Progress of mesenchymal stem cells (MSCs) & MSC-Exosomes combined with drugs intervention in liver fibrosis.

Liver fibrosis is an intrahepatic chronic damage repair response caused by various reasons such as alcoholic liver, fatty liver, viral hepatitis, autoimmune diseases, etc., and is closely related to the progression of liver disease. Currently, the mechanisms of liver fibrosis and its treatment are hot research topics in the field of liver disease remedy. Mesenchymal stem cells (MSCs) are a class of adult stem cells with self-renewal and multidirectional differentiation potential, which can ameliorate fibrosis through hepatic-directed differentiation, paracrine effects, and immunomodulation. However, the low inner-liver colonization rate, low survival rate, and short duration of intervention after stem cell transplantation have limited their wide clinical application. With the intensive research on liver fibrosis worldwide, it has been found that MSCs and MSCs-derived exosomes combined with drugs have shown better intervention efficiency than utilization of MSCs alone in many animal models of liver fibrosis. In this paper, we review the interventional effects and mechanisms of mesenchymal stem cells and their exosomes combined with drugs to alleviate hepatic fibrosis in vivo in animal models in recent years, which will provide new ideas to improve the efficacy of mesenchymal stem cells and their exosomes in treating hepatic fibrosis in the clinic.

Outcome of patients with different stages of acute-on-chronic liver failure treated with artificial liver support system.

Background: Elevated international normalized ratio of prothrombin time (PT-INR) is one of the key characteristics of acute-on-chronic liver failure (ACLF). Whether the staging of PT-INR has the ability to screen out subgroups of ACLF patients who would be more eligible for artificial liver support system (ALSS) treatment has not been studied in detail. Methods: A previous study enrolled patients receiving ALSS treatment with regional citrate anticoagulation from January 2018 to December 2019. Patients with different PT-INR intervals were retrospectively enrolled: 1.3 ≤ PT-INR < 1.5 (Pre-stage), 1.5 ≤ PT-INR < 2.0 (Early-stage), 2.0 ≤ PT-INR < 2.5 (Mid-stage), and PT-INR ≥ 2.5 (End-stage). The Cox proportional hazards models were used to estimate the association between stages of ACLF or sessions of ALSS treatment and 90 day mortality. Results: A total of 301 ACLF patients were enrolled. The 90 day mortality risk of Early-stage ACLF patients (adjusted hazard ratio (aHR) (95% confidence interval (CI)), 3.20 (1.15-8.89), p = 0.026), Mid-stage ACLF patients (3.68 (1.34-10.12), p = 0.011), and End-stage ACLF patients (12.74 (4.52-35.91), p < 0.001) were higher than that of Pre-stage ACLF patients, respectively. The 90 day mortality risk of Mid-stage ACLF patients was similar to that of Early-stage ACLF patients (1.15 (0.69-1.94), p = 0.591). The sessions of ALSS treatment was an independent protective factor (aHR (95% CI), 0.81 (0.73-0.90), p < 0.001). The 90 day mortality risk in ACLF patients received 3-5 sessions of ALSS treatment was lower than that of patients received 1-2 sessions (aHR (95% CI), 0.34 (0.20-0.60), p < 0.001), whereas the risk in patients received ≥6 sessions of ALSS treatment was similar to that of patients received 3-5 sessions (0.69 (0.43-1.11), p = 0.128). Conclusion: ACLF patients in Pre-, Early-, and Mid-stages might be more eligible for ALSS treatment. Application of 3-5 sessions of ALSS treatment might be reasonable.

Arthroscopic Repair of Acetabular Cartilage Delamination Using Chondral Nail Fixation in Patients With Femoroacetabular Impingement.

