An arteriovenous fistula model: Carotid artery-posterior facial vein fistula in rats.

OBJECTIVE: To describe an alternative arteriovenous fistula (AVF) model involving anastomosis of the common carotid artery (CCA) with the posterior facial vein (PFV). METHODS: Twenty-two male Sprague-Dawley rats (age 6-8 weeks) were used to establish the AVF model involving end-to-side anastomosis of PFV and CCA. The peak velocity of the CCA and the diameter of the outflow vein were recorded at 7, 14, and 42 days after the operation using Doppler ultrasound. Pathological examination of the intimal lesions was performed at 14 and 42 days after operation. RESULTS: One rat died within 24 h after surgery related to anesthesia. The patency rates at days 7, 14, and 42 were 85.7%, 81%, and 81%, respectively. The diameter of the carotid artery in rats is approximately 0.8 mm. The diameter of the outflow vein was increased by 1.7-fold and 2.2-fold at 7 days (1.1 ± 0.118 mm) and 14 days (1.4 ± 0.073 mm). At 42 days (1.96 ± 0.101 mm) after operation, the diameter was 3-fold greater compared to the unoperated control rat. The peak systolic flow velocity of the carotid artery at 7 days (593 ± 17.36 mm/s) and 14 days (767 ± 13.64 mm/s) after surgery was significantly greater compared to the control rat (314 ± 15.13 mm/s). The rate of increase was fastest at 7 days and leveled off from 14 to 42 days (875 ± 26 mm/s) after surgery. At 14 days, the intima area showed a nearly 50-fold increase (230 ± 9.93 µm2 × 103) compared to control (area 5 ± 0.37 µm2 × 103). Comparing 6 weeks with 2 weeks (280 ± 10.54 µm2 × 103) after surgery, the intima area increased 1.2 times. CONCLUSION: The CCA-PFV fistula in rats is a viable alternative AVF model.

Reno-protective Effects of Empagliflozin in High Fat Diet Induced Obesity-Related Glomerulopathy by Regulation of Gut-Kidney Axis.

BACKGROUND: The increasing prevalence of obesity-related glomerulopathy (ORG) poses a significant threat to public health. Sodium-glucose co-transporter-2 (SGLT2) inhibitors effectively reduce body weight and total fat mass in obese individuals and halt the progression of ORG. However, the underlying mechanisms of their reno-protective effects in ORG remain unclear. METHODS: We established a high-fat diet-induced ORG model using C57BL/6J mice, which were divided into three groups: normal chow diet (NCD group), high-fat diet (HFD) mice treated with placebo (ORG group), and HFD mice treated with Empagliflozin (EMPA group). We conducted 16S ribosomal RNA gene sequencing of feces and analyzed metabolites from kidney, feces, liver, and serum samples. RESULTS: ORG mice showed increased urinary albumin creatinine ratio, cholesterol, triglyceride levels, and glomerular diameter compared to NCD mice (all P < 0.05). EMPA treatment significantly alleviated these parameters (all P < 0.05). Multi-tissue metabolomics analysis revealed lipid metabolic reprogramming in ORG mice, which was significantly altered by EMPA treatment. MetOrigin analysis showed a close association between EMPA-related lipid metabolic pathways and gut microbiota alterations, characterized by reduced abundances of Firmicutes and Desulfovibrio and increased abundance of Akkermansia (all P < 0.05). CONCLUSION: The metabolic homeostasis of ORG mice, especially in lipid metabolism, was disrupted and closely associated with gut microbiota alterations, contributing to the progression of ORG. EMPA treatment improved kidney function and morphology by regulating lipid metabolism through the gut-kidney axis, highlighting a novel therapeutic approach for ORG.

A comprehensive exploration of hydrogel applications in multi-stage skin wound healing.

