Single-Atom Iron Catalyst as an Advanced Redox Mediator for Anodic Oxidation of Organic Electrosynthesis.

Homogeneous electrocatalysts can indirect oxidate the high overpotential substrates through single-electron transfer on the electrode surface, enabling efficient operation of organic electrosynthesis catalytic cycles. However, the problems of this chemistry still exist such as high dosage, difficult recovery, and low catalytic efficiency. Single-atom catalysts (SACs) exhibit high atom utilization and excellent catalytic activity, hold great promise in addressing the limitations of homogeneous catalysts. In view of this, we have employed Fe-SA@NC as an advanced redox mediator to try to change this situation. Fe-SA@NC was synthesized using an encapsulation-pyrolysis method, and it demonstrated remarkable performance as a redox mediator in a range of reported organic electrosynthesis reactions, and enabling the construction of various C-C/C-X bonds. Moreover, Fe-SA@NC demonstrated a great potential in exploring new synthetic method for organic electrosynthesis. We employed it to develop a new electro-oxidative ring-opening transformation of cyclopropyl amides. In this new reaction system, Fe-SA@NC showed good tolerance to drug molecules with complex structures, as well as enabling flow electrochemical syntheses and gram-scale transformations. This work highlights the great potential of SACs in organic electrosynthesis, thereby opening a new avenue in synthetic chemistry.

Association between obstructive sleep apnea and low bone mass in adults: a systematic review and meta-analysis.

Introduction: This study aimed to synthesize existing evidence on the potential association between obstructive sleep apnea (OSA) and low bone mass in adults. Methods: Electronic searches of four main databases were performed. The inclusion criteria consisted of observational studies investigating the relationship between OSA and bone mass, osteoporosis, fractures, or bone metabolism markers in adult population. Bone mineral density (BMD) and T score of lumbar and femur neck, incidence of osteoporosis and fractures, bone metabolism marker levels were extracted as primary outcomes. Results: Among the 693 relevant publications, 10 studies consisting of 158,427 participants met with the inclusion and exclusion criteria. Meta-analysis showed a significant lower BMD of lumbar (mean difference (MD) = - 0.03; 95% CI - 0.05, - 0.01; I2 = 46%), femur neck (MD = - 0.06; 95% CI - 0.12, 0.00; I2 = 71%), and a significant lower T score of lumbar (MD = - 0.42; 95% CI - 0.79, - 0.05; I2 = 63%) in the OSA group. The results suggested that both male (odds ratio (OR) = 2.03; 95% CI 1.23, 3.35; I2 = 38%) and female (OR = 2.56; 95% CI 1.96, 3.34; I2 = 0%) had higher risk of osteoporosis in the OSA group. Besides, meta-analysis also showed that bone-specific alkaline phosphatase was significantly lower in OSA patients (MD = - 1.90; 95% CI - 3.48, - 0.32; I2 = 48%). Conclusions: A potential association between OSA and lower bone mass in adults is preliminarily proved. It also seems plausible that both male and female with OSA have a higher risk of osteoporosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00481-1.

Iron overload in hypothalamic AgRP neurons contributes to obesity and related metabolic disorders.

Iron overload is closely associated with metabolic dysfunction. However, the role of iron in the hypothalamus remains unclear. Here, we find that hypothalamic iron levels are increased, particularly in agouti-related peptide (AgRP)-expressing neurons in high-fat-diet-fed mice. Using pharmacological or genetic approaches, we reduce iron overload in AgRP neurons by central deferoxamine administration or transferrin receptor 1 (Tfrc) deletion, ameliorating diet-induced obesity and related metabolic dysfunction. Conversely, Tfrc-mediated iron overload in AgRP neurons leads to overeating and adiposity. Mechanistically, the reduction of iron overload in AgRP neurons inhibits AgRP neuron activity; improves insulin and leptin sensitivity; and inhibits iron-induced oxidative stress, endoplasmic reticulum stress, nuclear factor κB signaling, and suppression of cytokine signaling 3 expression. These results highlight the critical role of hypothalamic iron in obesity development and suggest targets for treating obesity and related metabolic disorders.

Effects of Rhizopus-arrhizus-31-Assisted Pretreatment on the Extraction and Bioactivity of Total Flavonoids from Hibiscus manihot L.