Acetabular cartilage delamination is commonly seen in patients with femoroacetabular impingement (FAI), especially ones with the cam deformity. However, the definition and classification of acetabular cartilage injuries caused by FAI to guide clinical treatment remain controversial. Moreover, treatment of acetabular cartilage damage always causes a dilemma for surgeon during surgery. We believe a reliable repair of the acetabular cartilage delamination will lead to a better long-term outcome for patients with FAI. In this Technical Note, we introduce the chondral nail fixation under hip arthroscopy for treating acetabular cartilage delamination in patients with FAI. This technique contributes to eliminating intra-articular unstable factors, preserving native cartilage as much as possible, and restoring cartilage surface intact at best.

Legionella effector LnaB is a phosphoryl-AMPylase that impairs phosphosignalling.

AMPylation is a posttranslational modification that generally modifies amino acid side chains of proteins with adenosine monophosphate (AMP)1,2. Here we report that with ATP as the ligand and actin as the host activator, the effector protein LnaB of Legionella pneumophila exhibits AMPylase activity toward the phosphoryl group of phosphoribose on PRR42-Ub that is generated by the SidE family effectors and deubiquitinases DupA/B in an E1/E2-independent ubiquitination process3-7. The product of LnaB is further hydrolyzed by an ADP-ribosyl hydrolase, MavL, to be Ub, thereby preventing accumulation of PRR42-Ub and ADPRR42-Ub and protecting the canonical ubiquitination in host cells. LnaB represents a large family of AMPylases adopting a common structural fold, which is distinct from those of the previously known AMPylases, in bacterial pathogens of more than 20 species. Moreover, LnaB also exhibits robust phosphoryl AMPylase activity toward phosphorylated residues and produces unique ADPylation modification in proteins. During infection, LnaB AMPylates the conserved phosphorylated tyrosine residues in the activation loop of the Src family kinases8,9, which dampens the host downstream phosphorylation signaling. Structural studies revealed the actin-dependent activation and catalytic mechanisms of the LnaB family of AMPylases. This study presents an unprecedented regulation and molecular mechanism in bacterial pathogenesis and protein phosphorylation.

CXCR4-mediated neutrophil dynamics in periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis is a common oral disease closely related to immune response and this study is aimed to identify the key immune-related pathogenic genes and analyze the infiltration and function of immune cells in the disease using bioinformatics methods. METHODS: Transcriptome datasets and single-cell RNA sequencing (scRNA-seq) datasets were downloaded from the GEO database. We utilized weighted correlation network analysis and least absolute selection and shrinkage operator, protein-protein interaction network construction to screen out key pathogenic genes as well as conducted the cell-type identification by estimating relative subsets of RNA transcripts algorithm to analyze and characterize immune cell types in periodontal tissues. In addition to bioinformatics validations, clinical and cell samples were collected and mouse periodontitis models were constructed to validate the important role of key genes in periodontitis. RESULTS: Bioinformatics analysis pointed out the positive correlation between CXCR4 expression and periodontitis, and revealed the increased infiltration of neutrophils in periodontal inflammatory. Similar results were obtained from clinical samples and animal models. In addition, the clustering and functional enrichment results based on CXCR4 expression levels included activation of immune response and cell migration, implying the possible function of CXCR4 on regulating neutrophil dynamics, which might contribute to periodontitis. Subsequent validation experiments confirmed that the increased expression of CXCR4 in neutrophils under periodontitis, where cell migration-related pathways also were activated. CONCLUSION: CXCR4 could be the key pathogenic gene of periodontitis and CXCR4/CXCL12 signal axial might contribute to the development of periodontitis by mediating neutrophil dynamics, suggesting that CXCR4 could be a potential target to help identify novel strategies for the clinical diagnosis and treatment of periodontitis.

Venous thromboembolism in Black COVID-19 patients in a minority context compared to White, Asian and other racialized patients: A systematic review and meta-analysis.

