Effect of hydrogen sulfide (H2S) on the growth and development of tobacco seedlings in absence of stress.

BACKGROUND: Hydrogen sulfide (H2S) is a novel signaling molecule involved in the growth and development of plants and their response to stress. However, the involvement of H2S in promoting the growth and development of tobacco plants is still unclear. RESULTS: In this study, we explored the effect of pre-soaking or irrigating the roots of tobacco plants with 0.0, 2.0, 4.0, 6.0, and 8.0 mM of sodium hydrosulfide (NaHS) on endogenous H2S production, antioxidant enzymatic and cysteine desulfhydrase activities, seed germination, agronomic traits, photosynthetic pigments contents, and root vigor. The results revealed that exogenous NaHS treatment could significantly promote endogenous H2S production by inducing gene expression of D/L-CD and the activities of D/L-CD enzymes. Additionally, a significant increase in the agronomic traits and the contents of photosynthetic pigments, and no significant difference in carotenoid content among tobacco plants treated with 0.0 to 8.0 mM of NaHS was observed. Additionally, a significant increase in the germination speed, dry weight, and vigor of tobacco seeds, whereas no significant effect on the percentage of seed germination was observed on NaHS treatment. Furthermore, NaHS treatment could significantly increase the activity of superoxide dismutase (SOD) and peroxidase (POD) enzymes, which reduces damage due to oxidative stress by maintaining reactive oxygen species homeostasis. CONCLUSIONS: These results would aid in enhancing our understanding of the involvement of H2S, a novel signaling molecule to promote the growth and development of tobacco plants.

The progress and future of the treatment of Candida albicans infections based on nanotechnology.

Systemic infection with Candida albicans poses a significant risk for people with weakened immune systems and carries a mortality rate of up to 60%. However, current therapeutic options have several limitations, including increasing drug tolerance, notable off-target effects, and severe adverse reactions. Over the past four decades, the progress in developing drugs to treat Candida albicans infections has been sluggish. This comprehensive review addresses the limitations of existing drugs and summarizes the efforts made toward redesigning and innovating existing or novel drugs through nanotechnology. The discussion explores the potential applications of nanomedicine in Candida albicans infections from four perspectives: nano-preparations for anti-biofilm therapy, innovative formulations of "old drugs" targeting the cell membrane and cell wall, reverse drug resistance therapy targeting subcellular organelles, and virulence deprivation therapy leveraging the unique polymorphism of Candida albicans. These therapeutic approaches are promising to address the above challenges and enhance the efficiency of drug development for Candida albicans infections. By harnessing nano-preparation technology to transform existing and preclinical drugs, novel therapeutic targets will be uncovered, providing effective solutions and broader horizons to improve patient survival rates.

Alcohol in Baijiu Contributes to the Increased Probability of Host Infection by Clostridioides difficile Spores.

Clostridioides difficile and its endospores possess the characteristics of a foodborne pathogen and have been detected at several stages in the food chain. In the presence of an imbalance in host intestinal ecology, C. difficile can proliferate and cause intestinal infections. Multiple food source factors can substantially alter the host's gut ecosystem, including the consumption of baijiu. However, it remains to be known whether the gut ecological changes induced by the consumption of baijiu increase the risk of C. difficile invasion and infection. In this study, C. difficile cells were exposed to two commercially available baijiu to evaluate the effect of baijiu on C. difficile cells and to verify through a mouse model. The results showed that baijiu effectively inhibited the growth and biofilm production of C. difficile, downregulated the expression levels of tcdA and tcdB virulence genes but upregulated the expression level of spore-producing genes Spo0A, enhanced the spore production, as well as increased C. difficile cell adhesion to Caco-2 cells. The mouse model showed that the intake of baijiu promoted the invasion and infection of C. difficile spores, causing damage to the cecum tissue, accompanied by an increase in the gut lipid carrier protein-2 (Lcn-2) and TcdA toxin protein levels. Simultaneously, cholic acid was elevated, whereas deoxycholic acid was decreased. This study is the first to find a possible link between baijiu intake and C. difficile spore invasion and infection.

