Microbiota-derived 3-phenylpropionic acid promotes myotube hypertrophy by Foxo3/NAD+ signaling pathway.

BACKGROUND: Gut microbiota and their metabolites play a regulatory role in skeletal muscle growth and development, which be known as gut-muscle axis. 3-phenylpropionic acid (3-PPA), a metabolite produced by colonic microorganisms from phenylalanine in the gut, presents in large quantities in the blood circulation. But few study revealed its function in skeletal muscle development. RESULTS: Here, we demonstrated the beneficial effects of 3-PPA on muscle mass increase and myotubes hypertrophy both in vivo and vitro. Further, we discovered the 3-PPA effectively inhibited protein degradation and promoted protein acetylation in C2C12 and chick embryo primary skeletal muscle myotubes. Mechanistically, we supported that 3-PPA reduced NAD+ synthesis and subsequently suppressed tricarboxylic acid cycle and the mRNA expression of SIRT1/3, thus promoting the acetylation of total protein and Foxo3. Moreover, 3-PPA may inhibit Foxo3 activity by directly binding. CONCLUSIONS: This study firstly revealed the effect of 3-PPA on skeletal muscle growth and development, and newly discovered the interaction between 3-PPA and Foxo3/NAD+ which mechanically promote myotubes hypertrophy. These results expand new understanding for the regulation of gut microbiota metabolites on skeletal muscle growth and development.

The resistance patterns and molecular characteristics of ESBL/AmpC-producing Escherichia coli from captive panda ecosystem in China.

Escherichia coli (E. coli) plays an important ecological role, and is a useful bioindicator to recognize the evolution of resistance in human, animal and environment. Recently, extended-spectrum ß-lactamases (ESBL) producing E.coli has posed a threat to public health. Generally, captive healthy giant pandas are not exposed to antibiotics; however, they still acquire antimicrobial resistant bacteria. In order to understand whether there is an exchange of resistance genes within the ecosystems of captive giant pandas, this study explored resistance characteristics of 330 commensal E. coli isolates from feces of giant pandas, the surroundings, and breeders. Isolates from different sources showed similar resistance phenotype, and ESBL/AmpC-producing isolates showed more profound resistance to antibiotics than non-ESBL/AmpC-producing isolates (P<0.05). Furthermore, the occurrence of broad-spectrum ß-lactamase related resistance genes and colistin resistance genes was detected, and isolates phylogenetic typing and multilocus sequence typing (MLST) were applied in this study. Seven different ß-lactamase resistance genes (blaCTX-M-55, blaCTX-M-15, blaCTX-M-27, blaCTX-M-65, blaTEM-1, blaOXA-1 and blaCMY) and mcr-1 were found in 68 ESBL/AmpC-producing isolates. blaCTX-M-55 (48.53 %) was found the most predominant resistance genes, followed by blaTEM-1 (19.12 %) and blaCTX-M-27 (16.18 %). Nonetheless, blaCTX-M-55 was commonly detected in the isolates from giant pandas (63.16 %), the surroundings (43.48 %), and breeders (33.33 %). However, there were no carbapenemase genes detected in this study. mcr-1 was harbored in only one isolate from giant panda. Forty-five tansconjugants were successfully obtained in the conjugation experiments. The presence of antimicrobial resistance and related resistance genes tested were observed in the transconjugants. The results indicated that 52.63 % of the isolates from giant panda 73.91 % of the isolates from surroundings, and 100 % of the isolates from breeders were phylogroup A. Total of 27 sequence types (ST) were recognized from the isolate by MLST and found that ST48 (19/68; 27.94 %) was the predominant ST type, especially in the isolates from giant pandas and the surroundings. In conclusion, commensal ESBL/AmpC-producing E. coli becomes a reservoir of ESBL resistance genes, which is a potential threaten to health of giant pandas. The interaction between giant pandas, surroundings and breeders contribute to development of resistant phenotypes and genotypes which might transfer across species or the surroundings easily; hence, strict monitoring based on a "One Health" approach is recommended.

Super-Klein Tunneling in a Black-Phosphorus-Based N-P Junction Modulated by Linearly Polarized Light.