Hydrogels, as an emerging biomaterial, have found extensive use in the healing of wounds due to their distinctive physicochemical structure and functional properties. Moreover, hydrogels can be made to match a range of therapeutic requirements for materials used in wound healing through specific functional modifications. This review provides a step-by-step explanation of the processes involved in cutaneous wound healing, including hemostasis, inflammation, proliferation, and reconstitution, along with an investigation of the factors that impact these processes. Furthermore, a thorough analysis is conducted on the various stages of the wound healing process at which functional hydrogels are implemented, including hemostasis, anti-infection measures, encouraging regeneration, scar reduction, and wound monitoring. Next, the latest progress of multifunctional hydrogels for wound healing and the methods to achieve these functions are discussed in depth and categorized for elucidation. Finally, perspectives and challenges associated with the clinical applications of multifunctional hydrogels are discussed.

Micro/Nanomotor-Driven Intelligent Targeted Delivery Systems: Dynamics Sources and Frontier Applications.

Micro/nanomotors represent a promising class of drug delivery carriers capable of converting surrounding chemical or external energy into mechanical power, enabling autonomous movement. Their distinct autonomous propulsive force distinguishes them from other carriers, offering significant potential for enhancing drug penetration across cellular and tissue barriers. A comprehensive understanding of micro/nanomotor dynamics with various power sources is crucial to facilitate their transition from proof-of-concept to clinical application. In this review, micro/nanomotors are categorized into three classes based on their energy sources: endogenously stimulated, exogenously stimulated, and live cell-driven. The review summarizes the mechanisms governing micro/nanomotor movements under these energy sources and explores factors influencing autonomous motion. Furthermore, it discusses methods for controlling micro/nanomotor movement, encompassing aspects related to their structure, composition, and environmental factors. The remarkable propulsive force exhibited by micro/nanomotors makes them valuable for significant biomedical applications, including tumor therapy, bio-detection, bacterial infection therapy, inflammation therapy, gastrointestinal disease therapy, and environmental remediation. Finally, the review addresses the challenges and prospects for the application of micro/nanomotors. Overall, this review emphasizes the transformative potential of micro/nanomotors in overcoming biological barriers and enhancing therapeutic efficacy, highlighting their promising clinical applications across various biomedical fields.

Advances in biomimetic nanomaterial delivery systems: harnessing nature's inspiration for targeted drug delivery.

The properties of nanomaterials make them promising and advantageous for use in drug delivery systems, but challenges arise from the immune system's recognition of exogenous nanoparticles, leading to their clearance and reduced targeting efficiency. Drawing inspiration from nature, this paper explores biomimetic strategies to transform recognizable nanomaterials into a "camouflaged state." The focal point of this paper is the exploration of bionic nanoparticles, with a focus on cell membrane-coated nanoparticles. These biomimetic structures, particularly those mimicking red blood cells (RBCs), white blood cells (WBCs), platelets, and cancer cells, demonstrate enhanced drug delivery efficiency and prolonged circulation. This article underscores the versatility of these biomimetic structures across diverse diseases and explores the use of hybrid cell membrane-coated nanoparticles as a contemporary trend. This review also investigated exosomes and protein bionic nanoparticles, emphasizing their potential for specific targeting, immune evasion, and improved therapeutic outcomes. We expect that this continued development based on biomimetic nanomaterials will contribute to the efficiency and safety of disease treatment.

Puerarin-containing rhein-crosslinked tyramine-modified hyaluronic acid hydrogel for antibacterial and anti-inflammatory wound dressings.

