Photoactivated 9-methylacridine destroys midgut tissues of Aedes aegypti larvae by targeting ROS-mediated apoptosis in the mitochondrial pathway of midgut cells.

An aromatic ring-containing compound with a wide range of biological activities, 9-methylacridine (AD-9-Me) is a precursor for the synthesis of various drugs. However, its photoactivation properties and mechanism of damage as a photo activator against Aedes aegypti are unknown. The toxic effects of AD-9-Me on Aedes aegypti mosquitoes were determined under light and non-light conditions. The results showed that the toxicity of AD-9-Me to mosquito larvae was significantly higher than that of the dark treatment after 24 h of light exposure; AD-9-Me was mainly distributed in the midgut of larvae, after 24 h of treatment, it can cause an increase in calcium ion concentration, reactive oxygen species (ROS) eruption and ROS accumulation by blocking the ROS elimination pathway in midgut cells. This in turn caused an increase in protein carbonyl and malondialdehyde (MDA) content, a decrease in mitochondrial membrane potential (MMP), a disruption of the barrier function of midgut tissues, a significant decrease in midgut weight and chitin content, which induced the up-regulation of AeDronc, AeCaspase8 and AeCaspase7 genes, leading to apoptotic cell death. In this study, we confirmed that AD-9-Me has photoactivation activity and mainly acts on the midgut of mosquito larvae, which can generate a large amount of ROS in the cells of the midgut and induce apoptosis to occur, resulting in the disruption of the function of the tissues of mosquito larvae, accelerating the death and delaying the development of the mosquito larvae.

lncRNA-MIAT rs9625066 polymorphism could be a potential biomarker for ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a common and serious neurological condition that is highly fatal but so far no early diagnostic markers are available. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA) that could lead to IS by inducing autophagy and apoptosis in neuronal cells. However, there has been no report on the link between susceptibility to IS and the single-nucleotide polymorphisms (SNPs) of MIAT. This study aimed to investigate the association between MIAT gene polymorphisms and IS risk. METHODS: A total of 320 IS patients and 310 age-, sex- and race-matched controls were included in this study. Four polymorphisms (rs2157598, rs5761664, rs1894720, and rs9625066) were genotyped by using SNPscan technique. RESULTS: Among the 4 polymorphisms of MIAT, only rs9625066 was associated with IS risk (CA vs. CC: adjusted OR = 0.55, 95% CI, 0.37-0.85, P = 0.006; AA vs. CC: adjusted OR = 0.39, 95% CI, 0.16-0.94, P = 0.036; (AA + CA vs. CC: adjusted OR = 0.53, 95% CI, 0.35-0.80, P = 0.002; A vs. C adjusted OR = 0.59, 95% CI, 0.42-0.82, P = 0.002). Haplotype analysis showed a 1.32-fold increase (95% CI, 1.05-1.67, P = 0.017) in IS risk for rs2157598-rs5761664-rs1894720-rs9625066 (A-C-G-C). Logistic regression analysis identified some independent impact factors for IS including rs9625066 AA/AC, TC, TG, HDL-C (P < 0.05). CONCLUSION: The rs9625066 polymorphism of MIAT might be associated with IS susceptibility in Chinese population, in which AA/CA plays a protective role in IS, whereas the CC genotype increases the risk of developing IS, suggesting it might be a marker predictive of IS risk.

Association between miR-365 polymorphism and ischemic stroke in a Chinese population.