We investigate the role of the black-phosphorus-based n-p (BP-np) junction modulated by linearly polarized light (LPL) in governing the quantum transport behaviors. Following the analysis of the band structures, we find that the LPL can adjust the gap between the conduction and valence bands by reducing the impact of momentum mismatch caused by the band gap. In addition, LPL can also eliminate the angle dependence of transmission. This means that for BP with a fixed band gap, the transmission-forbidden region can be reduced and the transmission probability can be increased by applying LPL modulation of the band gap to achieve all-angle perfect transmission, i.e., super-Klein tunneling (SKT). Our investigation also found that the SKT is robust to different incident energies, resulting in a larger conductance platform. These findings could be useful for the development and application of optical-like electronic devices.

Conjugated linoleic acid (CLA) reduces intestinal fatty acid uptake and chylomicron formation in HFD-fed mice associated with the inhibition of DHHC7-mediated CD36 palmitoylation and the downstream ERK pathway.

The anti-obesity effect of conjugated linoleic acid (CLA) has been well elucidated, but whether CLA affects fat deposition by regulating intestinal dietary fat absorption remains largely unknown. Thus, this study aimed to investigate the effects of CLA on intestinal fatty acid uptake and chylomicron formation and explore the possible underlying mechanisms. We found that CLA supplementation reduced the intestinal fat absorption in HFD (high fat diet)-fed mice accompanied by the decreased serum TG level, increased fecal lipids and decreased intestinal expression of ApoB48 and MTTP. Correspondingly, c9, t11-CLA, but not t10, c12-CLA induced the reduction of fatty acid uptake and TG content in PA (palmitic acid)-treated MODE-K cells. In the mechanism of fatty acid uptake, c9, t11-CLA inhibited the binding of CD36 with palmitoyltransferase DHHC7, thus leading to the decreases of CD36 palmitoylation level and localization on the cell membrane of the PA-treated MODE-K cells. In the mechanism of chylomicron formation, c9, t11-CLA inhibited the formation of the CD36/FYN/LYN complex and the activation of the ERK pathway in the PA-treated MODE-K cells. In in vivo verification, CLA supplementation reduced the DHHC7-mediated total and cell membrane CD36 palmitoylation and suppressed the formation of the CD36/FYN/LYN complex and the activation of the ERK pathway in the jejunum of HFD-fed mice. Altogether, these data showed that CLA reduced intestinal fatty acid uptake and chylomicron formation in HFD-fed mice associated with the inhibition of DHHC7-mediated CD36 palmitoylation and the downstream ERK pathway.

Therapeutic effect of ZnO NPs-polyhexanide-hydrogel on Staphylococcus aureus-induced skin wound infection in mice.

Nanometer zinc oxide (ZnONPs) offers strong antibacterial, wound healing, hemostatic benefits, and UV protection. Additionally, poly(hexamethylene biguanide)hydrochloride (PHMB) is an environmentally friendly polymer with strong bactericidal properties. However, the synergistic effect of the combination of ZnONPs and PHMB has not been previously explored. The purpose of this study is to explore the synergies of ZnONPs and PHMB and the healing efficacy of ZnO NPs-PHMB-hydrogel on skin wounds in mice infected with Staphylococcus aureus. Therefore, the mice were subjected to skin trauma to create a wound model and were subsequently infected with S. aureus, and then divided into various experimental groups. The repair effect was evaluated by assessing the healing rate, as well as measuring the levels of TNF-α, IL-2, EGF, and TGF-ß1 contents in the tissue. On the 4th and 9th days post-modeling, the Z-P group exhibited notably higher healing rates compared to the control group. However, on the 15th day, both the Z-P and AC groups achieved healing rates exceeding 99%. ZnO NPs-PHMB-hydrogel promoted the formation of a fully restored epithelium, increased new hair follicles and sebaceous glands beneath the epidermis, and markedly reduced inflammatory cell infiltration, which was markedly distinct from the control group. On the 7th day, the Z-P group exhibited significantly higher levels of EGF and TGF-ß1, along with a considerable reduction in the TNF-α levels as compared with the control group. These results affirmed that ZnO NPs-PHMB-hydrogel effectively inhibits S. aureus infection and accelerates skin wound healing.

Tetramethylpyrazine Antagonizes the Subchronic Cadmium Exposure-Induced Oxidative Damage in Mouse Livers via the Nrf2/HO-1 Pathway.

