Use of bailing capsules (cordyceps sinensis) in the treatment of chronic kidney disease: a meta-analysis and network pharmacology.

The Bailing Capsule is a commonly used traditional Chinese medicine for the treatment of chronic kidney disease (CKD). However, its therapeutic effects and pharmacological mechanisms have not been fully explored. In this study, we integrated meta-analysis and network pharmacology to provide scientific evidence for the efficacy and pharmacological mechanism of Bailing Capsule in treating CKD. We conducted searches for randomized controlled studies matching the topic in PubMed, the Cochrane Library, Embase, Web of Science, and the Wanfang Database, and screened them according to predefined inclusion and exclusion criteria. Dates from the included studies were extracted for meta-analysis, including renal function indicators, such as 24-h urinary protein (24UP), blood urea nitrogen (BUN), and serum creatinine (Scr), as well as inflammatory indicators like high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Network pharmacology was employed to extract biological information, including active drug ingredients and potential targets of the drugs and diseases, for network construction and gene enrichment. Our findings indicated that 24UP, BUN, and Scr in the treatment group containing Bailing Capsule were lower than those in the control group. In terms of inflammatory indicators, hs-CRP, IL-6, and TNF-α, the treatment group containing Bailing Capsule also exhibited lower levels than the control group. Based on network pharmacology analysis, we identified 190 common targets of Bailing Capsule and CKD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that the pharmacological mechanism of Bailing Capsule might be related to immune response, inflammatory response, vascular endothelial damage, cell proliferation, and fibrosis. This demonstrates that Bailing Capsule can exert therapeutic effects through multiple targets and pathways, providing a theoretical basis for its use.

The pro-absorptive effect of glycosylated zein-fatty acid complexes on fucoxanthin via the lipid transporter protein delivery pathway.

Growing research confirms that lipid transport proteins play a key role in the trans-intestinal epithelial transport of carotenoids. In this study, to simultaneously improve the digestive stability and intestinal absorption of fucoxanthin (FX), functionalized vectors with a capability of up-regulating the expression of FX-specific lipid transporter proteins was fabricated. The results showed that myristic acid, palmitic acid, and stearic acid effectively promoted FX-specific lipid transporter protein expression and formed stable self-assembly complexes with Millard-modified zein (MZ). The FX was sufficiently encapsulated in the MZ-fatty acid (FA) particles, forming spherical nanoparticles with a "core-shell" structure. Simulated gastrointestinal digestion showed that FA introduction significantly increased the FX bioaccessibility. In vivo results further verified that adding FAs dramatically increased the FX serum response concentration. These findings suggest that incorporating nutrients that can promote lipid transporter protein expression into delivery vehicles should be an effective strategy for improving oral carotenoid absorption.

Genetic and pharmacological targeting of XBP1 alleviates hepatic ischemia reperfusion injury by enhancing FoxO1-dependent mitophagy.

Hepatic ischemia reperfusion (I/R) injury is a common clinical complication. X-box binding protein 1 (XBP1), as a critical regulator of the endoplasmic reticulum stress, has been implicated in a variety of diseases. In this study, we aimed to investigate the effects and the underlying mechanism of XBP1 in the progression of hepatic I/R injury. Hepatocyte-specific XBP1 knockout mice, multiple viral delivery systems and specific pharmacological inhibitors were applied in vivo in a partial hepatic I/R injury mouse model and in vitro in a cell model of hypoxia-reoxygenation (H/R) injury. Mitophagy and autophagic flux were evaluated and fluorescence resonance energy transfer (FRET) as well as immunoprecipitation were performed. The results demonstrated that reperfusion for 6 h represented a critical timepoint in hepatic I/R injury and resulted in significant intracellular mitochondrial dysfunction; led to the breakdown of hepatocytes accompanied by the highest expression levels of XBP1. Hepatocyte-specific XBP1 knockout alleviated hepatic I/R injury via enhanced mitophagy, as demonstrated by the reduction in hepatocellular damage/necrosis and increased expression of mitophagy markers. Mechanistically, XBP1 interacted with FoxO1 directly and catalyzed the ubiquitination of FoxO1 for proteasomal degradation. Targeting XBP1 by genetic or pharmacological techniques potentiated the protein levels of FoxO1, further promoting the activity of the PINK1/Parkin signaling pathway, thus augmenting mitophagy and exerting hepatoprotective effects upon I/R injury. In conclusion, the inhibition of XBP1 potentiated FoxO1-mediated mitophagy in hepatic I/R injury. Specific genetic and pharmacological treatment targeting XBP1 in the perioperative 6 h prior to reperfusion exerted beneficial effects, thus providing a novel therapeutic approach.