Background: Ischemic stroke (IS) represents a major cause of morbidity and mortality across the globe. The aberrant expression of miR-365 has been found to be implicated in a wide array of human diseases, including atherosclerosis and cancer. Studies on single-nucleotide polymorphisms (SNPs) in miRNA genes can help gain insight into the susceptibility to the condition. This study aimed to examine the relationship between miR-365 SNPs and the risk of IS. Methods: The study recruited 215 IS patients and 220 controls. The SNPscans genotyping was employed to genotype three polymorphic loci (rs121224, rs30230, and rs178553) of miR-365. The relative expression of miR-365 in peripheral blood mononuclear cells of the patients and controls was determined by using real-time quantitative PCR. Results: The miR-365 rs30230 polymorphism exhibited a significant association with the risk of developing IS (TC vs. CC: adjusted OR = 0.55, 95% CI: 0.33-0.92, P = 0.022; TT vs. CC: adjusted OR = 0.34, 95% CI: 0.14-0.85, P = 0.021; TC +TT vs. CC: adjusted OR = 0.51, 95% CI: 0.31-0.83, P = 0.007; T vs. C: adjusted OR = 0.57, 95% CI: 0.39-0.83, P = 0.004). Haplotype analysis revealed that the C-T-G haplotype was associated with a decreased risk of IS (OR = 0.68, 95% CI: 0.46-1.00, P = 0.047). Furthermore, miR-365 expression was significantly higher in IS patients than in controls (P < 0.001). Interestingly, patients with rs30230 TC or TT genotypes had lower miR-365 levels compared to their counterparts with CC genotypes (P < 0.001). Conclusions: The miR-365 rs30230 polymorphism might bear an association with IS susceptibility in the Chinese population, and the rs30230 TC/TT genotype might be a protective factor against IS.

Functional polymorphism in miR-208 is associated with increased risk for ischemic stroke.

BACKGROUND: The miR-208 gene is one of the microRNAs now under active studies, and has been found to play significant roles in an array of cardiovascular diseases. Nevertheless, until now, no studies have examined the relationship between the susceptibility to ischemic stroke (IS) and genetic variations in miR-208. This study explored the association between the miR-208 polymorphisms (rs178642, rs8022522, and rs12894524) and the risk of IS. METHODS: A total of 205 cases of IS and 211 control subjects were included. The SNPscans genotyping test was employed to determine the genotypes of the three polymorphisms. RESULTS: Significant correlation was observed between rs8022522 polymorphism and risk of IS on the basis of analyses of genotypes, models and alleles (GA vs. GG: adjusted OR = 2.159, 95% CI: 1.052-4.430, P = 0. 036; AA vs. GG: adjusted OR = 5.154, 95% CI: 1.123-23.660, P = 0.035; dominant model: adjusted OR = 1.746, 95% CI, 1.075-2.838, P = 0.025; G vs. A: adjusted OR = 2.451, 95% CI: 1.374-4.370, P = 0.002). CONCLUSIONS: The rs8022522 polymorphism of the miR-208 gene is significantly associated with an elevated risk of ischemic stroke in Chinese.

Comparison of the chronic and multigenerational toxicity of racemic glufosinate and l-glufosinate to Caenorhabditis elegans at environmental concentrations.

Glufosinate-ammonium, the second largest transgene crop resistant herbicide, is classified as a mobile persistent pollutant by the U.S. Environmental Protection Agencybecause of its slow decomposition and easy mobile transfer in a water environment. The chronic and multigeneration toxicity of this compound to environmental organisms are alarming. In this study, racemic glufosinate-ammonium and the effective isomer, l-glufosinate-ammonium, were used as the test agents. The developmental, neurotoxic and reproductive toxicities of Caenorhabditis elegans to their parents and progeny were studied by continuous exposure in water at concentrations of 0.1, 1, 10 and 100 µg/L. The causes of toxicity differences were analysed from oxidative stress and transcription levels. Through oxidative stress of C. elegans, racemic glufosinate-ammonium and l-glufosinate-ammonium both mediated the developmental toxicity (shortened developmental cycle, reduced body length and width, promoted ageingand decreased longevity), neurotoxicity (inhibited head swinging, body bending frequency and acetylcholinesterase [AchE] activity) and reproductive toxicity (significant reductions in the number of eggs and offspring in vivo and induced apoptosis of gonadal cells). These phenomena caused oxidative damage (protein and membrane lipid peroxidation) and further induced apoptosis. The changes in various indicators caused by racemic glufosinate-ammonium exposure were more significant than those caused by l-glufosinate-ammonium exposure, and the reproduction-related indicators were more significant than the developmental and neurological indicators. A continuous accumulation of toxicity was observed after multiple generations of continuous exposure. These research results provide a data reference for the ecotoxicological evaluation and risk assessment of glufosinate-ammonium and contribute to the revision and improvement of the related environmental policies of glufosinate-ammonium.

