Susceptibility to caspofungin is regulated by temperature and is dependent on calcineurin in Candida albicans.

IMPORTANCE: Echinocandins are the newest antifungal drugs and are first-line treatment option for life-threatening systemic infections. Due to lack of consensus regarding what temperature should be used when evaluating susceptibility of yeasts to echinocandins, typically either 30°C, 35°C, or 37°C is used. However, the impact of temperature on antifungal efficacy of echinocandins is unexplored. In the current study, we demonstrated that Candida albicans laboratory strain SC5314 was more susceptible to caspofungin at 37°C than at 30°C. We also found that calcineurin was required for temperature-modulated caspofungin susceptibility. Surprisingly, the altered caspofungin susceptibility was not due to differential expression of some canonical genes such as FKS, CHS, or CHT genes. The molecular mechanism of temperature-modulated caspofungin susceptibility is undetermined and deserves further investigations.

Reaction Mechanism of Nitrogen-Containing Heterocyclic Compounds Affecting Coal Spontaneous Combustion.

To uncover the reaction mechanism of nitrogen-containing heterocyclic compounds affecting coal self-heating, quantum chemical calculations and X-ray photoelectron spectroscopy (XPS) experiments were applied to elucidate the reaction pathways and thermodynamic characteristics of pyrrole, pyridine, indole, quinoline, and carbazole. Results show that in pyrrole, pyridine, indole, quinoline, and carbazole, the reaction with O2 captures the H atom and leads to the formation of ·OOH and pyrrolyl, pyridinyl, indolyl, quinolinyl, and carbazolyl radicals, respectively. The activation energies are 118.15, 86.642, 34.132, 21.004, and 47.259 kJ/mol, respectively. ROO· formed by spontaneous adsorption of O2 by nitrogen-containing radicals undergoes self-reaction, and the O-O bond is broken and dehydrogenated to generate ·OH. Subsequently, at room temperature, ·OH reacts with pyrrole, pyridine, indole, quinoline, and carbazole, resulting in the formation of H2O and pyrrolyl, pyridinyl, indolyl, quinolinyl, and carbazolyl radicals, respectively, thereby forming a cyclic chain reaction. The XPS analysis yielded the following findings: (i) when the temperature rises to 70 °C, the N-5 and N-6 content decrease, which is attributed to the activation energy; (ii) when the temperature reaches 200 °C, the N-5 content decreases, which can be attributed to the activation energy required for the oxidation of pyrrole (118.5 kJ/mol).

Effects of pH and salinity on survival, growth, and enzyme activities in juveniles of the sunray surf clam (Mactra chinensis Philippi).

The study investigated the impact of salinity and pH changes on the survival, growth, and antioxidant enzyme activity in Mactra chinensis Philippi (1.00 ± 0.10 cm shell length, 0.75 ± 0.04 cm shell height), a marine clam species. Juveniles were exposed to various pH levels (5.4 - 9.6) and salinities (5 - 35 psu) for up to 20 days at 19 ± 0.5 ˚C. The individual effect of salinity and pH on juveniles were evaluated under pH 8.0 and salinity 30 psu, respectively. The results indicated that the highest survival rates were observed at pH 8.0 (85%, salinity = 30 psu) and salinity 30 psu (95%, pH = 8.0). The survival rates were significantly reduced at extreme pH (≤ 7.2; ≥ 8.4) and salinities (≤ 15; 35 psu). Additionally, oxidative stress was observed in clams exposed to low pH and salinity as indicated by the decreased activities of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). Notably, no significant difference in relative growth rates was observed between salinity 25 and 30 psu, between pH 7.8/8.4 and pH 8.0. Our results provide information on potential impact of pH and salinity changes on economically important bivalve species and may be used to optimize pH and salinity in aquaculture.

Effects of herpes zoster vaccination and antiviral treatment on the risk of stroke: a systematic review and meta-analysis.

Background: Evidence suggests that there is an increased risk of stroke after herpes zoster (HZ). However, reports on the effects of HZ vaccination (HZV) and antiviral treatment on stroke risk are inconsistent. Thus, we examined these associations in a meta-analysis. Methods: To identify relevant studies, we searched three databases for articles published up to January 2023. Random-effect models were examined to determine overall pooled estimates and 95% confidence intervals (CIs). Results: This review included 12 observational studies (six on HZV and seven on antiviral treatment). When comparing vaccinated and unvaccinated patients, vaccination was found to be associated with a lower risk of stroke (OR, 0.78; 95% CI 0.68-0.9; P = 0.001). A meta-analysis of self-controlled case series (SCCS) revealed evidence of a reduced OR in individuals who received the vaccine (OR, 1.14; 95% CI 0.94-1.37; P = 0.181) compared with unvaccinated individuals (OR, 1.36; 95% CI 1.15-1.61; P < 0.001). Compared with untreated patients, antiviral therapy was not associated with a reduced risk of stroke (OR, 1.13; 95% CI 0.94-1.36; P = 0.201). The meta-analysis of the SCCS showed no evidence of a reduced OR in individuals who received antiviral therapy (OR, 1.33; 95% CI 1.17-1.51; P < 0.001) compared to untreated individuals (OR, 1.45; 95% CI 1.25-1.69; P < 0.001). Conclusions: This meta-analysis suggests that the HZV, but not antiviral treatment, decreases the odds of developing stroke.

