Expanding horizons of iminosugars as broad-spectrum anti-virals: mechanism, efficacy and novel developments.

Iminosugars, a class of polyhydroxylated cyclic alkaloids with intriguing properties, hold promising therapeutic potentials against a broad spectrum of enveloped viruses, including DENV, HCV, HIV, and influenza viruses. Mechanistically, iminosugars act as the competitive inhibitors of host endoplasmic reticular α-glucosidases I and II to  disrupt the proper folding of viral nascent glycoproteins, which thereby exerts antiviral effects. Remarkably, the glycoproteins of many enveloped viruses are significantly more dependent on the calnexin pathway of the protein folding than most host glycoproteins. Therefore, extensive interests and efforts have been devoted to exploit iminosugars as broad-spectrum antiviral agents. This review provides the summary and insights into the recent advancements in the development of novel iminosugars as effective and selective antiviral agents against a variety of enveloped viruses, as well as the understandings of their antiviral mechanisms.

Peritumoral radiomics increases the efficiency of classification of pure ground-glass lung nodules: a multicenter study.

PURPOSE: We aimed to evaluate the efficiency of computed tomography (CT) radiomic features extracted from gross tumor volume (GTV) and peritumoral volumes (PTV) of 5, 10, and 15 mm to identify the tumor grades corresponding to the new histological grading system proposed in 2020 by the Pathology Committee of the International Association for the Study of Lung Cancer (IASLC). METHODS: A total of 151 lung adenocarcinomas manifesting as pure ground-glass lung nodules (pGGNs) were included in this randomized multicenter retrospective study. Four radiomic models were constructed from GTV and GTV + 5/10/15-mm PTV, respectively, and compared. The diagnostic performance of the different models was evaluated using receiver operating characteristic curve analysis RESULTS: The pGGNs were classified into grade 1 (117), 2 (34), and 3 (0), according to the IASLC grading system. In all four radiomic models, pGGNs of grade 2 had significantly higher radiomic scores than those of grade 1 (P < 0.05). The AUC of the GTV and GTV + 5/10/15-mm PTV were 0.869, 0.910, 0.951, and 0.872 in the training cohort and 0.700, 0.715, 0.745, and 0.724 in the validation cohort, respectively. CONCLUSIONS: The radiomic features we extracted from the GTV and PTV of pGGNs could effectively be used to differentiate grade-1 and grade-2 tumors. In particular, the radiomic features from the PTV increased the efficiency of the diagnostic model, with GTV + 10 mm PTV exhibiting the highest efficacy.

Dietary supplementation with mulberry leaf flavonoids and carnosic acid complex enhances the growth performance and antioxidant capacity via regulating the p38 MAPK/Nrf2 pathway.

Introduction: This study aimed to investigate the regulatory effects of mulberry leaf flavonoids and carnosic acid complex (MCC) on the growth performance, intestinal morphology, antioxidant, and p38 MAPK/Nrf2 pathway in broilers. Methods: A total of 256 healthy 8-day-old female yellow-feathered broilers were randomly divided into 4 equal groups: a control group (CON) fed a basal diet, an antibiotic group (CTC) supplemented with 50 mg/kg chlortetracycline, and two experimental groups (MCC75, MCC150) fed basal diets with 75 mg/kg and 150 mg/kg of MCC, respectively. The experiment lasted for 56 days, with days 1-28 designated as the initial phase and days 29-56 as the growth phase. Results: The results on the growth performance showed that diets supplemented with MCC and CTC decreased the feed-to-gain ratio (F/G), diarrhea rate, and death rate, while significantly increasing the average daily weight gain (ADG) (p < 0.05). Specifically, the MCC150 group enhanced intestinal health, indicated by reduced crypt depth and increased villus height-to-crypt depth ratio (V/C) as well as amylase activity in the jejunum. Both the MCC and CTC groups exhibited increased villus height and V/C ratio in the ileal (p < 0.05). Additionally, all treated groups showed elevated serum total antioxidant capacity (T-AOC), and significant increases in catalase (CAT) and glutathione peroxidase (GSH-Px) activities were observed in both the MCC150 and CTC groups. Molecular analysis revealed an upregulation of the jejunal mRNA expression levels of PGC-1α, Nrf2, and Keap1 in the MCC and CTC groups, as well as an upregulation of ileum mRNA expression levels of P38, PGC-1α, Nrf2, and Keap1 in the MCC150 group, suggesting activation of the p38-MAPK/Nrf2 pathway. Discussion: These findings indicate that dietary supplementation with MCC, particularly at a dosage of 150 mg/kg, may serve as a viable antibiotic alternative, enhancing growth performance, intestinal health, and antioxidant capacity in broilers by regulating the p38-MAPK/Nrf2 pathway.