Impact of Viscosity on Human Hepatoma Spheroids in Soft Core-Shell Microcapsules.

The extracellular environment regulates the structures and functions of cells, from the molecular to the tissue level. However, the underlying mechanisms influencing the organization and adaptation of cancer in three-dimensional (3D) environments are not yet fully understood. In this study, the influence of the viscosity of the environment is investigated on the mechanical adaptability of human hepatoma cell (HepG2) spheroids in vitro, using 3D microcapsule reactors formed with droplet-based microfluidics. To mimic the environment with different mechanical properties, HepG2 cells are encapsulated in alginate core-shell reservoirs (i.e., microcapsules) with different core viscosities tuned by incorporating carboxymethylcellulose. The significant changes in cell and spheroid distribution, proliferation, and cytoskeleton are observed and quantified. Importantly, changes in the expression and distribution of F-actin and keratin 8 indicate the relation between spheroid stiffness and viscosity of the surrounding medium. The increase of F-actin levels in the viscous medium can indicate an enhanced ability of tumor cells to traverse dense tissue. These results demonstrate the ability of cancer cells to dynamically adapt to the changes in extracellular viscosity, which is an important physical cue regulating tumor development, and thus of relevance in cancer biology.

Enriched switching in a donor-acceptor Stenhouse adduct via reversible covalent bonding.

We have utilized reversible covalent bonding to expand the accessible states of a molecular switch. Introducing a hydroxyl group onto the donor moiety of a donor-acceptor Stenhouse adduct (DASA) imparts an acidity response by forming an oxazolidine ring through intramolecular nucleophilic addition. Furthermore, we observed distinct color changes under cryogenic conditions, extending the thermal responsiveness beyond the cyclization equilibrium observed at elevated temperatures. These unique responses present promising prospects for diverse applications compared to traditional photoinduced binary isomerization.

Exogenous pyruvate promotes gentamicin uptake to kill antibiotic-resistant Vibrio alginolyticus.

OBJECTIVES: Elucidating antibiotic resistance mechanisms is necessary for developing novel therapeutic strategies. The increasing incidence of antibiotic-resistant Vibrio alginolyticus infection threatens both human health and aquaculture, but the mechanism has not been fully elucidated. METHODS: Here, an isobaric tags for relative and absolute quantification (iTRAQ) functional proteomics analysis was performed on gentamicin-resistant V. alginolyticus (VA-RGEN) and a gentamicin-sensitive strain in order to characterize the global protein expression changes upon gentamicin resistance. Then, the bacterial killing assay and bacterial gentamicin pharmacokinetics were performed. RESULTS: Proteomics analysis demonstrated a global metabolic downshift in VA-RGEN, where the pyruvate cycle (the P cycle) was severely compromised. Exogenous pyruvate restored the P cycle activity, disrupting the redox state and increasing the membrane potential. It thereby potentiated gentamicin-mediated killing by approximately 3000- and 150-fold in vitro and in vivo, respectively. More importantly, bacterial gentamicin pharmacokinetics indicated that pyruvate enhanced gentamicin influx to a degree that exceeded the gentamicin expelled by the bacteria, increasing the intracellular gentamicin. CONCLUSION: Thus, our study suggests a metabolism-based approach to combating gentamicin-resistant V. algonolyticus, which paves the way for combating other types of antibiotic-resistant bacterial pathogens.

The essential role of arginine biosynthetic genes in lunate conidia formation, conidiation, mycelial growth, and virulence of nematophagous fungus, Esteya vermicola CBS115803.

