Crosstalk between gut microbiota and host immune system and its response to traumatic injury.

Millions of microorganisms make up the complex microbial ecosystem found in the human gut. The immune system's interaction with the gut microbiota is essential for preventing inflammation and maintaining intestinal homeostasis. Numerous metabolic products that can cross-talk between immune cells and the gut epithelium are metabolized by the gut microbiota. Traumatic injury elicits a great and multifaceted immune response in the minutes after the initial offense, containing simultaneous pro- and anti-inflammatory responses. The development of innovative therapies that improve patient outcomes depends on the gut microbiota and immunological responses to trauma. The altered makeup of gut microbes, or gut dysbiosis, can also dysregulate immunological responses, resulting in inflammation. Major human diseases may become more common as a result of chronic dysbiosis and the translocation of bacteria and the products of their metabolism beyond the mucosal barrier. In this review, we briefly summarize the interactions between the gut microbiota and the immune system and human disease and their therapeutic probiotic formulations. We also discuss the immune response to traumatic injury.

Protein blend extrusion: Crafting meat analogues with varied textural structures and characteristics.

With an increasing emphasis on health and environmental consciousness, there is a growing inclination toward plant protein-based meat substitutes as viable alternatives to animal meat. In the pursuit of creating diverse and functional plant protein-based substitutes, innovative plant proteins have been introduced in conjunction with soy protein isolate (SPI), encompassing pea protein isolate (PPI), rice bran protein (RBP), fava bean protein isolate (FPI), and spirulina protein isolate (SPPI). Notably, SPI-WG extrudates and SPI-PPI extrudates exhibited superior fiber structures (fiber degrees were 1.72 and 1.88, respectively), with coarse fibers in SPI-WG extrudates and fine, dense fibers in SPI-PPI extrudates. The addition of RBP, FPI and SPPI had minimal effect on fiber structure. Fresh SPI-FPI displayed the slowest rate of water loss, losing about 7.11% of their total weight in 5 h. Different plant proteins can be selected for the preparation of plant protein-based meat substitutes according to practical needs.

Decision-making regarding subcutaneous implantable cardioverter defibrillator as primary prevention in patients with low ejection fraction.

BACKGROUND: Conventional transvenous implantable cardioverter-defibrillator (TV-ICD) is the standard device used for primary prevention of sudden cardiac death (SCD) in patients with reduced left ventricular ejection fraction (LVEF). Nonetheless its use is associated with lead-related complications including infection and malfunction. A subcutaneous implantable cardioverter-defibrillator (S-ICD) offers an alternative option without the need for a transvenous lead but has limitations. The decision to implant a TV-ICD or S-ICD in patients with impaired LVEF for primary prevention of SCD is controversial. Several randomised controlled trials and large observational studies have confirmed similar safety and efficacy of S-ICDs and TV-ICDs in such population. METHODS: A literature review was conducted to compare the outcomes of subcutaneous (S-ICD) versus transvenous (TV-ICD) implantable cardioverter-defibrillators. Databases including PubMed, MEDLINE, and Cochrane were searched for relevant peer-reviewed articles. Studies were selected based on relevance and quality. Key outcomes like complication rates, efficacy, and patient survival were summarized in a comparative table. RESULTS: Different factors that influence the choice between an TV-ICD and S-ICD for primary prevention of SCD in patients with LVEF are highlighted to guide selection of the appropriate device in different patient populations. Moreover, future perspective on the combination of SICD with leadless pacemaker, and the latest development of the extravascular implantable cardioverter defibrillator are also discussed. CONCLUSIONS: S-ICD offers a safe and efficacious option to primary prevention in reduced ejection fraction. Future development including incorporation of leadless pacemaker will add to the arsenal of choice to protect patients from sudden cardiac death.

Ameliorating effects of the HIF-2α inhibitor PT2385 on high-altitude polycythemia.