The reduction of the carbon footprint of municipal solid waste management via source classification and supporting strategies: An analysis for the megacity of Shenzhen.

Municipal solid waste (MSW) management is a critical concern in megacities that depend heavily on external material and energy inputs but lack space for waste disposal. MSW treatment is a significant contributor to carbon emissions. The implementation of source classification improved the overall MSW management system and enhanced resource recovery from MSW. However, the precise contribution of source classification to carbon emissions reduction remains unclear. This study aimed to analyze the carbon emissions evolution in the MSW management of Shenzhen, a prototypical megacity in China, using data from 2006 to 2020 and employing carbon footprint assessment methodologies. The results demonstrated that source classification reduced the carbon emissions from 0.19-0.25 to 0.14-0.18 t CO2-eq/t MSW when considering the contribution of the urban environmental sanitation management department. The entire MSW management system becomes a carbon sink when considering recyclables collected by commercial enterprises. Although the source classification complicated the collection and transportation of MSW, the carbon offset effect of recycling food waste and recyclables was more significant than that of carbon emissions from collection and transport. Moreover, the landfill gas recovery rate critically influenced the carbon emissions of landfill-based MSW management systems. In contrast, the recovery of plastics was crucial for determining carbon emissions from incineration-based MSW management systems.

Modulation format recognition in a UVLC system based on an ultra-lightweight model with communication-informed knowledge distillation.

Modulation format recognition (MFR) is a key technology for adaptive optical systems, but it faces significant challenges in underwater visible light communication (UVLC) due to the complex channel environment. Recent advances in deep learning have enabled remarkable achievements in image recognition, owing to the powerful feature extraction of neural networks (NN). However, the high computational complexity of NN limits their practicality in UVLC systems. This paper proposes a communication-informed knowledge distillation (CIKD) method that achieves high-precision and low-latency MFR with an ultra-lightweight student model. The student model consists of only one linear dense layer under a communication-informed auxiliary system and is trained under the guidance of a high-complexity and high-precision teacher model. The MFR task involves eight modulation formats: PAM4, QPSK, 8QAM-CIR, 8QAM-DIA, 16QAM, 16APSK, 32QAM, and 32APSK. Experimental results show that the student model based on CIKD can achieve comparable accuracy to the teacher model. After knowledge transfer, the prediction accuracy of the student model can be increased by up to 87%. Besides, it is worth noting that CIKD's inference accuracy can reach up to 100%. Moreover, the parameters constituting the student model in CIKD correspond to merely 18% of the parameters found in the teacher model, which facilitates the hardware deployment and online data processing of MFR algorithms in UVLC systems.

Isolation and Evaluation of Erinacine A Contents in Mycelia of Hericium erinaceus Strains.

Hericium erinaceus has long been favored for its remarkable nutritional and health-promoting benefits, and erinacine A is the key component responsible for the neuroprotective properties of H. erinaceus. Establishing an efficient method for separating erinacine A from H. erinaceus and screening the erinacine A-enriched strains is crucial to maximizing its benefits. Herein, we first reported that high-speed counter current chromatography (HSCCC) is an effective method for separating high-purity erinacine A. Using a two-phase solvent system composed of n-hexane/ethyl acetate/methanol/water (4.5:5:4.5:5, v/v/v/v), erinacine A with a purity of over 95% was separated. Then, we evaluated the content and yield of erinacine A in the liquid-fermented mycelia of Hericium germplasms. Both the content and yield of erinacine A varied greatly among the surveyed strains. The significant effect of the strain on the erinacine A content and yield was revealed by an analysis of variance. The highest erinacine A content and yield were observed in the mycelia of a wild strain HeG, reaching 42.16 mg/g and 358.78 mg/L, which is superior to the current highest outcomes achieved using submerged cultivation. The isolation method established and the strains screened in this study can be beneficial for the scaling up of erinacine A extraction and nutraceutical development to industrial levels.