Wound infections, posing a grave risk of severe physical consequences and even mortality, exact a substantial financial toll on society, rendering them among the most formidable challenges confronting our world today. A critical imperative is the development of hydrogel dressings endowed with immune-regulating and antibacterial properties. This study is founded upon the symbiotic physical and efficacious attributes of two small natural molecules. An injectable hydrogel is meticulously crafted by encapsulating puerarin (PUE) into tyramine-modified hyaluronic acid, subsequently introducing rhein (RHE), and catalyzing the formation of inter-phenol crosslinks with H2O2/horseradish peroxidase (HA-Tyr-R@P). Exhibiting a favorable microenvironmental impact the developed hydrogel attains an antibacterial efficacy exceeding 95 %, coupled with a wound closure rate twice that of the control group. HA-Tyr-R@P hydrogels not only inhibit bacterial growth but also mitigate inflammation, fostering wound healing, owing to their harmonized physicochemical characteristics and synergistic therapeutic effects. This work underscores the creation of a singular, versatile hydrogel platform, negating the complexities and side effects associated with pharmaceutical preparations. Furthermore, it offers new ideas for the formulation of RHE-based hydrogels for wound healing, emphasizing the pivotal role of natural small molecules in advancing biological materials.

Antibacterial and antioxidant bifunctional hydrogel based on hyaluronic acid complex MoS2-dithiothreitol nanozyme for treatment of infected wounds.

Wound repair is a complex physiological process that often leads to bacterial infections, which significantly threaten human health. Therefore, developing wound-healing materials that promote healing and prevent bacterial infections is crucial. In this study, the coordination interaction between sulfhydryl groups on dithiothreitol (DTT) and MoS2 nanosheets is investigated to synthesize a MoS2-DTT nanozyme with photothermal properties and an improved free-radical scavenging ability. Double-bond-modified hyaluronic acid is used as a monomer and is cross-linked with a PF127-DA agent. PHMoD is prepared in coordination with MoS2-DTT as the functional component. This hydrogel exhibits antioxidant and antibacterial properties, attributed to the catalytic activity of catalase-like enzymes and photothermal effects. Under the near-infrared (NIR), it exhibits potent antibacterial effects against gram-positive (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli), achieving bactericidal rates of 99.76% and 99.42%, respectively. Furthermore, the hydrogel exhibits remarkable reactive oxygen species scavenging and antioxidant capabilities, effectively countering oxidative stress in L929 cells. Remarkably, in an animal model, wounds treated with the PHMoD(2.0) and NIR laser heal the fastest, sealing completely within 10 days. These results indicate the unique biocompatibility and bifunctionality of the PHMoD, which make it a promising material for wound-healing applications.

A synergistically antimicrobial and antioxidant hyaluronic acid hydrogel for infected wounds.

Bacterial infections during wound healing impede the healing process and trigger local or systemic inflammatory reactions. Consequently, there is an urgent need to develop a new material with antimicrobial and antioxidant properties to promote infected wound healing. A synergistically antimicrobial and antioxidant hyaluronic acid hydrogel (HMn) is prepared by employing MnO2 nanosheets into 4ARM-PEG5000-SH crosslinked methacrylated hyaluronic acid (HAMA) network. The coordination between sulfhydryl groups of 4ARM-PEG5000-SH and MnO2 nanosheets ensures entrapment of the nanosheets within the hydrogel, while the interaction between 4ARM-PEG5000-SH and HAMA results in facile gelation through thiol-ene click reaction. MnO2 nanosheets exhibit strong photothermal properties and reactive oxygen species (ROS) scavenging abilities, while hyaluronic acid promotes wound healing. When subjected to near-infrared (NIR) irradiation, the HMn achieves a bactericidal rate of 95.24 % for Staphylococcus aureus and nearly 100 % for Escherichia coli. In animal experiments, treatment with the HMn under NIR irradiation results in the best wound healing outcomes. Both in vitro and vivo biocompatible assays demonstrate that the HMn has rarely cell cytotoxicity and tissue damage. The HMn is easy to prepare and has good biocompatibility as well as efficient antibacterial and antioxidant properties, providing a novel method for the treatment of infected wounds.

The formation of multi-metal(loid)s contaminated groundwater at smelting site: Critical role of natural colloids.

