Hydrogel-Encapsulated Pancreatic Islet Cells as a Promising Strategy for Diabetic Cell Therapy.

Islet transplantation has now become a promising treatment for insulin-deficient diabetes mellitus. Compared to traditional diabetes treatments, cell therapy can restore endogenous insulin supplementation, but its large-scale clinical application is impeded by donor shortages, immune rejection, and unsuitable transplantation sites. To overcome these challenges, an increasing number of studies have attempted to transplant hydrogel-encapsulated islet cells to treat diabetes. This review mainly focuses on the strategy of hydrogel-encapsulated pancreatic islet cells for diabetic cell therapy, including different cell sources encapsulated in hydrogels, encapsulation methods, hydrogel types, and a series of accessorial manners to improve transplantation outcomes. In addition, the formation and application challenges as well as prospects are also presented.

Effectiveness and safety of brucea javanica oil assisted TACE versus TACE in the treatment of liver cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: The effectiveness and safety of using Brucea javanica oil (BJO) in combination with Transarterial Chemoembolization (TACE) for liver cancer treatment are subjects of debate. This study aims to assess the comparative effectiveness and safety of BJO-assisted TACE versus TACE alone and quantifies the differences between these two treatment methods. Methods: A systematic search was conducted in multiple databases including PubMed, Cochrane, CNKI, and Wanfang, until 1 July 2023. Meta-analysis was conducted, and the results were presented as mean difference (MD), risk ratio (RR), and 95% confidence intervals (CI). Results: The search yielded 11 RCTs, with a combined sample size of 1054 patients. Meta-analysis revealed that BJO-assisted TACE exhibited superior outcomes compared to standalone TACE. Specific data revealed that BJO-assisted TACE improves clinical benefit rate by 22% [RR = 1.22, 95% CI (1.15, 1.30)], increases the number of people with improved quality of life by 32%, resulting in an average score improvement of 9.53 points [RR = 1.32, 95% CI (1.22, 1.43); MD = 9.53, 95% CI (6.95, 12.10)]. Furthermore, AFP improvement rate improved significantly by approximately 134% [RR = 2.34, 95% CI (1.58, 3.46)], accompanied by notable improvements in liver function indicators, with an average reduction of 27.19 U/L in AST [MD = -27.19, 95% CI (-40.36, -14.02)], 20.77 U/L in ALT [MD = -20.77, 95% CI (-39.46, -2.08)], 12.17 µmol/L in TBIL [MD = -12.17, 95% CI (-19.38, -4.97)], and a decrease of 43.72 pg/mL in VEGF [MD = -43.72, 95% CI (-63.29, -24.15)]. Most importantly, there was a 29% reduction in the occurrence of adverse reactions [RR = 0.71, 95% CI (0.60, 0.84)]. Conclusion: These findings indicate that BJO-assisted TACE may be considered as a potentially beneficial treatment option for liver cancer patients when compared to standalone TACE. It appears to contribute to improved treatment outcomes, enhanced quality of life, and potentially reduced adverse reactions, suggesting it warrants further investigation as a promising approach for liver cancer treatment. Systematic Review Registration: identifier CRD42023428948.

Research progress on long non­coding RNAs in non­infectious spinal diseases (Review).

Spinal diseases, including intervertebral disc degeneration (IDD), ankylosing spondylitis, spinal cord injury and other non­infectious spinal diseases, severely affect the quality of life of patients. Current treatments for IDD and other spinal diseases can only relieve symptoms and do not completely cure the disease. Therefore, there is an urgent need to explore the causes of these diseases and develop new treatment approaches. Long non­coding RNA (lncRNA), a form of non­coding RNA, is abundant in diverse sources, has numerous functions, and plays an important role in the occurrence and development of spinal diseases such as IDD. However, the mechanism of action of lncRNAs has not been fully elucidated, and significant challenges remain in the use of lncRNAs as new therapeutic targets. The present article reviews the sources, classification and functions of lncRNAs, and introduces the role of lncRNAs in spinal diseases, such as IDD, and their therapeutic potential.

Bushen Huoxue decotion-containing serum prevents chondrocyte pyroptosis in a m6A-dependent manner in facet joint osteoarthritis.