The Hibiscus manihot L. (HML) Medic, an edible hibiscus of the Malvaceae family, is abundant with flavonoids. The study investigated how Rhizopus-arrhizus-31-assisted pretreatment affects the extraction and bioactivity of flavonoids from HML. The fiber structure of the fermented flavonoid sample (RFF) appears looser, more porous, and more disordered than the unfermented flavonoid sample (RUF). RFF demonstrates milder conditions and yields higher extraction rates. According to the Box-Behnken response surface optimization experiment, the optimal conditions for RFF include a material-liquid ratio of 1:41 g/mL, a 2 h extraction time, a 57% ethanol concentration, and an extraction temperature of 800 °C, resulting in a 3.69% extraction yield, which is 39.25% higher than that of RUF. Additionally, RFF exhibits greater activity than RUF in the radical-scavenging system. The IC50 values for DPPH, OH, and ABTS radicals are 83.43 µg/mL and 82.62 µg/mL, 208.38 µg/mL and 175.99 µg/mL, and 108.59 µg/mL and 75.39 µg/mL for RUF and RFF, respectively. UPLC-QTOF-MS analysis of the active components in the HML flavonoid sample revealed significant differences in the chromatograms of RUF and RFF, indicating that biofermentation led to substantial changes in composition and content from HML.

Integrated microbiome and metabolomics revealed the protective effect of baicalin on alveolar bone inflammatory resorption in aging.

BACKGROUND: With the growing aging population and longer life expectancy, periodontitis and tooth loss have become major health concerns. The gut microbiota, as a key regulator in bone homeostasis, has gathered immense interest. Baicalin, a flavonoid compound extracted from Scutellaria baicalensis Georgi, has shown antioxidant and anti-inflammatory activities. PURPOSE: This study investigated, for the first time, the protective mechanism of baicalin against alveolar bone inflammatory resorption in aging mice by regulating intestinal flora and metabolites, as well as intestinal barrier function. METHODS: A ligature-induced periodontitis model was established in d-galactose (D-gal)-induced aging mice, and baicalin was administered at different dosages for 13 weeks. Body weight was measured weekly. The antioxidant and anti-inflammatory activity of baicalin were evaluated using serum superoxide dismutase (SOD), malonaldehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. The immune capability was assessed by thymus and spleen indices. Histopathological changes were observed in the heart, liver, ileum, and periodontal tissues. Alveolar bone absorption of maxillary second molars was examined, and osteoclasts were counted by tartrate-resistant acid phosphatase (TRAP) staining. Furthermore, fecal samples were analyzed using 16S rRNA sequencing and non-targeted metabolomics to identify differences in intestinal bacterial composition and metabolites. RESULTS: Baicalin exhibited anti-aging properties, as evidenced by increased SOD activity and decreased levels of MDA, IL-6, and TNF-α in serum compared to the control group. Baicalin also ameliorated alveolar bone loss in the d-gal-induced aging-periodontitis group (p < 0.05). Furthermore, baicalin restored ileal permeability by up-regulating the expression of ZO-1 and occludin in aging-periodontitis groups (p < 0.05). Alpha diversity analysis indicated that baicalin-treated mice harbored a higher diversity of gut microbe. PCoA and ANOSIM results revealed significant dissimilarity between groups. The Firmicutes/Bacteroidetes (F/B) ratio, which decreased in periodontitis mice, was restored by baicalin treatment. Additionally, medium-dosage baicalin promoted the production of beneficial flavonoids, and enriched short-chain fatty acids (SCFAs)-producing bacteria. CONCLUSION: Intestinal homeostasis is a potential avenue for treating age-related alveolar bone loss. Baicalin exerts anti-inflammatory, antioxidant, and osteo-protective properties by regulating the gut microbiota and metabolites.

Knowledge Graph Enhanced Transformers for Diagnosis Generation of Chinese Medicine.

