Additive Manufacturing of Biodegradable Molybdenum - From Powder to Vascular Stent.

Magnesium, iron, and zinc-based biodegradable metals are widely recognized as promising candidate materials for the next generation of bioresorbable stent (BVS). However, none of those metal BVSs are perfect at this stage. Here, a brand-new BVS based on a novel biodegradable metal (Molybdenum, Mo) through additive manufacturing is developed. Nearly full-dense and crack-free thin-wall Mo is directly manufactured through selective laser melting (SLM) with fine Mo powder. Systemic analyses considering the forming quality, wall-thickness, microstructure, mechanical properties, and in vitro degradation behaviors are performed. Then, Mo-based thin-strut (≤ 100 µm) stents are successfully obtained through an optimized single-track laser melting route. The SLMed thin-wall Mo owns comparable strength to its Mg and Zn based counterparts (as-drawn), while, it exhibits remarkable biocompatibility in vitro. Vessel related cells are well adhered and spread on SLMed Mo, and it exhibits a low risk of hemolysis and thrombus. The SLMed stent is compatible to vessel tissues in rat abdominal aorta, and it can provide sufficient support in an animal model as an extravascular stent. This work possibly opens a new era of manufacturing Mo-based stents through additive manufacturing.

Chinese botanical drugs targeting mitophagy to alleviate diabetic kidney disease, a comprehensive review.

Diabetic kidney disease (DKD) is one of the chronic microvascular complications caused by diabetes, which is characterized by persistent albuminuria and/or progressive decline of estimated glomerular filtration rate (eGFR), and has been the major cause of dialysis around the world. At present, although the treatments for DKD including lifestyle modification, glycemic control and even using of Sodium-glucose cotransporter 2 (SGLT2) inhibitors can relieve kidney damage caused to a certain extent, there is still a lack of effective treatment schemes that can prevent DKD progressing to ESRD. It is urgent to find new complementary and effective therapeutic agents. Growing animal researches have shown that mitophagy makes a great difference to the pathogenesis of DKD, therefore, exploration of new drugs that target the restoration of mitophagy maybe a potential perspective treatment for DKD. The use of Chinese botanical drugs (CBD) has been identified to be an effective treatment option for DKD. There is growing concern on the molecular mechanism of CBD for treatment of DKD by regulating mitophagy. In this review, we highlight the current findings regarding the function of mitophagy in the pathological damages and progression of DKD and summarize the contributions of CBD that ameliorate renal injuries in DKD by interfering with mitophagy, which will help us further explain the mechanism of CBD in treatment for DKD and explore potential therapeutic strategies for DKD.

Long-term efficacy, safety and biocompatibility of a novel sirolimus eluting iron bioresorbable scaffold in a porcine model.

Iron is considered as an attractive alternative material for bioresorbable scaffolds (BRS). The sirolimus eluting iron bioresorbable scaffold (IBS), developed by Biotyx Medical (Shenzhen, China), is the only iron-based BRS with an ultrathin-wall design. The study aims to investigate the long-term efficacy, safety, biocompatibility, and lumen changes during the biodegradation process of the IBS in a porcine model. A total of 90 IBSs and 70 cobalt-chromium everolimus eluting stents (EES) were randomly implanted into nonatherosclerotic coronary artery of healthy mini swine. The multimodality assessments including coronary angiography, optical coherence tomography, micro-computed tomography, magnetic resonance imaging, real-time polymerase chain reaction (PCR), and histopathological evaluations, were performed at different time points. There was no statistical difference in area stenosis between IBS group and EES group at 6 months, 1year, 2 years and 5 years. Although the scaffolded vessels narrowed at 9 months, expansive remodeling with increased mean lumen area was found at 3 and 5 years. The IBS struts remained intact at 6 months, and the corrosion was detectable at 9 months. At 5 years, the iron struts were completely degraded and absorbed in situ, without in-scaffold restenosis or thrombosis, lumen collapse, aneurysm formation, and chronic inflammation. No local or systemic toxicity and abnormal histopathologic manifestation were found in all experiments. Results from real-time PCR indicated that no sign of iron overload was reported in scaffolded segments. Therefore, the IBS shows comparable efficacy, safety, and biocompatibility with EES, and late lumen enlargement is considered as a unique feature in the IBS-implanted vessels.