Hepatic oxidative stress is an important mechanism of Cd-induced hepatotoxicity, and it is ameliorated by TMP. However, this underlying mechanism remains to be elucidated. To investigate the mechanism of the protective effect of TMP on liver injuries in mice induced by subchronic cadmium exposure, 60 healthy male ICR mice were randomly divided into five groups of 12 mice each, namely, control (CON), Cd (2 mg/kg of CdCl2), Cd + 100 mg/kg of TMP, Cd + 150 mg/kg of TMP, and Cd + 200 mg/kg of TMP, and were acclimatized and fed for 7 d. The five groups of mice were gavaged for 28 consecutive days with a maximum dose of 0.2 mL/10 g/day. Except for the control group, all groups were given fluoride (35 mg/kg) by an intraperitoneal injection on the last day of the experiment. The results of this study show that compared with the Cd group, TMP attenuated CdCl2-induced pathological changes in the liver and improved the ultrastructure of liver cells, and TMP significantly decreased the MDA level (p < 0.05) and increased the levels of T-AOC, T-SOD, and GSH (p < 0.05). The results of mRNA detection show that TMP significantly increased the levels of Nrf2 in the liver compared with the Cd group as well as the HO-1 and mRNA expression levels in the liver (p < 0.05). In conclusion, TMP could inhibit oxidative stress and attenuate Cd group-induced liver injuries by activating the Nrf2 pathway.

Effect of High Energy Low Protein Diet on Lipid Metabolism and Inflammation in the Liver and Abdominal Adipose Tissue of Laying Hens.

The aim of this study was to evaluate the effects of a high-energy low-protein (HELP) diet on lipid metabolism and inflammation in the liver and abdominal adipose tissue (AAT) of laying hens. A total of 200 Roman laying hens (120 days old) were randomly divided into two experimental groups: negative control group (NC group) and HELP group, with 100 hens per group. The chickens in the NC group were fed with a basic diet, whereas those in the HELP group were given a HELP diet. Blood, liver, and AAT samples were collected from 20 chickens per group at each experimental time point (30, 60, and 90 d). The morphological and histological changes in the liver and AAT were observed, and the level of serum biochemical indicators and the relative expression abundance of key related genes were determined. The results showed that on day 90, the chickens in the HELP group developed hepatic steatosis and inflammation. However, the diameter of the adipocytes of AAT in the HELP group was significantly larger than that of the NC group. Furthermore, the results showed that the extension of the feeding time significantly increased the lipid contents, lipid deposition, inflammatory parameters, and peroxide levels in the HELP group compared with the NC group, whereas the antioxidant parameters decreased significantly. The mRNA expression levels of genes related to lipid synthesis such as fatty acid synthase (FASN), stearoyl-coA desaturase (SCD), fatty acid binding protein 4 (FABP4), and peroxisome proliferator-activated receptor gamma (PPARγ) increased significantly in the liver and AAT of the HELP group, whereas genes related to lipid catabolism decreased significantly in the liver. In addition, the expression of genes related to lipid transport and adipokine synthesis decreased significantly in the AAT, whereas in the HELP group, the expression levels of pro-inflammatory parameters such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) increased significantly in the liver and AAT. Conversely, the expression level of the anti-inflammatory parameter interleukin-10 (IL-10) decreased significantly in the liver. The results indicated that the HELP diet induced lipid peroxidation and inflammation in the liver and AAT of the laying hens. Hence, these results suggest that chicken AAT may be involved in the development of fatty liver.

RNA-Seq Analysis Reveals the Molecular Mechanisms Regulating the Development of Different Adipose Tissues in Broiler Chicks.

In an effort to enhance growth rates, chicken breeders have undertaken intensive genetic selection. In the selection process, the primary aim is to accelerate growth, inadvertently leading to new chicken breeds having an increased capacity for rapid adipose tissue accumulation. However, little is known about the relationship between changes in gene expression and adipose tissue accumulation and deposition in chickens. Therefore, in this study, RNA-seq analysis was utilized, and transcriptome data were obtained from the abdominal fat, thoracic subcutaneous fat, and clavicular fat on day 1 (d1), day 4, day 7, day 11, and day 15 to reveal the molecular mechanisms regulating the development and deposition of different adipose tissues in broiler chicks. The results showed that the key period for adipocyte differentiation and proliferation was between d4 and d7 (abdominal fat development) and between d1 and d4 (chest subcutaneous fat and clavicular fat). In addition, candidate genes such as MYOG, S100A9, CIDEC, THRSP, CXCL13, and NMU related to adipose tissue growth and development were identified. Further, genes (HOXC9, AGT, TMEM182, ANGPTL3, CRP, and DSG2) associated with the distribution of adipose tissue were identified, and genes (MN1, ANK2, and CAP2) related to adipose tissue growth were also identified. Taken together, the results from this study provide the basis for future studies on the mechanisms regulating adipose tissue development in chickens. Further, the candidate genes identified could be used in the selection process.