Chinese medicine (CM) diagnosis intellectualization is one of the hotspots in the research of CM modernization. The traditional CM intelligent diagnosis models transform the CM diagnosis issues into classification issues, however, it is difficult to solve the problems such as excessive or similar categories. With the development of natural language processing techniques, text generation technique has become increasingly mature. In this study, we aimed to establish the CM diagnosis generation model by transforming the CM diagnosis issues into text generation issues. The semantic context characteristic learning capacity was enhanced referring to Bidirectional Long Short-Term Memory (BILSTM) with Transformer as the backbone network. Meanwhile, the CM diagnosis generation model Knowledge Graph Enhanced Transformer (KGET) was established by introducing the knowledge in medical field to enhance the inferential capability. The KGET model was established based on 566 CM case texts, and was compared with the classic text generation models including Long Short-Term Memory sequence-to-sequence (LSTM-seq2seq), Bidirectional and Auto-Regression Transformer (BART), and Chinese Pre-trained Unbalanced Transformer (CPT), so as to analyze the model manifestations. Finally, the ablation experiments were performed to explore the influence of the optimized part on the KGET model. The results of Bilingual Evaluation Understudy (BLEU), Recall-Oriented Understudy for Gisting Evaluation 1 (ROUGE1), ROUGE2 and Edit distance of KGET model were 45.85, 73.93, 54.59 and 7.12, respectively in this study. Compared with LSTM-seq2seq, BART and CPT models, the KGET model was higher in BLEU, ROUGE1 and ROUGE2 by 6.00-17.09, 1.65-9.39 and 0.51-17.62, respectively, and lower in Edit distance by 0.47-3.21. The ablation experiment results revealed that introduction of BILSTM model and prior knowledge could significantly increase the model performance. Additionally, the manual assessment indicated that the CM diagnosis results of the KGET model used in this study were highly consistent with the practical diagnosis results. In conclusion, text generation technology can be effectively applied to CM diagnostic modeling. It can effectively avoid the problem of poor diagnostic performance caused by excessive and similar categories in traditional CM diagnostic classification models. CM diagnostic text generation technology has broad application prospects in the future.

Establishment and application of high throughput screening cell model for nutrient regulation of embryonic development.

Embryo development exerts far-reaching influence on pregnancy outcome, postnatal development and lifelong health. Thereafter, to select functional nutrients to improve embryo development is of great importance. Herein, a stable porcine trophectoderm cell line expressing a luciferase reporter gene driven by a 1,009 bp PCNA gene promoter was constructed through lentiviral transduction and G418 selection. A high throughput screening assay was subsequently developed using the stable reporter cell line to screen a library of 225 nutrients. Seven nutrients with a minimum Z-score of 2.0 were initially identified to be capable of enhancing embryonic development. Among these nutrients, resveratrol, apigenin, and retinol palmitate were furtherly confirmed the beneficial effects for embryo development. Resveratrol significantly increased the expression of key genes involved in pTr cell proliferation and the number of S-phase cells. Resveratrol was furtherly confirmed to promote the expression of key genes in trophoblast development and increase embryo adhesion rate in vitro. Similarly, dietary 0.05% resveratrol supplementation significantly increased the number of embryo attachment and serum level of P4 and E2 in rats. Resveratrol could also improve maternal antioxidant levels and reduce intracellular ROS. Collectively, a high throughput screening cell model for nutrient regulation of embryonic development was established, which can be used to highly effectively select the potential candidates for embryo development. These findings have great implications for exploring optimal functional nutrients to improve embryo development, ultimately beneficial for pregnancy outcome, offspring postnatal development and lifelong health for human beings and mammalian animals.

Integration of Deep Learning and Sequential Metabolism to Rapidly Screen Dipeptidyl Peptidase (DPP)-IV Inhibitors from Gardenia jasminoides Ellis.

