Copper Sulfate Combined with Photodynamic Therapy Enhances Antifungal Effect by Downregulating AIF1.

Candida albicans is a clinically significant opportunistic fungus that is generally treated with antifungal drugs such as itraconazole and fluconazole. However, the recent emergence of fungal resistance has made treatment increasingly difficult. Therefore, novel antifungal treatment methods are urgently required. Hexanol ethosome photodynamic therapy (HE-PDT) is a method that uses photosensitizers (PS), such as hexanol ethosome, to exert antifungal effects, and can be used to treat resistant fungal strains. However, due to the high dose of PS required for antifungal treatment, excess photosensitizers may remain. Furthermore, once exposed to light, normal tissues or cells are damaged after photodynamic therapy, which limits the clinical application of HE-PDT. Therefore, improving the efficacy without increasing the dose is the key to this treatment. In this study, the antifungal effect of copper sulfate combined with HE-PDT was investigated, and its mechanism was explored. The results suggested that exogenous copper sulfate significantly increased the antifungal effect of HE-PDT by enhancing the rate of C. albicans inhibition, increasing reactive oxygen species (ROS) accumulation, increasing the rate of apoptosis, and altering the mitochondrial membrane potential (MMP) and ATP concentration, which is related to the downregulation of apoptosis-inducing factor (AIF1) expression. In conclusion, copper sulfate combined with photodynamic therapy significantly inhibited the activity of C. albicans by inducing apoptosis. The combined approach reported herein provides new insights for future antifungal therapy.

A variety of death modes of neutrophils and their role in the etiology of autoimmune diseases.

Neutrophils are important in the context of innate immunity and actively contribute to the progression of diverse autoimmune disorders. Distinct death mechanisms of neutrophils may exhibit specific and pivotal roles in autoimmune diseases and disease pathogenesis through the orchestration of immune homeostasis, the facilitation of autoantibody production, the induction of tissue and organ damage, and the incitement of pathological alterations. In recent years, more studies have provided in-depth examination of various neutrophil death modes, revealing nuances that challenge conventional understanding and underscoring their potential clinical utility in diagnosis and treatment. This review explores the multifaceted processes and characteristics of neutrophil death, with a focus on tailored investigations within various autoimmune diseases. It also highlights the potential interplay between neutrophil death and the landscape of autoimmune disorders. The review encapsulates the pertinent pathways implicated in various neutrophil death mechanisms across diverse autoimmune diseases while also charts possible avenues for future research.

Systematic Analysis of NRAMP Family Genes in Areca catechu and Its Response to Zn/Fe Deficiency Stress.

Areca catechu is a commercially important medicinal plant widely cultivated in tropical regions. The natural resistance-associated macrophage protein (NRAMP) is widespread in plants and plays critical roles in transporting metal ions, plant growth, and development. However, the information on NRAMPs in A. catechu is quite limited. In this study, we identified 12 NRAMPs genes in the areca genome, which were classified into five groups by phylogenetic analysis. Subcellular localization analysis reveals that, except for NRAMP2, NRAMP3, and NRAMP11, which are localized in chloroplasts, all other NRAMPs are localized on the plasma membrane. Genomic distribution analysis shows that 12 NRAMPs genes are unevenly spread on seven chromosomes. Sequence analysis shows that motif 1 and motif 6 are highly conserved motifs in 12 NRAMPs. Synteny analysis provided deep insight into the evolutionary characteristics of AcNRAMP genes. Among the A. catechu and the other three representative species, we identified a total of 19 syntenic gene pairs. Analysis of Ka/Ks values indicates that AcNRAMP genes are subjected to purifying selection in the evolutionary process. Analysis of cis-acting elements reveals that AcNRAMP genes promoter sequences contain light-responsive elements, defense- and stress-responsive elements, and plant growth/development-responsive elements. Expression profiling confirms distinct expression patterns of AcNRAMP genes in different organs and responses to Zn/Fe deficiency stress in leaves and roots. Taken together, our results lay a foundation for further exploration of the AcNRAMPs regulatory function in areca response to Fe and Zn deficiency.