Chromosome 1 trisomy confers resistance to aureobasidin A in Candida albicans.

Introduction: Candida albicans is a prevalent opportunistic human fungal pathogen. However, there are currently very few antifungal treatments available. Inositol phosphoryl ceramide synthase is an essential and fungal-specific protein that also provides a novel and promising antifungal target. Aureobasidin A is a widely used inhibitor of inositol phosphoryl ceramide synthase, however the mechanism of resistance to aureobasidin A is largely unknown in pathogenic fungi. Methods: Here we investigated how C. albicans adapted to low and high concentrations of aureobasidin A. Results and discussions: We identified trisomy of chromosome 1 as the predominant mechanism of rapid adaptation. Resistance to aureobasidin A was unstable because of the inherent instability of aneuploids. Importantly, chromosome 1 trisomy simultaneously regulated genes which were associated with aureobasidin A resistance that are on this aneuploid chromosome as well as on other chromosomes. Furthermore, the pleiotropic effect of aneuploidy caused altered resistance not only to aureobasidin A but also to other antifungal drugs including caspofungin and 5-flucytosine. We posit aneuploidy provides a rapid and reversible mechanism of development of drug resistance and cross resistance in C. albicans.

Sesquiterpene Lactones and Cancer: New Insight into Antitumor and Anti-inflammatory Effects of Parthenolide-Derived Dimethylaminomicheliolide and Micheliolide.

Applied science nowadays works on the isolation and application of biological macromolecules (BMM). These BMM are isolates from plants using different techniques and used as anticancer, antimicrobial, and anti-inflammatory drugs. Parthenolide (PLT) is one of the most important biological macromolecules and a naturally occurring sesquiterpene lactone that is isolated from a plant species Tanacetum parthenium (T. parthenium). The anti-cancer and anti-inflammatory effects of PTL isolated from T. parthenium were previously reported and summarized in detail. These biological activities make it a vital candidate for further researches and drugs development. As per the previously obtained findings, the sesquiterpene is very much known for some biological activities; therefore, the anti-cancer and anti-inflammatory activities of the sesquiterpene were critically reviewed. During the research process, PTL was found to be unstable in both acidic and basic conditions with low solubility, so structurally related compounds micheliolide (MCL) and Dimethylaminomicheliolide (DMAMCL) (a prodrug of MCL) were developed. In this article, we briefly review the therapeutic effects of PTL and its derivative DMAPT on inflammatory diseases and tumors, focusing on the current application of PTL in targeted therapy and combination therapy, together with anti-inflammatory and anti-tumor functions of MCL and DMAMCL. The uniqueness of this biological macromolecule is not to harm the normal cell but target the cancerous cells. Therefore, the current literature review might be helpful and useful for prospects based on the effects of MCL and DMAMCL on cancer.

Generation of two ERF gene knockout human embryonic stem cell lines using CRISPR/Cas9 system.

Human ERF gene is a transcription factor involved in development, trophoblast differentiation, apoptosis, and cancer progress. To further understand the exact roles of ERF in these processes, here we report that establishment of two ERF knockout human embryonic stem cell (hESC) lines by CRISPR/Cas9 mediated gene targeting. These cell lines exhibited classical hESC morphology and normal karyotype, and highly expressed pluripotent markers, and had differentiation potential in vitro. These cell lines provide good materials to understand the roles of ERF in development, trophoblast differentiation and craniosynostosis for further studies.

11ß-Hydroxysteroid dehydrogenase 1 inhibition attenuates collagen-induced arthritis.

11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) plays an important role in inflammation. However, the role of 11ß-HSD1 in rheumatoid arthritis (RA) remains unknown. The purpose of this study was to evaluate the therapeutic effects of a selective 11ß-HSD1 inhibitor BVT-2733 in collagen-induced arthritis (CIA) and its underlying mechanisms. CIA mice were treated with BVT-2733 (100 mg/kg, orally) or vehicle twice daily for 2 weeks. Arthritis score and joint histology were investigated. The levels of pro-inflammatory cytokines as well as anti-type II collagen antibody (anti-CII) were detected by ELISA. Western blot analysis was used to assess the activation of NF-κB and NLRP1 inflammasome in joint tissues and in human RA synovial cells. BVT-2733 treatment attenuated the arthritis severity and anti-CII level in CIA mice. BVT-2733 also decreased the levels of serum TNF-α, IL-1ß, IL-6 and IL-17. BVT-2733 treatment also significantly reduced synovial inflammation and joint destruction. NF-κB activation and NLRP1 inflammasome assembly were also inhibited in arthritic joints and human RA synovial cells. In conclusion, BVT-2733 exhibits an anti-inflammatory effect on CIA. This protective effect is, at least partly, mediated by inhibition of the NF-κB and NLRP1 inflammasome signaling pathways. 11ß-HSD1 inhibition may represent a potential therapeutic target for RA patients.