Traditional Chinese medicine (TCM) possesses unique advantages in the management of blood glucose and lipids. However, there is still a significant gap in the exploration of its pharmacologically active components. Integrated strategies encompassing deep-learning prediction models and active validation based on absorbable ingredients can greatly improve the identification rate and screening efficiency in TCM. In this study, the affinity prediction of 11,549 compounds from the traditional Chinese medicine system's pharmacology database (TCMSP) with dipeptidyl peptidase-IV (DPP-IV) based on a deep-learning model was firstly conducted. With the results, Gardenia jasminoides Ellis (GJE), a food medicine with homologous properties, was selected as a model drug. The absorbed components of GJE were subsequently identified through in vivo intestinal perfusion and oral administration. As a result, a total of 38 prototypical absorbed components of GJE were identified. These components were analyzed to determine their absorption patterns after intestinal, hepatic, and systemic metabolism. Virtual docking and DPP-IV enzyme activity experiments were further conducted to validate the inhibitory effects and potential binding sites of the common constituents of deep learning and sequential metabolism. The results showed a significant DPP-IV inhibitory activity (IC50 53 ± 0.63 µg/mL) of the iridoid glycosides' potent fractions, which is a novel finding. Genipin 1-gentiobioside was screened as a promising new DPP-IV inhibitor in GJE. These findings highlight the potential of this innovative approach for the rapid screening of active ingredients in TCM and provide insights into the molecular mechanisms underlying the anti-diabetic activity of GJE.

Effect of Trichoderma viride on insoluble phosphorus absorption ability and growth of Melilotus officinalis.

Phosphorus (Pi) deficiency is a major factor of limiting plant growth. Using Phosphate-solubilizing microorganism (PSM) in synergy with plant root system which supply soluble Pi to plants is an environmentally friendly and efficient way to utilize Pi. Trichoderma viride (T. viride) is a biocontrol agent which able to solubilize soil nutrients, but little is known about its Pi solubilizing properties. The study used T. viride to inoculate Melilotus officinalis (M. officinalis) under different Pi levels and in order to investigate the effect on Pi absorption and growth of seedlings. The results found that T. viride could not only solubilizate insoluble inorganic Pi but also mineralize insoluble organic Pi. In addition, the ability of mineralization to insoluble organic Pi is more stronger. Under different Pi levels, inoculation of T. viride showed that promoted the growth of aboveground parts of seedlings and regulated the morphology of roots, thus increasing the dry weight of seedlings. The effect of T. viride on seedling growth was also reflected the increasing of chlorophyll fluorescence parameters and photosynthetic pigment content. Moreover, compared to the uninoculated treatments, inoculation of T. viride also enhanced Pi content in seedlings. Thus, the T. viride was a beneficial fungus for synergistic the plant Pi uptake and growth.

Toxicity, formation, contamination, determination and mitigation of acrylamide in thermally processed plant-based foods and herbal medicines: A review.

Thermal processing is one of the important techniques for most of the plant-based food and herb medicines before consumption and application in order to meet the specific requirement. The plant and herbs are rich in amino acids and reducing sugars, and thermal processing may lead to Maillard reaction, resulting as a high risk of acrylamide pollution. Acrylamide, an organic pollutant that can be absorbed by the body through the respiratory tract, digestive tract, skin and mucous membranes, has potential carcinogenicity, neurological, genetic, reproductive and developmental toxicity. Therefore, it is significant to conduct pollution determination and risk assessment for quality assurance and security of medication. This review demonstrates state-of-the-art research of acrylamide focusing on the toxicity, formation, contamination, determination, and mitigation in taking food and herb medicine, to provide reference for scientific processing and ensure the security of consumers.

Regulation of capsule spine formation in castor.

Castor (Ricinus communis L.) is a dicotyledonous oilseed crop that can have either spineless or spiny capsules. Spines are protuberant structures that differ from thorns or prickles. The developmental regulatory mechanisms governing spine formation in castor or other plants have remained largely unknown. Herein, using map-based cloning in 2 independent F2 populations, F2-LYY5/DL01 and F2-LYY9/DL01, we identified the RcMYB106 (myb domain protein 106) transcription factor as a key regulator of capsule spine development in castor. Haplotype analyses demonstrated that either a 4,353-bp deletion in the promoter or a single nucleotide polymorphism leading to a premature stop codon in the RcMYB106 gene could cause the spineless capsule phenotype in castor. Results of our experiments indicated that RcMYB106 might target the downstream gene RcWIN1 (WAX INDUCER1), which encodes an ethylene response factor known to be involved in trichome formation in Arabidopsis (Arabidopsis thaliana) to control capsule spine development in castor. This hypothesis, however, remains to be further tested. Nevertheless, our study reveals a potential molecular regulatory mechanism underlying the spine capsule trait in a nonmodel plant species.

Molecular profile-based recommendations for postoperative adjuvant therapy in early endometrial cancer with high-intermediate or intermediate risk: a Chinese randomized phase III trial (PROBEAT).