The role of single and mixed biofilms in Clostridioides difficile infection and strategies for prevention and inhibition.

Clostridioides difficile infection (CDI) is a serious disease with a high recurrence rate. The single and mixed biofilms formed by C. difficile in the gut contribute to the formation of recurrent CDI (rCDI). In parallel, other gut microbes influence the formation and development of C. difficile biofilms, also known as symbiotic biofilms. Interactions between members within the symbiotic biofilm are associated with the worsening or alleviation of CDI. These interactions include effects on C. difficile adhesion and chemotaxis, modulation of LuxS/AI-2 quorum sensing (QS) system activity, promotion of cross-feeding by microbial metabolites, and regulation of intestinal bile acid and pyruvate levels. In the process of C. difficile biofilms control, inhibition of C. difficile initial biofilm formation and killing of C. difficile vegetative cells and spores are the main targets of action. The role of symbiotic biofilms in CDI suggested that targeting interventions of C. difficile-promoting gut microbes could indirectly inhibit the formation of C. difficile mixed biofilms and improved the ultimate therapeutic effect. In summary, this review outlines the mechanisms of C. difficile biofilm formation and summarises the treatment strategies for such single and mixed biofilms, aiming to provide new ideas for the prevention and treatment of CDI.

Recent development in Se-enriched yeast, lactic acid bacteria and bifidobacteria.

Endemic selenium (Se) deficiency is a major worldwide nutritional challenge. Organic Se can be synthesized through physical and chemical methods that are conducive to human absorption, but its high production cost and low output cannot meet the actual demand for Se supplementation. Some microbes are known to convert inorganic Se into organic forms of high nutritional value and Se-enriched probiotics are the main representatives. The aim of the present review is to describe the characteristics of Se-enriched yeast, lactic acid bacteria, bifidobacteria and discuss their Se enrichment mechanisms. Se products metabolized by Se-enriched probiotics have been classified, such as Se nanoparticles (SeNPs) and selenoprotein, and their bioactivities have been assessed. The factors affecting the Se enrichment capacity of probiotics and their application in animal feed, food additives, and functional food production have been summarized. Moreover, a brief summary and the development of Se-enriched probiotics, particularly their potential applications in the field of biomedicine have been provided. In conclusion, Se-enriched probiotics not just have a wide range of applications in the food industry but also have great potential for application in the field of biomedicine in the future.

Combination of Bifidobacterium breve and antibiotics against Clostridioides difficile: effect of the time interval of combination on antagonistic activity.

Co-administration of probiotics and antibiotics has been used to prevent or treat primary Clostridioides difficile (pCDI), and the closer the interval between the combination, the more effective it is, but the reason behind this is unknown. In this study, the cell-free culture supernatant (CFCS) of Bifidobacterium breve YH68 was used in combination with vancomycin (VAN) and metronidazole (MTR) to treat C. difficile cells. The growth and biofilm production of C. difficile under different co-administration time interval treatments were determined by optical density and crystalline violet staining, respectively. The toxin production of C. difficile was determined by enzyme immunoassay, and the relative expressions of C. difficile virulence genes tcdA and tcdB were determined by real-time qPCR method. Meanwhile, the types and contents of organic acids in YH68-CFCS were investigated by LC-MS/MS. The results showed that YH68-CFCS in combination with VAN or MTR significantly inhibited the growth, biofilm production, and toxin production of C. difficile in the effective time interval range (0-12 h) but did not affect the expression level of C. difficile virulence genes. In addition, the effective antibacterial component of YH68-CFCS is lactic acid (LA).

The triple interactions between gut microbiota, mycobiota and host immunity.