Potential Chemoprevention of Paeoniflorin in Colitis-Associated Colorectal Cancer by Network Pharmacology, Molecular Docking, and In Vivo Experiment.

Chronic inflammation plays a positive role in the development and progression of colitis-associated colorectal cancer (CAC). Medicinal plants and their extracts with anti-inflammatory and immunoregulatory properties may be an effective treatment and prevention strategy for CAC. This research aimed to explore the potential chemoprevention of paeoniflorin (PF) for CAC by network pharmacology, molecular docking technology, and in vivo experiments. The results showed that interleukin-6 (IL-6) is a key target of PF against CAC. In the CAC mouse model, PF increased the survival rate of mice and decreased the number and size of colon tumors. Moreover, reduced histological score of colitis and expression of Ki-67 and PCNA were observed in PF-treated mice. In addition, the chemoprevention mechanisms of PF in CAC may be associated with suppression of the IL-6/STAT3 signaling pathway and the IL-17 level. This research provides experimental evidence of potential chemoprevention strategies for CAC treatment.

[Effects of ketoconazole on physiological function of liver and testis in mice].

Objective: To investigate the effects of different doses of ketoconazole (KCZ) on the physiological functions of the liver and testis in Kunming mice. Methods: Forty male Kunming mice were randomly divided into four groups (n=10): normal group, KCZ low-dose group (30 mg/kg), medium-dose group (50 mg/kg), and high-dose group (70 mg/kg). The mice in the drug groups were injected subcutaneously (0.1 ml/10 g) with the corresponding dose of KCZ once a day, and the concentrations of KCZ in the KCZ low, middle, and high dose groups were 3 mg/ml, 5 mg/ml and 7 mg/ml respectively, and the normal group was injected with the same amount of normal saline for 3 weeks. The activities of aspartate transaminase (AST) and alanine aminotransferase (ALT) in serum, and γ-glutamyl transpeptidase (γ-GT), lactate dehydrogenase (LDH) and acid phosphatase (ACP) in testicular tissue were measured. HE staining was used to observe the pathological changes of the liver and testis. Results: Compared with the normal group, the activities of AST and ALT were increased significantly (P＜0.01), and the activities of γ-GT, ACP and LDH were decreased markedly in KCZ groups (P＜0.01). KCZ could affect the above indexes in a dose-dependent manner. HE staining showed that the hepatocytes were denatured, arranged loosely, and the cytoplasm was light in color. The lumen of the seminiferous tubules of the testis were enlarged, and the number of spermatogenic cells and sperm at all levels were decreased. Conclusion: KCZ could cause physiological function damage and pathological histological changes of the liver and testis, increase the levels of liver transaminase, reduce the activities of testicular specific enzymes of mice. Besides, the degree of damage was increased with the increase of dose.

Continual Decline in Azole Susceptibility Rates in Candida tropicalis Over a 9-Year Period in China.