BACKGROUND: The pinewood nematode (Bursaphelenchus xylophilus) causes severe damage to pine trees. The nematophagous fungus, Esteya vermicola, exhibits considerable promise in the biological control of Bursaphelenchus xylophilus due to its infectivity. Notably, the lunate conidia produced by E. vermicola can infect Bursaphelenchus xylophilus. In the study, we aim to investigate the genes involved in the formation of the lunate conidia of E. vermicola CBS115803. RESULTS: Esteya vermicola CBS115803 yielded 95% lunate conidia on the complete medium (CM) and 86% bacilloid conidia on the minimal medium (MM). Transcriptomic analysis of conidia from both media revealed a significant enrichment of differentially expressed genes in the pathway related to 'cellular amino acid biosynthesis and metabolism'. Functional assessment showed that the knockout of two arginine biosynthesis genes (EV232 and EV289) resulted in defects in conidia germination, mycelial growth, lunate conidia formation, and virulence of E. vermicola CBS115803 in Bursaphelenchus xylophilus. Remarkably, the addition of arginine to the MM improved mycelial growth, conidiation and lunate conidia formation in the mutants and notably increased conidia yield and the lunate conidia ratio in the wild-type E. vermicola CBS115803. CONCLUSION: This investigation confirms the essential role of two arginine biosynthesis genes in lunate conidia formation in E. vermicola CBS115803. The findings also suggest that the supplementation of arginine to the culture medium can enhance the lunate conidia yield. These insights contribute significantly to the application of E. vermicola CBS115803 in managing Bursaphelenchus xylophilus infections. © 2023 Society of Chemical Industry.

The impact of month and season on the incidence of giant cell arteritis: an Intelligent Research in Sight (IRIS) Registry analysis.

PURPOSE: Previous investigations into the relationship between season and the incidence of giant cell arteritis (GCA) have produced conflicting results. This study aimed to explore the impact of season and new diagnoses of GCA in a more definitive sense by employing the large dataset of the Intelligent Research in Sight (IRIS) database. METHODS: The IRIS Registry was queried to identify new cases of GCA from 2013 to 2021. Statistical analyses were performed to determine the significance of the relationship between the time of year and the incidence of GCA on regional and nationwide bases via Cochran's Q statistical test. RESULTS: A total of 27,339 eyes with a new diagnosis of GCA were identified. Neither the month nor the season of the year correlated with the incidence of GCA, regardless of geographic location within the USA (p > 0.05 for each variable). CONCLUSIONS: In the USA, the incidence of GCA does not appear to vary by month or season. While this finding contradicts certain previous studies that identified a relationship, the cohort of patients identified from the IRIS Registry is much larger than that of previous investigations. Clinicians should be mindful of the possibility of GCA, regardless of the time of the year.

Elevated proton motive force is a tetracycline resistance mechanism that leads to the sensitivity to gentamicin in Edwardsiella tarda.

Tetracycline is a commonly used human and veterinary antibiotic that is mostly discharged into environment and thereby tetracycline-resistant bacteria are widely isolated. To combat these resistant bacteria, further understanding for tetracycline resistance mechanisms is needed. Here, GC-MS based untargeted metabolomics with biochemistry and molecular biology techniques was used to explore tetracycline resistance mechanisms of Edwardsiella tarda. Tetracycline-resistant E. tarda (LTB4-RTET ) exhibited a globally repressed metabolism against elevated proton motive force (PMF) as the most characteristic feature. The elevated PMF contributed to the resistance, which was supported by the three results: (i) viability was decreased with increasing PMF inhibitor carbonylcyanide-3-chlorophenylhydrazone; (ii) survival is related to PMF regulated by pH; (iii) LTB4-RTET were sensitive to gentamicin, an antibiotic that is dependent upon PMF to kill bacteria. Meanwhile, gentamicin-resistant E. tarda with low PMF are sensitive to tetracycline is also demonstrated. These results together indicate that the combination of tetracycline with gentamycin will effectively kill both gentamycin and tetracycline resistant bacteria. Therefore, the present study reveals a PMF-enhanced tetracycline resistance mechanism in LTB4-RTET and provides an effective approach to combat resistant bacteria.

A glucose-mediated antibiotic resistance metabolic flux from glycolysis, the pyruvate cycle, and glutamate metabolism to purine metabolism.