The occurrence and migration of colloids at smelting sites are crucial for the formation of multi-metal(loid)s pollution in groundwater. In this study, the behavior of natural colloids (1 nm-0.45 µm) at an abandoned smelting site was investigated by analyzing groundwater samples filtered through progressively decreasing pore sizes. Smelting activities in this site had negatively impacted the groundwater quality, leading to elevated concentrations of zinc (Zn), lead (Pb), arsenic (As), and cadmium (Cd). The results showed that heavy metal(loid)-bearing colloids were ubiquitous in the groundwater with the larger colloidal fractions (∼75 -450 nm) containing higher abundances of pollutants. It was also observed that the predominant colloids consisted of Zn-Al layered double hydroxide (LDH), sphalerite, kaolinite, and hematite. By employing multiple analytical techniques, including leaching experiments, soil colloid characterization, and Pb stable isotope measurements, the origin of groundwater colloids was successfully traced to the topsoil colloids. Most notably, our findings highlighted the increased risk of heavy metal(loid)s migration from polluted soils into adjacent sites through the groundwater because of colloid-mediated transport of contaminants. This field-scale investigation provides valuable insights into the geochemical processes governing heavy metal(loid) behavior as well as offering pollution remediation strategies specifically tailored for contaminated groundwater.

MicroRNAs in spermatogenesis dysfunction and male infertility: clinical phenotypes, mechanisms and potential diagnostic biomarkers.

Infertility affects approximately 10-15% of couples worldwide who are attempting to conceive, with male infertility accounting for 50% of infertility cases. Male infertility is related to various factors such as hormone imbalance, urogenital diseases, environmental factors, and genetic factors. Owing to its relationship with genetic factors, male infertility cannot be diagnosed through routine examination in most cases, and is clinically called 'idiopathic male infertility.' Recent studies have provided evidence that microRNAs (miRNAs) are expressed in a cell-or stage-specific manner during spermatogenesis. This review focuses on the role of miRNAs in male infertility and spermatogenesis. Data were collected from published studies that investigated the effects of miRNAs on spermatogenesis, sperm quality and quantity, fertilization, embryo development, and assisted reproductive technology (ART) outcomes. Based on the findings of these studies, we summarize the targets of miRNAs and the resulting functional effects that occur due to changes in miRNA expression at various stages of spermatogenesis, including undifferentiated and differentiating spermatogonia, spermatocytes, spermatids, and Sertoli cells (SCs). In addition, we discuss potential markers for diagnosing male infertility and predicting the varicocele grade, surgical outcomes, ART outcomes, and sperm retrieval rates in patients with non-obstructive azoospermia (NOA).

Orchestrating Precision within the Tumor Microenvironment by Biomimetic Nanoprodrugs for Effective Tumor Therapy.

Malignant tumors are still one of the most deadly diseases that threaten human life and health. However, developing new drugs is challenging due to lengthy trials, funding constraints, and regulatory approval procedures. Consequently, researchers have devoted themselves to transforming some clinically approved old drugs into antitumor drugs with certain active ingredients, which have become an attractive alternative. Disulfiram (DSF), an antialcohol medication, can rapidly metabolize in the physiological environment into diethyldithiocarbamate (DTC) which can readily react with Cu2+ ions in situ to form the highly toxic bis(N,N-diethyldithiocarbamate)-copper(II) (CuET) complex. In this study, DSF is loaded into mesoporous dopamine nanocarriers and surface-chelated with tannin and Cu2+ to construct M-MDTC nanoprodrugs under the camouflage of K7 tumor cell membranes. After intravenous injection, M-MDTC nanoprodrugs successfully reach the tumor sites with the help of mediated cell membranes. Under slightly acidic pH and photothermal stimulation conditions, DSF and Cu2+ are simultaneously released, forming a highly toxic CuET to kill tumor cells in situ. The generated CuET can also induce immunogenic cell death of tumor cells, increase the proportion of CD86+ CD80+ cells, and promote dendritic cell maturation. In vitro and in vivo studies of M-MDTC nanoprodrugs have shown excellent tumor-cell-killing ability and solid tumor suppression. This approach enables in situ amplification of chemotherapy in the tumor microenvironment, achieving an effective antitumor treatment.