BACKGROUND: There have been reports of increasing azole resistance in Candida tropicalis, especially in the Asia-Pacific region. Here we report on the epidemiology and antifungal susceptibility of C. tropicalis causing invasive candidiasis in China, from a 9-year surveillance study. METHODS: From August 2009 to July 2018, C. tropicalis isolates (n = 3702) were collected from 87 hospitals across China. Species identification was carried out by mass spectrometry or rDNA sequencing. Antifungal susceptibility was determined by Clinical and Laboratory Standards Institute disk diffusion (CHIF-NET10-14, n = 1510) or Sensititre YeastOne (CHIF-NET15-18, n = 2192) methods. RESULTS: Overall, 22.2% (823/3702) of the isolates were resistant to fluconazole, with 90.4% (744/823) being cross-resistant to voriconazole. In addition, 16.9 (370/2192) and 71.7% (1572/2192) of the isolates were of non-wild-type phenotype to itraconazole and posaconazole, respectively. Over the 9 years of surveillance, the fluconazole resistance rate continued to increase, rising from 5.7 (7/122) to 31.8% (236/741), while that for voriconazole was almost the same, rising from 5.7 (7/122) to 29.1% (216/741), with no significant statistical differences across the geographic regions. However, significant difference in fluconazole resistance rate was noted between isolates cultured from blood (27.2%, 489/1799) and those from non-blood (17.6%, 334/1903) specimens (P-value < 0.05), and amongst isolates collected from medical wards (28.1%, 312/1110) versus intensive care units (19.6%, 214/1092) and surgical wards (17.9%, 194/1086) (Bonferroni adjusted P-value < 0.05). Although echinocandin resistance remained low (0.8%, 18/2192) during the surveillance period, it was observed in most administrative regions, and one-third (6/18) of these isolates were simultaneously resistant to fluconazole. CONCLUSION: The continual decrease in the rate of azole susceptibility among C. tropicalis strains has become a nationwide challenge in China, and the emergence of multi-drug resistance could pose further threats. These phenomena call for effective efforts in future interventions.

Aureoverticillactam, a Potent Antifungal Macrocyclic Lactam from Streptomyces aureoverticillatus HN6, Generates Calcium Dyshomeostasis-Induced Cell Apoptosis via the Phospholipase C Pathway in Fusarium oxysporum f. sp. cubense Race 4.

Extensive efforts have been made to discover new biofungicides of high efficiency for control of Fusarium oxysporum f. sp. cubense race 4, a catastrophic soilborne phytopathogen causing banana Fusarium wilt worldwide. We confirmed for the first time that aureoverticillactam (YY3) has potent antifungal activity against F. oxysporum f. sp. cubense race 4, with effective dose for 50% inhibition (EC50) of 20.80 µg/ml against hyphal growth and 12.62 µg/ml against spore germination. To investigate its mechanism of action, we observed the cellular ultrastructures of F. oxysporum f. sp. cubense race 4 with YY3 treatment and found that YY3 led to cell wall thinning, mitochondrial deformities, apoptotic degradation of the subcellular fractions, and entocyte leakage. Consistent with these variations, increased permeability of cell membrane and mitochondrial membrane also occurred after YY3 treatment. On the enzymatic level, the activity of mitochondrial complex III, as well as the ATP synthase, was significantly suppressed by YY3 at a concentration >12.50 µg/ml. Moreover, YY3 elevated the cytosolic Ca2+ level to promote mitochondrial reactive oxygen species (ROS) production. Cell apoptosis also occurred as expected. On the transcriptome level, key genes involved in the phosphatidylinositol signaling pathway were significantly affected, with the expression level of Plc1 increased approximately fourfold. The expression levels of two apoptotic genes, casA1 and casA2, were also significantly increased by YY3. Of note, phospholipase C activation was observed with YY3 treatment in F. oxysporum f. sp. cubense race 4. These findings indicate that YY3 exerts its antifungal activity by activating the phospholipase C calcium-dependent ROS signaling pathway, which makes it a promising biofungicide.

Anti-echinococcal effect of verapamil involving the regulation of the calcium/calmodulin-dependent protein kinase II response in vitro and in a murine infection model.