IMPORTANCE: COVID-19 has disproportionately affected racialized populations, with particular impact among individuals of Black individuals. However, it is unclear whether disparities in venous thromboembolic (VTE) complications exist between Black individuals and those belonging to other racial groups with confirmed SARS-CoV2 infections. OBJECTIVE: To summarize the prevalence and moderators associated with VTE among Black COVID-19 patients in minoritized settings, and to compare this to White and Asian COVID-19 patients according to sex, age, and comorbid health conditions (heart failure, cancer, obesity, hypertension). DESIGN SETTING, AND PARTICIPANTS: A systematic search of MEDLINE, Embase, CINAHL and CENTRAL for articles or reports published from inception to February 15, 2023. STUDY SELECTION: Reports on VTE among Black individuals infected with SARS-CoV2, in countries where Black people are considered a minority population group. DATA EXTRACTION AND SYNTHESIS: Study characteristics and results of eligible studies were independently extracted by 2 pairs of reviewers. VTE prevalence was extracted, and risk of bias was assessed. Prevalence estimates of VTE prevalence among Black individuals with COVID19 in each study were pooled. Where studies provided race-stratified VTE prevalence among COVID19 patients, odds ratios were generated using a random-effects model. MAIN OUTCOMES AND MEASURES: Prevalence of VTE, comprising of deep vein thrombosis and pulmonary embolism. RESULTS: Ten studies with 66,185 Black individuals reporting the prevalence of COVID-19 associated VTE were included. Weighted median age of included studies was 47.60. Pooled prevalence of COVID-19 associated VTE was 7.2 % (95 % CI, 3.8 % - 11.5 %) among Black individuals. Among individuals with SARS-CoV2 infections, Black population had higher risks of VTE compared to their White (OR = 1.79, [95 % CI 1.28-2.53], p < .001) or Asian (OR = 2.01, [95 % CI, 1.14-3.60], p = .017) counterparts, or patients with other racial identities (OR = 2.01, [95 % CI, 1.39, 2.92]; p < .001). CONCLUSIONS AND RELEVANCE: Black individuals with COVID-19 had substantially higher risk of VTE compared to White or Asian individuals. Given racial disparities in thrombotic disease burden related to COVID-19, medical education, research, and health policy interventions are direly needed to ensure adequate disease awareness among Black individuals, to facilitate appropriate diagnosis and treatment among Black patients with suspected and confirmed VTE, and to advocate for culturally safe VTE prevention strategies, including pre-existing inequalities to the COVID-19 pandemic that persist after the crisis.

Diagnostic Efficiency of ACR-TIRADS Score for Differentiating Benign and Malignant Thyroid Nodules of Various Pathological Types.

BACKGROUND Thyroid nodule prevalence reaches 65% in the general population. Hence, appropriate ultrasonic examination is key in disease monitoring and management. We investigated the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS) score for diagnosis of benign and malignant thyroid nodules and pathological types. MATERIAL AND METHODS A retrospective study was conducted. According to ultrasound images, ultrasonic characteristics of benign and malignant thyroid nodules and different pathological types were analyzed using ACR-TIRADS score, and diagnostic value was determined. AUCs were compared for tumor diagnosis and differentiation. RESULTS Overall, 1675 thyroid nodules from 1614 patients were included. AUC value of papillary thyroid carcinoma (PTC) diagnosed with ACR-TIRADS was highest (0.955 [95% CI=0.946-0.965]), while that of follicular thyroid carcinoma (FTC) was lowest (0.877 [95% CI=0.843-0.912]). FTC had the highest sensitivity (95.1%) and lowest specificity (64.8%). When the cut-off value was 5.5 points, accuracy of diagnosing PTC and anaplastic thyroid carcinoma (ATC) was highest, 80.5% and 78.7% respectively. Comparison of the multi-index prediction model constructed by multivariable logistic regression analysis and prediction model constructed by ACR-TIRADS score showed, when evaluating PTC and ATC, the multi-index model was better: AUCs of PTC were 0.966 vs 0.955, and AUCs of ATC were 0.982 vs 0.952, respectively, (P<0.05). CONCLUSIONS ACR-TIRADS score-based ultrasound examination of thyroid nodules aids diagnosis of benign and malignant thyroid nodules. TIRADS criteria favor diagnosis of PTC (and ATC) over FTC. ACR-TIRADS score can help clinicians diagnose thyroid nodules quickly and earlier, exhibits good clinical value, and can prevent missed diagnoses.