Discovery of meisoindigo derivatives as noncovalent and orally available Mpro inhibitors: their therapeutic implications in the treatment of COVID-19.

The progressive emergence of SARS-CoV-2 variants has necessitated the urgent exploration of novel therapeutic strategies to combat the COVID-19 pandemic. The SARS-CoV-2 main protease (Mpro) represents an evolutionarily conserved therapeutic target for drug discovery. This study highlights the discovery of meisoindigo (Mei), derived from the traditional Chinese medicine (TCM) Indigo naturalis, as a novel non-covalent and nonpeptidic Mpro inhibitor. Substantial optimizations and structure-activity relationship (SAR) studies, guided by a structure-based drug design approach, led to the identification of several Mei derivatives, including S5-27 and S5-28, exhibiting low micromolar inhibition against SARS-CoV-2 Mpro with high binding affinity. Notably, S5-28 provided significant protection against wild-type SARS-CoV-2 in HeLa-hACE2 cells, with EC50 up to 2.66 µM. Furthermore, it displayed favorable physiochemical properties and remarkable gastrointestinal and metabolic stability, demonstrating its potential as an orally bioavailable drug for anti-COVID-19 therapy. This research presents a promising avenue for the development of new antiviral agents, offering hope in the ongoing battle against COVID-19.

In vivo Labeling and Intravital Imaging of Bacterial Infection using a Near-infrared Fluorescent D-Amino Acid Probe.

Bacterial infections still pose a severe threat to public health, necessitating novel tools for real-time analysis of microbial behaviors in living organisms. While genetically engineered strains with fluorescent or luminescent reporters are commonly used in tracking bacteria, their in vivo uses are often limited. Here, we report a near-infrared fluorescent D-amino acid (FDAA) probe, Cy7ADA, for in situ labeling and intravital imaging of bacterial infections in mice. Cy7ADA probe effectively labels various bacteria in vitro and pathogenic Staphylococcus aureus in mice after intraperitoneal injection. Because of Cy7's high tissue penetration and the quick excretion of free probes via urine, real-time visualization of the pathogens in a liver abscess model via intravital confocal microscopy is achieved. The biodistributions, including their intracellular localization within Kupffer cells, are revealed. Monitoring bacterial responses to antibiotics also demonstrates Cy7ADA's capability to reflect the bacterial load dynamics within the host. Furthermore, Cy7ADA facilitates three-dimensional pathogen imaging in tissue-cleared liver samples, showcasing its potential for studying the biogeography of microbes in different organs. Integrating near-infrared FDAA probes with intravital microscopy holds promise for wide applications in studying bacterial infections in vivo.

Catalytic asymmetric carbenoid α-C-H insertion of ether.

Significant advancements have been made in catalytic asymmetric α-C-H bond functionalization of ethers via carbenoid insertion over the past decade. Effective asymmetric catalytic systems, featuring a range of chiral metal catalysts, have been established for the enantioselective synthesis of diverse ether substrates. This has led to the generation of various enantioenriched, highly functionalized oxygen-containing structural motifs, facilitating their application in the asymmetric synthesis of bioactive natural products.

Renoprotective effects of Schoenoplectus tabernaemontani rhizomes aqueous extracts against Adriamycin-induced nephropathy in rats.

In recent years, chronic kidney disease (CKD) has emerged as an increasingly significant issue due to the growing prevalence and high treatment costs. While recorded the positive diuretic effect of Schoenoplectus tabernaemontani, there is a lack of reports on its efficacy in treating CKD. The pharmacological effects and mechanisms of Schoenoplectus tabernaemontani rhizomes aqueous extracts (STE) in CKD were investigated by inducing a rodent model of CKD via injection of Adriamycin (ADR; 7.5 mg/kg) into the tail vein of Wistar rats. In summary, our findings suggest that STE has a beneficial effect on anti-renal fibrosis and can reverse ADR-induced renal injury by suppressing oxidative stress and inflammation. Therefore, STE holds promising potential as a treatment option for CKD.

