, LVEF, LVFS, BNP, urine output, EST, T4, heart and liver weight index, HS-CRP, Ang II, CA125 were significantly improved in each QXG group (P < 0.05, P < 0.01). Moreover, TSH was improved in the QXGL and QXG(M) groups (P < 0.05); ear temperature and T3 in the QXG(M) were also improved (P < 0.05); the lung weight index decreased in the QXG(M) and QXG(H) groups (P < 0.01). Compared with the WM group, T4 and CA125 were obviously improved in all QXG groups (P < 0.01); BNP and ear temperature were obviously improved in QXG(L) and QXG(M) groups (P < 0.05, P < 0.01); LVEF, LVFS and TSH were obviously improved in the QXG(M) group (P < 0.05, P < 0.01). And as far as each treatment group, LVEF, LVFS, urine output increased significantly after treatment (P < 0.01); EST obviously increased in QXG(M) and QXG(H) groups (P < 0.01); ear temperature increased in all QXG groups (P < 0.05, P < 0.01). Moreover, compared with the model group, pathological changes of heart, lung, and liver were improved to some degree in each treatment group, especially in the QXG(M) group. CONCLUSIONS: Good curative effect was shown in each QXG group. QXG could improve LVEF, LVFS and BNP of CHF rats of XQD-BS-ES, as well as T3, T4, TSH, EST, urine output, and ear temperature. Moreover, QXG showed superiority than WM group in this respect.

Synthesis and antimicrobial evaluation of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety.

Three series of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety (5a-k, 6a-i, and 7a-i) have been synthesized, characterized and evaluated for their antibacterial activity. Some of these displayed potent antibacterial activity against several Gram-positive and Gram-negative bacterial strains (including multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC) values in the range of 4-64 µg/mL and minimum bactericidal concentration (MBC) values in the range of 8-256 µg/mL. Compared with previously reported rhodanine derivatives, these compounds exhibited a broad spectrum of antibacterial activity by means of introducing 4-amino-5-aryl-1,2,4-triazole-3-thione moiety. Notably, compound 5f exhibited good antibacterial activity against Staphylococcus aureus RN 4220, S. aureus 209, S. aureus 503, Gram-negative bacteria (Escherichia coli 1924), and Candida albicans 7535 with MBC values of 8 or 16 µg/ml. All of the compounds synthesized in the current Letter were characterized by (1)H NMR, (13)C NMR, infrared and mass spectroscopy.