Introduction: Bacterial metabolic environment influences antibiotic killing efficacy. Thus, a full understanding for the metabolic resistance mechanisms is especially important to combat antibiotic-resistant bacteria. Methods: Isobaric tags for relative and absolute quantification-based proteomics approach was employed to compare proteomes between ceftazidime-resistant and -sensitive Edwarsiella tarda LTB4 (LTB4-RCAZ and LTB4-S, respectively). Results: This analysis suggested the possibility that the ceftazidime resistance mediated by depressed glucose is implemented through an inefficient metabolic flux from glycolysis, the pyruvate cycle, glutamate metabolism to purine metabolism. The inefficient flux was demonstrated by the reduced expression of genes and the decreased activity of enzymes in the four metabolic pathways. However, supplement upstream glucose and downstream guanosine separately restored ceftazidime killing, which not only supports the conclusion that the inefficient metabolic flux is responsible for the resistance, but also provides an effective approach to reverse the resistance. In addition, the present study showed that ceftazidime is bound to pts promoter in E. tarda. Discussion: Our study highlights the way in fully understanding metabolic resistance mechanisms and establishing metabolites-based metabolic reprogramming to combat antibiotic resistance.

Exogenous L-Alanine promotes phagocytosis of multidrug-resistant bacterial pathogens.

Multidrug-resistant bacteria present a major threat to public health that urgently requires new drugs or treatment approaches. Here, we conduct integrated proteomic and metabolomics analyses to screen for molecular candidates improving survival of mice infected with Vibrio parahaemolyticus, which indicate that L-Alanine metabolism and phagocytosis are strongly correlated with mouse survival. We also assess the role of L-Alanine in improving mouse survival by in vivo bacterial challenge experiments using various bacteria species, including V. parahaemolyticus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Functional studies demonstrate that exogenous L-Alanine promotes phagocytosis of these multidrug-resistant pathogen species. We reveal that the underlying mechanism involves two events boosted by L-Alanine: TLR4 expression and L-Alanine-enhanced TLR4 signaling via increased biosynthesis and secretion of fatty acids, including palmitate. Palmitate enhances binding of lipopolysaccharide to TLR4, thereby promoting TLR4 dimer formation and endocytosis for subsequent activation of the PI3K/Akt and NF-κB pathways and bacteria phagocytosis. Our data suggest that modulation of the metabolic environment is a plausible approach for combating multidrug-resistant bacteria infection.

pts promoter influences antibiotic resistance via proton motive force and ROS in Escherichia coli.

Introduction: Glucose level is related to antibiotic resistance. However, underlying mechanisms are largely unknown. Methods: Since glucose transport is performed by phosphotransferase system (PTS) in bacteria, pts promoter-deleted K12 (Δpts-P) was used as a model to investigate effect of glucose metabolism on antibiotic resistance. Gas chromatography-mass spectrometry based metabolomics was employed to identify a differential metabolome in Δpts-P compared with K12, and with glucose as controls. Results: Δpts-P exhibits the resistance to ß-lactams and aminoglycosides but not to quinolones, tetracyclines, and macrolide antibiotics. Inactivated pyruvate cycle was determined as the most characteristic feature in Δpts-P, which may influence proton motive force (PMF), reactive oxygen species (ROS), and nitric oxide (NO) that are related to antibiotic resistance. Thus, they were regarded as three ways for the following study. Glucose promoted PMF and ß-lactams-, aminoglycosides-, quinolones-mediated killing in K12, which was inhibited by carbonyl cyanide 3-chlorophenylhydrazone. Exogenous glucose did not elevated ROS in K12 and Δpts-P, but the loss of pts promoter reduced ROS by approximately 1/5, which was related to antibiotic resistance. However, NO was neither changed nor related to antibiotic resistance. Discussion: These results reveal that pts promoter regulation confers antibiotic resistance via PMF and ROS in Escherichia coli.

Functional Role of RING Ubiquitin E3 Ligase VdBre1 and VdHrd1 in the Pathogenicity and Penetration Structure Formation of Verticillium dahliae.