Knockdown of the VEGFB/VEGFR1 signaling suppresses pubertal mammary gland development of mice via the inhibition of PI3K/Akt pathway.

Vascular endothelial growth factor B (VEGFB) has been well demonstrated to play a crucial role in regulating vascular function by binding to the VEGF receptors (VEGFRs). However, the specific role of VEGFB and VEGFRs in pubertal mammary gland development remains unclear. In this study, we observed that blocking the VEGF receptors with Axitinib suppressed the pubertal mammary gland development. Meanwhile, the proliferation of mammary epithelial cells (HC11) was repressed by blocking the VEGF receptors with Axitinib. Additionally, knockdown of VEGFR1 rather than VEGFR2 and NRP1 elicited the inhibition of HC11 proliferation, suggesting the essential role of VEGFR1 during this process. Furthermore, Axitinib or VEGFR1 knockdown led to the inhibition of the PI3K/Akt pathway. However, the inhibition of HC11 proliferation induced by Axitinib and or VEGFR1 knockdown was eliminated by the Akt activator SC79, indicating the involvement of the PI3K/Akt pathway. Finally, the knockdown of VEGFB and VEGFR1 suppressed the pubertal development of mice mammary gland with the inhibition of the PI3K/Akt pathway. In summary, the results showed that knockdown of the VEGFB/VEGFR1 signaling suppresses pubertal mammary gland development of mice via the inhibition of the PI3K/Akt pathway, which provides a new target for the regulation of pubertal mammary gland development.

Conjugated linoleic acid (CLA) reduces HFD-induced obesity by enhancing BAT thermogenesis and iWAT browning via the CD36-AMPK pathway.

The antiobesity effect of conjugated linoleic acid (CLA) has been reported. However, the underlying mechanisms have not been fully clarified. Thus, this study aimed to investigate the effects of CLA on thermogenesis of interscapular brown adipose tissue (iBAT) and browning of inguinal subcutaneous white adipose tissue (iWAT) and explore the possible signaling pathway. The in vivo results showed that CLA enhanced the O2 consumption and heat production in HFD (high-fat diet)-fed female mice by roughly 38%. Meanwhile, CLA increased the average iBAT temperature by 2°C at the room temperature and cold exposure, respectively. Correspondingly, CLA caused 1.6- and 2.4-fold increases in the expression of UCP1 (uncoupling protein 1) of BAT and iWAT, respectively, suggesting the activated iBAT thermogenesis and iWAT browning in HFD-fed female mice. Meanwhile, CLA could promote the formation of brown and beige adipocytes in differentiated stromal vascular cells (SVCs) isolated from iBAT and iWAT (the expressions of UCP1 were promoted by about twofold changes). In possible mechanisms, CLA stimulated the expression of CD36 and the activation of the AMPK pathway in mice iBAT and iWAT as well as the differentiated SVCs. However, inhibition of CD36 and AMPK (adenosine 5'-monophosphate-activated protein kinase) abolished the promotive effects of CLA on brown and beige adipocytes formation. Hence, we showed that CLA reduced HFD-induced obesity through enhancing iBAT thermogenesis and iWAT browning via the  CD36-AMPK pathway.

Microbiota derived D-malate inhibits skeletal muscle growth and angiogenesis during aging via acetylation of Cyclin A.

Metabolites derived from the intestinal microbiota play an important role in maintaining skeletal muscle growth, function, and metabolism. Here, we found that D-malate (DMA) is produced by mouse intestinal microorganisms and its levels increase during aging. Moreover, we observed that dietary supplementation of 2% DMA inhibits metabolism in mice, resulting in reduced muscle mass, strength, and the number of blood vessels, as well as the skeletal muscle fiber type I/IIb ratio. In vitro assays demonstrate that DMA decreases the proliferation of vascular endothelial cells and suppresses the formation of blood vessels. In vivo, we further demonstrated that boosting angiogenesis by muscular VEGFB injection rescues the inhibitory effects of D-malate on muscle mass and fiber area. By transcriptomics analysis, we identified that the mechanism underlying the effects of DMA depends on the elevated intracellular acetyl-CoA content and increased Cyclin A acetylation rather than redox balance. This study reveals a novel mechanism by which gut microbes impair muscle angiogenesis and may provide a therapeutic target for skeletal muscle dysfunction in cancer or aging.