BACKGROUND: The use of molecular categorisation is shifting paradigm towards the use of molecular information to refine risk stratification in endometrial cancer (EC). To date, evidence to support molecular-guided therapies is limited to retrospective studies and secondary molecular analyses of patients receiving standard treatment. The PROBEAT study is the first randomized phase III trial to evaluate tailored adjuvant treatment based on WHO-endorsed molecular classification in Chinese EC patients. It is expected to provide a clinical decision-making tool for adjuvant treatment of patients with high-intermediate risk (HIR) or intermediate risk (IR) EC to better optimise and personalise patient care and increase relapse-free survival. METHODS: The PROBEAT trial is a prospective, multicentre study led by Women's Hospital of Zhejiang University Gynaecologic Oncology Group. Recruitment started on January 24, 2022, and 590 patients with HIR or IR endometrioid EC are expected to be recruited from 13 clinical centres in China. All tumor tissues will be classified into four molecular subtypes (POLEmut, MMRd, p53abn, or NSMP) based on WHO-endorsed molecular classification. Patients will be randomly assigned at a 2:1 ratio to either experimental arm and will receive molecular profile-based adjuvant treatment (observation in the POLEmut subgroup, vaginal brachytherapy in the MMRd or NSMP subgroup, or chemoradiotherapy in the p53abn subgroup) or to standard arm and will receive preferred adjuvant radiotherapy as recommended by the recent National Comprehensive Cancer Network guidelines version 1 (2022). The primary outcome is 3-year rates of recurrence. Secondary outcomes are relapse-free survival, overall survival, adverse events and health-related cancer-specific quality of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05179447.

Anti-inflammatory flavonoid derivatives from the heartwood of Dalbergia odorifera T. Chen.

Two pairs of flavonoid enantiomers (1a/1b and 2a/2b) together with three known analogues (3-5) were isolated from the heartwood of Dalbergia odorifera T. Chen. Their structures were elucidated by extensive spectroscopic analysis (1 D and 2 D NMR, UV, IR, and HRMS) and experimental and calculated ECD data. Compound 2 features an unusual 2-methyl-3(2H)-furanone moiety forming the C-ring of flavonoid, and its putative biosynthetic pathway is also proposed. Compounds 3‒5 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 values of 14.7 ± 0.3 µM, 40.2 ± 1.1 µM, and 3.2 ± 0.1 µM, respectively.

Regulatory effects mediated by ulvan oligosaccharide and its zinc complex on lipid metabolism in high-fat diet-fed mice.

Obesity-induced lipid metabolism disorders are risk factors for hyperlipidemia, atherosclerosis, and non-alcoholic fatty liver disease. Seaweed oligosaccharides and Zn supplements are potential alternatives to alleviate obesity. Herein, ulvan oligosaccharide (UO) was used as a ligand to prepare a novel Zn supplement (UO-Zn). Subsequently, we explored potential mechanisms underlying UO- and UO-Zn-mediated improvements in lipid metabolism in mice fed a high-fat diet. We found that UO enhanced the abundance of key species (Blautia and Turicibacter) and functions (glycolytic, pentose phosphate, and histidine/lysine biosynthesis pathways) in the gut microbiota, thereby increasing the production of short-chain fatty acids and activating AMPK. Accordingly, UO treatment regulated the transcription of lipid metabolism genes, including ACOX1, ACC, and FASN, thereby reducing blood lipid levels and hepatic lipid accumulation. Zn could act synergistically with UO, enhancing the reversal of cholesterol transport and fatty acid ß-oxidation via the MTF1/PPARα pathway, markedly reducing body and adipose tissue weights.

Trait Mindfulness and Physical Health among Chinese Middle-Older Adults: The Mediating Role of Mental Health.

Few studies have focused on the specific effects of trait mindfulness on physical health status, especially from a resilient aging perspective. This study examined the mediating role of mental health in the association between trait mindfulness and physical health status among middle-older adults in urban China. The participants included 188 individuals who were recruited from a community senior university and five community senior care centers. The findings reveal: (1) trait mindfulness has a strong effect on two physical health indicators (self-rated physical health and subjective sleep quality); (2) mental health is a significant mediator in the relationship between trait mindfulness and physical health status; and (3) the mediation role of mental health is more evident in the self-rated physical health model (24.15%) than subjective sleep quality (18.10%). This study improves our knowledge of how trait mindfulness can lead to a better physical health in middle-older adults and can lead to the development of social value communication and effective prevention.