High-altitude polycythemia (HAPC) is a common chronic altitude disease caused by living in low-pressure and low-oxygen environment. At present, there is still no effective cure for HAPC. HIF-2α may play an important role in the development of HAPC in regulating the increased red blood cell excessively induced by HIF-EPO and the blood vessel formation induced by VEGF-VEGFR. Here, we established a rat HAPC model and treated it with the HIF-2α inhibitor PT2385. We mainly evaluated the therapeutic effect of PT2385 on HAPC rats by observing the changes in rat phenotype, tissue and organ damage, red blood cell and hemoglobin content, angiogenesis, lipid peroxidation reaction, and inflammatory factors. The results showed that PT2385 treatment improved the congestion phenotype characteristics, inhibited increased erythrocytes and hemoglobin, reduced blood vessel formation, lipid peroxidation, and inflammation, and reduced tissue and organ damage in HAPC rats. This study preliminarly explains the physiological, pathological, and immunological effects of PT2385 treatment for HAPC. It provides a new idea, a reliable experimental basis, and theoretical support for the clinical prevention and treatment of HAPC.

A systematic review and meta-analysis of the risk of hepatitis B virus (HBV) resistance in people treated with entecavir or tenofovir.

BACKGROUND: As nucleos/tide analogue (NA) therapy (e.g. entecavir and tenofovir) for chronic Hepatitis B virus (HBV) infection becomes more widely indicated and available, understanding drug resistance is essential. A systematic review to quantify resistance to these agents has not previously been undertaken. METHODS: We performed a systematic review and random-effects meta-analysis to estimate the risk of HBV resistance to entecavir and tenofovir. We searched nine databases up to 29-Aug-23. We included studies of HBV infection featuring >10 individuals, written in English, reporting treatment ≥48 weeks, with assessment of HBV resistance based on viral sequence data. Data were analysed according to prior exposure history to NA, and choice of NA agent. Analyses were performed in R. FINDINGS: 62 studies involving a total of 12,358 participants were included. For entecavir, in treatment-naive individuals (22 studies; 4326 individuals), resistance increased over time to 0.9 % at ≥5 years (95 %CI 0.1-2.3 %), and resistance was increased in NA-experienced individuals (18 studies; 1112 individuals), to 20.1 % (95 %CI 1.6-50.1 %) at ≥5 years. For tenofovir, pooled resistance risk was 0.0 % at all time points, whether previously NA naive (11 studies; 3778 individuals) or experienced (19 studies; 2059 individuals). There was a lack of consistent definitions, poor global representation and insufficient metadata to support subgroup analysis. INTERPRETATION: We have generated the first pooled estimates of HBV entecavir and tenofovir resistance over time. HBV resistance to entecavir in treatment-experienced groups in particular may represent a clinical and public health challenge. To date, tenofovir appears to have an excellent resistance profile, but due to data gaps, we caution that existing studies under-estimate the true real-world risk of resistance. Robust prospective data collection is crucial to reduce health inequities and reduce blind-spots in surveillance as treatment is rolled out more widely.

Comprehensive transcriptomic analysis identifies SLC25A4 as a key predictor of prognosis in osteosarcoma.

Background: Osteosarcoma (OS) is highly malignant and prone to local infiltration and distant metastasis. Due to the poor outcomes of OS patients, the study aimed to identify differentially expressed genes (DEGs) in OS and explore their role in the carcinogenesis and progression of OS. Methods: RNA sequencing was performed to identify DEGs in OS. The functions of the DEGs in OS were investigated using bioinformatics analysis, and DEG expression was verified using RT-qPCR and Western blotting. The role of SLC25A4 was evaluated using gene set enrichment analysis (GSEA) and then investigated using functional assays in OS cells. Results: In all, 8353 DEGs were screened. GO and KEGG enrichment analyses indicated these DEGs showed strong enrichment in the calcium signaling pathway and pathways in cancer. Moreover, the Kaplan-Meier survival analysis showed ten hub genes were related to the outcomes of OS patients. Both SLC25A4 transcript and protein expression were significantly reduced in OS, and GSEA suggested that SLC25A4 was associated with cell cycle, apoptosis and inflammation. SLC25A4-overexpressing OS cells exhibited suppressed proliferation, migration, invasion and enhanced apoptosis. Conclusion: SLC25A4 was found to be significantly downregulated in OS patients, which was associated with poor prognosis. Modulation of SLC25A4 expression levels may be beneficial in OS treatment.

