Single-cell sequencing technology in diabetic wound healing: New insights into the progenitors-based repair strategies.

Diabetes mellitus (DM), an increasingly prevalent chronic metabolic disease, is characterised by prolonged hyperglycaemia, which leads to long-term health consequences. Although much effort has been put into understanding the pathogenesis of diabetic wounds, the underlying mechanisms remain unclear. The advent of single-cell RNA sequencing (scRNAseq) has revolutionised biological research by enabling the identification of novel cell types, the discovery of cellular markers, the analysis of gene expression patterns and the prediction of developmental trajectories. This powerful tool allows for an in-depth exploration of pathogenesis at the cellular and molecular levels. In this editorial, we focus on progenitor-based repair strategies for diabetic wound healing as revealed by scRNAseq and highlight the biological behaviour of various healing-related cells and the alteration of signalling pathways in the process of diabetic wound healing. ScRNAseq could not only deepen our understanding of the complex biology of diabetic wounds but also identify and validate new targets for intervention, offering hope for improved patient outcomes in the management of this challenging complication of DM.

Lycium barbarum polysaccharide remodels colon inflammatory microenvironment and improves gut health.

Aim: Disturbed intestinal microbiota has been implicated in the inflammatory microenvironment of the colon, which usually results in ulcerative colitis (UC). Given the limitations of these drugs, it is important to explore alternative means of protecting the gut health from UC. This study aimed to investigate the potential of polysaccharides as beneficial nutrients in the regulation of the gut microbiota, which determines the inflammatory microenvironment of the colon. Materials and methods: Mice were treated with dextran sulfate sodium (DSS) to evaluate the effects and mechanisms of Lycium barbarum polysaccharide (LBP) in remodeling the inflammatory microenvironment and improving gut health. Body weight and disease activity indices were monitored daily. Hematoxylin and eosin staining was used to analyze colon dynamics. The levels of inflammatory indicators and expression of MUC-2, claudin-1, ZO-1, and G-protein-coupled receptor 5 (TGR5) were determined using assay kits and immunohistochemistry, respectively. 16S rRNA high-throughput sequencing of the intestinal microbiota and liquid chromatography-tandem mass spectrometry for related bile acids were used. Results: LBP significantly improved the colonic tissue structure by upregulating MUC-2, claudin-1, and ZO-1 protein expression. The bacterial genus Dubosiella was dominant in healthy mice, but significantly decreased in mice treated with DSS. LBP rehabilitated Dubosiella in the sick guts of DSS mice to a level close to that of healthy mice. The levels of other beneficial bacterial genera Akkermansia and Bifidobacterium were also increased, whereas those of the harmful bacterial genera Turicibacter, Clostridium_sensu_stricto_1, Escherichia-Shigella, and Faecalibaculum decreased. The activity of beneficial bacteria promoted the bile acids lithocholic and deoxycholic acids in mice with UC, which improved the gut barrier function through the upregulation of TGR5. Conclusion: The inflammatory microenvironment in the gut is determined by the balance of the gut microbiota. LBP showed great potential as a beneficial nutrient for rehabilitating Dubosiella which is dominant in the gut of healthy mice. Nutrient-related LBP may play an important role in gut health management.

Exploring the Localization of Siderophore-Mediated Cargo Delivery in Gram-Negative Bacteria Using 3-Hydroxypyridin-4(1H)-one-Fluorescein Probes.

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.

Chalkophomycin Biosynthesis Revealing Unique Enzyme Architecture for a Hybrid Nonribosomal Peptide Synthetase and Polyketide Synthase.

Chalkophomycin is a novel chalkophore with antibiotic activities isolated from Streptomyces sp. CB00271, while its potential in studying cellular copper homeostasis makes it an important probe and drug lead. The constellation of N-hydroxylpyrrole, 2H-oxazoline, diazeniumdiolate, and methoxypyrrolinone functional groups into one compact molecular architecture capable of coordinating cupric ions draws interest to unprecedented enzymology responsible for chalkophomycin biosynthesis. To elucidate the biosynthetic machinery for chalkophomycin production, the chm biosynthetic gene cluster from S. sp. CB00271 was identified, and its involvement in chalkophomycin biosynthesis was confirmed by gene replacement. The chm cluster was localized to a ~31 kb DNA region, consisting of 19 open reading frames that encode five nonribosomal peptide synthetases (ChmHIJLO), one modular polyketide synthase (ChmP), six tailoring enzymes (ChmFGMNQR), two regulatory proteins (ChmAB), and four resistance proteins (ChmA'CDE). A model for chalkophomycin biosynthesis is proposed based on functional assignments from sequence analysis and structure modelling, and is further supported by analogy to over 100 chm-type gene clusters in public databases. Our studies thus set the stage to fully investigate chalkophomycin biosynthesis and to engineer chalkophomycin analogues through a synthetic biology approach.