BACKGROUND: Echinococcosis, which is caused by the larvae of cestodes of the genus Echinococcus, is a parasitic zoonosis that poses a serious threat to the health of humans and animals globally. Albendazole is the drug of choice for the treatment of echinococcosis, but it is difficult to meet clinical goals with this chemotherapy due to its low cure rate and associated side effects after its long-term use. Hence, novel anti-parasitic targets and effective treatment alternatives are urgently needed. A previous study showed that verapamil (Vepm) can suppress the growth of Echinococcus granulosus larvae; however, the mechanism of this effect remains unclear. The aim of the present study was to gain insight into the anti-echinococcal effect of Vepm on Echinococcus with a particular focus on the regulatory effect of Vepm on calcium/calmodulin-dependent protein kinase II (Ca2+/CaM-CaMKII) in infected mice. METHODS: The anti-echinococcal effects of Vepm on Echinococcus granulosus protoscoleces (PSC) in vitro and Echinococcus multilocularis metacestodes in infected mice were assessed. The morphological alterations in Echinococcus spp. induced by Vepm were observed by scanning electron microscopy (SEM), and the changes in calcium content in both the parasite and mouse serum and liver were measured by SEM-energy dispersive spectrometry, inductively coupled plasma mass spectrometry and alizarin red staining. Additionally, the changes in the protein and mRNA levels of CaM and CaMKII in infected mice, and in the mRNA levels of CaMKII in E. granulosus PSC, were evaluated after treatment with Vepm by immunohistochemistry and/or real-time quantitative polymerase chain reaction. RESULTS: In vitro, E. granulosus PSC could be killed by Vepm at a concentration of 0.5 µg/ml or higher within 8 days. Under these conditions, the ultrastructure of PSC was damaged, and this damage was accompanied by obvious calcium loss and downregulation of CaMKII mRNA expression. In vivo, the weight and the calcium content of E. multilocularis metacestodes from mice were reduced after treatment with 40 mg/kg Vepm, and an elevation of the calcium content in the sera and livers of infected mice was observed. In addition, downregulation of CaM and CaMKII protein and mRNA expression in the livers of mice infected with E. multilocularis metacestodes was found after treatment with Vepm. CONCLUSIONS: Vepm exerted a parasiticidal effect against Echinococcus both in vitro and in vivo through downregulating the expression of Ca2+/CaM-CaMKII, which was over-activated by parasitic infection. The results suggest that Ca2+/CaM-CaMKII may be a novel drug target, and that Vepm is a potential anti-echinococcal drug for the future control of echinococcosis.

A national survey on fungal infection diagnostic capacity in the clinical mycology laboratories of tertiary care hospitals in China.

BACKGROUND/PURPOSE: As the incidence of fungal infections in China increases, the demand for rapid and accurate diagnosis of mycoses is growing. Yet, information on current diagnostic capacity is scarce. METHODS: An online survey was conducted in February 2018 to collect information on mycology testing from tertiary care hospitals across China. Responses from 348 hospitals were analyzed, and a scoring system was designed and employed to assess the overall diagnostic capacity. RESULTS: Most of the surveyed hospitals did not have separate laboratory space, manpower, or equipment dedicated for fungal testing. Conventional staining methods were widely available (>70%), whereas GMS and fluorescent staining were less common. Fungal identification services were offered mostly with chromogenic medium, morphological characterization or automated identification systems, other than more advanced methods such as MALDI-TOF MS and DNA sequencing. Fungal serology testing was available in 81.1%, with G test being the most often used. Though 91.8% of the respondents had the ability to perform antifungal susceptibility testing for yeasts, less than 13% conducted such testing for molds. The percentage of laboratories participating in External Quality Assessment programs and research was 57.5% and 32.5%, respectively. The average score for the 348 surveyed hospitals was 37.2 (out of a maximum of 89 points), with only 15 hospitals scoring >60, suggesting a general lack of high-quality mycology laboratories. CONCLUSIONS: The overall clinical testing capacity for fungal infection in China is insufficient. More investment and training efforts are warranted to establish centers of excellence and promote access to high-quality diagnostic services.

Cell death induced by α-terthienyl via reactive oxygen species-mediated mitochondrial dysfunction and oxidative stress in the midgut of Aedes aegypti larvae.