The gut microbiome is mainly composed of microbiota and mycobiota, both of which play important roles in the development of the host immune system, metabolic regulation, and maintenance of intestinal homeostasis. With the increasing awareness of the pathogenic essence of infectious, immunodeficiency, and tumor-related diseases, the interactions between gut bacteria, fungi, and host immunity have been shown to directly influence the disease process or final therapeutic outcome, and collaborative and antagonistic relationships are commonly found between bacteria and fungi. Interventions represented by probiotics, prebiotics, engineered probiotics, fecal microbiota transplantation (FMT), and drugs can effectively modulate the triple interactions. In particular, traditional probiotics represented by Bifidobacterium and Lactobacillus and next-generation probiotics represented by Akkermansia muciniphila and Faecalibacterium prausnitzii showed a high enrichment trend in the gut of patients with a high response to inflammation remission and tumor immunotherapy, which predicts the potential medicinal value of these beneficial microbial formulations. However, there are bottlenecks in all these interventions that need to be broken. Meanwhile, further unraveling the underlying mechanisms of the "triple interactions" model can guide precise interventions and ultimately improve the efficiency of interventions on the host gut microbiome and immune modulation, thus directly or indirectly improving anti-inflammatory and tumor immunotherapy effects.

Gut microbiota and mycobiota significantly influence the host disease pathology and therapeutic efficacy in a cooperative or antagonistic manner.Probiotics represented by Bifidobacterium spp. are highly enriched in the gut of patients with a high response to immunotherapy implies that probiotics have medicinal potential.

Antagonistic activity of selenium-enriched Bifidobacterium breve against Clostridioides difficile.

Probiotics have the potential to be used in the prevention of Clostridioides difficile infection (CDI). In this study, selenium (Se)-enriched Bifidobacterium breve YH68-Se was obtained under optimal culture conditions with single-factor and response surface optimization. The overall environmental resistance of YH68-Se was superior to that of the parental strain YH68, mainly reflected in the substantial improvement of antioxidant activity and gastrointestinal tolerance. YH68-Se dramatically inhibited C. difficile growth, spore, biofilm, toxin production, and virulence gene expression, rapidly disrupted C. difficile cell membrane permeability and integrity, and altered the membrane proton motive force (PMF), induced a large outflow of intracellular substances and eventually caused bacterial death. The main factor inducing this process originated from the lactic acid (LD) in YH68-Se. In addition, the LD production of YH68 increased with increasing selenite concentration and was accompanied by enhanced activities of thioredoxin reductase (TrxR), glutathione peroxidase (GSH-Px), and increased concentration of autoinducer-2 (AI-2), which may be the crucial factors contributing to the outstanding probiotic properties of YH68-Se and their potent antagonism of C. difficile. KEY POINTS: • Compared with the parental strain B. breve YH68, the environmental resistance of YH68-Se was improved. • YH68-Se was able to produce more lactic acid, which suppressed the important physiological activities of C. difficile and rapidly disrupted their cell membrane structures. • Sodium selenite in the suitable concentration range gradually increases the yield of lactic acid and phenylacetic acid, increased the concentration of autoinducer-2, and enhanced the activities of antioxidant enzymes TrxR and GSH-Px in YH68.

Evaluation of the therapeutic effect and dose-effect of Bifidobacterium breve on the primary Clostridioides difficile infected mice.

Probiotics are widely used as an adjuvant agent for the prevention of primary Clostridioides difficile infection (pCDI) and are less commonly used in the treatment of pCDI. Here, the different doses of Bifidobacterium breve YH68 were used to treat the pCDI mouse model and the actual therapeutic effect was evaluated. Fecal samples of pCDI mice were collected from the pre-infection, post-infection, and post-treatment stages. Simultaneous 16S rRNA amplicon sequencing and non-targeted metabolite assays were performed on these mouse feces, followed by correlation analysis. We found that high doses of B. breve YH68 exerted prominent therapeutic effects and no side effects in pCDI mice, resulted in a high survival rate, accompanied by a dose-effect relationship. YH68 enhanced the levels of caffeine, butyric acid, secondary bile acids in the feces of pCDI mice and significantly upregulated the abundance of genera associated with these metabolites, including Akkermansia, Coprococcus, Oscillospira, and Ruminococcus. Meanwhile, YH68 downregulated the levels of cortisol and phytosphingosine, and these metabolites were positively correlated with the abundance of the Klebsiella and Pseudomonas genera. These findings indicated that YH68 has outstanding therapeutic effects on the pCDI mouse model and is expected to be a potential new option for clinical pCDI therapy.Key points• Bifidobacterium breve YH68 has therapeutic effects on the pCDI mice and was accompanied by a dose-effect relationship.• Bifidobacterium breve YH68 enhanced the levels of caffeine, butyric acid, secondary bile acids in the feces of pCDI mice after treatment, as well as upregulated the abundance of beneficial microbes.• Bifidobacterium breve YH68 decreased the levels of cortisol and phytosphingosine and downregulated the abundance of harmful microbes.