An adaptive biodegradable zinc alloy with bidirectional regulation of bone homeostasis for treating fractures and aged bone defects.

Healing of fractures or bone defects is significantly hindered by overactivated osteoclasts and inhibited osteogenesis in patients with abnormal bone metabolism. Current clinical approaches using titanium alloys or stainless steel provide mechanical support but have no biological effects on bone regeneration. Therefore, designing and fabricating degradable metal materials with sufficient mechanical strength and bidirectional regulation of both osteoblasts and osteoclasts is a substantial challenge. Here, this study first reported an adaptive biodegradable Zn-0.8 Mg alloy with bidirectional regulation of bone homeostasis, which promotes osteogenic differentiation by activating the Pi3k/Akt pathway and inhibits osteoclast differentiation by inhibiting the GRB2/ERK pathway. The anti-osteolytic ability of the Zn-0.8 Mg alloy was verified in a mouse calvarial osteolysis model and its suitability for internal fracture fixation with high-strength screws was confirmed in the rabbit femoral condyle fracture model. Furthermore, in an aged postmenopausal rat femoral condyle defect model, 3D printed Zn-0.8 Mg scaffolds promoted excellent bone regeneration through adaptive structures with good mechanical properties and bidirectionally regulated bone metabolism, enabling personalized bone defect repair. These findings demonstrate the substantial potential of the Zn-0.8 Mg alloy for treating fractures or bone defects in patients with aberrant bone metabolism.

The road to evolution of ProTx2: how to be a subtype-specific inhibition of human Nav1.7.

The human voltage-gated sodium channel Nav1.7 is a widely proven target for analgesic drug studies. ProTx2, a 30-residue polypeptide from Peruvian green tarantula venom, shows high specificity to activity against human Nav1.7, suggesting its potential to become a non-addictive analgesic. However, its high sensitivity to human Nav1.4 raises concerns about muscle side effects. Here, we engineered three mutants (R13A, R13D, and K27Y) of ProTx2 to evaluate their pharmacological activities toward Nav1.7 and Nav1.4. It is demonstrated that the mutant R13D maintained the analgesic effect in mice while dramatically reducing its muscle toxicity compared with ProTx2. The main reason is the formation of a strong electrostatic interaction between R13D and the negatively charged amino acid residues in DII/S3-S4 of Nav1.7, which is absent in Nav1.4. This study advances our understanding and insights on peptide toxins, paving the way for safer, effective non-addictive analgesic development.

[Mechanism of Fushen Granules treat peritoneal dialysis-related peritonitis by regulating TLR4/NF-κB pathway:based on network pharmacology and animal experiments].

Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active components of Fushen Granules were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted. PDRP-related targets were retrieved from DisGeNET and other databases. The common targets shared by the drug and the disease were identified by the online tool, and protein-protein interaction(PPI) network of the common targets. The obtained 276 common targets were imported into DAVID for GO function enrichment and KEGG pathway enrichment. The main signaling pathway of Fushen Granules in the treatment of PDRP was predicted as Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB. The rat model of uremia was induced by 5/6 nephrectomy. From two weeks after operation, the rat model of peritoneal dialysis(PD) was established by intraperitoneal injection of 20 mL dialysate with 1.25% glucose every day. The sham operation group and model group received 2 mL normal saline by gavage every day. The rats in Fushen Gra-nules groups were administrated with 2 mL solutions of low-(0.54 g·kg~(-1)), medium-(1.08 g·kg~(-1)) and high-dose(2.16 g·kg~(-1)) Fushen Granules every day. The bifico group received 2 mL(113.4 mg·kg~(-1)) of bifico solution every day. At the end of the 8th week, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in each group were measured. The serum levels of hypersensitive C reactive protein(hs-CRP), tumor necrosis factor(TNF)-α, and interleukin(IL)-6 were measured, and the pathological changes in the colon tissue were observed by hematoxylin-eosin(HE) staining. The serum levels of lipopolysaccharide(LPS) and lipopolysaccharide-binding protein(LBP) of rats were measured, and the expression levels of LBP, TLR4, NF-κB p65, inhibitor of κB kinase α(IκBα), TNF-α, and IL-1ß in the colon tissue were determined. Compared with sham operation group, the model group had abnormal structure of all layers of colon tissue, sparse and shorter intestinal villi, visible edema in mucosal layer, wider gap, obvious local inflammatory cell infiltration, significantly decreased body weight(P<0.01), and significantly increased kidney function index(Scr, BUN) content(P<0.01). Serum levels of inflammatory cytokines(hs-CRP, TNF-α, IL-6), LPS and LBP were significantly increased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß were significantly increased(P<0.01), and protein expressions of IκBα were significantly decreased(P<0.01). Compared with model group, intestinal villi damage in colonic tissue of rats in low-, medium-and high-dose Fushen Granules groups and bifico group were alleviated to different degrees, edema in submucosa was alleviated, space was narrowed, and inflammatory cell infiltration in lamina propria was reduced. The contents of renal function index(Scr, BUN) and serum inflammatory factors(hs-CRP, TNF-α, IL-6) were significantly decreased(P<0.05 or P<0.01) in medium-and high-dose Fushen Granules groups and bifico group(P<0.05 or P<0.01). Serum LPS and LBP contents in Fushen Granules group and bifico group were significantly decreased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß in Fushen Granules group were significantly decreased(P<0.05 or P<0.01), and protein expressions of IκBα were significantly increased(P<0.01). The expression of LBP protein in bifico group was significantly decreased(P<0.01). The results suggest that Fushen Granules can protect the residual renal function of PD rats, reduce the inflammatory response, and protect the colon tissue. Based on network pharmacology, TLR4/NF-κB pathway may be the main signaling pathway of Fushen granule in the treatment of PDRP. The results showed that Fushen Granules could improve intestinal inflammation and protect intestinal barrier to prevent PDRP by regulating the expression of key factors in TLR4/NF-κB pathway in colon of PD rats.

Multiscale architecture design of 3D printed biodegradable Zn-based porous scaffolds for immunomodulatory osteogenesis.

Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.

Efficacy and Safety of Gabapentinoids for Acute Herpes Zoster Neuralgia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This study aimed to systematically evaluate the clinical efficacy of gabapentin and pregabalin in the treatment of acute herpes zoster (HZ) neuralgia, including pain control and the occurrence of adverse effects. METHODS: A systematic computerized search was conducted in October 2023 in PubMed, Embase, Web of Science, Cochrane Library, VIP, CNKI, and Wanfang databases. Data from randomized controlled trials (RCTs) comparing gabapentin analogs for the treatment of acute HZ neuralgia were searched. Endpoints were visual analog scores (Visual Analog Scale) and adverse effects at 1, 2, and 4 weeks. Data from studies that met the inclusion criteria were extracted for meta-analysis and sensitivity analysis using Revman 5.4 and Stata16. RESULTS: The study included 292 patients from 6 RCTs. Of these, 118 were in the gabapentin-treated group, 37 were in the pregabalin-treated group, and 137 were in the placebo-controlled group. The gabapentin group showed superior pain reduction compared with the placebo group ( P < 0.05), but adverse events were more frequent. CONCLUSION: Gabapentin can effectively reduce acute HZ neuralgia in patients. Pregabalin requires additional RCTs to supplement the analysis.

Fabrication of a Nanoscale Magnesium/Copper Metal-Organic Framework on Zn-Based Guided Bone Generation Membranes for Enhancing Osteogenesis, Angiogenesis, and Bacteriostasis Properties.