Verticillium dahliae, a virulent soil-borne fungus, elicits Verticillium wilt in numerous dicotyledonous plants through intricate pathogenic mechanisms. Ubiquitination, an evolutionarily conserved post-translational modification, marks and labels proteins for degradation, thereby maintaining cellular homeostasis. Within the ubiquitination cascade, ubiquitin ligase E3 demonstrates a unique capability for target protein recognition, a function often implicated in phytopathogenic virulence. Our research indicates that two ubiquitin ligase E3s, VdBre1 and VdHrd1, are intrinsically associated with virulence. Our findings demonstrate that the deletion of these two genes significantly impairs the ability of V. dahliae to colonize the vascular bundles of plants and to form typical penetration pegs. Furthermore, transcriptomic analysis suggests that VdBre1 governs the lipid metabolism pathway, while VdHrd1 participates in endoplasmic-reticulum-related processes. Western blot analyses reveal a significant decrease in histone ubiquitination and histone H3K4 trimethylation levels in the ΔVdBre1 mutant. This research illuminates the function of ubiquitin ligase E3 in V. dahliae and offers fresh theoretical perspectives. Our research identifies two novel virulence-related genes and partially explicates their roles in virulence-associated structures and gene regulatory pathways. These findings augment our understanding of the molecular mechanisms inherent to V. dahliae.

Two-dimensional self-assembly and co-assembly of two tetracarboxylic acid derivatives investigated by STM.

In this work, the two-dimensional self-assembly and co-assembly behaviors of two tetracarboxylic acid derivatives (H4BDETP and H4BTB) were investigated by scanning tunneling microscopy (STM). H4BDETP molecules self-assembled into linear nanostructures, and H4BTB molecules formed lamellar and tetragonal nanostructures. The formation of a H4BDETP/H4BTB co-assembly nanostructure was closely related to the deposition sequence of H4BDETP and H4BTB on highly oriented pyrolytic graphite (HOPG). The introduction of H4BTB into the self-assembly system of H4BDETP resulted in the emergence of the H4BDETP/H4BTB nanostructure, while the addition of H4BDETP had no effect on the self-assembly system of H4BTB and a H4BDETP/H4BTB co-assembly nanostructure was not obtained.

Dysbiosis of vaginal and cervical microbiome is associated with uterine fibroids.

Dysbiosis of the female reproductive tract is closely associated with gynecologic diseases. Here, we aim to explore the association between dysbiosis in the genital tract and uterine fibroids (UFs) to further provide new insights into UF etiology. We present an observational study to profile vaginal and cervical microbiome from 29 women with UFs and 38 healthy women, and 125 samples were obtained and sequenced. By comparing the microbial profiles between different parts of the reproductive tract, there is no significant difference in microbial diversity between healthy subjects and UF patients. However, alpha diversity of UF patients was negatively correlated with the number of fibroids. Increased Firmicutes were observed in both the cervical and vaginal microbiome of UF patients at the phylum level. In differential analysis of relative abundance, some genera were shown to be significantly enriched (e.g., Erysipelatoclostridium, Mucispirillum, and Finegoldia) and depleted (e.g., Erysipelotrichaceae UCG-003 and Sporolactobacillus) in UF patients. Furthermore, the microbial co-occurrence networks of UF patients showed lower connectivity and complexity, suggesting reduced interactions and stability of the cervical and vaginal microbiota in UF patients. In summary, our findings revealed the perturbation of microbiome in the presence of UFs and a distinct pattern of characteristic vaginal and cervical microbiome involved in UFs, offering new options to further improve prevention and management strategies.

Call for next-generation drugs that remove the uptake barrier to combat antibiotic resistance.

Existing antibacterial agents can be categorized into two generations, but bacterial insensitivity towards both of these generations poses a serious public health challenge worldwide. Thus, novel approaches and/or novel antibacterials are urgently needed to maintain a concentration of antibacterials that is lethal to bacteria that are resistant to existing antibiotic treatments. Metabolite(s)-based adjuvants that promote antibiotic uptake and enhance antibiotic efficacy are an effective strategy that is unlikely to develop resistance. Thus, we propose a metabolite(s)-based approach, in which metabolites and antibacterials are combined, as a promising strategy for the development of next-generation agents to combat a variety of antibiotic-resistant pathogens.