BACKGROUND: Facet joint osteoarthritis (FJOA) is a common lumbar osteoarthritis characterized by degeneration of small joint cartilage. Bushen Huoxue decotion (BSHXD) has good therapeutic effects on OA. Our work aimed to further probe the pharmacological effects of BSHXD-containing serum (BSHXD-CS) on FJOA and define underlying the mechanisms invovled. METHODS: To establish a FJOA cell model, primary rat chondrocytes were treated with LPS. The mRNA and protein expressions were assessed using qRT-PCR and western blot, respectively. The secretion levels of pro-inflammatory cytokines were measured by ELISA. Cell viability was determined by CCK8 assay. The global m6A level was detected by the kit, and NLRP3 mRNA m6A level was determined by Me-RIP assay. The molecular interactions were analyzed by RIP and RNA pull-down assays. RESULTS: BSHXD-CS treatment relieved LPS-induced cell injury, inflammation, NLRP3 inflammasome and pyroptosis in chondrocytes (all p < 0.05). LPS-induced NLRP3 upregulation in chondrocytes was related to its high m6A modification level (p < 0.05). It was also observed that BSHXD-CS reduced LPS-induced m6A modification in chondrocytes via repressing STAT3 (all p < 0.05), suggesting BSHXD-CS could repress NLRP3 expression via m6A-dependent manner. Moreover, DAA, a m6A specific inhibitor, was proved to strengthen the protectively roles of BSHXD-CS on LPS-challenged pytoptosis (all p < 0.05). CONCLUSION: BSHXD-CS inhibited NLRP3 inflammasome activation and pyroptosis in chondrocytes to repress OA progression by reducing RNA m6A modification.

Remote coupling of electrical and mechanical cues by diurnal photothermal irradiation synergistically promotes bone regeneration.

Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.

Emerging mRNA Technology for Liver Disease Therapy.

Liver diseases have consistently posed substantial challenges to global health. It is crucial to find innovative methods to effectively prevent and treat these diseases. In recent times, there has been an increasing interest in the use of mRNA formulations that accumulate in liver tissue for the treatment of hepatic diseases. In this review, we start by providing a detailed introduction to the mRNA technology. Afterward, we highlight types of liver diseases, discussing their causes, risks, and common therapeutic strategies. Additionally, we summarize the latest advancements in mRNA technology for the treatment of liver diseases. This includes systems based on hepatocyte growth factor, hepatitis B virus antibody, left-right determination factor 1, human hepatocyte nuclear factor α, interleukin-12, methylmalonyl-coenzyme A mutase, etc. Lastly, we provide an outlook on the potential of mRNA technology for the treatment of liver diseases, while also highlighting the various technical challenges that need to be addressed. Despite these difficulties, mRNA-based therapeutic strategies may change traditional treatment methods, bringing hope to patients with liver diseases.

Melt-electrowriting-enabled anisotropic scaffolds loaded with valve interstitial cells for heart valve tissue Engineering.

Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.

Biomimetic bone-periosteum scaffold for spatiotemporal regulated innervated bone regeneration and therapy of osteosarcoma.

The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.

Gut microbiota's influence on erysipelas: evidence from a two-sample Mendelian randomization analysis.

Background: Previous studies have suggested a link between gut microbiota and skin diseases, including erysipelas, an inflammatory skin condition. Despite this, the precise nature of the relationship between erysipelas and gut microbiota remains unclear and subject to debate. Methods: We conducted a Mendelian Randomization (MR) analysis using publicly available summary data from genome-wide association studies (GWAS) to explore the potential causal relationship between gut microbiota and erysipelas. Instrumental variables (IVs) were identified using a comprehensive set of screening methods. We then performed MR analyses primarily using the Inverse Variance Weighted (IVW) method, complemented by alternative approaches such as MR Egger, weighted median, simple mode, and weighted mode. A series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test, and a leave-one-out test, were executed to ensure the robustness and validity of our findings. Results: We identified potential associations between erysipelas and various gut microbiota, including Alcaligenaceae (OR 1.23; 95% CI 1.06-1.43; p=0.006), Rikenellaceae (OR 0.77; 95% CI 0.67-0.90; p=0.001), and others. Notably, associations with Actinomyces, Lachnospiraceae NC2004 group, Ruminiclostridium 9, Ruminococcaceae UCG014, Odoribacter, and Actinobacteria were also observed. Sensitivity analyses confirmed the robustness of these associations. Conclusion: Our MR analysis suggests both potentially beneficial and harmful causal relationships between various gut microbiota and the incidence of erysipelas. This study provides new theoretical and empirical insights into the pathogenesis of erysipelas and underscores the potential for innovative preventive and therapeutic approaches.