A Red-Emission Fluorescent Probe with Large Stokes Shift for Detection of Viscosity in Living Cells and Tumor-Bearing Mice.

Abnormal viscosity is closely related to the occurrence of many diseases, such as cancer. Therefore, real-time detection of changes in viscosity in living cells is of great importance. Fluorescent molecular rotors play a critical role in detecting changes in cellular viscosity. Developing red emission viscosity probes with large Stokes shifts and high sensitivity and specificity remains an urgent and important topic. Herein, a novel viscosity-sensitive fluorescent probe (TCF-VIS1) with a large stokes shift and red emission was prepared based on the 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) skeleton. Due to intramolecular rotation, the probe itself does not fluorescence at low viscosity. With the increase in viscosity, the rotation of TCF-VIS1 is limited, and its fluorescence is obviously enhanced. The probe has the advantages of simple preparation, large Stokes shift, good sensitivity and selectivity, and low cytotoxicity, which make it successfully used for viscosity detection in living cells. Moreover, TCF-VIS1 showed its potential for cancer diagnosis at the cell level and in tumor-bearing mice by detecting viscosity. Therefore, the probe is expected to enrich strategies for the detection of viscosity in biological systems and offer a potential tool for cancer diagnosis.

Plant-derived exosome-like nanovesicles: A novel nanotool for disease therapy.

Exosomes are extracellular vesicles comprising bilayer phospholipid membranes and are secreted by eukaryotic cells. They are released via cellular exocytosis, contain DNA, RNA, proteins, and other substances, and participate in various cellular communications between tissues and organs. Since the discovery of exosomes in 1983, animal-derived exosomes have become a research focus for small-molecule drug delivery in biology, medicine, and other fields owing to their good biocompatibility and homing effects. Recent studies have found that plant-derived exosome-like nanovesicles (PELNVs) exhibit certain biological effects, such as anti-inflammatory and anti-tumor abilities, and have minimal toxic side effects. Because they are rich in active lipid molecules with certain pharmacological effects, PELNVs could be novel carriers for drug delivery. In this review, the biological formation and effects, isolation, and extraction of PELNVs, as well as characteristics of transporting drugs as carriers are summarized to provide new ideas and methods for future research on plant-derived exosome-like nanovesicles.

Dexmedetomidine inhibited arrhythmia susceptibility to adrenergic stress in RyR2R2474S mice through regulating the coupling of membrane potential and intracellular calcium.

BACKGROUND: Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, can decrease the incidence of arrhythmias, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the underlying mechanisms by which DEX affects cardiac electrophysiological function remain unclear. METHODS: Ryanodine receptor (RyR2) heterozygous R2474S mice were used as a model for CPVT. WT and RyR2R2474S/+ mice were treated with isoproterenol (ISO) and DEX, and electrocardiograms were continuously monitored during both in vivo and ex vivo experiments. Dual-dye optical mapping was used to explore the anti-arrhythmic mechanism of DEX. RESULTS: DEX significantly reduced the occurrence and duration of ISO-induced of VT/VF in RyR2R2474S/+ mice in vivo and ex vivo. DEX remarkably prolonged action potential duration (APD80) and calcium transient duration (CaTD80) in both RyR2R2474S/+ and WT hearts, whereas it reduced APD heterogeneity and CaT alternans in RyR2R2474S/+ hearts. DEX inhibited ectopy and reentry formation, and stabilized voltage-calcium latency. CONCLUSION: DEX exhibited an antiarrhythmic effect through stabilizing membrane voltage and intracellular Ca2+. DEX can be used as a beneficial perioperative anesthetic for patients with CPVT or other tachy-arrhythmias.

Targeted gene delivery systems for T-cell engineering.