Non-antibiotic therapy for Clostridioides difficile infection: a review.

Clostridioides difficile infection (CDI) is a common infectious disease that is mainly caused by antibiotics. Antibiotic therapy is still the dominant treatment for CDI, although it is accompanied by side effects. Probiotics, fecal microbiota transplantation (FMT), engineered microorganisms, bacteriophages, diet, natural active substances, nanoparticles and compounds are examples of emerging non-antibiotic therapies that have received a great amount of attention. In this review, we collected data about different non-antibiotic therapies for CDI and provided a comprehensive analysis and detailed comparison of these therapies. The mechanism of action, therapeutic efficacy, and the strengths and weaknesses of these non-antibiotic therapies have been investigated to provide a basis for the reasonable alternative of non-antibiotic therapies for CDI. In summary, probiotics and FMT are currently the best choice for non-antibiotic therapy for CDI.

Antibacterial activity of selenium-enriched lactic acid bacteria against common food-borne pathogens in vitro.

Selenium (Se) is an essential trace element for human health and animal nutrition. The aim of this study was to evaluate the inhibitory activities of Se-enriched lactic acid bacteria (LAB), Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus, against pathogenic Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes in vitro. The results indicated that the accumulation amount of Se by Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus reached 12.05 ± 0.43 µg/mL and 11.56 ± 0.25 µg/mL, respectively, accompanied by the relative maximum living cells when sodium selenite was 80 µg/mL. Oxford cup double plate assay showed that bacterial culture solution and cell-free culture supernatant (CFCS) from Se-enriched LAB exerted stronger antibacterial activity than those from the non-Se strains. The growth of pathogenic bacterial culture with CFCS at any growth stages was worse than that without CFCS; moreover, the inhibiting effect of CFCS of Se-enriched LAB was more significant than that of non-Se strains. Results from a scanning electron microscope equipped with energy dispersion X-ray spectrometry showed that elemental Se nanoparticles, which characteristically energy peak around 1.42 keV, were deposited on the cell surfaces of Lactobacillus delbrueckii ssp. bulgaricus. In addition, CFCS of Se-enriched LAB induced more serious cell structure damage of pathogenic bacteria than did non-Se LAB.

Efficacy Assessment of the Co-Administration of Vancomycin and Metronidazole in Clostridioides difficile-Infected Mice Based on Changes in Intestinal Ecology.

Vancomycin (VAN) and metronidazole (MTR) remain the current drugs of choice for the treatment of non-severe Clostridioides difficile infection (CDI); however, while their co-administration has appeared in clinical treatment, the efficacy varies greatly and the mechanism is unknown. In this study, a CDI mouse model was constructed to evaluate the therapeutic effects of VAN and MTR alone or in combination. For a perspective on the intestinal ecology, 16S rRNA amplicon sequencing and non-targeted metabolomics techniques were used to investigate changes in the fecal microbiota and metabolome of mice under the co-administration treatment. As a result, the survival rate of mice under co-administration was not dramatically different compared to that of single antibiotics, and the former caused intestinal tissue hyperplasia and edema. Co-administration also significantly enhanced the activity of amino acid metabolic pathways represented by phenylalanine, arginine, proline, and histidine, decreased the level of deoxycholic acid (DCA), and downregulated the abundance of beneficial microbes, such as Bifidobacterium and Akkermansia. VAN plays a dominant role in microbiota regulation in co-administration. In addition, co-administration reduced or increased the relative abundance of antibiotic-sensitive bacteria, including beneficial and harmful microbes, without a difference. Taken together, there are some risks associated with the co-administration of VAN and MTR, and this combination mode should be used with caution in CDI treatment.

Probiotics Influence Gut Microbiota and Tumor Immune Microenvironment to Enhance Anti-Tumor Efficacy of Doxorubicin.