α-Terthienyl (α-T) is a photosensitizer that produces many reactive oxygen species (ROS) under ultraviolet light. Here, we aimed to evaluate the oxidation mechanism of the 25%, 50%, and 75% lethal concentrations in Aedes aegypti larvae; the lethal concentration of α-T was used as the test value. The effects on mitochondria, oxidative stress, and cell death patterns caused by ROS were evaluated. The results showed that α-T mainly produced large amounts of ROS in the midgut of larvae. Moreover, mitochondrial ROS were increased in midgut cells, and the production of ROS sites, such as complex enzymes, was inhibited, resulting in enhanced production of ROS. Ultrastructural analysis of mitochondria revealed significant vacuolation, decreased activity of tricarboxylic acid cycle enzymes, and reduced ATP content and mitochondrial membrane potential in the high concentration group compared with those in the control group. Additionally, mitochondrial biosynthesis was blocked in the high concentration group. Thus, exposure to α-T disrupted mitochondrial function, although the mitochondrial DNA content may have increased because of mitochondrial self-protection mechanisms against oxidative stress. Furthermore, high concentrations of α-T aggravated oxidative stress and increased the number of intracellular oxidative damage products. Reverse transcription polymerase chain reaction and fluorescence staining showed that ROS induced by low α-T concentrations upregulated apoptotic genes, including Dronc (P < 0.05), thereby promoting apoptosis. Moderate concentrations of α-T promoted autophagy through induction of ROS, inhibited apoptosis, and induced necrosis. In contrast, high α-T concentrations induced high levels of ROS, which caused mitochondrial dysfunction and increased cytoplasmic Ca2+ concentration, directly inducing cell necrosis. We also found that α-T may disrupt the permeability of the peritrophic membrane, leading to intestinal barrier dysfunction. These results provided insights into the mode of action of α-T in Aedes aegypti.

Anti-parasitic effects of water-soluble alkaloid fractions from ethanolic extracts of Sophora moorcroftiana seeds in Caenorhabditis elegans.

Parasite infections of humans and animals remain a major global health problem, with limited choice of drugs being available to the treatment of parasitosis in the clinic. Sophora moorcroftiana (S. moorcroftiana) is a shrub that grows in Tibet Plateau of China. Decoction of the seeds has been used as a traditional Tibetan medicine to treat parasitosis for years. But the anti-parasitic effects of water-soluble fractions in the seeds need further investigation. In the present study, the water-soluble alkaloid fractions (E2) were obtained from S. moorcroftiana seeds by refluxing extraction with 60% ethanol and low polarity fraction (E2-a) and high polarity fraction (E2-b) were subsequently isolated from E2 using column chromatography. As a parasite model, Caenorhabditis elegans (C. elegans) were treated with different fractions and their survivals were recorded. The results showed that that E2-a induced a lower survival rate in C. elegans than E2-b and E2. The protoscoleces of Echinococcus granulosus (E. granulosus) were cultured in the presence of E2-a. Compared with E2-b and E2, protoscoleces exhibited decreased survival rate following E2-a treatment. Furtherly, the effects of E2-a on the behavior, brood size, and lifespan of the worms were investigated. Body bend frequencies of the worms treated with the high concentration of E2-a were reduced by two-thirds compared with the control group (P < 0.01). Compared with non-E2-a-treated group, exposure of nematodes to E2-a led to a decrease in head thrashes and pharyngeal pumps frequency (P < 0.01). E2-a treatment resulted in a significantly lower brood size (P < 0.01). Additional E2-a treatment induced a significantly shortened lifespan, compared with the control (P < 0.05). These findings indicated that water-soluble fraction E2-a from S. moorcroftiana seeds was a potential helminthic agent.

Osteoclastogenesis Inhibitory Polyketides from the Sponge-Associated Fungus Xylaria feejeensis.

A new ten-membered macrolide (1) and a new α-pyrone derivative, (-)-annularin C (2), together with 14 known analogs (3-16) were isolated from the AcOEt extract of the fungus Xylaria feejeensis isolated from the South China Sea sponge Stylissa massa. The structures of the new compounds were elucidated by the spectroscopic analysis and by comparison with reported data. The absolute configuration was determined by the optical rotation and ECD experiments. In an in vitro test, compounds 1, 5 and 9 exhibited significant down-regulating activity of osteoclast cell differentiation at 0.5 and 1 µm. This is the first report of the fungus X. feejeensis from a marine sponge and of osteoclastogenesis inhibitory activity for the metabolites of these kinds.