A multifunctional chitosan based porous membrane for pH-responsive antibacterial activity and promotion of infected wound healing.

Unsatisfactory mechanical and antibacterial properties restricted the solo use of chitosan (CS) as a wound dressing. In this work, a novel CS/hydroxyapatite/ZIF-8 (CS/HAp/ZIF-8, CHZ-10) porous membrane was facilely constructed by in situ loading of ZIF-8 on CS/HAp. The advantages of the three compositions were rationally integrated, and the multifunctionality and practicality of this CS-based dressing were improved. HAp not only improved the mechanical strength and stability of CS, but also promoted cell proliferation and accelerated hemostasis with its released Ca2+. Meanwhile, ZIF-8 enhanced the antibacterial activity of CS by releasing antibacterial Zn2+ in a pH-responsive and sustainable manner, avoiding the bio-accumulation toxicity of heavy metals. Compared with CS/HAp and conventionally used gauze, CHZ-10 exhibited superior coagulation and hemolytic ability, as well as outstanding antibacterial activity against E. coli and S. aureus. Besides, both in vivo observation and histological evaluation demonstrated that CHZ-10 could not only effectively inhibit bacterial infection and reduce inflammation of the wound, but also promote its re-epithelialization, granulation, tissue formation and collagen fibre growth, leading to effectively enhanced wound-healing. This work provides a new method for the easy construction of multifunctional antibacterial dressings based on CS, showing promise for application in clinical wound care.

Advanced Cardiac Patches for the Treatment of Myocardial Infarction.

Myocardial infarction is a cardiovascular disease characterized by a high incidence rate and mortality. It leads to various cardiac pathophysiological changes, including ischemia/reperfusion injury, inflammation, fibrosis, and ventricular remodeling, which ultimately result in heart failure and pose a significant threat to global health. Although clinical reperfusion therapies and conventional pharmacological interventions improve emergency survival rates and short-term prognoses, they are still limited in providing long-lasting improvements in cardiac function or reversing pathological progression. Recently, cardiac patches have gained considerable attention as a promising therapy for myocardial infarction. These patches consist of scaffolds or loaded therapeutic agents that provide mechanical reinforcement, synchronous electrical conduction, and localized delivery within the infarct zone to promote cardiac restoration. This review elucidates the pathophysiological progression from myocardial infarction to heart failure, highlighting therapeutic targets and various cardiac patches. The review considers the primary scaffold materials, including synthetic, natural, and conductive materials, and the prevalent fabrication techniques and optimal properties of the patch, as well as advanced delivery strategies. Last, the current limitations and prospects of cardiac patch research are considered, with the goal of shedding light on innovative products poised for clinical application.

Antibacterial, Fatigue-Resistant, and Self-Healing Dressing from Natural-Based Composite Hydrogels for Infected Wound Healing.

The treatment of infected wounds faces substantial challenges due to the high incidence and serious infection-related complications. Natural-based hydrogel dressings with favorable antibacterial properties and strong applicability are urgently needed. Herein, we developed a composite hydrogel by constructing multiple networks and loading ciprofloxacin for infected wound healing. The hydrogel was synthesized via a Schiff base reaction between carboxymethyl chitosan and oxidized sodium alginate, followed by the polymerization of the acrylamide monomer. The resultant hydrogel dressing possessed a good self-healing ability, considerable compression strength, and reliable compression fatigue resistance. In vitro assessment showed that the composite hydrogel effectively eliminated bacteria and exhibited an excellent biocompatibility. In a model of Staphylococcus aureus-infected full-thickness wounds, wound healing was significantly accelerated without scars through the composite hydrogel by reducing wound inflammation. Overall, this study opens up a new way for developing multifunctional hydrogel wound dressings to treat wound infections.

Photopolymerizable and Antibacterial Hydrogels Loaded with Metabolites from Lacticaseibacillus rhamnosus GG for Infected Wound Healing.