Probiotics have been reported to influence the gut microbiota and immune system in various diseases. Now, the potential impacts of probiotics on tumor treatment still need to be investigated. In this study, three strains of probiotics, Bifidobacterium breve BBr60 (BBr60), Pediococcus pentosaceus PP06 (PP06), and Bifidobacterium longum subsp. longum BL21 (BL21) were investigated for their combination with chemotherapeutic drugs doxorubicin (DOX). Our study showed that PP06 and BL21 have good performance in gastric acid, bile salt, and intestinal fluid tolerance, antimicrobial activity to pathogenic Staphylococcus aureus, and adhesion to Caco-2 cells. Besides, the probiotics all exhibited antioxidant effect, especially BL21. In vitro cytotoxicity and in vivo animal studies revealed that probiotics used alone could not directly induce anti-tumor effects, but the combination of PP06/BL21 and DOX exhibits a higher inhibition rate than DOX alone, via recruitment and infiltration of immune cells in the tumor region. After 16S rRNA analysis of fecal samples from animal models, it was found that BL21 could increase the abundance of Akkermansia, which may also play a role in regulating the tumor microenvironment to improve immune response. In conclusion, BL21 and PP06 in this study could enhance the anti-tumor efficacy by influencing the gut microbiota and tumor immune microenvironment.

Assessment of the Effectiveness of Probiotics-assisted Physical Interventions in the Management of Chronic Periodontitis: A Randomized Controlled Clinical Trial.

Live micro-ecological agents, such as probiotics, have demonstrated a significant role in the preservation of human health, encompassing oral health maintenance and regulation of oral microbiota. Here, a total of 20 patients diagnosed with chronic periodontitis were recruited and randomly assigned into two cohorts based on completion of physiotherapy: a placebo group (n = 10) and a probiotic group (n = 10). The actual efficacy was assessed by administering chewable tablets (5 × 109 CFU/tablet) containing the probiotics Lactobacillus salivarius LS97, Lactobacillus paracasei LC86, and Lactobacillus acidophilus LA85 to patients with chronic periodontitis. For the placebo group, chewable tablets without probiotics were administered, while maintaining consistency with the rest of the ingredients used in the probiotic group. Saliva and plaque samples were collected at different time points (0, 1, and 3 months) and subjected to 16S amplicon sequencing for microbial structure analysis. Salivary IgA content was determined using enzyme immunoassay, whereas clinical chronic periodontal pocket depth (PD) and bleeding on probe index (BOP +) were employed to evaluate the actual efficacy of probiotic-assisted physiological intervention in chronic periodontitis treatment. Compared to the placebo group, the probiotic intervention resulted in a significant increase in salivary IgA levels among patients, accompanied by a notable decrease in PD and BOP + levels. Furthermore, the probiotic intervention led to a substantial reduction in Fusobacterium and Porphyromonas counts, while significantly increasing Lactobacillus abundance within the dental plaque microbiota of patients. Importantly, no significant alterations were observed in the overall structure of both salivary and dental plaque microbiota following the probiotic intervention. The administration of this live probiotic agent consistently and significantly enhances the oral immune response in patients with chronic periodontitis, thereby augmenting the effectiveness of physical interventions for this condition. Moreover, it effectively reduces the abundance of pathogenic microbes associated with chronic periodontitis without causing substantial alterations to the salivary and dental plaque microbiota composition. Trial registration: Chinese Clinical Trial Registry (ChiCTR) ( https://www.chictr.org.cn ) under the registration number ChiCTR2300074108.

Potential Applications of Blautia wexlerae in the Regulation of Host Metabolism.

Blautia wexlerae (B. wexlerae) is a strong candidate with the potential to become a next-generation probiotics (NGPs) and has recently been shown for the first time to exhibit potential in modulating host metabolic levels and alleviating metabolic diseases. However, the factors affecting the change in abundance of B. wexlerae and the pattern of its abundance change in the associated indications remain to be further investigated. Here, we summarize information from published studies related to B. wexlerae; analyze the effects of food source factors such as prebiotics, probiotics, low protein foods, polyphenols, vitamins, and other factors on the abundance of B. wexlerae; and explore the patterns of changes in the abundance of B. wexlerae in metabolic diseases, neurological diseases, and other diseases. At the same time, the development potential of B. wexlerae was evaluated in the direction of functional foods and special medical foods.