Recently, zinc (Zn) and its alloys have demonstrated great potential as guided bone regeneration (GBR) membranes to treat the problems of insufficient alveolar bone volume and long-term osseointegration instability during dental implantology. However, bone regeneration is a complex process consisting of osteogenesis, angiogenesis, and antibacterial function. For now, the in vivo osteogenic performance and antibacterial activity of pure Zn are inadequate, and thus fabricating a platform to endow Zn membranes with multifunctions may be essential to address these issues. In this study, various bimetallic magnesium/copper metal-organic framework (Mg/Cu-MOF) coatings were fabricated and immobilized on pure Zn. The results indicated that the degradation rate and water stability of Mg/Cu-MOF coatings could be regulated by controlling the feeding ratio of Cu2+. As the coating and Zn substrate degraded, an alkaline microenvironment enriched with Zn2+, Mg2+, and Cu2+ was generated. It significantly improved calcium phosphate deposition, differentiation of osteoblasts, and vascularization of endothelial cells in the extracts. Among them, Mg/Cu1 showed the best comprehensive performance. The superior antibacterial activity of Mg/Cu1 was demonstrated in vitro and in vivo, which indicated significantly enhanced bacteriostatic activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli as compared to that of the bare sample. Bimetallic Mg/Cu-MOF coating could properly coordinate the multifunction on a Zn membrane and could be a promising platform for promoting its bone regeneration, which could pave the way for Zn-based materials to be used as barrier membranes in oral clinical trials.

A Dose-Dependent Spatiotemporal Response of Angiogenesis Elicited by Zn Biodegradation during the Initial Stage of Bone Regeneration.

Zinc (Zn) plays a crucial role in bone metabolism and imbues biodegradable Zn-based materials with the ability to promote bone regeneration in bone trauma. However, the impact of Zn biodegradation on bone repair, particularly its influence on angiogenesis, remains unexplored. This study reveals that Zn biodegradation induces a consistent dose-dependent spatiotemporal response in angiogenesis,both in vivo and in vitro. In a critical bone defect model, an increase in Zn release intensity from day 3 to 10 post-surgery is observed. By day 10, the CD31-positive area around the Zn implant significantly surpasses that of the Ti implant, indicating enhanced angiogenesis. Furthermore,angiogenesis exhibits a distance-dependent pattern closely mirroring the distribution of Zn signals from the implant. In vitro experiments demonstrate that Zn extraction fosters the proliferation and migration of human umbilical vein endothelial cells and upregulates the key genes associated with tube formation, such as HIF-1α and VEGF-A, peaking at a concentration of 22.5 µM. Additionally, Zn concentrations within the range of 11.25-45 µM promote the polarization of M0-type macrophages toward the M2-type, while inhibiting polarization toward the M1-type. These findings provide essential insights into the biological effects of Zn on bone repair, shedding light on its potential applications.

Psoralen synergies with zinc implants to promote bone repair by regulating ZIP4 in rats with bone defect.

BACKGROUND: The regulation of dose-dependent biological effects induced by biodegradation is a challenge for the production of biodegradable bone-substitute materials, especially biodegradable zinc (Zn) -based materials. Cytotoxicity caused by excess local Zn ions (Zn2+) from degradation is one of the factors limiting the wide application of Zn implants. Given that previous studies have revealed that delayed degradation of Zn materials by surface modification does not reduce cytotoxicity; in the present study, we explore whether preventing the entry of excess Zn2+ into cells may can reduce local Zn toxicity by applying Psoralen (PRL) to Zn implants and assessing its ability to regulate intracellular Zn2+ concentrations. METHODS: The effects of different concentrations of Zn2+ on cellular activity and cytotoxicity were investigated; briefly, we identified natural compounds that regulate Zn transporters, thereby regulating the concentrations of intracellular Zn2+, and applied them to Zn materials. Of these materials, PRL, a natural, tricyclic, coumarin-like aromatic compound that promotes the proliferation and differentiation of osteoblasts and enhances osteogenic activity, was loaded onto the surface of a Zn material using peptides and chitosan (CS), and the surface characteristics, electrochemical properties, and activity of the modified Zn material were evaluated. In addition, the ability of Zn + CS/pPRL implants to promote bone formation and accelerate large-scale bone defect repairs was assessed both in vitro and in vivo. RESULTS: We determined that 180 µM Zn2+ significantly induced pre-osteoblast cytotoxicity, and a 23-fold increase in Zrt- and Irt-like protein 4 (ZIP4) expression. We also found that PRL dynamically regulates the expression of ZIP4 in response to Zn2+ concentration. To address the problem of cytotoxicity caused by excessive Zn2+ in local Zn implants, PRL was loaded onto the surface of Zn implants in vivo using peptides and CS, which dynamically regulated ZIP4 levels, maintained the balance of intracellular Zn2+ concentrations, and enhanced the osteogenic activity of Zn implants. CONCLUSIONS: This study reveals the importance of Zn2+ concentration when using Zn materials to promote bone formation and introduces a natural active ingredient, PRL, that can regulate intracellular Zn2+ levels, and thus may be clinically applicable to Zn implants for the treatment of critical bone defects.