Identification, Screening, and Comprehensive Evaluation of Novel DPP-IV Inhibitory Peptides from the Tilapia Skin Gelatin Hydrolysate Produced Using Ginger Protease.

PURPOSE: Inhibition of dipeptidyl peptidase-IV (DPP-IV) is an effective therapy for treating type II diabetes (T2D) that has been widely applied in clinical practice. We aimed to evaluate the DPP-IV inhibitory properties of ginger protease hydrolysate (GPH) and propose a comprehensive approach to screen and evaluate DPP-IV inhibitors. METHODS: We evaluated the in vitro inhibitory properties of fish skin gelatin hydrolysates produced by five proteases, namely, neutral protease, alkaline protease, bromelain, papain, and ginger protease, toward DPP-IV. We screened the most potent DPP-IV inhibitory peptide (DIP) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with in silico analysis. Next, surface plasmon resonance (SPR) technology was innovatively introduced to explore the interactions between DPP-IV and DIP, as well as the IC50. Furthermore, we performed oral administration of DIP in rats to study its in vivo absorption. RESULTS: GPH displayed the highest degree of hydrolysis (20.37%) and DPP-IV inhibitory activity (65.18%). A total of 292 peptides from the GPH were identified using LC-MS/MS combined with de novo sequencing. Gly-Pro-Hyp-Gly-Pro-Pro-Gly-Pro-Gly-Pro (GPXGPPGPGP) was identified as the most potent DPP-IV inhibitory peptide after in silico screening (Peptide Ranker and molecular docking). Then, the in vitro study revealed that GPXGPPGPGP had a high inhibitory effect on DPP-IV (IC50: 1012.3 ± 23.3 µM) and exhibited fast kinetics with rapid binding and dissociation with DPP-IV. In vivo analysis indicated that GPXGPPGPGP was not absorbed intact but partially, in the form of dipeptides and tripeptides. CONCLUSION: Overall, the results suggested that GPH would be a natural functional food for treating T2D and provided new ideas for searching and evaluating potential antidiabetic compounds. The obtained GPXGPPGPGP can be structurally optimized for in-depth evaluation in animal and cellular experiments.

Pharmacodynamic Interactions between Puerarin and Metformin in Type-2 Diabetic Rats.

Herb-drug interactions are vital in effectively managing type-2-diabetes complications. Puerarin is a natural isoflavonoid in the Pueraria genus, and its pharmacological activities, including antidiabetic activity, are well established. The similar modes of action of puerarin and metformin in diabetic models suggest their positive pharmacodynamic interactions. This study investigated this in streptozotocin/nicotinamide-induced type-2 diabetic rats. Puerarin at doses of 80 mg/kg, 120 mg/kg and 160 mg/kg improved the activity of metformin in reversing hyperglycaemia, dysregulated lipid profiles, dysfunction of the liver, kidney, and pancreas, and inflammation. The treatment with either puerarin (high dose, 160 mg/kg intraperitoneally) or metformin (100 mg/kg intraperitoneally) did not bring the dysregulated biomarkers to normal levels in 4 weeks. By contrast, the combination of puerarin (160 mg/kg) and metformin (100 mg/kg) did. This study is the first to report scientific evidence for the positive pharmacodynamic interactions between puerarin and metformin.

Thiolated hyaluronic acid and catalase-enhanced CD44-targeting and oxygen self-supplying nanoplatforms with photothermal/photodynamic effects against hypoxic breast cancer cells.