Evaluating the Role of Postbiotics in the Modulation of Human Oral Microbiota: A Randomized Controlled Clinical Trial.

There is a lack of clinical data to support the effectiveness and safety of postbiotics in the modulation of human oral microbiota and oral health care. Here, volunteers were recruited and randomly assigned to two cohorts: a placebo group (n = 15) and a postbiotic group (n = 16). The placebo group used toothpaste that did not contain postbiotics, while the postbiotic group used toothpaste with postbiotics (3 × 1010 CFU inactivated Lactobacillus salivarius LS97, L. paracasei LC86, and L. acidophilus LA85). Saliva samples were collected at different time points and the immunoglobulin A (IgA) and short-chain fatty acid (SCFA) levels were determined, while the salivary microbiota was analyzed by 16S rRNA amplicon sequencing. The results showed that salivary IgA levels and acetic and propionic acid levels were notably higher in the postbiotic group (P < 0.05), accompanied by an increase in the level of alpha diversity of the salivary microbiota, and these indexes remained high 1 month after discontinuing the use of toothpaste with or without postbiotics. A notable decrease in the relative abundance of the unclassified_Enterobacteriaceae, Klebsiella, Escherichia, etc. in the postbiotic group was accompanied by a notable increase in Ruminofilibacter and Lactobacillus. However, both groups did not cause significant changes in the overall structure of the host salivary microbiota. In conclusion, postbiotics dramatically and consistently improved oral immunity levels and SCFA content in the host. In addition, postbiotics were able to increase the level of microbial alpha diversity and down-regulate the abundance of some harmful microbes without significantly altering the structure of the host salivary microbiota. Chinese Clinical Trial Registry (ChiCTR) ( www.chictr.org.cn ) under the registration number ChiCTR2300074088.

Symbiotic biofilms formed by Clostridioides difficile and bacteroides thetaiotaomicron in the presence of vancomycin.

Vancomycin (VAN) treatment in Clostridioides difficile infection (CDI) suffers from a relatively high rate of recurrence, with a variety of reasons behind this, including biofilm-induced recurrent infections. C. difficile can form monophyletic or symbiotic biofilms with other microbes in the gut, and these biofilms protect C. difficile from being killed by antibiotics. In this study, we analyzed the ecological relationship between Bacteroides thetaiotaomicron and C. difficile and their formation of symbiotic biofilm in the VAN environment. The production of symbiotic biofilm formed by C. difficile and B. thetaiotaomicron was higher than that of C. difficile and B. thetaiotaomicron alone in the VAN environment. In symbiotic biofilms, C. difficile was characterized by increased production of the toxin protein TcdA and TcdB, up-regulation of the expression levels of the virulence genes tcdA and tcdB, enhanced bacterial cell swimming motility and c-di-GMP content, and increased adhesion to Caco-2 cells. The scanning electron microscope (SEM) combined with confocal laser scanning microscopy (CLSM) results indicated that the symbiotic biofilm was elevated in thickness, dense, and had an increased amount of mixed bacteria, while the fluorescence in situ hybridization (FISH) probe and plate colony counting results further indicated that the symbiotic biofilm had a significant increase in the amount of C. difficile cells, and was able to better tolerate the killing of the simulated intestinal fluid. Taken together, C. difficile and B. thetaiotaomicron become collaborative in the VAN environment, and targeted deletion or attenuation of host gut B. thetaiotaomicron content may improve the actual efficacy of VAN in CDI treatment.

The impact of fangxian huangjiu on the fermentation quality and microbial community dynamics of cigar wrapper leaves.