Inactivation of Mst/Nrf2/Keap1 signaling flexibly mitigates MAPK/NQO-HO1 activation in the reproductive axis of experimental fluorosis.

Fluoride induced reprotoxicity through oxidative stress-mediated reproductive cell death. Hence, the current study evaluated the importance of the MST/Nrf2/MAPK/NQO-HO1 signaling pathway in fluorosis-induced reproductive toxicity. For this purpose, the reproductive toxicity of sodium fluoride (NaF) at physiological, biochemical, and intracellular levels was evaluated. In-vivo, NaF at 100 mg/L instigated physiological dysfunction, morphological, stereological, and structural injuries in the gut-gonadal axis of fluorosis mice through weakening the antioxidant signaling, Nrf2/HO-1/NQO1signaling pathway, causing the gut-gonadal barrier disintegrated via oxidative stress-induced inflammation, mitochondrial damage, apoptosis, and autophagy. Similar trends were also observed in-vitro in the isolated Leydig cells (LCs) challenging with 20 mg/L NaF. Henceforth, activating the cellular antioxidant signaling pathway, Nrf2/HO-1/NQO1, inactivating autophagy and apoptosis, or attenuating lipopolysaccharide (LPS) can be the theoretical basis and valuable therapeutic targets for coping with NaF-induced reproductive toxicity.

Oxaloacetic acid induces muscle energy substrate depletion and fatigue by JNK-mediated mitochondrial uncoupling.

Fatigue is a common phenomenon closely related to physical discomfort and numerous diseases, which is severely threatening the life quality and health of people. However, the exact mechanisms underlying fatigue are not fully characterized. Herein, we demonstrate that oxaloacetic acid (OAA), a crucial tricarboxylic acid cycle intermediate, modulates the muscle fatigue. The results showed that serum OAA level was positively correlated with fatigue state of mice. OAA-treated induced muscle fatigue impaired the exercise performance of mice. Mechanistically, OAA increased the c-Jun N-terminal kinase (JNK) phosphorylation and uncoupling protein 2 (UCP2) levels in skeletal muscle, which led to decreased energy substrate and enhanced glycolysis. On the other hand, OAA boosted muscle mitochondrial oxidative phosphorylation uncoupled with energy production. In addition, either UCP2 knockout or JNK inhibition totally reversed the effects of OAA on skeletal muscle. Therein, JNK mediated UCP2 activation with OAA-treated. Our studies reveal a novel role of OAA in skeletal muscle metabolism, which would shed light on the mechanism of muscle fatigue and weakness.

Enhancement of dissolution rate and oral bioavailability of poorly soluble drug florfenicol by using solid dispersion and effervescent disintegration technology.

OBJECTIVE: Florfenicol(FF) is an excellent veterinary antibiotic, limited by poor solubility and poor bioavailability. SIGNIFICANCE: Here in, we aimed to explore the applicability of fast disintegrating tablets compressed from Florfenicol-loaded solid dispersions (FF-SD-FDTs) to improve the dissolution rate and oral bioavailability of Florfenicol. METHODS: Utilizing selecting appropriate preparation methods and carriers, the solid dispersions of Florfenicol (FF-SDs) were prepared by solvent evaporation and the fast disintegrating tablets (FF-SD-FDTs) were prepared by the direct compression (DC) method. RESULTS: The tablet properties including hardness, friability, disintegration time, weight variation, etc. all met the specifications of Chinese Veterinary Pharmacopeia(CVP). FF-SD-FDTs significantly improved drug dissolution and dispersion of FF in vitro compared to florfenicol conventional tablets (FF-CTs). A pharmacokinetics study in German shepherd dogs proved the AUC0-∞ and Cmax values of FF-SD-FDTs are 1.38 and 1.38 times more than FF-CTs, respectively. CONCLUSIONS: Overall, it can be concluded that FF-SD-FDTs with excellent disintegration and dissolution properties were successfully produced, which greatly improved the oral bioavailability of the poorly soluble drug FF, and the study provided a new idea for a broader role of FF in pet clinics.