Efficacy of early administration of sacubitril/valsartan after coronary artery revascularization in patients with acute myocardial infarction complicated by moderate-to-severe mitral regurgitation: a randomized controlled trial.

Effects of angiotensin receptor/neprilysin inhibitors (ARNI) on ventricular remodeling in patients with heart failure, especially heart failure with reduced ejection fraction (HFrEF), are better than those of angiotensin-converting enzyme inhibitors (ACEI). Acute myocardial infarction (AMI) complicated by mitral regurgitation exacerbates ventricular remodeling and increases the risk of heart failure. There is limited evidence on the effects of early administration of ARNI in patients with AMI complicated by mitral regurgitation. The aim of this trial was to examine the effectiveness and the safety of early administration of sacubitril/valsartan after coronary artery revascularization in patients with AMI complicated by moderate-to-severe mitral regurgitation. This was a randomized, single-blind, parallel-group, controlled trial. From June 2021 to June 2022, we enrolled 142 consecutive patients with AMI complicated by moderate-to-severe mitral regurgitation and followed them for 12 months. The patients received standard treatment for AMI and were randomly assigned to receive ARNI or benazepril. The primary efficacy end points were the differences in mitral regurgitant jet area (MRJA), mitral regurgitant volume (MRV), concentration of n-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume and end-systolic volume (LVEDV and LVESV) between groups and within groups at baseline, 1, 3, 6, and 12 months. Secondary end points included the rates of heart failure hospitalization, all-cause mortality, refractory angina, malignant arrhythmias, recurrent myocardial infarction, and stroke. Safety end points included the rates of hyperkalemia, renal dysfunction, hypotension, angioedema, and cough. The ARNI group had significantly lower NT-proBNP levels than the benazepril group at 1 month and later (P < 0.001). MRJA and MRV significantly improved in the ARNI group compared with the benazepril group at 12 months (MRJA: - 3.21 ± 2.18 cm2 vs. - 1.83 ± 2.81 cm2, P < 0.05; MRV: - 27.22 ± 15.22 mL vs. - 13.67 ± 21.02 mL, P < 0.001). The ARNI group also showed significant reductions in LVEDV and LVESV (P < 0.05) and improvement in LVEF (P < 0.05). Secondary end point analysis showed a significantly higher rate of heart failure hospitalization in the benazepril group compared with the ARNI group (HR = 2.03, 95% CI 1.12-3.68, P = 0.021). Safety end point analysis showed a higher rate of hypotension in the ARNI group (P < 0.05). Early use of sacubitril/valsartan after coronary artery revascularization in patients with AMI complicated by moderate-to-severe mitral regurgitation can significantly reduce mitral regurgitation, improve ventricular remodeling, and decrease heart failure hospitalization. Nevertheless, caution is needed to avoid hypotension. Chinese Clinical Trial Registry (ChiCTR2100054255) registered on December 11, 2021.

Discovery of a Meisoindigo-Derived PROTAC as the ATM Degrader: Revolutionizing Colorectal Cancer Therapy via Synthetic Lethality with ATR Inhibitors.

Meisoindigo (Mei) has long been recognized in chronic myeloid leukemia (CML) treatment. To elucidate its molecular target and mechanisms, we embarked on designing and synthesizing a series of Mei-derived PROTACs. Through this endeavor, VHL-type PROTAC 9b was identified to be highly cytotoxic against SW620, SW480, and K562 cells. Employing DiaPASEF-based quantitative proteomic analysis, in combination with extensive validation assays, we unveiled that 9b potently and selectively degraded ATM across SW620 and SW480 cells in a ubiquitin-proteasome-dependent manner. 9b-induced selective ATM degradation prompted DNA damage response cascades, thereby leading to the cell cycle arrest and cell apoptosis. This pioneering discovery renders the advent of ATM degradation for anti-cancer therapy. Notably, 9b-induced ATM degradation synergistically enhanced the efficacy of ATR inhibitor AZD6738 both in vitro and in vivo. This work establishes the synthetic lethality-inducing properties of ATR inhibitors in the ATM-deficient context, thereby providing new avenues to innovative therapies for colorectal cancer.