Synthesis of Nitrones and Nitroalkanes via Chiral Cyclic Imines.

A series of structurally chiral cyclic imines efficiently yields chiral nitrones and nitroalkanes. This is the first report of the synthesis of nitro groups by C═N bond cleavage of imines through a nitrone intermediate.

A combination influenza mRNA vaccine candidate provided broad protection against diverse influenza virus challenge.

Influenza viruses present a significant threat to global health. The production of a universal vaccine is considered essential due to the ineffectiveness of current seasonal influenza vaccines against mutant strains. mRNA technology offers new prospects in vaccinology, with various candidates for different infectious diseases currently in development and testing phases. In this study, we encapsulated a universal influenza mRNA vaccine. The vaccine encoded influenza hemagglutinin (HA), nucleoprotein (NP), and three tandem repeats of matrix protein 2 (3M2e). Twice-vaccinated mice exhibited strong humoral and cell-mediated immune responses in vivo. Notably, these immune responses led to a significant reduction in viral load of the lungs in challenged mice, and also conferred protection against future wild-type H1N1, H3N2, or H5N1 influenza virus challenges. Our findings suggest that this mRNA-universal vaccine strategy for influenza virus may be instrumental in mitigating the impact of future influenza pandemics.

Synthesis and characterisation of K2CO3-activated carbon produced from distilled spent grains for the adsorption of CO2.

Activated carbon was prepared from distilled spent grains (DSG) using K2CO3 activation and chitosan modification. The effects of activator dosage, activation temperature, and the incorporation of chitosan as a nitrogen source on the adsorption performance were studied in this paper. The activated carbons were characterised by scanning electron microscopy, X-ray photoelectron spectroscopy, and nitrogen and carbon dioxide gas adsorption. Under the optimal conditions, the BET-specific surface area, total pore volume, and microporous volume of the activated carbon were as high as 1142 m2/g, 0.62 cm3/g, and 0.40 cm3/g, respectively. Chitosan was used as the nitrogen source, and surface modification was carried out concurrently with the K2CO3 activation process. The results revealed a carbon dioxide adsorption capacity of 5.2 mmol/g at 273.15 K and 1 bar without a nitrogen source, which increased to 5.76 mmol/g after chitosan modification. The isosteric heat of adsorption of CO2 all exceed 20 kJ/mol, hinting at the coexistence of both physisorption and chemisorption. The adsorption behaviour of the DSG-based activated carbon can be well-described by the Freundlich model.

Exploring immune evasion of SARS-CoV-2 variants using a pseudotyped system.

In the United States, coronavirus disease 2019 (COVID-19) cases have consistently been linked to the prevailing variant XBB.1.5 of SARS-CoV-2 since late 2022. A system has been developed for producing and infecting cells with a pseudovirus (PsV) of SARS-CoV-2 to investigate the infection in a Biosafety Level 2 (BSL-2) laboratory. This system utilizes a lentiviral vector carrying ZsGreen1 and Firefly luciferase (Fluc) dual reporter genes, facilitating the analysis of experimental results. In addition, we have created a panel of PsV variants that depict both previous and presently circulating mutations found in circulating SARS-CoV-2 strains. A series of PsVs includes the prototype SARS-CoV-2, Delta B.1.617.2, BA.5, XBB.1, and XBB.1.5. To facilitate the study of infections caused by different variants of SARS-CoV-2 PsV, we have developed a HEK-293T cell line expressing mCherry and human angiotensin converting enzyme 2 (ACE2). To validate whether different SARS-CoV-2 PsV variants can be used for neutralization assays, we employed serum from rats immunized with the PF-D-Trimer protein vaccine to investigate its inhibitory effect on the infectivity of various SARS-CoV-2 PsV variants. According to our observations, the XBB variant, particularly XBB.1.5, exhibits stronger immune evasion capabilities than the prototype SARS-CoV-2, Delta B.1.617.2, and BA.5 PsV variants. Hence, utilizing the neutralization test, this study has the capability to forecast the effectiveness in preventing future SARS-CoV-2 variants infections.