Achieving Complete Tumor Clearance: A Minimalist Manganese Hydrogel for Magnetic Resonance Imaging-Guided Synergetic Microwave Ablation and Chemodynamic Therapy.

The combination of microwave ablation (MWA) and chemodynamic therapy (CDT) presents a promising strategy for complete eradication of residual tumor after MWA. However, it remains challenging and urgent to develop a facile, biocompatible, and imaging-guided platform for the achievement of this goal. Herein, a minimalist manganese hydrogel (ALG-Mn hydrogel) is proposed for synergistic MWA and CDT to completely eradicate tumor in vivo. The ALG-Mn hydrogel is prepared using a simple mixing method and exhibits excellent syringeability, remarkable microwave sensitivity, and potent Fenton-like activity. By assisting in MWA procedures, the ALG-Mn hydrogel enables both elimination of primary tumor mass through enhanced MWA efficacy and eradication of potential residual tumor tissues via robust CDT. This approach achieves complete tumor clearance without additional drug loading. Furthermore, the paramagnetic Mn2+ component allows real-time dynamic visualization of the ALG-Mn hydrogel at the tumor site via magnetic resonance imaging. To the best of knowledge, the proposed ALG-Mn hydrogel represents the minimalist biocompatible platform for imaging-guided synergistic MWA and CDT toward achieving complete tumor clearance.

Metallic artifacts-free spectral computed tomography angiography based on renal clearable bismuth chelate.

Computed tomography angiography (CTA) is one of the most important diagnosis techniques for various vascular diseases in clinic. However, metallic artifacts caused by metal implants and calcified plaques in more and more patients severely hinder its wide applications. Herein, we propose an improved metallic artifacts-free spectral CTA technique based on renal clearable bismuth chelate (Bi-DTPA dimeglumine) for the first time. Bi-DTPA dimeglumine owns the merits of ultra-simple synthetic process, approximately 100% of yield, large-scale production capability, good biocompatibility, and favorable renal clearable ability. More importantly, Bi-DTPA dimeglumine shows superior contrast-enhanced effect in CTA compared with clinical iohexol at a wide range of X-ray energies especially in higher X-ray energy. In rabbits' model with metallic transplants, Bi-DTPA dimeglumine assisted-spectral CTA can not only effectively mitigate metallic artifacts by reducing beam hardening effect under high X-ray energy, but also enables accurate delineation of vascular structure. Our proposed strategy opens a revolutionary way to solve the bottleneck problem of metallic artifacts in CTA examinations.

Rhamnolipid Micelles Assist Azithromycin in Efficiently Disrupting Staphylococcus aureus Biofilms and Impeding Their Re-Formation.

Introduction: Biofilm is highly resistant to antibiotics due to its heterogeneity and is implicated in over 80% of chronic infections; these refractory and relapse-prone infections pose a huge medical burden. Methods: In this study, rhamnolipid (RHL), a biosurfactant with antibiofilm activity, was loaded with the antibiotic azithromycin (AZI) to construct a stable nanomicelle (AZI@RHL) that promotes Staphylococcus aureus (S. aureus) biofilm disruption. Results: AZI@RHL micelles made a destruction in biofilms. The biofilm biomasses were reduced significantly by 48.2% (P<0.05), and the main components polysaccharides and proteins were reduced by 47.5% and 36.8%, respectively. These decreases were about 3.1 (15.9%), 7.3 (6.5%), and 1.9 (19.5%) times higher compared with those reported for free AZI. The disruption of biofilm structure was observed under a confocal microscope with fluorescent labeling, and 48.2% of the cells in the biofilm were killed. By contrast, the clearance rates of cells were only 20% and 17% when treated alone with blank micelles or free AZI. Biofilm formation was inhibited up to 92% in the AZI@RHL group due to effects on cell auto-aggregation and eDNA release. The rates for the other groups were significantly lower, with only 27.7% for the RHL group and 12% for the AZI group (P<0.05). The low cell survival and great formation inhibition could reduce biofilm recolonization and re-formation. Conclusion: The antibiofilm efficacy of rhamnolipid was improved through micellar nanoparticle effects when loading azithromycin. AZI@RHL provides a one-step solution that covers biofilm disruption, bacteria inactivation, recolonization avoidance, and biofilm re-formation inhibition.