Leveraging multimodal MRI-based radiomics analysis with diverse machine learning models to evaluate lymphovascular invasion in clinically node-negative breast cancer.

Objective: This study aimed to investigate and validate the effectiveness of diverse radiomics models for preoperatively differentiating lymphovascular invasion (LVI) in clinically node-negative breast cancer (BC). Methods: This study included 198 patients diagnosed with clinically node-negative bc and pathologically confirmed LVI status from January 2018-July 2023. The training dataset consisted of 138 patients, while the validation dataset included 60. Radiomics features were extracted from multimodal magnetic resonance imaging obtained from T1WI, T2WI, DCE, DWI, and ADC sequences. Dimensionality reduction and feature selection techniques were applied to the extracted features. Subsequently, machine learning approaches, including logistic regression, support vector machine, classification and regression trees, k-nearest neighbors, and gradient boosting machine models (GBM), were constructed using the radiomics features. The best-performing radiomic model was selected based on its performance using the confusion matrix. Univariate and multivariable logistic regression analyses were conducted to identify variables for developing a clinical-radiological (Clin-Rad) model. Finally, a combined model incorporating both radiomics and clinical-radiological model features was created. Results: A total of 6195 radiomic features were extracted from multimodal magnetic resonance imaging. After applying dimensionality reduction and feature selection, seven valuable radiomics features were identified. Among the radiomics models, the GBM model demonstrated superior predictive efficiency and robustness, achieving area under the curve values (AUC) of 0.881 (0.823,0.940) and 0.820 (0.693,0.947) in the training and validation datasets, respectively. The Clin-Rad model was developed based on the peritumoral edema and DWI rim sign. In the training dataset, it achieved an AUC of 0.767 (0.681, 0.854), while in the validation dataset, it achieved an AUC of 0.734 (0.555-0.913). The combined model, which incorporated radiomics and the Clin-Rad model, showed the highest discriminatory capability. In the training dataset, it had an AUC value of 0.936 (0.892, 0.981), and in the validation dataset, it had an AUC value of 0.876 (0.757, 0.995). Additionally, decision curve analysis of the combined model revealed its optimal clinical efficacy. Conclusion: The combined model, integrating radiomics and clinical-radiological features, exhibited excellent performance in distinguishing LVI status. This non-invasive and efficient approach holds promise for aiding clinical decision-making in the context of clinically node-negative BC.

Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.

Assessment of Lymphovascular Invasion in Breast Cancer Using a Combined MRI Morphological Features, Radiomics, and Deep Learning Approach Based on Dynamic Contrast-Enhanced MRI.

BACKGROUND: Assessment of lymphovascular invasion (LVI) in breast cancer (BC) primarily relies on preoperative needle biopsy. There is an urgent need to develop a non-invasive assessment method. PURPOSE: To develop an effective model to assess the LVI status in patients with BC using magnetic resonance imaging morphological features (MRI-MF), Radiomics, and deep learning (DL) approaches based on dynamic contrast-enhanced MRI (DCE-MRI). STUDY TYPE: Cross-sectional retrospective cohort study. POPULATION: The study included 206 BC patients, with 136 in the training set [97 LVI(-) and 39 LVI(+) cases; median age: 51.5 years] and 70 in the test set [52 LVI(-) and 18 LVI(+) cases; median age: 48 years]. FIELD STRENGTH/SEQUENCE: 1.5 T/T1-weighted images, fat-suppressed T2-weighted images, diffusion-weighted imaging (DWI), and DCE-MRI. ASSESSMENT: The MRI-MF model was developed with conventional MR features using logistic analyses. The Radiomic feature extraction process involved collecting data from categorized DCE-MRI datasets, specifically the first and second post-contrast images (A1 and A2). Next, a DL model was implemented to determine LVI. Finally, we established a joint diagnosis model by combining the MRI-MF, Radiomics, and DL approaches. STATISTICAL TESTS: Diagnostic performance was compared using receiver operating characteristic curve analysis, confusion matrix, and decision curve analysis. RESULTS: Rim sign and peritumoral edema features were used to develop the MRI-MF model, while six Radiomics signature from the A1 and A2 images were used for the Radiomics model. The joint model (MRI-MF + Radiomics + DL models) achieved the highest accuracy (area under the curve [AUC] = 0.857), being significantly superior to the MRI-MF (AUC = 0.724), Radiomics (AUC = 0.736), or DL (AUC = 0.740) model. Furthermore, it also outperformed the pairwise combination models: Radiomics + MRI-MF (AUC = 0.796), DL + MRI-MF (AUC = 0.796), or DL + Radiomics (AUC = 0.826). DATA CONCLUSION: The joint model incorporating MRI-MF, Radiomics, and DL approaches can effectively determine the LVI status in patients with BC before surgery. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Rapid access to icetexane diterpenes: Their protective effects against lipopolysaccharides-induced acute lung injury via PI3K/AKT/NF-κB axis in macrophages.