Unraveling the relationships between processing conditions and PhIP formation in chemical model system and roast pork patty via principal component analysis.

2-amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP) is one of the higher levels of HAAs produced in protein foods during heating. The effects of heating temperature, time, and concentration of precursors on PhIP and related substances in the chemical model system and roast pork patty were studied using HPLC-Q-Orbitrap-HRMS and GC-MS. Results showed that the heating temperature, time, and concentration of four precursors significantly affected PhIP and its related substances (P < 0.05) in the chemical model system. Among them, PhIP production was greatest when heating at 200 min with 220 °C, and the concentrations of phenylalanine, creatinine, glucose, and creatine added were 10, 20, 20, and 20 mmol/L, respectively. Moreover, as the fat proportion of roast pork patties increased, PhIP and its intermediate-phenylacetaldehyde concentrations increased substantially (P < 0.05). PCA results showed that the samples of PhIP and related substances gradually dispersed as the temperature and time increased, and there were obvious effects among them.

Identifying Variables Influencing Traditional Food Solid-State Fermentation by Statistical Modeling.

Solid-state fermentation is widely used in traditional food production, but most of the complex processes involved were designed and are carried out without a scientific basis. Often, mathematical models can be established to describe mass and heat transfer with the assistance of chemical engineering tools. However, due to the complex nature of solid-state fermentation, mathematical models alone cannot explain the many dynamic changes that occur during these processes. For example, it is hard to identify the most important variables influencing product yield and quality fluctuations. Here, using solid-state fermentation of Chinese liquor as a case study, we established statistical models to correlate the final liquor yield with available industrial data, including the starting content of starch, water and acid; starting temperature; and substrate temperature profiles throughout the process. Models based on starting concentrations and temperature profiles gave unsatisfactory yield predictions. Although the most obvious factor is the starting month, ambient temperature is unlikely to be the direct driver of differences. A lactic-acid-inhibition model indicates that lactic acid from lactic acid bacteria is likely the reason for the reduction in yield between April and December. Further integrated study strategies are necessary to confirm the most crucial variables from both microbiological and engineering perspectives. Our findings can facilitate better understanding and improvement of complex solid-state fermentations.

Infliximab for parenchymal neuro-Behçet's syndrome: case series and meta-analysis.

OBJECTIVES: This study aims to evaluate the efficacy and safety of infliximab (IFX) in patients with parenchymal neuro-Behçet's syndrome (p-NBS). METHODS: We retrospectively analysed eleven p-NBS patients treated with IFX at our institution and combined them with studies from database searches for a meta-analysis. Pooled estimates of clinical response (complete and partial remission) and MRI improvement at months 3, 6, and 12 were calculated. RESULTS: One patient achieved CR and the other ten patients achieved PR at our institution. 8 studies (77 patients) were included in the meta-analysis. At 3, 6, and 12 months, 97% (95%CI 61.9-100%), 89.6% (95%CI 45.9-100%), 100% (95%CI 96.0-100%) of patients showed clinical response and 100% (95%CI 89.7-100%), 89.1% (95% CI 26.3-100%), 99.5% (95% CI 96.0-100%) of patients showed radiological improvement, respectively. Severe adverse events were observed in 7 patients. CONCLUSIONS: IFX was effective and relatively safe for p-NBS. Patients should be re-evaluated after 3 months of IFX to determine further therapy.

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.

Rapid and Sensitive Detection by Combining Electric Field Effects and Surface Plasmon Resonance: A Theoretical Study.