In response to increasing antibiotic resistance and the pressing demand for safer infected wound care, probiotics have emerged as promising bioactive agents. To address the challenges associated with the safe and efficient application of probiotics, this study successfully loaded metabolites from Lacticaseibacillus rhamnosus GG (LGG) into a gelatin cross-linked macromolecular network by an in situ blending and photopolymerization method. The obtained LM-GelMA possesses injectability and autonomous healing capabilities. Importantly, the incorporation of LGG metabolites endows LM-GelMA with excellent antibacterial properties against Staphylococcus aureus and Escherichia coli, while maintaining good biocompatibility. In vivo assessments revealed that LM-GelMA can accelerate wound healing by mitigating infections induced by pathogenic bacteria. This is accompanied by a reduction in the expression of key proinflammatory cytokines such as TNF-α, IL-6, VEGFR2, and TGF-ß, leading to increased re-epithelialization and collagen formation. Moreover, microbiological analysis confirmed that LM-GelMA can modulate the abundance of beneficial wound microbiota at family and genus levels. This study provides a facile strategy and insights into the functional design of hydrogels from the perspective of wound microenvironment regulation.

cGAS-STING, an important signaling pathway in diseases and their therapy.

Since cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway was discovered in 2013, great progress has been made to elucidate the origin, function, and regulating mechanism of cGAS-STING signaling pathway in the past decade. Meanwhile, the triggering and transduction mechanisms have been continuously illuminated. cGAS-STING plays a key role in human diseases, particularly DNA-triggered inflammatory diseases, making it a potentially effective therapeutic target for inflammation-related diseases. Here, we aim to summarize the ancient origin of the cGAS-STING defense mechanism, as well as the triggers, transduction, and regulating mechanisms of the cGAS-STING. We will also focus on the important roles of cGAS-STING signal under pathological conditions, such as infections, cancers, autoimmune diseases, neurological diseases, and visceral inflammations, and review the progress in drug development targeting cGAS-STING signaling pathway. The main directions and potential obstacles in the regulating mechanism research and therapeutic drug development of the cGAS-STING signaling pathway for inflammatory diseases and cancers will be discussed. These research advancements expand our understanding of cGAS-STING, provide a theoretical basis for further exploration of the roles of cGAS-STING in diseases, and open up new strategies for targeting cGAS-STING as a promising therapeutic intervention in multiple diseases.

Advances and Trends of Photoresponsive Hydrogels for Bone Tissue Engineering.

The development of static hydrogels as an optimal choice for bone tissue engineering (BTE) remains a difficult challenge primarily due to the intricate nature of bone healing processes, continuous physiological functions, and pathological changes. Hence, there is an urgent need to exploit smart hydrogels with programmable properties that can effectively enhance bone regeneration. Increasing evidence suggests that photoresponsive hydrogels are promising bioscaffolds for BTE due to their advantages such as controlled drug release, cell fate modulation, and the photothermal effect. Here, we review the current advances in photoresponsive hydrogels. The mechanism of photoresponsiveness and its advanced applications in bone repair are also elucidated. Future research would focus on the development of more efficient, safer, and smarter photoresponsive hydrogels for BTE. This review is aimed at offering comprehensive guidance on the trends of photoresponsive hydrogels and shedding light on their potential clinical application in BTE.

Robot-assisted Percutaneous Radiofrequency Ablation for the Treatment of Osteoid Osteomas.