How do corporate social responsibility and green finance strategies impact sustainable development in China's renewable energy sector?

As the globe transitions to a low-carbon economy, China's renewable energy (RE) sector is crucial to attaining sustainable growth. Green financing and corporate social responsibility (CSR) strategies have become increasingly important in promoting the growth and sustainability of the RE sector. In order to evaluate CSR factors and green finance strategies for effective integration in supporting the RE industry, this research employs hybrid Fuzzy Analytic Hierarchy Process (FAHP) and Fuzzy VIekriterijumsko KOmpromisno Rangiranje (FVIKOR) approaches in the context of China. The FAHP method is used to determine the various CSR factors and subfactors, while the FVIKOR method is employed to prioritize the key green finance strategies. The findings of the FAHP method highlight the importance of socioeconomic development, environmental protection, and stakeholder engagement as critical CSR factors for RE sectors. Moreover, the results of the FVIKOR method reveal that innovative financing mechanisms, green bonds, and green banks emerged as significant green finance strategies for mobilizing capital and resources for RE projects. The study highlights the value of aspects of CSR and green financing techniques in fostering sustainable development in the RE industry. The results can aid in the promotion of sustainable practices and the assistance of China's transition to a more resource- and environment-wise economy by firms, investors, governments, and other stakeholders.

Gas6/AXL pathway: immunological landscape and therapeutic potential.

Cancer is a disease with ecological and evolutionary unity, which seriously affects the survival and quality of human beings. Currently, many reports have suggested Gas6 plays an important role in cancer. Binding of gas6 to TAM receptors is associated with the carcinogenetic mechanisms of multiple malignancies, such as in breast cancer, chronic lymphocytic leukemia, non-small cell lung cancer, melanoma, prostate cancer, etc., and shortened overall survival. It is accepted that the Gas6/TAM pathway can promote the malignant transformation of various types of cancer cells. Gas6 has the highest affinity for Axl, an important member of the TAM receptor family. Knockdown of the TAM receptors Axl significantly affects cell cycle progression in tumor cells. Interestingly, Gas6 also has an essential function in the tumor microenvironment. The Gas6/AXL pathway regulates angiogenesis, immune-related molecular markers and the secretion of certain cytokines in the tumor microenvironment, and also modulates the functions of a variety of immune cells. In addition, evidence suggests that the Gas6/AXL pathway is involved in tumor therapy resistance. Recently, multiple studies have begun to explore in depth the importance of the Gas6/AXL pathway as a potential tumor therapeutic target as well as its broad promise in immunotherapy; therefore, a timely review of the characteristics of the Gas6/AXL pathway and its value in tumor treatment strategies is warranted. This comprehensive review assessed the roles of Gas6 and AXL receptors and their associated pathways in carcinogenesis and cancer progression, summarized the impact of Gas6/AXL on the tumor microenvironment, and highlighted the recent research progress on the relationship between Gas6/AXL and cancer drug resistance.

Alleviatory effects of salicylic acid on postharvest softening and cell wall degradation of 'Jinshayou' pummelo (Citrus maxima Merr.): A comparative physiological and transcriptomic analysis.

The regulatory mechanisms underlying the salicylic acid (SA)-mediated inhibition of senescence in pummelo fruit, the largest known citrus variety, remain unclear. Herein, postharvest 0.3% SA treatment was demonstrated to delay postharvest 'Jinshayou' pummelo senescence, as evidenced by the inhibitions in firmness loss, electrolyte leakage increase, and color change. Using comparative transcriptomic data, a total of 4367, 3769, and 1659 DEGs were identified between CK0 and CK60, CK0 and SA60, and CK60 and SA60, respectively. Further GO analysis revealed that DEGs were mainly implicated in the processes of cell wall modification and phenylpropanoid pathway during fruit senescence. More importantly, postharvest exogenous 0.3% SA treatment was observed to inhibit CWDEs activities and their encoding gene expression, retain higher protopectin, cellulose, and hemicelluloses contents, as well as reduce WSP content, thus maintaining cell wall structure. These findings collectively indicated that postharvest SA treatment was a green and useful preservative for alleviating fruit senescence and prolonging the storage life of harvested 'Jiashayou' pummelo fruit.