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Intracellular Nitric Oxide and cAMP Are Involved in Cellulolytic Enzyme Production in Neurospora crassa
Although molecular regulation of cellulolytic enzyme production in filamentous fungi has been actively explored, the underlying signaling processes in fungal cells are still not clearly understood. In this study, the molecular signaling mechanism regulating cellulase production in Neurospora crassa was investigated. We found that the transcription and extracellular cellulolytic activity of four cellulolytic enzymes (cbh1, gh6-2, gh5-1, and gh3-4) increased in Avicel (microcrystalline cellulose) medium. Intracellular nitric oxide (NO) and reactive oxygen species (ROS) detected by fluorescent dyes were observed in larger areas of fungal hyphae grown in Avicel medium compared to those grown in glucose medium. The transcription of the four cellulolytic enzyme genes in fungal hyphae grown in Avicel medium was significantly decreased and increased after NO was intracellularly removed and extracellularly added, respectively. Furthermore, we found that the cyclic AMP (cAMP) level in fungal cells was significantly decreased after intracellular NO removal, and the addition of cAMP could enhance cellulolytic enzyme activity. Taken together, our data suggest that the increase in intracellular NO in response to cellulose in media may have promoted the transcription of cellulolytic enzymes and participated in the elevation of intracellular cAMP, eventually leading to improved extracellular cellulolytic enzyme activity.
Journal Article
Photodegradation of carbon dots cause cytotoxicity
Carbon dots (CDs) are photoluminescent nanomaterials with wide-ranging applications. Despite their photoactivity, it remains unknown whether CDs degrade under illumination and whether such photodegradation poses any cytotoxic effects. Here, we show laboratory-synthesized CDs irradiated with light degrade into molecules that are toxic to both normal (HEK-293) and cancerous (HeLa and HepG2) human cells. Eight days of irradiation photolyzes 28.6-59.8% of the CDs to <3 kilo Dalton molecules, 1431 of which are detected by high-throughput, non-target high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Molecular network and community analysis further reveal 499 cytotoxicity-related molecules, 212 of which contain polyethylene glycol, glucose, or benzene-related structures. Photo-induced production of hydroxyl and alkyl radicals play important roles in CD degradation as affected by temperature, pH, light intensity and wavelength. Commercial CDs show similar photodegraded products and cytotoxicity profiles, demonstrating that photodegradation-induced cytotoxicity is likely common to CDs regardless of their chemical composition. Our results highlight the importance of light in cytocompatibility studies of CDs.
Carbon dots have attracted much attention for biomedical applications but potential degradation and associated toxicity are still poorly understood. Here, the authors report on a study into the photo-degradation of carbon dots, the products produced and associated cytotoxicity.
Journal Article
Comparison of the efficacy and safety of low-dose antihypertensive combinations in patients with hypertension: protocol for a systematic review and network meta-analysis
IntroductionHypertension, a prevalent cardiovascular disease globally, poses significant health risks and economic burden. Evolving treatment targets necessitate more intensive strategies, such as low-dose triple or quadruple drug combinations. However, a systematic comparison of different low-dose antihypertensive combinations is still lacking. The aim of the present study is to systematically and comprehensively evaluate the blood pressure-lowering effect and the associated safety of diverse low-dose polypharmacy combinations in patients with hypertension.Methods and analysisIn this systematic review and network meta-analysis, randomised controlled trials comparing diverse low-dose polypharmacy combinations with placebo or active treatments in patients with hypertension will be eligible for inclusion. The primary outcomes are a reduction in systolic/diastolic blood pressure, the rate of target blood pressure, adverse effects, serious adverse effects and all-cause dropout after treatment. PubMed, Web of Science, Embase, Cochrane Library, Chinese Science Citation Database, Wanfang Medical Network, VIP Database and clinical trial registries will be systematically searched for relevant studies published from inception date to 18 January 2024. No language restrictions will be applied during the search process. Two independent reviewers will identify eligible trials and extract the data. Traditional pairwise meta-analysis will be conducted to analyse direct comparisons. A frequentist approach will be used to analyse the primary outcome for network comparisons, and cumulative rank probabilities will present the treatment hierarchy of all endpoints. Sensitivity analysis will be conducted using a Bayesian framework under a random-effects model. Subgroup analyses will be conducted according to sample size, quality of study and sponsorship, if the data allow. The Cochrane Risk of Bias Tool 2.0 will be used to assess the quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation system will be used to assess the strength of evidence.Ethics and disseminationSince this study relies solely on published literature, no ethics approval is necessary. The results will be submitted to a peer-reviewed journal.PROSPERO registration numberCRD42024503239.