OBJECTIVE: Percutaneous CT-guided radiofrequency ablation (CT-RFA) is a widely accepted procedure for treatment of osteoid osteomas. However, the application of CT-RFA was restricted as a result of some drawbacks, such as radiation exposure, and inconvenience in general anesthesia. The primary aim of this study is to evaluate the safety and efficacy of intra-operative TiRobot-assisted percutaneous RFA of osteoid osteomas. METHODS: We retrospectively reviewed 21 medical files of patients who were treated with percutaneous RFA of osteoid osteomas guided by the TiRobot system in our institution between March 2021 and April 2022. The three-dimensional images obtained by a 3D C-arm intra-operatively were sent to the TiRobot system. The puncture point and trajectory were designed. Then the guide pin was positioned to the lesion with the assistance of TiRobot and the biopsy sheath was inserted into the lesion through the guide pin. The tumor was biopsied for pathological examination. Then the RFA needle was inserted into the nidus through the biopsy sheath for thermal ablation. Data were extracted on the associated complications, the reduction in pain at 1 month and 1 year postoperatively assessed by the visual analogue scale (VAS). A paired t-test was used to compare the pre-operative and post-operative VAS scores. RESULTS: The patients included 17 males and four females with a mean age of 19.5 ± 10.4 years (range 3-45 years). Lesions were located on the femur in nine cases, on the tibia in nine cases, on the humerus in one case, on the calcaneus in one case, and on the acetabulum in one case. TiRobot-assisted percutaneous RFA was successfully performed on all 21 patients. There was no intra-operative or post-operative complications observed. Pathological diagnosis of osteoid osteoma was obtained in 11 patients, but the other 10 cases were not pathologically diagnosed. The mean follow-up time was 18.8 months (range: 12-26 months).Post-operative VAS scores were reduced significantly in all cases. The mean VAS score decreased from 6.5 pre-operatively to 0.5 at 1 month post-operatively and to 0.1 at 1 year post-operatively. CONCLUSION: As a reliable technique for localizing and resection of nidus, TiRobot-assisted percutaneous RFA is a safe and effective option for the treatment of osteoid osteomas.

Low-dose GBCA administration for brain tumour dynamic contrast enhanced MRI: a feasibility study.

A key limitation of current dynamic contrast enhanced (DCE) MRI techniques is the requirement for full-dose gadolinium-based contrast agent (GBCA) administration. The purpose of this feasibility study was to develop and assess a new low GBCA dose protocol for deriving high-spatial resolution kinetic parameters from brain DCE-MRI. Nineteen patients with intracranial skull base tumours were prospectively imaged at 1.5 T using a single-injection, fixed-volume low GBCA dose, dual temporal resolution interleaved DCE-MRI acquisition. The accuracy of kinetic parameters (ve, Ktrans, vp) derived using this new low GBCA dose technique was evaluated through both Monte-Carlo simulations (mean percent deviation, PD, of measured from true values) and an in vivo study incorporating comparison with a conventional full-dose GBCA protocol and correlation with histopathological data. The mean PD of data from the interleaved high-temporal-high-spatial resolution approach outperformed use of high-spatial, low temporal resolution datasets alone (p < 0.0001, t-test). Kinetic parameters derived using the low-dose interleaved protocol correlated significantly with parameters derived from a full-dose acquisition (p < 0.001) and demonstrated a significant association with tissue markers of microvessel density (p < 0.05). Our results suggest accurate high-spatial resolution kinetic parameter mapping is feasible with significantly reduced GBCA dose.

Oxygen-supplying ROS-responsive prodrug for synergistic chemotherapy and photodynamic therapy of colon cancer.

Introduction: The synergistic treatment of chemotherapy and photodynamic therapy (PDT) has remarkable potential in cancer therapy. However, challenges remain, such as unstable chemotherapeutic drug release, suboptimal targeting, and reduced efficacy of PDT under hypoxic conditions commonly found in solid tumors. Methods: To address these issues, we use camptothecin (CPT) and pheophorbide a (Pa) incorporated through the functional thioketal, which serves as the reactive oxygen species (ROS)-responsive trigger, to construct a ROS-responsive prodrug (CPT-TK-Pa). Subsequently, we co-loaded it with a platinum nanozyme (PtNP) in distearylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) to obtain the ROS-responsive prodrug nanoparticle (CPT-TK-Pa/Pt NP). Results and Discussion: Specifically, the incorporated PtNP within CPT-TK-Pa/Pt NP positively catalyzes the conversion of hydrogen peroxide (H2O2) to oxygen, thereby ameliorating the hypoxic state of the tumor. This enhanced oxygen generation could replenish the oxygen that is consumed by Pa during 660 nm exposure, enabling controlled CPT release and amplifying the photodynamic response. In vitro investigations reveal the potency of CPT-TK-Pa/Pt NPs in inhibiting colon tumor cells. Given its ROS-responsive release mechanism and enhanced PDT efficacy, CPT-TK-Pa/Pt NP has the potential to be a promising candidate for cancer therapy.