T lymphocytes are indispensable for the host systems of defense against pathogens, tumors, and environmental threats. The therapeutic potential of harnessing the cytotoxic properties of T lymphocytes for antigen-specific cell elimination is both evident and efficacious. Genetically engineered T-cells, such as those employed in CAR-T and TCR-T cell therapies, have demonstrated significant clinical benefits in treating cancer and autoimmune disorders. However, the current landscape of T-cell genetic engineering is dominated by strategies that necessitate in vitro T-cell isolation and modification, which introduce complexity and prolong the development timeline of T-cell based immunotherapies. This review explores the complexities of gene delivery systems designed for T cells, covering both viral and nonviral vectors. Viral vectors are known for their high transduction efficiency, yet they face significant limitations, such as potential immunogenicity and the complexities involved in large-scale production. Nonviral vectors, conversely, offer a safer profile and the potential for scalable manufacturing, yet they often struggle with lower transduction efficiency. The pursuit of gene delivery systems that can achieve targeted gene transfer to T cell without the need for isolation represents a significant advancement in the field. This review assesses the design principles and current research progress of such systems, highlighting the potential for in vivo gene modification therapies that could revolutionize T-cell based treatments. By providing a comprehensive analysis of these systems, we aim to contribute valuable insights into the future development of T-cell immunotherapy.

Combinatorial metabolic engineering of Streptomyces sp. CB03234-S for the enhanced production of anthraquinone-fused enediyne tiancimycins.

BACKGROUND: Anthraquinone-fused enediynes (AFEs) are excellent payloads for antibody-drug conjugates (ADCs). The yields of AFEs in the original bacterial hosts are extremely low. Multiple traditional methods had been adopted to enhance the production of the AFEs. Despite these efforts, the production titers of these compounds are still low, presenting a practical challenge for their development. Tiancimycins (TNMs) are a class of AFEs produced by Streptomyces sp. CB03234. One of their salient features is that they exhibit rapid and complete cell killing ability against various cancer cell lines. RESULTS: In this study, a combinatorial metabolic engineering strategy guided by the CB03234-S genome and transcriptome was employed to improve the titers of TNMs. First, re-sequencing of CB03234-S (Ribosome engineered mutant strains) genome revealed the deletion of a 583-kb DNA fragment, accounting for about 7.5% of its genome. Second, by individual or combined inactivation of seven potential precursor competitive biosynthetic gene clusters (BGCs) in CB03234-S, a double-BGC inactivation mutant, S1009, was identified with an improved TNMs titer of 28.2 ± 0.8 mg/L. Third, overexpression of five essential biosynthetic genes, including two post-modification genes, and three self-resistance auxiliary genes, was also conducted, through which we discovered that mutants carrying the core genes, tnmE or tnmE10, exhibited enhanced TNMs production. The average TNMs yield reached 43.5 ± 2.4 mg/L in a 30-L fermenter, representing an approximately 360% increase over CB03234-S and the highest titer among all AFEs to date. Moreover, the resulting mutant produced TNM-W, a unique TNM derivative with a double bond instead of a common ethylene oxide moiety. Preliminary studies suggested that TNM-W was probably converted from TNM-A by both TnmE and TnmE10. CONCLUSIONS: Based on the genome and transcriptome analyses, we adopted a combined metabolic engineering strategy for precursor enrichment and biosynthetic pathway reorganization to construct a high-yield strain of TNMs based on CB03234-S. Our study establishes a solid basis for the clinical development of AFE-based ADCs.

CYP4G subfamily genes mediate larval integument development in Spodoptera frugiperda.

Cytochrome P450 (CYP) 4G subfamily is closely related to the synthesis of cuticular hydrocarbons, leading to the enhanced desiccation and insecticide resistance of pests. However, functions of CYP4Gs in larval integument development remain unknown in Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), which is a major transboundary migratory pest and become a common pest in China. On the basis of the genome and transcriptome datasets of S. frugiperda, CYP4G74, CYP4G75, CYP4G108, and CYP4G109 were identified, which contained the conserved domains of P450s and CYP4Gs. The spatial and temporal expression analysis showed that CYP4G74 and CYP4G75 were significantly highly expressed in adults and larval integuments, while CYP4G108 and CYP4G109 had low expressions in larval integuments. After silencing CYP4G74 and CYP4G75 by RNA interference, abnormal integument development occurred in larvae, some of which became smaller and dead, indicating important roles of CYP4G74 and CYP4G75 in the synthesis and development of integuments. The results clarify the functions of CYP4Gs in S. frugiperda and provide potential targets for the control of this pest.