Photothermal and photodynamic therapies (PTT/PDT) have been widely accepted as noninvasive therapeutic methods for cancer treatment. However, tumor hypoxia and insufficient delivery of photoactive compounds to cancer cells can reduce the efficacy of phototherapy. Herein, we first synthesized thiolated hyaluronic acid (THA) and then conjugated it with catalase (CAT) onto chlorin e6 (Ce6)-adsorbed small gold nanorods (Ce6@sAuNRs) with near-infrared (NIR)/visible light activated photothermal/photodynamic effects. The conjugation of THA and CAT on Ce6@sAuNRs resulted in a red-shift of the longitudinal LSPR absorption band of sAuNRs up to 1000 nm and maintained the excellent enzymatic activity of catalase. Modification of Ce6@sAuNRs with THA resulted in efficient internalization of the nanocomposite into MCF-7/ADR multidrug-resistant (MDR) breast cancer cells (CD44+), thereby significantly enhancing the intracellular accumulation of the photosensitizer Ce6. CAT endows Ce6@sAuNRs with self-supporting oxygen production, which enables them to efficiently generate singlet oxygen (1O2) under 660 nm laser irradiation and enhances the photodynamic effect against hypoxic breast cancer cells. The results highlight the prospect of this novel multi-functional nanoplatform integrating active biological macromolecules (THA and CAT) into photosensitizer/photothermal gold nanocomposites in overcoming the limitations of hypoxic MDR breast cancer cell treatment.

Alnustone inhibits Streptococcus pneumoniae virulence by targeting pneumolysin and sortase A.

Streptococcus pneumoniae (S. pneumoniae) is a major Gram-positive opportunistic pathogen that causes pneumonia, bacteremia, and other fatal infections. This bacterium is responsible for more deaths than any other single pathogen in the world. Inexplicably, these symptoms persist despite the administration of effective antibiotics. Targeting pneumolysin (PLY) and sortase A (SrtA), the major virulence factors of S. pneumoniae, this study uncovered a novel resistance mechanism to S. pneumoniae infection. Using protein phenotype assays, we determined that the small molecule inhibitor alnustone is a potent drug that inhibits both PLY and SrtA. As essential virulence factors of S. pneumoniae, PLY and SrtA play a significant role in the occurrence of infection. Furthermore, evaluation using PLY-mediated hemolysis assay demonstrated alunstone had the potential to interrupt the haemolytic activity of PLY with treatment alunstone (4 µg/ml). Co-incubation of S. pneumoniae D39 SrtA with small-molecule inhibitors decreases cell wall-bound Nan A (pneumococcal-anchored surface protein SrtA), inhibits biofilm formation, and reduces biomass significantly. The protective effect of invasive pneumococcal disease (IPD) on murine S. pneumoniae was demonstrated further. Our study proposes a comprehensive bacteriostatic mechanism for S. pneumoniae and highlights the significant translational potential of targeting both PLY and SrtA to prevent pneumococcal infections. Our findings indicate that the antibacterial strategy of directly targeting PLY and SrtA with alnustone is a promising treatment option for S. pneumoniae and that alnustone is a potent inhibitor of PLY and SrtA.

Exploring Ganweikang Tablet as a Candidate Drug for NAFLD Through Network Pharmacology Analysis and Experimental Validation.

Nonalcoholic fatty liver disease (NAFLD) is defined as liver disease in which more than 5% of hepatocytes are steatotic with little or no alcohol consumption. NAFLD includes benign nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Importantly, NASH is an advanced progression of NAFL and is characterized by steatosis, hepatocyte ballooning, lobular inflammation, and fibrosis. However, to date, no drugs specifically targeting NAFLD have been approved by the FDA. Therefore, a new drug or strategy for NAFLD treatment is necessary. However, the pathogenesis of NAFLD is complex and no single-target drugs have achieved the desired results. Noticeably, traditional Chinese medicine formulations are a complex system with multiple components, multiple targets, and synergistic effects between components. The Ganweikang tablet is a compound formula based on traditional Chinese medicine theory and clinical experience. In this study, network pharmacology analysis indicates Ganweikang tablet as a candidate for NAFLD treatment. Furthermore, we evaluated the therapeutic effects of Ganweikang tablet on the NAFL and NASH and tried to clarify the underlying molecular mechanisms in animal models and cell experiments. As expected, Ganweikang tablet was found to improve NAFL and NASH by modulating inflammation, apoptosis, and fatty acid oxidation by inhibiting NFκB, caspase-8, and activating PPARα, which not only indicates that Ganweikang tablet as a drug candidate but also provides a theoretical basis of Ganweikang tablet for the treatment of NAFL and NASH.