[Effect of compatibility of ginkgolide A, ginkgolide B and ginkgolide K].

To investigate the best active compatibility of ginkgolide A, B and K (GA，GB，GK). The effects of GA, GB, GK alone, combinations of each two of them, and combinations of these three components on platelet-activating factor (PAF)-induced platelet aggregation activity and rat cerebral ischemia reperfusion model (tMCAO) were compared in this study. Different compatibilities of GA, GB and GK could significantly reduce the maximum aggregation rate of PAF-induced platelet aggregation, and the effect was most obvious in combination of the three. Different compatibilities of GA, GB and GK could alleviate the neural function, cerebral infarction volume and cerebral edema in the tMCAO model of rats to different degrees, and the effect of combinations of the three was stronger than those of combinations of two and single use. The combination of all of GA, GB and GK had the strongest effect on nerve injury caused by anti-platelet aggregation in tMCAO rats.

Constituent and effects of polysaccharides isolated from Sophora moorcroftiana seeds on lifespan, reproduction, stress resistance, and antimicrobial capacity in Caenorhabditis elegans.

Sophora moorcroftiana (S. moorcroftiana) is an endemic leguminous dwarf shrub in Tibet, China. Decoctions of the seeds have been used in Chinese folk medicine for dephlogistication, detoxication, and infectious diseases. The present study aimed to investigate the constituent and biological effects of polysaccharides from S. moorcroftiana seeds in Caenorhabditis elegans (C. elegans). Polysaccharides from S. moorcroftiana seeds (SMpol) were extracted with 60% ethanol and constituent was analyzed by GC-MS. SMpol was composed of glucose, galactose and inositol in the molar ratio of 35.7 : 1.3 : 17.0. Synchronized worms were treated with SMpol and then lifespan, motility, reproduction, stress resistance and antimicrobial activity were examined. Compared with the control group, the lifespan was increased to the average of 27.3 days and the number of laying eggs showed a 1.3-fold increase in nematodes treated with SMpol (4 mg·mL-1). In SMpol (4 mg·mL-1) treated worms, there was a 1.1-fold increase in 24-h survival of acute heat stress and a 1.6-fold increase in 2-h survival of oxidative stress The colonization of the bacteria in the SMpol treated nematode was significantly lower than that of the untreated group by 68.3%. In vivo studies showed SMpol significantly extended the life span, improved reproduction, increased stress resistance and antimicrobial capacity of C. elegans. In conclusion, those results indicated that the polysaccharides from S. moorcroftiana seeds were involved in a variety of biological activities leading to its modulatory effects on C. elegans which may be developed as a natural supplement agent.

Molecular epidemiology and antimicrobial susceptibility of Clostridium difficile isolated from the Chinese People's Liberation Army General Hospital in China.

Clostridium difficile is a Gram-positive, spore-forming obligate anaerobe responsible for antibiotic-associated diarrhoea. Its virulence is associated with the production of endotoxins A and B and endospores, which can cause symptoms, such as diarrhoea, toxic megacolon, and pseudomembranous colitis. Given the increasing elderly population and the well-recognized problem of over-prescribing of broad-spectrum antibiotics, it is critical to have an understanding of molecular epidemiology and antimicrobial susceptibility in China. This study analyzed the toxin types and multilocus sequence typing (MLST) results of 74 clinical isolates of C. difficile after the glutamate dehydrogenase (GDH) screening test and anaerobic culture. The minimum inhibitory concentrations (MICs) of four different antibiotics were determined for all of the isolates, and the bacterial resistance mechanisms were investigated. Sixty-five strains (75%) were toxigenic, including 54 tcdA-positive, tcdB-positive, and cdtA/cdtB-negative strains (A+B+CDT-) and nine A-B+CDT- strains. Eleven strains (14.9%) were non-toxigenic. All clinical isolates were classified into 26 MLST genotypes, with the predominant type being ST-54 (18.9%). All isolates were susceptible to vancomycin. The tetracycline, clindamycin, and levofloxacin resistance rates were 1.4%, 36.5%, and 20.3%, respectively. The expression of tet(M), erm(B), and mutations of gyrA and/or gyrB were observed in the tetracycline-, clindamycin-, and levofloxacin-resistant isolates, respectively.