Prediction of Type and Recurrence of Atrial Fibrillation after Catheter Ablation via Left Atrial Electroanatomical Voltage Mapping Registration and Multilayer Perceptron Classification: A Retrospective Study.

Atrial fibrillation (AF) is a common cardiac arrhythmia and affects one to two percent of the population. In this work, we leverage the three-dimensional atrial endocardial unipolar/bipolar voltage map to predict the AF type and recurrence of AF in 1 year. This problem is challenging for two reasons: (1) the unipolar/bipolar voltages are collected at different locations on the endocardium and the shapes of the endocardium vary widely in different patients, and thus the unipolar/bipolar voltage maps need aligning to the same coordinate; (2) the collected dataset size is very limited. To address these issues, we exploit a pretrained 3D point cloud registration approach and finetune it on left atrial voltage maps to learn the geometric feature and align all voltage maps into the same coordinate. After alignment, we feed the unipolar/bipolar voltages from the registered points into a multilayer perceptron (MLP) classifier to predict whether patients have paroxysmal or persistent AF, and the risk of recurrence of AF in 1 year for patients in sinus rhythm. The experiment shows our method classifies the type and recurrence of AF effectively.

Overexpression of a Gene Encoding Trigonelline Synthase from Areca catechu L. Promotes Drought Resilience in Transgenic Arabidopsis.

Areca catechu L. is a commercially important palm tree widely cultured in tropical and subtropical areas. Its growth and production are severely hindered by the increasing threat of drought. In the present study, we investigated the physiological responses of areca seedlings to drought stress. The results showed that prolonged drought-induced yellowing on the overall area of most leaves significantly altered the chlorophyll fluorescence parameters, including maximum chemical efficiency (Fv/Fm), photochemical efficiency of PSII (Y(II)), photochemical chlorophyll fluorescence quenching (qP) and non-photochemical chlorophyll fluorescence quenching (NPQ). On the 10th day of drought treatment, the contents of proline in the areca leaves and roots increased, respectively, by 12.2 times and 8.4 times compared to normal watering. The trigonelline levels in the leaves rose from 695.35 µg/g to 1125.21 µg/g under 10 days of water shortage, while no significant changes were detected in the content of trigonelline in the roots. We determined the gene encoding areca trigonelline synthase (AcTS) by conducting a bioinformatic search of the areca genome database. Sequence analysis revealed that AcTS is highly homologous to the trigonelline synthases in Coffea arabica (CaTS 1 and CaTS 2) and all possess a conserved S-adenosyl- L-methionine binding motif. The overexpression of AcTS in Arabidopsis thaliana demonstrated that AcTS is responsible for the generation of trigonelline in transgenic Arabidopsis, which in turn improves the drought resilience of transgenic Arabidopsis. This finding enriches our understanding of the molecular regulatory mechanism of the response of areca to water shortage and provides a foundation for improving the drought tolerance of areca seedlings.

Genome-wide investigation of ZINC-IRON PERMEASE (ZIP) genes in Areca catechu and potential roles of ZIPs in Fe and Zn uptake and transport.

Iron (Fe) and Zinc (Zn) are essential nutrient elements for plant growth and development. Here, we observed the effects of Fe and Zn deficiency in seedlings of Areca catechu L. (areca palm), one of the most cultured palm trees in tropic regions. Results revealed that Fe deficiency causes strong chlorosis with the significantly decreased chlorophyll biosynthesis level and photosynthetic activities in the top third young leaf (L3) of seedlings. Zn deficiency caused light chlorosis in all three young leaves which slightly decreased chlorophyll biosynthesis and photosynthetic activities. Analysis of the Fe and Zn concentration in leaves and roots indicated that absorption and distribution of these two ions share cooperative pathways, since Zn deficiency caused Fe increasing, and vice versa. Therefore, we focused on the ZINC-IRON PERMEASE (ZIP) genes in areca trees. From the whole-genome data set we obtained, 6 ZIP genes were classified, and a phylogenetic tree was constructed with other 38 ZIP genes from model plants to find their potential functions. We also analyzed the expression pattern of AcZIP1-6 genes under Zn and Fe deficiency by transcriptomic approaches. With these results, we constructed an expression atlas of AcZIP1-6 genes in leaves and roots of areca seedlings with the dynamic expression levels under Fe and Zn deficient conditions. In conclusion, we provide evidence to understand the absorption and transport of nutrient elements, Fe and Zn, in the tropic agricultural plant A. catechu.