Performance evaluation of the effect of humic acid on Anammox granular sludge: Apparent morphology, nitrogen removal and microbial community.

Humic acid (HA) is a typical refractory organic matter, so it is of great significance to investigate its effect on the performance of Anammox granular sludge. When the dosage of HA ≤ 50 mg/L, HA promotes the total nitrogen removal rate (NRR) to 1.45 kg/(m3·day). When HA was between 50 and 100 mg/L, the NRR of Anammox was stable. At this time, the adsorption of HA causes the sludge to gradually turn from red to brown, but the activities of heme and enzymes showed that its capacity was not affected. When HA levels reached 250 mg/L, the NRR dropped to 0.11 kg/(m3·day). Moderate HA levels promoted the release of extracellular polymeric substance (EPS), but excessive HA levels lead to a decrease in EPS concentrations. HA inhibited Anammox activity, which indirectly hindered the transmission of substrate and accumulated substrate toxicity. Although HA promoted the increase of heterotrophic microbial abundance in Anammox system, the microbial diversity decreased gradually. With the increase of HA concentration, the abundance of Candidatus_Brocadia, the main functional microorganism of Anammox system, decreased gradually, while the abundance of Candidatus_Kuenenia increased gradually.

Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer's disease.

Communication between glial cells has a profound impact on the pathophysiology of Alzheimer's disease (AD). We reveal here that reactive astrocytes control cell distancing in peri-plaque glial nets, which restricts microglial access to amyloid deposits. This process is governed by guidance receptor Plexin-B1 (PLXNB1), a network hub gene in individuals with late-onset AD that is upregulated in plaque-associated astrocytes. Plexin-B1 deletion in a mouse AD model led to reduced number of reactive astrocytes and microglia in peri-plaque glial nets, but higher coverage of plaques by glial processes, along with transcriptional changes signifying reduced neuroinflammation. Additionally, a reduced footprint of glial nets was associated with overall lower plaque burden, a shift toward dense-core-type plaques and reduced neuritic dystrophy. Altogether, our study demonstrates that Plexin-B1 regulates peri-plaque glial net activation in AD. Relaxing glial spacing by targeting guidance receptors may present an alternative strategy to increase plaque compaction and reduce neuroinflammation in AD.

The Involvement of Ascorbic Acid in Cancer Treatment.

Vitamin C (VC), also known as ascorbic acid, plays a crucial role as a water-soluble nutrient within the human body, contributing to a variety of metabolic processes. Research findings suggest that increased doses of VC demonstrate potential anti-tumor capabilities. This review delves into the mechanisms of VC absorption and its implications for cancer management. Building upon these foundational insights, we explore modern delivery systems for VC, evaluating its use in diverse cancer treatment methods. These include starvation therapy, chemodynamic therapy (CDT), photothermal/photodynamic therapy (PTT/PDT), electrothermal therapy, immunotherapy, cellular reprogramming, chemotherapy, radiotherapy, and various combination therapies.

A nursing note-aware deep neural network for predicting mortality risk after hospital discharge.

BACKGROUND: ICU readmissions and post-discharge mortality pose significant challenges. Previous studies used EHRs and machine learning models, but mostly focused on structured data. Nursing records contain crucial unstructured information, but their utilization is challenging. Natural language processing (NLP) can extract structured features from clinical text. This study proposes the Crucial Nursing Description Extractor (CNDE) to predict post-ICU discharge mortality rates and identify high-risk patients for unplanned readmission by analyzing electronic nursing records. OBJECTIVE: Developed a deep neural network (NurnaNet) with the ability to perceive nursing records, combined with a bio-clinical medicine pre-trained language model (BioClinicalBERT) to analyze the electronic health records (EHRs) in the MIMIC III dataset to predict the death of patients within six month and two year risk. DESIGN: A cohort and system development design was used. SETTING(S): Based on data extracted from MIMIC-III, a database of critically ill in the US between 2001 and 2012, the results were analyzed. PARTICIPANTS: We calculated patients' age using admission time and date of birth information from the MIMIC dataset. Patients under 18 or over 89 years old, or who died in the hospital, were excluded. We analyzed 16,973 nursing records from patients' ICU stays. METHODS: We have developed a technology called the Crucial Nursing Description Extractor (CNDE), which extracts key content from text. We use the logarithmic likelihood ratio to extract keywords and combine BioClinicalBERT. We predict the survival of discharged patients after six months and two years and evaluate the performance of the model using precision, recall, the F1-score, the receiver operating characteristic curve (ROC curve), the area under the curve (AUC), and the precision-recall curve (PR curve). RESULTS: The research findings indicate that NurnaNet achieved good F1-scores (0.67030, 0.70874) within six months and two years. Compared to using BioClinicalBERT alone, there was an improvement in performance of 2.05 % and 1.08 % for predictions within six months and two years, respectively. CONCLUSIONS: CNDE can effectively reduce long-form records and extract key content. NurnaNet has a good F1-score in analyzing the data of nursing records, which helps to identify the risk of death of patients after leaving the hospital and adjust the regular follow-up and treatment plan of relevant medical care as soon as possible.