Journal Article
Deep-Sea Fungi Could Be the New Arsenal for Bioactive Molecules
Growing microbial resistance to existing drugs and the search for new natural products of pharmaceutical importance have forced researchers to investigate unexplored environments, such as extreme ecosystems. The deep-sea (>1000 m below water surface) has a variety of extreme environments, such as deep-sea sediments, hydrothermal vents, and deep-sea cold region, which are considered to be new arsenals of natural products. Organisms living in the extreme environments of the deep-sea encounter harsh conditions, such as high salinity, extreme pH, absence of sun light, low temperature and oxygen, high hydrostatic pressure, and low availability of growth nutrients. The production of secondary metabolites is one of the strategies these organisms use to survive in such harsh conditions. Fungi growing in such extreme environments produce unique secondary metabolites for defense and communication, some of which also have clinical significance. Despite being the producer of many important bioactive molecules, deep-sea fungi have not been explored thoroughly. Here, we made a brief review of the structure, biological activity, and distribution of secondary metabolites produced by deep-sea fungi in the last five years.
Journal Article
Effect of non-thermal plasma (NTP) on common sunflower (Helianthus annus L.) seed growth via upregulation of antioxidant activity and energy metabolism-related gene expression
In recent years, non-thermal plasma (NTP) technology has been extensively applied in medical, environmental, biological, and agricultural fields. The sunflower (Helianthus annus L.) is valued by farmers as a relatively common, economically valuable agricultural crop. In this study, our purpose was to use NTP technology to identify suitable conditions to promote sunflower seed germination and seedling growth, and to elucidate the mechanism of action. Our research found that 16.8 kV treatment for 15 s had the greatest effect on seed germination and growth in Chinese sunflower seeds. Interestingly, American sunflower seeds were not sensitive to this treatment. NTP treatment increased the concentration of solubilized protein, antioxidant enzyme activity and expression, and adenosine triphosphate (ATP) production. It also upregulated ATPa2, ATPb1–3, the target of rapamycin (TOR), and growth-regulating factors (GRF) 1–3 and 6, while it downregulated ATPMI25 mRNA expression in 14-day-old sunflower leaves. These results indicate that argon NTP promoted sunflower seed germination and growth by regulating superoxide dismutase 2 (SOD2), catalase (CAT), ATP, TOR, and GRFs. Transcriptome analysis showed that various key genes are involved in starch and sucrose metabolism, pentose and glucoronate interconversions, DNA replication, and plant hormone signal transduction. Our analysis provides comprehensive gene expression information at the transcriptional level, which lays the foundation for further analysis of the function of candidate genes required for the development and growth of sunflower, and contributes to the understanding of the molecular mechanism of sunflower growth.
Journal Article
Association between serum anion gap and all-cause mortality in critically ill patients with diabetic kidney disease: Analysis of the MIMIC-IV database
Diabetic kidney disease (DKD) is one of the most common diabetic complications and is closely related to metabolic acidosis. The serum anion gap (AG), an important index of acid-base balance, may reflect disturbed metabolism and be correlated with increased mortality risk. However, the role of AG in all-cause mortality risk in individuals suffering from severe DKD is not yet clear.
In this study, patients identified with a diagnosis of severe DKD utilizing MIMIC-IV database were determined. They were subsequently divided into four quartiles based on their serum AG levels. The findings consisted of in-hospital deaths and ICU deaths. The relationship between serum AG levels of severe DKD patients and clinical outcomes was elucidated using Cox proportional hazards regression analysis and RCS analysis.
In total, 1,716 patients (66.43% male) received treatment, with in-hospital and ICU mortality rates reaching 16.43% and 13.17%, respectively. Multivariate Cox regression analysis revealed that elevated serum AG levels were remarkably linked to all-cause mortalities. When adjusted for confounders, elevated serum AG levels correlated notably with in-hospital mortality [HR = 1.09(95%CI:1.07,1.11)P < 0.0001] and ICU mortality [HR = 1.10(95%CI:1.07,1.12)P < 0.0001]. RCS analysis showed that serum AG levels were positively correlated in a linear fashion with all-cause death risk.
Serum AG shows a significant positive correlation with all-cause mortalities in hospitals and ICU settings among patients with severe DKD. This suggests that serum AG could serve as a potential indication for recognizing DKD individuals with an increased overall risk of all-cause death.
Journal Article