Acute lung injury (ALI) is a life-threatening disease with limited therapeutic options available in clinic. Development of novel strategies and drugs for anti-ALI therapy are urgently needed. In this study, a facile synthesis of 21 icetexane diterpenes and derivatives with widely-varied oxidation states, particularly the taxamairins that are otherwise challenging to access, were developed from the readily available carnosic acid. Further explorations of their biological implications led to the identification of taxamairin B (6) as a potent anti-inflammatory agent by decreasing the gene expressions of proinflammatory cytokines (TNF-α, IL-1ß and IL-6), as well as mitigating NO and ROS production, within LPS-induced RAW264.7 cells. Taxamairin B (6, 25 mg/kg) also exerted significant protective effects against in LPS-induced ALI in mice. Mechanistic insights drawn from the transcriptomic analysis revealed that taxamairin B (6) down-regulated the PI3K-AKT pathway, along with the suppression of the nuclear translocation of NF-κB. This study not only paves a new pathway to taxamairins, but also provides novel drug leads for the development of anti-inflammatory agents with unique mode of actions.

Auricularia auricula-judae (Bull.) polysaccharides improve obesity in mice by regulating gut microbiota and TLR4/JNK signaling pathway.

Obesity has emerged as a crucial factor impacting people's lives, and gut microbiota disorders contribute to its development and progression. Auricularia auricula-judae (Bull.) polysaccharides (AAPs), a traditional functional food in Asia, exhibit potential anti-obesity effects. However, the specific mechanism still needs to be further confirmed. This study investigated the beneficial effects and specific mechanisms of AAPs on obesity. Firstly, AAPs showed significant improvements in overweight, insulin resistance, glucose and lipid metabolism disorders, and liver damage in obese mice. Additionally, AAPs ameliorated gut microbiota disorders, promoting the proliferation of beneficial bacteria like Lactobacillus and Roseburia, resulting in increased levels of SCFAs, folate, and cobalamin. Simultaneously, AAPs inhibited the growth of harmful bacteria, thereby protecting intestinal barrier function, improving endotoxemia, and decreasing the levels of inflammatory factors such as TNF-α and IL-6. Furthermore, AAPs can inhibit the TLR4/JNK signaling pathway while promoting the activation of AKT and AMPK. Importantly, our study underscored the pivotal role of gut microbiota in the anti-obesity effects of AAPs, as evidenced by fecal microbiota transplantation experiments. In conclusion, our findings elucidated that AAPs improve obesity by regulating gut microbiota and TLR4/JNK signaling pathway, offering novel perspectives for further conclusion the anti-obesity potential of AAPs.

Optimization of fermentation conditions for surfactin production by B. subtilis YPS-32.