Norcantharidin Enhances the Antitumor Effect of 5-Fluorouracil by Inducing Apoptosis of Cervical Cancer Cells: Network Pharmacology, Molecular Docking, and Experimental Validation.

The high recurrence rate of cervical cancer is a leading cause of cancer deaths in women. 5-Fluorouracil (5-FU) is an antitumor drug used to treat many types of cancer, but its diminishing effectiveness and side effects limit its use. Norcantharidin (NCTD), a demethylated derivative of cantharidin, exhibits various biological activities. Here, we investigated whether NCTD could potentiate 5-FU to induce cervical cancer cell death. To assess the cell viability and synergistic effects of the drugs, cell counting kit-8 and colony formation assays were performed using HR-HPV-positive cervical cancer cell lines. Annexin V-FITC/PI staining and TUNEL assays were performed to confirm the induction of apoptosis. The synergistic effect of NCTD on the antitumor activity of 5-FU was analyzed using network pharmacology, molecular docking, and molecular dynamics simulations. Apoptosis-related proteins were examined using immunoblotting. The combination of NCTD and 5-FU was synergistic in cervical cancer cell lines. Network pharmacological analysis identified 10 common targets of NCTD and 5-FU for cervical cancer treatment. Molecular docking showed the strong binding affinity of both compounds with CA12, CASP9, and PTGS1. Molecular dynamics simulations showed that the complex system of both drugs with caspase-9 could be in a stable state. NCTD enhanced 5-FU-mediated cytotoxicity by activating apoptosis-related proteins. NCTD acts synergistically with 5-FU to inhibit cervical cancer cell proliferation. NCTD enhances 5-FU-induced apoptosis in cervical cancer cell lines via the caspase-dependent pathway.

Strategies in product engineering of mesenchymal stem cell-derived exosomes: unveiling the mechanisms underpinning the promotive effects of mesenchymal stem cell-derived exosomes.

Articular cartilage injuries present a significant global challenge, particularly in the aging population. These injuries not only restrict movement due to primary damage but also exacerbate elderly degenerative lesions, leading to secondary cartilage injury and osteoarthritis. Addressing osteoarthritis and cartilage damage involves overcoming several technical challenges in biological treatment. The use of induced mesenchymal stem cells (iMSCs) with functional gene modifications emerges as a solution, providing a more stable and controllable source of Mesenchymal Stem Cells (MSCs) with reduced heterogeneity. Furthermore, In addition, this review encompasses strategies aimed at enhancing exosome efficacy, comprising the cultivation of MSCs in three-dimensional matrices, augmentation of functional constituents within MSC-derived exosomes, and modification of their surface characteristics. Finally, we delve into the mechanisms through which MSC-exosomes, sourced from diverse tissues, thwart osteoarthritis (OA) progression and facilitate cartilage repair. This review lays a foundational framework for engineering iMSC-exosomes treatment of patients suffering from osteoarthritis and articular cartilage injuries, highlighting cutting-edge research and potential therapeutic pathways.

Identification and characterization of the capsule depolymerase Dpo27 from phage IME-Ap7 specific to Acinetobacter pittii.