[Protective effects of Ginkgo Terpene Lactones Meglumine Injection on focal cerebral ischemia in rats].

To investigate the protective effects of ginkgo diterpene lactone meglumine injection (GDLMI) on cerebral focal ischemia reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats, and explore its possible mechanism. One hundred and forty male SD rats were randomly divided into sham operation group, model group, ginkgo biloba extract injection (Ginaton, 1.0 mL•kg⁻¹) group, nimodipine (0.4 mg•kg⁻¹) group, and GDLMI (5.2, 2.6, 1.3 mg•kg⁻¹) groups; All of rats received corresponding drugs by tail vein injection 4 days before operation (normal saline in model group and sham operation group). Except the sham operation group, the cerebral ischemic stroke model was established by MCAO method in right brain of the other rats. After 3 h of ischemia, all the animals received intravenous administration again. The neurobehavioral scores of rats after ischemia-reperfusion were evaluated and the infarct rate of brain tissue was observed by TTC staining. The super oxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and lactic acid (LA) contents in brain tissue homogenate and the concentration of Ca2+, glutamate (Glu) and aspartate (Asp), creatine phosphate kinase (CK-BB) and lactate dehydrogenase (LDH) content changes in cerebrospinal fluid were measured. As compared with the sham operation group, the cerebral infarction rate was increased significantly in the model group; the content of MDA and LA in the homogenate of brain tissue was increased, and the content of GSH and SOD was decreased; in cerebrospinal fluid, Ca2+ concentration was decreased, and the content of Glu and Asp, CK-BB and LDH increased significantly. As compared with the model group, the high and medium dose GDLMI groups can significantly reduce the cerebral infarction rate and improve the symptoms of neurological impairment; increase SOD and GSH activity, reduce MDA and LA content in serum; increase Ca2+ concentration in cerebrospinal fluid and decrease the content of neurotransmitter Glu and Asp as well as CK-BB and LDH. GDLMI could obviously improve neurologic impairment in model rats, and the mechanism may be related to recovering the blood brain barrier, scavenging free radicals, decreasing free Ca2+ inflow into the cells and the content of excitatory amino acid in cerebrospinal fluid to improve its protective effect on cerebral ischemia.

Highly Stable Mesoporous Zirconium Porphyrinic Frameworks with Distinct Flexibility.

The construction of highly stable metal-porphyrinic frameworks (MPFs) is appealing as these materials offer great opportunities for applications in artificial light-harvesting systems, gas storage, heterogeneous catalysis, etc. Herein, we report the synthesis of a novel mesoporous metal-porphyrinic framework (denoted as NUPF-1) and its catalytic properties. NUPF-1 is constructed from a new porphyrin linker and a Zr6 O8 structural building unit, possessing an unprecedented doubly interpenetrating scu net. The structure exhibits not only remarkable chemical and thermal stabilities, but also a distinct structural flexibility, which is seldom seen in metal-organic framework (MOF) materials. By the merit of high chemical stability, NUPF-1 could be easily post-metallized with [Ru3 (CO)12 ], and the resulting {NUPF-1-RuCO} is catalytically active as a heterogeneous catalyst for intermolecular C(sp(3) )-H amination. Excellent yields and good recyclability for amination of small substrates with various organic azides have been achieved.

Hollow-structured Si/SiC@C nanospheres as highly active catalysts for cycloaddition of epoxides with CO2 under mild conditions.

Hollow-structured Si/SiC@C nanospheres were prepared through a magnesiothermic reduction of resin-coated SiO2 spheres. These nanostructured materials with high surface area not only show high adsorption capacities of industrial dyes from wastewater, but also exhibit excellent catalytic activities for chemical fixation of CO2 under mild, solvent-free conditions.