Microwave-Assisted Hydrothermal Synthesis of Na3V2(PO4)2F3 Nanocuboid@Reduced Graphene Oxide as an Ultrahigh-Rate and Superlong-Lifespan Cathode for Fast-Charging Sodium-Ion Batteries.

Na3V2(PO4)2F3 (NVPF) has been regarded as a favorable cathode for sodium-ion batteries (SIBs) due to its high voltage and stable structure. However, the limited electronic conductivity restricts its rate performance. NVPF@reduced graphene oxide (rGO) was synthesized by a facile microwave-assisted hydrothermal approach with subsequent calcination to shorten the hydrothermal time. NVPF nanocuboids with sizes of 50-150 nm distributed on rGO can be obtained, delivering excellent electrochemical performance such as a longevity life (a high capacity retention of 85.6% after 7000 cycles at 10 C) and distinguished rate capability (116 mAh g-1 at 50 C with a short discharging/charging time of 1.2 min). The full battery with a Cu2Se anode represents a capacity of 116 mAh g-1 at 0.2 A g-1. The introduction of rGO can augment the electronic conductivity and advance the Na+ diffusion speed, boosting the cycling and rate capability. Besides, the small lattice change (3.3%) and high structural reversibility during the phase transition process between Na3V2(PO4)2F3 and NaV2(PO4)2F3 testified by in situ X-ray diffraction are also advantageous for Na storage behavior. This work furnishes a simple method to synthesize polyanionic cathodes with ultrahigh rate and ultralong lifespan for fast-charging SIBs.

Research hotspots and trend of wrist arthroscopy: A bibliometrics analysis from 2013 to 2023.

BACKGROUND: Wrist arthroscopy technology is a surgical technology invented in recent years and widely used in clinical treatment of various wrist diseases. This study uses the methods of bibliometrics and visual analysis to understand the global research status, research hotspots, and future development trends of wrist arthroscopy. METHODS: The relevant literature of global publications on wrist arthroscopy from 2013 to 2023 was extracted from the Web of Science Core Collection database, and the annual output, cooperation, hot spots, research status, and development trend of this field were analyzed by using the bibliometric software (VOSviewers, CiteSpace, and the R package "Bibliometrix"). RESULTS: A total of 635 articles were included, from 2013 to 2023, the number of publications related to wrist arthroscopy showed an overall upward trend, the USA, France, and China are the top 3 countries in terms of the number of publications, whereas Mayo Clinic is the institution with the highest number of publications, Ho PC holds a core position in this field, keyword analysis indicates that the research hotspots are the applications of wrist arthroscopy in triangular fibrocartilage complex injuries, scaphoid nonunion, and avascular necrosis of the lunate. CONCLUSION SUBSECTIONS: Wrist arthroscopy has shown tremendous potential in treating various wrist diseases. However, there are still some challenges in its research domain. With continuous deep research, strengthened international collaboration, and ongoing technological advancements, wrist arthroscopy has the potential to become the standard treatment in hand surgery, offering more efficient and safer treatment options for patients worldwide.

Urethral-sparing laparoscopic simple prostatectomy for the treatment of benign prostatic hyperplasia with asymptomatic urethral stricture after urethral stricture surgery.