Among the Acinetobacter genus, Acinetobacter pittii stands out as an important opportunistic infection causative agent commonly found in hospital settings, which poses a serious threat to human health. Recently, the high prevalence of carbapenem-resistant A. pittii isolates has created significant therapeutic challenges for clinicians. Bacteriophages and their derived enzymes are promising therapeutic alternatives or adjuncts to antibiotics effective against multidrug-resistant bacterial infections. However, studies investigating the depolymerases specific to A. pittii strains are scarce. In this study, we identified and characterized a capsule depolymerase, Dpo27, encoded by the bacteriophage IME-Ap7, which targets A. pittii. A total of 23 clinical isolates of Acinetobacter spp. were identified as A. pittii (21.91%, 23/105), and seven A. pittii strains with various K locus (KL) types (KL14, KL32, KL38, KL111, KL163, KL207, and KL220) were used as host bacteria for phage screening. The lytic phage IME-Ap7 was isolated using A. pittii 7 (KL220) as an indicator bacterium and was observed for depolymerase activity. A putative tail fiber gene encoding a polysaccharide-degrading enzyme (Dpo27) was identified and expressed. The results of the modified single-spot assay showed that both A. pittii 7 and 1492 were sensitive to Dpo27, which was assigned the KL220 type. After incubation with Dpo27, A. pittii strain was susceptible to killing by human serum; moreover, the protein displayed no hemolytic activity against erythrocytes. Furthermore, the protein exhibited sustained activity across a wide pH range (5.0-10.0) and at temperatures between 20 and 50°C. In summary, the identified capsule depolymerase Dpo27 holds promise as an alternative treatment for combating KL220-type A. pittii infections.

Quercetin ameliorates bone loss in OVX rats by modulating the intestinal flora-SCFAs-inflammatory signaling axis.

BACKGROUND: Osteoporosis (OP) is a common systemic skeletal disorder characterized by an imbalance in bone homeostasis, involving increased osteoclastic bone formation and decreased osteoblastic bone resorption. Quercetin is a plant polyphenol that has been found to exhibit various biological activities, including antioxidant, anti-inflammatory, and antimicrobial effects. Previous studies have demonstrated its potential to improve postmenopausal OP, although the exact mechanism remains unclear. This study aims to investigate the anti-osteoporotic mechanism of quercetin based on the "intestinal flora - short-chain fatty acids (SCFAs) - inflammatory" signaling axis. METHODS: In this study, we established an ovariectomized (OVX)-induced rat model, quercetin intervention and evaluated the effects on rats following antibiotic (ABX) treatment and fecal microbiota transplantation (FMT). After 6 weeks of intervention, the rats were euthanized, and samples from their femur, tibia, lumbar spine, serum, colon and feces were collected, and bone strength, intestinal flora structure, SCFAs levels and cytokine levels were assessed. RESULTS: Quercetin modulates the intestinal flora by increasing potentially probiotic bacteria (i.e., Lactobacillales, Prevotellaceae, and Blautia) and decreasing potentially pathogenic bacteria (Desulfobacterota, Erysipelotrichales, Romboutsia, and Butyricoccaceae). It also increases SCFAs content and reduces colonic permeability by enhancing tight junction proteins (ZO-1, Occludin). Furthermore, quercetin lowers proinflammatory cytokine levels (LPS, IL-1ß, and TNF-α), which enhances bone strength and prevents OVX-induced bone loss. CONCLUSIONS: Quercetin may effectively reduce bone loss in OVX rats via the "intestinal flora - SCFAs - inflammatory" signaling pathway.

Manganese-based nanomaterials in diagnostics and chemodynamic therapy of cancers: new development.

In the realm of cancer treatment, traditional modalities like radiotherapy and chemotherapy have achieved certain advancements but continue to grapple with challenges including harm to healthy tissues, resistance to treatment, and adverse drug reactions. The swift progress in nanotechnology recently has opened avenues for investigating innovative approaches to cancer therapy. Especially, chemodynamic therapy (CDT) utilizing metal nanomaterials stands out as an effective cancer treatment choice owing to its minimal side effects and independence from external energy sources. Transition metals like manganese are capable of exerting anti-tumor effects through a Fenton-like mechanism, with their distinctive magnetic properties playing a crucial role as contrast agents in tumor diagnosis and treatment. Against this backdrop, this review emphasizes the recent five-year advancements in the application of manganese (Mn) metal ions within nanomaterials, particularly highlighting their unique capabilities in catalyzing CDT and enhancing MRI imaging. Initially, we delineate the biomedical properties of manganese, followed by an integrated discussion on the utilization of manganese-based nanomaterials in CDT alongside multimodal therapies, and delve into the application and future outlook of manganese-based nanomaterial-mediated MRI imaging techniques in cancer therapy. By this means, the objective is to furnish novel viewpoints and possibilities for the research and development in future cancer therapies.