BACKGROUND: Surfactin produced by microbial fermentation has attracted increasing attention because of its low toxicity and excellent antibacterial activity. However, its application is greatly limited by high production costs and low yield. Therefore, it is important to produce surfactin efficiently while reducing the cost. In this study, B. subtilis strain YPS-32 was used as a fermentative strain for the production of surfactin, and the medium and culture conditions for the fermentation of B. subtilis YPS-32 for surfactin production were optimized. RESULTS: First, Landy 1 medium was screened as the basal medium for surfactin production by B. subtilis strain YPS-32. Then, using single-factor optimization, the optimal carbon source for surfactin production by B. subtilis YPS-32 strain was determined to be molasses, nitrogen sources were glutamic acid and soybean meal, and inorganic salts were KCl, K2HPO4, MgSO4, and Fe2(SO4)3. Subsequently, using Plackett-Burman design, MgSO4, time (h) and temperature (°C) were identified as the main effect factors. Finally, Box-Behnken design were performed on the main effect factors to obtain optimal fermentation conditions: temperature of 42.9 °C, time of 42.8 h, MgSO4 = 0.4 g·L- 1. This modified Landy medium was predicted to be an optimal fermentation medium: molasses 20 g·L- 1, glutamic acid 15 g·L- 1, soybean meal 4.5 g·L- 1, KCl 0.375 g·L- 1, K2HPO4 0.5 g·L- 1, Fe2(SO4)3 1.725 mg·L- 1, MgSO4 0.4 g·L- 1. Using the modified Landy medium, the yield of surfactin reached 1.82 g·L- 1 at pH 5.0, 42.9 ℃, and 2% inoculum for 42.8 h, which was 2.27-fold higher than that of the Landy 1 medium in shake flask fermentation. Additionally, under these optimal process conditions, further fermentation was carried out at the 5 L fermenter level by foam reflux method, and at 42.8 h of fermentation, surfactin reached a maximum yield of 2.39 g·L- 1, which was 2.96-fold higher than that of the Landy 1 medium in 5 L fermenter. CONCLUSION: In this study, the fermentation process of surfactin production by B. subtilis YPS-32 was improved by using a combination of single-factor tests and response surface methodology for test optimization, which laid the foundation for its industrial development and application.

Solid-state fermentation of Apocynum venetum L. by Aspergillus niger: Effect on phenolic compounds, antioxidant activities and metabolic syndrome-associated enzymes.

This study aimed to evaluate the effect of solid-state fermentation (SSF) with Aspergillus niger on the total phenolic content (TPC), the total flavonoid content (TFC), individual phenolic contents, and antioxidant and inhibitory activities against metabolic syndrome-associated enzymes in an ethanol extract from Apocynum venetum L. (AVL). TPC, TFC, and the contents of quercetin and kaempferol during SSF were 1.52-, 1.33-, 3.64-, and 2.22-fold higher than those of native AVL in the ethyl acetate (EA) subfraction of the ethanol extract. The ABTS·+, DPPH· scavenging, and inhibitory activities against α-glucosidase and pancreatic lipase were found to be highest in the EA subfraction. Fermentation significantly increased the ABTS radical cation, DPPH radical scavenging, and pancreatic lipase inhibitory activities by 1.33, 1.39, and 1.28 times, respectively. TPC showed a significantly positive correlation with antioxidant activities or inhibition against metabolic syndrome-associated enzymes. This study provides a theoretical basis for producing tea products with enhanced antioxidant, antidiabetic, and antihyperlipidemic activities.

Impairment of ovarian follicular development caused by titanium dioxide nanoparticles exposure involved in the TGF-ß/BMP/Smad pathway.

Titanium dioxide nanoparticles (TiO2 NPs) have been shown to induce reproductive system damages in animals. To better underline how TiO2 NPs act in reproductive system, female mice were exposed to 2.5, 5, or 10 mg/kg TiO2 NPs by gavage administration for 60 days, the ovary injuries, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels as well as ovarian follicular development-related molecule expression were investigated. The results showed that TiO2 NPs exposure resulted in reduction of ovary weight and inhibition of ovarian follicular development. Furthermore, the suppression of follicular development was demonstrated to be closely related to higher FSH and LH levels, and higher expression of activin, follistatin, BMP2, BMP4, TGF-ß1, Smad2, Smad3, and Smad4 as well as decreased inhibin-α expression in mouse ovary in a dose-dependent manner. It implies that the impairment of ovarian follicular development caused by TiO2 NPs exposure may be mediated by TGF-ß signal pathway.