Identification of potential diagnostic biomarkers associated with periodontitis by comprehensive bioinformatics analysis.

Periodontitis is a chronic inflammatory disease that affects the tissues surrounding the teeth, including the gums and the bones supporting the teeth. Early detection and intervention are crucial for effective management of periodontitis. Our study aims to identify a diagnostic biomarker for periodontitis and explore the pathways associated with the occurrence and development of periodontitis. The expression of gingival tissue from periodontitis and healthy control were downloaded from the Gene Expression Omnibus. The weighted gene co-expression network analysis (WGCNA) were used to analyze module genes associated with periodontitis and DESeq2 were performed to identify differently expressed genes (DEGs) between periodontitis and healthy control. Then the candidate genes were obtained by intersecting the genes from interest modules and DEGs. Functional enrichment analysis was performed using gene ontology and kyoto encyclopedia of gene and genomes, followed by the protein-protein interaction (PPI) network analysis. The hub genes were identified by the cytoCNA plugin in Cytoscape. Finally, immunohistochemical staining of the hub genes was performed to validate the findings. WGCNA analysis found that the expression of the MEblack module was significantly higher in individuals with periodontitis compared to those in the healthy control group. A total of 888 DEGs, including 750 upregulated and 138 downregulated genes, were identified. Finally, 427 candidate genes were identified potentially associated with periodontitis after intersecting the DEGs and the black module genes. Several critical signaling pathways were identified associated with periodontitis by functional enrichment analysis, including cytokine-cytokine receptor interaction, neutrophil extracellular trap formation, Staphylococcus aureus infection, and Interleukin-17 signaling pathway. The PPI network analysis revealed that C-X-C motif chemokine ligand 5 (CXCL5) and C-X-C motif chemokine ligand 6 (CXCL6) could play an important role in the process of periodontitis. The gene expression level of CXCL5 and CXCL6 detected using immunohistochemical verified the findings. In conclusion, we found that CXCL5 and CXCL6 are closely associated with the occurrence of periodontitis. Our present pilot study suggests that CXCL5 and CXCL6 have the potential to be used as a diagnostic biomarker of periodontitis.

Single-cell transcriptomic analyses of tumor microenvironment and molecular reprograming landscape of metastatic laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor with a high probability of metastasis. The tumor microenvironment (TME) plays a critical role in cancer metastasis. To gain insights into the TME of LSCC, we conducted single-cell RNA-seq (scRNA-seq) on samples collected from LSCC patients with or without lymphatic metastasis. The stem and immune cell signatures in LSCC suggest their roles in tumor invasion and metastasis. Infiltration of a large number of regulatory T cells, dysplastic plasma cells, and macrophages that are at the early development stage in the cancerous tissue indicates an immunosuppressive state. Abundant neutrophils detected at the cancer margins reflect the inflammatory microenvironment. In addition to dynamic ligand-receptor interactions between the stromal and myeloid cells, the enhanced autophagy in endothelial cells and fibroblasts implies a role in nutrient supply. Taken together, the comprehensive atlas of LSCC obtained allowed us to identify a complex yet unique TME of LSCC, which may help identify potential diagnostic biomarkers and therapeutic targets for LSCC.

Cancer Cell Membrane-Based Materials for Biomedical Applications.

The nanodelivery system provides a novel direction for disease diagnosis and treatment; however, its delivery effectiveness is restricted by the short biological half-life and inadequate tumor targeting. The immune evasion properties and homologous targeting capabilities of natural cell membranes, particularly those of cancer cell membranes (CCM), have gained significant interest. The integration of CCM and nanoparticles has resulted in the emergence of CCM-based nanoplatforms (CCM-NPs), which have gained significant attention due to their unique properties. CCM-NPs not only prolong the blood circulation time of core nanoparticles, but also direct them for homologous tumor targeting. Herein, the history and development of CCM-NPs as well as how these platforms have been used for biomedical applications are discussed. The application of CCM-NPs for cancer therapy will be described in detail. Translational efforts are currently under way and further research to address key areas of need will ultimately be required to facilitate the successful clinical adoption of CCM-NPs.