Accelerated Diffusion of a Copper(I)-Functionalized COF Packed Bed Reactor for Efficient Continuous Flow Catalysis.

Flow chemistry provides a neo-orientation for the research and development of chemical technology, in which heterogeneous continuous catalysis based on packed beds can realize rapid separation and recycling. However, options for heterogeneous catalysts are still limited. In this work, we gradually grow covalent organic frameworks (COFs, TpBpy) on the surface of a silica gel (SiO2)-supported substrate to obtain a stable copper(I)-chelated high-loading heterogeneous catalyst (SiO2@CuI-TpBpy). SiO2@CuI-TpBpy shows high catalytic activity in three-component Huisgen 1,3-dipolar cycloaddition, giving the corresponding triazoles with excellent yields and reposeful recyclability under batch conditions. The structures of the catalysts remain steady, and the copper contents are basically unchanged after five cycles. Then, the catalysts are successfully applied for three-component heterogeneous catalysis in a one-pot continuous flow to prepare rufinamide in 89% yield for 24 h stably and efficiently with mere traces of copper ions remaining. More importantly, the catalytic system reveals a minuscule effect of catalyst particle size on internal diffusion. This COF encapsulation strategy presents a new possibility for the design of industrial heterogeneous catalysts with high metal loading and low internal diffusion resistance.

A controlled light-induced gas-foaming porous hydrogel with adhesion property for infected wound healing.

Porous hydrogels as scaffolds have great potential in tissue engineering. However, there are still challenges in preparing porous hydrogels with tunable pore size and controlled porosity. Here, we successfully established a photoinduced gas-foaming method of porous hydrogels with controlled macro-micro-nano multiscale. A diazirine (DZ)-modified gelatin (GelDZ) biomaterial was prepared by introducing photocrosslinked DZ group into gelatin. Upon exposure to 365 nm UV light, DZ could be converted to the active group carbene, which could randomly insert into OH, NH, or CH bonds to form covalent crosslinks. GelDZ generated N2 by photodegradation and formed gas-induced porous hydrogels by intermolecular crosslinking without initiator. The loose porous structure of the hydrogel can promote the infiltration of host cells and blood vessels, which was conducive to tissue repair. The interfacial crosslinking of photoactivated GelDZ with tissue proteins imparted adhesion properties to the hydrogel. GelDZ also possessed photoreduction ability, which can reduce silver ions from metal precursors to silver nanoparticles (Ag NPs) in situ, and showed great antibacterial activity due to the sustained release of Ag NPs. GelDZ-Ag NPs prepared by in situ photoreaction can effectively inhibit wound infection and promote skin wound healing, providing a new strategy for designing porous hydrogel in tissue engineering.

Quality Evaluation of Metabolic-Associated Fatty Liver Disease Guidelines and Expert Consensus.

The purpose of this study is to evaluate and analyze the quality of guidelines and expert consensus on clinical practice regarding metabolically associated fatty liver disease (MAFLD) over the past five years. Data from the websites were retrieved using computers. We evaluated guidelines and expert consensus on MAFLD that were officially published between January 1, 2018 and March 24, 2023. Two evaluators independently examined the literature and extracted data. The included literature on guidelines and expert consensus was then subjected to quality review and analysis using assessment tools from Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) (2016). The intraclass correlation coefficient (ICC) values of all items on the AGREE II scale for the two evaluators were greater than 0.75, indicating a high degree of agreement between their assessments. Scope and purpose (48.90%), participants (49.21%), rigor in the formulation process (56.97%), clarity of expression (90.08%), applicability (66.08%), and independence of file compiling (60.12%) were the AGREE II scoring items with the standardized average scores. Apart from the participants, the average scores of all the scoring items in the guidelines from other countries other than China were higher than those from China (|Z|+>+2.272, p+<+0.05). MAFLD guidelines must be revised to enhance their methodological quality. When creating guidelines, it is recommended that the formulators strictly adhere to the formulation and drafting standards of AGREE II and elevate the quality of the guidelines.