Prevention of endotoxin-induced cardiomyopathy using sodium tanshinone IIA sulfonate: Involvement of augmented autophagy and NLRP3 inflammasome suppression.

Increasing evidence indicates that patients or experimental animals exposure to endotoxin (lipopolysaccharides, LPS) exert deleterious cardiac functions that greatly contribute to morbidity and mortality. The pathophysiologic processes, including NLRP3 inflammasome overactivation and cardiac inflammatory injury, are complicated. Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, is a naturally occurring compound extracted from Salvia miltiorrhiza and has anti-inflammatory and cardioprotective properties. In this study we examined the effect of STS on endotoxin-induced cardiomyopathy and investigated the underlying mechanisms. An endotoxemic mouse model was established by injecting LPS (10 mg/kg). Different doses of STS were administered intraperitoneally (5, 10, or 50 mg/kg) at different time points (2/12 h, 4/12 h, and 8/12 h) after LPS challenge to assess its effect on survival of mice with endotoxemia. In parallel, cardiac function, myocardial inflammatory cytokines, cardiomyocyte pyroptosis and autophagy were evaluated to determine the extent of myocardial damage due to sepsis in the presence and absence of STS at the optimal dose (10 mg/kg) and time-point (2/12 h). The results demonstrated that STS increased the survival rates, improved the compromised cardiac function and reduced myocardial inflammatory injury associated with enhanced autophagy and mitigated NLRP3 inflammasome activation. Moreover, inhibiting of autophagy or blocking the AMPK pathway reversed STS-elicited prevention of cardiomyopathy and activated the NLRP3 inflammasome in endotoxemic mice. Collectively, our study demonstrates that STS attenuates endotoxemia-induced mortality and cardiomyopathy, which may be associated with promotion of autophagy and inhibition of NLRP3 inflammasome overactivation.

Enhanced neutrophil autophagy and increased concentrations of IL-6, IL-8, IL-10 and MCP-1 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a high morbidity and disability disease with numerous inflammatory cells infiltrating in interstitial of articular cartilages and bones. As the most abundant inflammatory cells, neutrophil has been reported that their apoptosis changed gradually in the circumstance of RA. Apoptosis, one modality of programmed cell death (PCD), is closely associated with autophagy, which indicates neutrophil autophagy may also alter in RA. Flow cytometry, western blotting, immunohistochemistry, immunofluorescence, transmission electron microscope and multiplex antibody microarray were used to comparative investigate the status of neutrophil autophagy in patients with RA and in vitro. The results showed that the expression of autophagy related LC3 protein was up-regulated with lower lysosomal pH in neutrophils from synovial fluid of RA and changed under stimulation of CQ and small RNA interferences (siRNAs) Atg5 transfection, which proved in acute promyelocytic leukemia HL-60 cell lines, predominantly a neutrophilic promyelocyte, treated by plasma and synovial fluid from RA. We further found out the concentration of IL-6, IL-8, IL-10 and MCP-1 was higher in their synovial fluid which may mediate neutrophil autophagy in RA via cytokine-cytokine receptor interaction and IL-17 signaling pathway. Our results indicate that neutrophil autophagy may be a novel perspective to understand the pathology which may provide a new maker to diagnose RA and IL-8, IL-10, MCP-1 specific antagonists and neutrophil autophagy target inhibitors may improve the therapeutic effect of RA someday.