Therapeutic effects of Chinese herbal medicines for treatment of urolithiasis: A review.

Urolithiasis is a common and complex disease of the urinary system, which can cause urinary tract blockage, urinary tract infection, and even damage to urinary system-related tissues. Although urolithiasis can be cured, its high recurrence rate and the development of chronic kidney disease in some patients have drawn the attention of nephrologists. Although the application of extracorporeal lithotripsy, percutaneous nephrolithotomy and other minimally invasive techniques have made the treatment of urolithiasis more efficient, pharmacotherapy plays an indispensable role in reducing their morbidity and recurrence rates. Traditional Chinese medicine (TCM) has been used for treatment and prevention of urolithiasis in developing countries for centuries, known for its unquestionable efficacy and safety. This article reviews the progress of clinical trials and pharmacological studies on the treatment of urolithiasis with Chinese herbal medicines (CHMs). The mechanism of CHMs in the treatment of urolithiasis mainly involve preventing further growth and aggregation of urolithiasis, reducing the PH of urine, promoting calculus dissolution. Furthermore, some CHMs can increase urine output, relax smooth muscles, and promote the removal of calculus. These findings provide new treatment strategies and options for urolithiasis and secondary kidney damage.

In-center Automated Peritoneal Dialysis: Clinical Features, Practice Patterns, and Patient Survival From a 6-year Cohort Study in China.

INTRODUCTION: In-center automated peritoneal dialysis (APD) has been more frequently adopted in clinical practice for maintenance PD patients in China. For a better understanding of its clinical uptake, this retrospective study reviewed incident PD patients for a period of 6 years, investigating the practice pattern of in-center APD, factors associated with the use of in-center APD, and report on the patient survival compared to the non-users of APD among hospitalised PD patients. METHODS: This was a cohort study of all incident PD patients who met the inclusion criteria from 2013/01/01 to 2018/09/30, and were followed until death, cessation of PD, loss to follow-up, or 2018/12/31. Clinical characteristics, patient outcomes, and detailed data on APD sessions were recorded. We used time-dependent Cox model to estimate the variables associated with the initiation of in-center APD, and marginal structural model through inverse probability weighting to adjust for time-varying APD use on the causal pathway to all-cause mortality. RESULTS: A total of 651 subjects over 17501 patient-months were enrolled. Of these, 633 (97.2%) PD patients were hospitalised at least once during follow-up, and 369 (56.7%) received in-center APD at a certain point, and the timing of APD use during the first 3 months, first year and first 2 years since PD inception were 14.8%, 45.4% and 74.8%, respectively. A total of 12553 in-center APD sessions were recorded, where 85.9% used 4 bags of 5L-exchanges per prescription. Time-dependent Cox model showed that diabetes (hazard ratio [HR], 1.39, 95% confidence interval [CI], 1.09-1.76), urine output (HR 0.80, 95% CI 0.70-0.92), serum albumin (HR 0.84, 95%CI 0.72-0.99), hemoglobin (HR 0.88, 95%CI 0.77-0.99), and Ca×P (HR 1.19, 95%CI 1.06-1.35) were significantly associated with in-center APD use. Among all hospitalised PD patients, the estimated hazard ratio corresponding to the marginal causal effect of in-center APD use on all-cause mortality is 0.13 (95% CI 0.05-0.31, P<0.001). Significant survival benefit (adjusted-HR 0.56, 95%CI 0.33-0.95) associated with starting APD after the first PD year was observed among in-center APD users. CONCLUSIONS: In-center APD is used intensively during the first 2 years of PD and is associated with certain clinical features. Over all a significant survival benefit of in-center APD use was observed.

Exogenous abscisic acid improves grain filling capacity under heat stress by enhancing antioxidative defense capability in rice.