Surface plasmon resonance (SPR) has been extensively employed in biological sensing, environmental detection, as well as chemical industry. Nevertheless, the performance possessed by conventional surface plasmon resonance (SPR) biosensors can be further limited by the transport of analyte molecules to the sensing surface, noteworthily when small molecules or low levels of substances are being detected. In this study, a rapid and highly sensitive SPR biosensor is introduced to enhance the ability of the target analytes' collection by integrating AC electroosmosis (ACEO) and dielectrophoresis (DEP). Both the above-mentioned phenomena principally arise from the generation of the AC electric fields. This generation can be tailored by shaping the interdigitated electrodes (IDEs) that also serve as the SPR biomarker sensing area. The effects exerted by different parameters (e.g., the frequency and voltage of the AC electric field as well as microelectrode structures) are considered in the iSPR (interdigitated SPR) biosensor operation, and the iSPR biosensors are optimized with the sensitivity. The results of this study confirm that the iSPR can efficiently concentrate small molecules into the SPR sensing area, such that SPR reactions achieve an order of magnitude increase, and the detection time is shortened. The rapid and sensitive sensor takes on critical significance in the development of on-site diagnostics in a wide variety of human and animal health applications.

Fucoidan Improves D-Galactose-Induced Cognitive Dysfunction by Promoting Mitochondrial Biogenesis and Maintaining Gut Microbiome Homeostasis.

Recent studies have indicated that fucoidan has the potential to improve cognitive impairment. The objective of this study was to demonstrate the protective effect and possible mechanisms of fucoidan in D-galactose (D-gal)-induced cognitive dysfunction. Sprague Dawley rats were injected with D-galactose (200 mg/kg, sc) and administrated with fucoidan (100 mg/kg or 200 mg/kg, ig) for 8 weeks. Our results suggested that fucoidan significantly ameliorated cognitive impairment in D-gal-exposed rats and reversed histopathological changes in the hippocampus. Fucoidan reduced D-gal-induced oxidative stress, declined the inflammation level and improved mitochondrial dysfunction in hippocampal. Fucoidan promoted mitochondrial biogenesis by regulating the PGC-1α/NRF1/TFAM pathway, thereby improving D-gal-induced mitochondrial dysfunction. The regulation effect of fucoidan on PGC-1α is linked to the upstream protein of APN/AMPK/SIRT1. Additionally, the neuroprotective action of fucoidan could be related to maintaining intestinal flora homeostasis with up-regulation of Bacteroidota, Muribaculaceae and Akkermansia and down-regulation of Firmicutes. In summary, fucoidan may be a natural, promising candidate active ingredient for age-related cognitive impairment interventions.

Bibliometric analysis of hotspots and trends of global myopia research.

AIM: To gain insights into the global research hotspots and trends of myopia. METHODS: Articles were downloaded from January 1, 2013 to December 31, 2022 from the Science Core Database website and were mainly statistically analyzed by bibliometrics software. RESULTS: A total of 444 institutions in 87 countries published 4124 articles. Between 2013 and 2022, China had the highest number of publications (n=1865) and the highest H-index (61). Sun Yat-sen University had the highest number of publications (n=229) and the highest H-index (33). Ophthalmology is the main category in related journals. Citations from 2020 to 2022 highlight keywords of options and reference, child health (pediatrics), myopic traction mechanism, public health, and machine learning, which represent research frontiers. CONCLUSION: Myopia has become a hot research field. China and Chinese institutions have the strongest academic influence in the field from 2013 to 2022. The main driver of myopic research is still medical or ophthalmologists. This study highlights the importance of public health in addressing the global rise in myopia, especially its impact on children's health. At present, a unified theoretical system is still needed. Accurate surgical and therapeutic solutions must be proposed for people with different characteristics to manage and intervene refractive errors. In addition, the benefits of artificial intelligence (AI) models are also reflected in disease monitoring and prediction.