OBJECTIVE: To evaluate the efficacy of urethral-sparing laparoscopic simple prostatectomy (US-LSP) for the treatment of large-volume (>80 ml) benign prostatic hyperplasia (BPH) with asymptomatic urethral stricture (urethral lumen > 16 Fr) after urethral stricture surgery. METHODS: We retrospectively analyzed clinical data of 39 large-volume BPH patients with asymptomatic urethral stricture after urethral stricture surgery who underwent US-LSP from January 2016 to October 2021. Postoperative follow-ups were scheduled at 1, 3, and 6 months. RESULTS: All patients affected by significant BPH-related lower urinary tract symptoms (LUTS) including 22 cases with asymptomatic anterior urethral stricture and 17 cases with asymptomatic posterior urethral stricture. Median operative time was 118 min (interquartile range [IQR]100-145). Median estimated blood loss was 224 ml (IQR: 190-255). 33 patients(84.6%) avoided continuous bladder irrigation. Postoperative complications occurred in 5 patients (12.8%), including 4 cases with Clavien-Dindo grade 1 and grade 2 and 1 case with grade 3a. During follow-up, US-LSP presented statistically significant improvements in LUTS compared to baseline (P < 0.05). A total of 25 patients had normal ejaculation preoperatively and 3 patients (12%) complained retrograde ejaculation postoperatively. Two patients (5.1%) reported stress urinary incontinence (SUI) and no patient reported aggravated urethral stricture during follow-up. CONCLUSIONS: US-LSP was safe and effective in treating large-volume BPH with asymptomatic urethral stricture after urethral stricture surgery. Meanwhile, US-LSP could reduce the risk of SUI in patients with asymptomatic posterior urethral stricture and maintain ejaculatory function in a high percentage of patients.

Biomimetic Anticoagulated Porous Particles with Self-Reporting Structural Colors.

Anticoagulation is vital to maintain blood fluidic status and physiological functions in the field of clinical blood-related procedures. Here, novel biomimetic anticoagulated porous inverse opal hydrogel particles is presented as anticoagulant bearing dynamic screening capability. The inverse opal hydrogel particles possess abundant sulfonic and carboxyl groups, which serve as binding sites with multiple coagulation factors and inhibit the blood coagulation process. Owing to the variations of refractive index and pore sizes during the binding process, the particles appeared corresponding structure color variations, which can be adopted as sensory index of anticoagulation. Based on these features, a sensor containing these diverse structure color particle units is constructed for pattern recognition of coagulation factors level in clinical plasma samples. By analyzing the sensory information of the unit, the colorimetric "fingerprint" for each target can be obtained and summarized as a database. Besides, a portable test-strip integrating sensory units is developed to distinguish the sample regarding abnormal coagulation factors-derived diseases via multivariate data analysis. It is believed that such biomimetic anticoagulated structural color particles and their derived sensor will open new avenue for clinical detection and disease diagnosis.

Gut-immunity-joint axis: a new therapeutic target for gouty arthritis.

Gouty arthritis (GA) is an inflammatory disease characterized by pain. The primary goal of current treatment strategies during GA flares remains the reduction of inflammation and pain. Research suggests that the gut microbiota and microbial metabolites contribute to the modulation of the inflammatory mechanism associated with GA, particularly through their effect on macrophage polarization. The increasing understanding of the gut-joint axis emphasizes the importance of this interaction. The primary objective of this review is to summarize existing research on the gut-immune-joint axis in GA, aiming to enhance understanding of the intricate processes and pathogenic pathways associated with pain and inflammation in GA, as documented in the published literature. The refined comprehension of the gut-joint axis may potentially contribute to the future development of analgesic drugs targeting gut microbes for GA.

Multi-omics revealed molecular mechanism of biphenyl phytoalexin formation in response to yeast extract-induced oxidative stress in Sorbus aucuparia suspension cells.

KEY MESSAGE: Yeast extract-induced oxidative stress in Sorbus aucuparia suspension cells leads to the biosynthesis of various hormones, which activates specific signaling pathways that augments biphenyl phytoalexin production. Pathogen incursions pose a significant threat to crop yield and can have a pronounced effect on agricultural productivity and food security. Biphenyl phytoalexins are a specialized group of secondary metabolites that are mainly biosynthesized by Pyrinae plants as a defense mechanism against various pathogens. Despite previous research demonstrating that biphenyl phytoalexin production increased dramatically in Sorbus aucuparia suspension cells (SASCs) treated with yeast extract (YE), the underlying mechanisms remain poorly understood. To address this gap, we conducted an in-depth, multi-omics analysis of transcriptome, proteome, and metabolite (including biphenyl phytoalexins and phytohormones) dynamics in SASCs exposed to YE. Our results indicated that exposure to YE-induced oxidative stress in SASCs, leading to the biosynthesis of a range of hormones, including jasmonic acid (JA), jasmonic acid isoleucine (JA-ILE), gibberellin A4 (GA4), indole-3-carboxylic acid (ICA), and indole-3-acetic acid (IAA). These hormones activated specific signaling pathways that promoted phenylpropanoid biosynthesis and augmented biphenyl phytoalexin production. Moreover, reactive oxygen species (ROS) generated during this process also acted as signaling molecules, amplifying the phenylpropanoid biosynthesis cascade through activation of the mitogen-activated protein kinase (MAPK) pathway. Key genes involved in these signaling pathways included SaBIS1, SaBIS2, SaBIS3, SaPAL, SaB4H, SaOMT, SaUGT1, SaLOX2, SaPR1, SaCHIB1, SaCHIB2 and SaCHIB3. Collectively, this study provided intensive insights into biphenyl phytoalexin accumulation in YE-treated SASCs, which would inform the development of more efficient disease-resistance strategies in economically significant cultivars.