Introduction: Cigar wrapper leaves (CWLs) plays a crucial role in reflecting cigar overall quality. Originating from the Qinba region of China, Fangxian Huangjiu (FHJ) is distinctive from other varieties of Huangjiu. Methods: To investigate the effects of FHJ on enhancing the aroma and quality of CWLs, as well as the consequent alterations in microbial communities, Gas Chromatography-Mass Spectrometry (GC-MS) coupled with Odor Active Value (OAV) analysis was utilized to evaluate the volatile aroma components of CWLs. Results and Discussion: The results indicated that the total amount of aroma compounds in CWLs reached 3,086.88 ug/g, increasing of 270.50% and 166.31% compared to the unfermented and naturally fermented groups, respectively. Among them, ß-ionone and 4,7,9-megastigmatrien-3-one from the FHJ fermentation group significantly influenced the sensory characteristics of CWLs. Metagenomic results demonstrated that FHJ fermentation enriched the abundance of both shared and unique microbial species in CWLs, while also increased the diversity of differential microbial species. Addition of FHJ effectively altered the microbial community structure of CWLs from a dominance of Staphylococcus to a prevalence of Staphylococcus, Aspergillus, Pseudomonas, and Acinetobacter. The interactions among these diverse microorganisms collectively contribute to the enhancement of the intrinsic quality of CWLs. This paper provides a theoretical basis for improving the quality of CWLs by FHJ and exploring the changes of microbial community structure and interaction between CWLs and FHJ.

Biomimetic Nanomedicine Targeting Orchestrated Metabolism Coupled with Regulatory Factors to Disrupt the Metabolic Plasticity of Breast Cancer.

Targeting nutrient metabolism has been proposed as an effective therapeutic strategy to combat breast cancer because of its high nutrient requirements. However, metabolic plasticity enables breast cancer cells to survive under unfavorable starvation conditions. The key mammalian target regulators rapamycin (mTOR) and hypoxia-inducible-factor-1 (HIF-1) tightly link the dynamic metabolism of glutamine and glucose to maintain nutrient flux. Blocking nutrient flow also induces autophagy to recycle nutrients in the autophagosome, which exacerbates metastasis and tumor progression. Compared to other common cancers, breast cancer is even more dependent on mTOR and HIF-1 to orchestrate the metabolic network. Therefore, we develop a cascade-boosting integrated nanomedicine to reprogram complementary metabolism coupled with regulators in breast cancer. Glucose oxidase efficiently consumes glucose, while the delivery of rapamycin inside limits the metabolic flux of glutamine and uncouples the feedback regulation of mTOR and HIF-1. The hydroxyl radical generated in a cascade blocks the later phase of autophagy without nutrient recycling. This nanomedicine targeting orchestrated metabolism can disrupt the coordination of glucose, amino acids, nucleotides, lipids, and other metabolic pathways in breast cancer tissues, effectively improving the durable antitumor effect and prognosis of breast cancer. Overall, the cascade-boosting integrated system provides a viable strategy to address cellular plasticity and efficient enzyme delivery.

Strategies for applying probiotics in the antibiotic management of Clostridioides difficile infection.

The vital role of probiotics in the food field has been widely recognized, and at the same time, probiotics are gradually exhibiting surprising effects in the field of nutraceuticals, especially in regulating gut inflammation and the nutritional environment. As a dietary supplement in clinical nutrition, the coadministration of probiotics with antibiotics model has been applied to prevent intestinal infections caused by Clostridioides difficile. However, the mechanism behind this "bacteria-drug combination" model remains unclear. In particular, the selection of specific probiotic strains, the order of probiotics or antibiotics, and the time interval of coadministration are key issues that need to be further explored and clarified. Here, we focus on the issues mentioned above and give reasonable opinions, mainly including: (1) probiotics are safer and more effective when they intervene after antibiotics have been used; (2) the choice of the time interval between coadministration should be based on the metabolism of antibiotics in the host, differences in probiotic strains, the baseline ecological environment of the host's intestine, and the host immune level; in addition, the selection of the coadministration regime should also take into account factors such as the antibiotic sensitivity of probiotics and dosage of probiotics; and (3) by encapsulating probiotics, combining probiotics with prebiotics, and developing next-generation probiotics (NGPs) and postbiotic formulations, we can provide a more reasonable reference for this type of "bacteria-drug combination" model, and also provide targeted guidance for the application of probiotic dietary supplements in the antibiotic management of C. difficile infection.