BACKGROUND: Heat stress is a major restrictive factor that causes yield loss in rice. We previously reported the priming effect of abscisic acid (ABA) on rice for enhanced thermotolerance at the germination, seedling and heading stages. In the present study, we aimed to understand the priming effect and mechanism of ABA on grain filling capacity in rice under heat stress. RESULTS: Rice plants were pretreated with distilled water, 50 µM ABA and 10 µM fluridone by leaf spraying at 8 d or 15 d after initial heading (AIH) stage and then were subjected to heat stress conditions of 38 °C day/30 °C night for 7 days, respectively. Exogenous ABA pretreatment significantly super-activated the ABA signaling pathway and improved the SOD, POD, CAT and APX enzyme activity levels, as well as upregulated the ROS-scavenging genes; and decreased the heat stress-induced ROS content (O2- and H2O2) by 15.0-25.5% in rice grain under heat stress. ABA pretreatment also increased starch synthetase activities in rice grain under heat stress. Furthermore, ABA pretreatment significantly improved yield component indices and grain yield by 14.4-16.5% under heat stress. ABA pretreatment improved the milling quality and the quality of appearance and decreased the incidence of chalky kernels and chalkiness in rice grain and improved the rice grain cooking quality by improving starch content and gel consistence and decreasing the amylose percentage under heat stress. The application of paraquat caused overaccumulation of ROS, decreased starch synthetase activities and ultimately decreased starch content and grain yield. Exogenous antioxidants decreased ROS overaccumulation and increased starch content and grain yield under heat stress. CONCLUSION: Taken together, these results suggest that exogenous ABA has a potential priming effect for enhancing rice grain filling capacity under heat stress at grain filling stage mainly by inhibiting ROS overaccumulation and improving starch synthetase activities in rice grain.

A Cellulose Reinforced Multifunctional Binder for High-Performance Silicon Anodes.

Silicon (Si) has garnered significant interest as a potential anode material for next-generation lithium-ion batteries due to its high theoretical capacity. However, Si anodes suffer from substantial volume expansion during the charge and discharge processes, which severely undermines their cycling stability. To address this issue, developing novel binders has become an effective strategy to suppress the volume expansion of Si anodes. In this study, a multifunctional polymer binder (DCCS) was designed by the cross-linking of dialdehyde cellulose nanocrystal (DACNC) and carboxymethyl chitosan (CMCS), which forms a 3D network structure via Schiff-base bonds. The DCCS binder with abundant chemical and hydroxyl bonds shows strong adhesion between Si nanoparticles and current collectors, thus enhancing the mechanical properties of the electrode. Furthermore, the DACNC also served as the protecting buffer layer to release the inner stress and stabilize the solid electrolyte interface (SEI). At 4 A g-1, the resulting Si@25%DCCS electrode demonstrated a capacity of 1637 mAh g-1 after 500 cycles, with an average capacity fading rate of 0.07% per cycle. Therefore, this multifunctional binder is considered a promising binder for high-performance Si anodes.

The potential mechanism of gut microbiota-microbial metabolites-mitochondrial axis in progression of diabetic kidney disease.

Diabetic kidney disease (DKD), has become the main cause of end-stage renal disease (ESRD) worldwide. Lately, it has been shown that the onset and advancement of DKD are linked to imbalances of gut microbiota and the abnormal generation of microbial metabolites. Similarly, a body of recent evidence revealed that biological alterations of mitochondria ranging from mitochondrial dysfunction and morphology can also exert significant effects on the occurrence of DKD. Based on the prevailing theory of endosymbiosis, it is believed that human mitochondria originated from microorganisms and share comparable biological characteristics with the microbiota found in the gut. Recent research has shown a strong correlation between the gut microbiome and mitochondrial function in the occurrence and development of metabolic disorders. The gut microbiome's metabolites may play a vital role in this communication. However, the relationship between the gut microbiome and mitochondrial function in the development of DKD is not yet fully understood, and the role of microbial metabolites is still unclear. Recent studies are highlighted in this review to examine the possible mechanism of the gut microbiota-microbial metabolites-mitochondrial axis in the progression of DKD and the new therapeutic approaches for preventing or reducing DKD based on this biological axis in the future.