Copper and conjugated carbonyls of metal-organic polymers as dual redox centers for Na storage.

Metal-organic polymers (MOPs) are fascinating electrode materials for high-performance sodium-ion batteries due to their multiple redox centers and low cost. Herein, a flower-like π-d conjugated MOP (Cu-TABQ) was synthesized using tetramino-benzoquinone (TABQ) as an organic ligand and Cu2+ as a transition metal node under the slow release of Cu2+ from [Cu(NH3)4]2+ and subsequent dehydrogenation. It possesses dual redox centers of Cu2+/Cu+ and C[double bond, length as m-dash]O/C-O to render a three-electron transfer reaction for each coordination unit with a high reversible capacity of 322.9 mA h g-1 at 50 mA g-1 in the voltage range of 1.0 to 3.0 V. The flower-like structure enhances fast Na+ diffusion and highly reversible organic/inorganic redox centers. This results in excellent cycling performance with almost no degradation within 700 cycles and great rate performance with 198.8 mA h g-1 at 4000 mA g-1. The investigation of the Na-storage mechanism and attractive performance will shed light on the insightful design of MOP cathode materials for further batteries.

Capacitive-Coupling-Responsive Hydrogel Scaffolds Offering Wireless In Situ Electrical Stimulation Promotes Nerve Regeneration.

Electrical stimulation (ES) has shown beneficial effects in repairing injured tissues. However, current ES techniques that use tissue-traversing leads and bulky external power suppliers have significant limitations in translational medicine. Hence, exploring noninvasive in vivo ES to provide controllable electrical cues in tissue engineering is an imminent necessity. Herein, a conductive hydrogel with in situ electrical generation capability as a biodegradable regeneration scaffold and wireless ES platform for spinal cord injury (SCI) repair is demonstrated. When a soft insulated metal plate is placed on top of the injury site as a wireless power transmitter, the conductive hydrogel implanted at the injury site can serve as a wireless power receiver, and the capacitive coupling between the receiver and transmitter can generate an alternating current in the hydrogel scaffold owing to electrostatic induction effect. In a complete transection model of SCI rats, the implanted conductive hydrogels with capacitive-coupling in situ ES enhance functional recovery and neural tissue repair by promoting remyelination, accelerating axon regeneration, and facilitating endogenous neural stem cell differentiation. This facile wireless-powered electroactive-hydrogel strategy thus offers on-demand in vivo ES with an adjustable timeline, duration, and strength and holds great promise in translational medicine.

Customizing biomimetic surface attributes of dendritic lipopeptide nanoplatforms for extended circulation.

The pressing demand for innovative approaches to create delivery systems with heightened drug loading and prolonged circulation has spurred numerous efforts, yielding some successes but accompanied by constraints. Our study proposes employing dendritic lipopeptide with precisely balanced opposing charges to extend blood residency for biomimetic nanoplatforms. Neutrally mixed-charged zwitterionic nanoparticles (NNPs) achieved a notable 19 % simvastatin loading content and kept stable even after one-month storage at 4 °C. These nanoplatforms demonstrated low cytotoxicity in NIH-3T3 and L02 cells and negligible hemolysis (<5 %). NNPs inhibited protein adhesion (>95 %) from positively and negatively charged sources through surface hydration. In comparison to positively charged CNPs, NNPs demonstrated an 86 % decrease in phagocytic rate by BMDMs, highlighting their efficacy. Importantly, NNPs showed prolonged circulation compared to CNPs and free simvastatin. These findings highlight the potential of this biomimetic nanoplatform for future therapeutic applications with enhanced drug loading and circulation traits.