Synergistic reinforcement of immunogenic cell death and transformation of tumor-associated macrophages via an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform.

The immune system's role in tumor growth and spread has led to the importance of activating immune function in tumor therapy. We present a strategy using an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform (M1mDDTF) to synergistically reinforce immunogenic cell death (ICD) and transform tumor-associated macrophages (TAMs) against tumors. The M1mDDTF nanoparticles consist of doxorubicin-loaded dendritic mesoporous silica nanoparticles chelated with FeIII-tannic acid (FeIIITA) and coated with M1-type macrophage membranes. In the acidic tumor microenvironment, FeIIITA releases Fe2+ and generates ·OH, aided by near infrared irradiation for enhanced doxorubicin release. Furthermore, the M1mDDTF nanoplatform not only directly kills tumor cells but stimulates ICD, which can increase the proportion of CD86+ CD80+ cells and promote dendritic cell maturation. Particularly, the M1mDDTF nanoplatform can also promote the gradual polarization of TAMs into the M1-type and promote tumor cell killing. This study demonstrates the safety and multifunctionality of M1mDDTF nanoparticles, highlighting their potential for clinical tumor treatment. STATEMENT OF SIGNIFICANCE: Malignant tumors are a global concern and a major cause of death. Nanoparticles' passive targeting is ineffective and hindered by reticuloendothelial system clearance. Therefore, enhancing nanoparticle accumulation in tumors while minimizing toxicity is a challenge. Coating nanoparticles with cell membranes enhances biocompatibility, immune evasion, and specific targeting. This approach has led to the development of numerous cell membrane-mimicking nanomaterials with remarkable properties and functions. This study developed an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform, boosting immunogenic cell death and transforming tumor-associated macrophages. Tannic acid in the tumor microenvironment reduced Fe3+ to Fe2+, generating ·OH. M1mDDTF nanosystem induced M1-type macrophage polarization, inhibiting tumor growth and triggering immune cell death. Safe and versatile, these M1mDDTF nanoparticles hold promise for clinical tumor treatment.

Growth factors in the treatment of Achilles tendon injury.

Achilles tendon (AT) injury is one of the most common tendon injuries, especially in athletes, the elderly, and working-age people. In AT injury, the biomechanical properties of the tendon are severely affected, leading to abnormal function. In recent years, many efforts have been underway to develop effective treatments for AT injuries to enable patients to return to sports faster. For instance, several new techniques for tissue-engineered biological augmentation for tendon healing, growth factors (GFs), gene therapy, and mesenchymal stem cells were introduced. Increasing evidence has suggested that GFs can reduce inflammation, promote extracellular matrix production, and accelerate AT repair. In this review, we highlighted some recent investigations regarding the role of GFs, such as transforming GF-ß(TGF-ß), bone morphogenetic proteins (BMP), fibroblast GF (FGF), vascular endothelial GF (VEGF), platelet-derived GF (PDGF), and insulin-like GF (IGF), in tendon healing. In addition, we summarized the clinical trials and animal experiments on the efficacy of GFs in AT repair. We also highlighted the advantages and disadvantages of the different isoforms of TGF-ß and BMPs, including GFs combined with stem cells, scaffolds, or other GFs. The strategies discussed in this review are currently in the early stages of development. It is noteworthy that although these emerging technologies may potentially develop into substantial clinical treatment options for AT injury, definitive conclusions on the use of these techniques for routine management of tendon ailments could not be drawn due to the lack of data.

Sensitive and Direct Analysis of Pseudomonas aeruginosa through Self-Primer-Assisted Chain Extension and CRISPR-Cas12a-Based Color Reaction.