Study on Mechanical Properties and Failure Mechanisms of Highly Filled Hydroxy-Terminated Polybutadiene Propellant under Different Tensile Loading Conditions.

To study the mechanical properties of highly filled hydroxy-terminated polybutadiene (HTPB) propellant with 90 wt% solid fillers, the stress-strain curves of the propellant under different temperatures (-50 to 70 °C) and strain rates (0.000476 to 0.119048 s-1) were obtained by uniaxial tensile test. Moreover, to obtain the glass transition temperature and understand the effect of low temperatures on the mechanical properties of the propellant, DMA experiments were carried out. On this basis, the mechanical response laws of the propellant were analyzed, and the master curves of mechanical properties were established. Furthermore, the fracture features of the propellant under typical loading conditions were obtained by SEM, and the corresponding failure mechanisms were analyzed. The results show that the maximum strength decreases with increasing temperature, while the maximum elongation increases with increasing temperature at the same strain rate. The maximum tensile strength increases with increasing strain rate, while the maximum elongation decreases with increasing strain rate at the same temperature. The maximum tensile strength is lowest with a value of 0.35 MPa when the temperature is 343.15 K and the strain rate is 0.000476 s-1, at which time the maximum elongation reaches the highest with a value of 44%. In terms of failure mechanisms, the propellant shows no particle fracture, and the failure modes of the propellant are mainly matrix tearing and dewetting.

Immunomodulatory biomaterials against bacterial infections: Progress, challenges, and future perspectives.

Bacterial infectious diseases are one of the leading causes of death worldwide. Even with the use of multiple antibiotic treatment strategies, 4.95 million people died from drug-resistant bacterial infections in 2019. By 2050, the number of deaths will reach 10 million annually. The increasing mortality may be partly due to bacterial heterogeneity in the infection microenvironment, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants. In addition, the complexity of the immune microenvironment at different stages of infection makes biomaterials with direct antimicrobial activity unsatisfactory for the long-term treatment of chronic bacterial infections. The increasing mortality may be partly attributed to the biomaterials failing to modulate the active antimicrobial action of immune cells. Therefore, there is an urgent need for effective alternatives to treat bacterial infections. Accordingly, the development of immunomodulatory antimicrobial biomaterials has recently received considerable interest; however, a comprehensive review of their research progress is lacking. In this review, we focus mainly on the research progress and future perspectives of immunomodulatory antimicrobial biomaterials used at different stages of infection. First, we describe the characteristics of the immune microenvironment in the acute and chronic phases of bacterial infections. Then, we highlight the immunomodulatory strategies for antimicrobial biomaterials at different stages of infection and their corresponding advantages and disadvantages. Moreover, we discuss biomaterial-mediated bacterial vaccines' potential applications and challenges for activating innate and adaptive immune memory. This review will serve as a reference for future studies to develop next-generation immunomodulatory biomaterials and accelerate their translation into clinical practice.

Preliminary Design and On-Site Testing Methodology of Roof-Cutting for Entry Retaining in Underground Coal Mine.

Entry retaining via roof cutting is a new longwall mining method that has emerged in recent years, and is characterized by high resource utilization and environmental friendliness. Due to the complexity of this method, a field study is commonly employed for process optimization. Roof blasting is a key operation for retaining the entry, and the current practice involves dynamically adjusting blasting parameters through on-site testing and postblasting monitoring. However, the existing literature lacks detailed descriptions of blasting operations, making it difficult for field engineers to replicate the results. In this study, based on a roof cutting project for entry retaining, a preliminary design of blasting parameters is made based on theories and on-site geological conditions. The on-site test methods and equipment for roof-cutting blasting are described in detail, and the fractural patterns under different blasting parameters are analyzed. After the retreat of the working face, the state of roof caving in the goaf is analyzed based on monitoring data, and the effectiveness of top cutting is evaluated through reverse analysis, leading to dynamic adjustments of the blasting parameters. This research provides a reproducible construction method for roof-cutting operations and establishes the relationship between blasting parameters and post-mining monitoring data. It contributes to the development of fundamental theories and systematic technical systems for entry retaining via roof cutting, offering high-quality case studies for similar geological engineering projects.