Browning of Mammary Fat Suppresses Pubertal Mammary Gland Development of Mice via Elevation of Serum Phosphatidylcholine and Inhibition of PI3K/Akt Pathway.

Mammary fat plays a profound role in the postnatal development of mammary glands. However, the specific types (white, brown, or beige) of adipocytes in mammary fat and their potential regulatory effects on modulating mammary gland development remain poorly understood. This study aimed to investigate the role of the browning of mammary fat on pubertal mammary gland development and explore the underlying mechanisms. Thus, the mammary gland development and the serum lipid profile were evaluated in mice treated with CL316243, a ß3-adrenoceptor agonist, to induce mammary fat browning. In addition, the proliferation of HC11 cells co-cultured with brown adipocytes or treated with the altered serum lipid metabolite was determined. Our results showed that the browning of mammary fat by injection of CL316243 suppressed the pubertal development of mice mammary glands, accompanied by the significant elevation of serum dioleoylphosphocholine (DOPC). In addition, the proliferation of HC11 was repressed when co-cultured with brown adipocytes or treated with DOPC. Furthermore, DOPC suppressed the activation of the PI3K/Akt pathway, while the DOPC-inhibited HC11 proliferation was reversed by SC79, an Akt activator, suggesting the involvement of the PI3K/Akt pathway in the DOPC-inhibited proliferation of HC11. Together, the browning of mammary fat suppressed the development of the pubertal mammary gland, which was associated with the elevated serum DOPC and the inhibition of the PI3K/Akt pathway.

Unveiling the Potential of Bacillus safensis Y246 for Enhanced Suppression of Rhizoctonia solani.

Rhizoctonia solani is a significant pathogen affecting various crops, including tobacco. In this study, a bacterial strain, namely Y246, was isolated from the soil of healthy plants and exhibited high antifungal activity. Based on morphological identification and DNA sequencing, this bacterial strain was identified as Bacillus safensis. The aim of this investigation was to explore the antifungal potential of strain Y246, to test the antifungal stability of Y246 by adjusting different cultivation conditions, and to utilize gas chromatography-mass spectrometry (GC-MS) to predict the volatile compounds related to antifungal activity in Y246. In vitro assays demonstrated that strain Y246 exhibited a high fungal inhibition rate of 76.3%. The fermentation broth and suspension of strain Y246 inhibited the mycelial growth of R. solani by 66.59% and 63.75%, respectively. Interestingly, treatment with volatile compounds derived from the fermentation broth of strain Y246 resulted in abnormal mycelial growth of R. solani. Scanning electron microscopy analysis revealed bent and deformed mycelium structures with a rough surface. Furthermore, the stability of antifungal activity of the fermentation broth of strain Y246 was assessed. Changes in temperature, pH value, and UV irradiation time had minimal impact on the antifungal activity, indicating the stability of the antifungal activity of strain Y246. A GC-MS analysis of the volatile organic compounds (VOCs) produced by strain Y246 identified a total of 34 compounds with inhibitory effects against different fungi. Notably, the strain demonstrated broad-spectrum activity, exhibiting varying degrees of inhibition against seven pathogens (Alternaria alternata, Phomopsis. sp., Gloeosporium musarum, Dwiroopa punicae, Colletotrichum karstii, Botryosphaeria auasmontanum, and Botrytis cinerea). In our extensive experiments, strain Y246 not only exhibited strong inhibition against R. solani but also demonstrated remarkable inhibitory effects on A. alternata-induced tobacco brown spot and kiwifruit black spot, with impressive inhibition rates of 62.96% and 46.23%, respectively. Overall, these findings highlight the significant antifungal activity of B. safensis Y246 against R. solani. In addition, Y246 has an excellent antifungal stability, with an inhibition rate > 30% under different treatments (temperature, pH, UV). The results showed that the VOCs of strain Y246 had a strong inhibitory effect on the colony growth of R. solani, and the volatile substances produced by strain Y246 had an inhibitory effect on R. solani at rate of 70.19%. Based on these results, we can conclude that Y246 inhibits the normal growth of R. solani. These findings can provide valuable insights for developing sustainable agricultural strategies.