Pseudomonas aeruginosa (P. aeruginosa) is a common opportunistic Gram-negative pathogen that may cause infections to immunocompromised patients. However, sensitive and reliable analysis of P. aeruginosa remains a huge challenge. In this method, target recognition assists the formation of a self-primer and initiates single-stranded chain production. The produced single-stranded DNA chain is identified by CRISPR-Cas12a, and consequently, the trans-cleavage activity of the Cas12a enzyme is activated to parallelly digest Ag+ aptamer sequences that are chelated with silver ions (Ag+). The released Ag+ reacted with 3,3',5,5'-tetramethylbenzidine (TMB) for coloring. Compared with the traditional color developing strategies, which mainly rely on the DNA hybridization, the color developing strategy in this approach exhibits a higher efficiency due to the robust trans-cleavage activity of the Cas12a enzyme. Consequently, the method shows a low limit of detection of a wide detection of 5 orders of magnitudes and a low limit of detection of 21 cfu/mL, holding a promising prospect in early diagnosis of infections. Herein, we develop a sensitive and reliable method for direct and colorimetric detection of P. aeruginosa by integrating self-primer-assisted chain production and CRISPR-Cas12a-based color reaction and believe that the established approach will facilitate the development of bacteria-analyzing sensors.

In vitro enzymatic degradation of the PTMC/cross-linked PEGDA blends.

Introduction: Poly(1,3-trimethylene carbonate) (PTMC) is a flexible amorphous polymer with good degradability and biocompatibility. The degradation of PTMC is critical for its application as a degradable polymer, more convenient and easy-to-control cross-linking strategies for preparing PTMC are required. Methods: The blends of poly(trimethylene carbonate) (PTMC) and cross-linked poly(ethylene glycol) diacrylate (PEGDA) were prepared by mixing photoactive PEGDA and PTMC and subsequently photopolymerizing the mixture with uv light. The physical properties and in vitro enzymatic degradation of the resultant PTMC/cross-linked PEGDA blends were investigated. Results: The results showed that the gel fraction of PTMC/cross-linked PEGDA blends increased while the swelling degree decreased with the content of PEGDA dosage. The results of in vitro enzymatic degradation confirmed that the degradation of PTMC/cross-linked PEGDA blends in the lipase solution occurred under the surface erosion mechanism, and the introduction of the uv cross-linked PEGDA significantly improved the resistance to lipase erosion of PTMC; the higher the cross-linking degree, the lower the mass loss. Discussion: The results indicated that the blends/cross-linking via PEGDA is a simple and effective strategy to tailor the degradation rate of PTMC.

The role of microbial metabolites in diabetic kidney disease.

Background: Growing evidence suggests a complex bidirectional interaction between gut microbes, gut-derived microbial metabolites, and diabetic kidney disease (DKD), known as the "gut-kidney axis" theory. The present study aimed to characterize the role of microbial metabolites in DKD. Methods: Six-week-old db/db and littermate db/m mice were raised to 20 weeks old. The serum, urine, feces, liver, perinephric fat, and kidney were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomic analyses. Results: The db/db mice showed obvious pathological changes and worse renal functions than db/m mice. Indoleacetaldehyde (IAld) and 5-hydroxy-l-tryptophan (5-HTP) in kidney samples, and serotonin (5-HT) in fecal samples were increased in the db/db group. Phosphatidylcholine (PC), phosphatidate (PA), and 1-acylglycerophosphocholine (lysoPC) were decreased in liver and serum samples of the db/db group, while PC and lysoPC were decreased in kidney and perinephric fat samples. Suggested metabolomic homeostasis was disrupted in DKD mice, especially glycerophospholipid and tryptophan metabolism, which are closely related to the gut microbiome. Conclusions: Our findings reveal the perturbation of gut microbial metabolism in db/db mice with DKD, which may be useful for building a bridge between the gut microbiota and the progression of DKD and provide a theoretical basis for the intestinal treatment of DKD.