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Chicken claw products with their unique texture are loved by consumers, and cooking is a key step to affect the taste of chicken claw consumption, through the moderate hydrolysis of proteins and a series of physicochemical changes, so that the chicken claw gets tender and presents a crispy taste, but the current research on the optimal cooking conditions for chicken claw is still relatively small. In the present work, combinations of time (11, 13, 15, 17, and 19 min) and temperature (82, 86, 90, 94, and 98°C) were applied to the cooking of chicken claws. The effects of different cooking conditions on the quality characteristics of chicken claws were investigated, with special emphasis on the cooking loss rate, color, texture properties, lipid oxidation, myofibrillar fragmentation index (MFI), and total sulfhydryl content. The results showed that the cooking loss rate, lipid oxidation, and MFI value of chicken claws gradually increased, and the total color difference (∆E), puncture force, shear force, and total sulfhydryl content gradually decreased with the increase of cooking temperature and cooking time. Overall, chicken claws cooked at 86, 90, and 94°C for 15 and 17 min had better texture and flavor.
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Coordinate-based meta-analysis combines evidence from a collection of neuroimaging studies to estimate brain activation. In such analyses, a key practical challenge is to find a computationally efficient approach with good statistical interpretability to model the locations of activation foci. In this article, we propose a generative coordinate-based meta-regression (CBMR) framework to approximate a smooth activation intensity function and investigate the effect of study-level covariates (e.g. year of publication, sample size). We employ a spline parameterization to model the spatial structure of brain activation and consider four stochastic models for modeling the random variation in foci. To examine the validity of CBMR, we estimate brain activation on 20 meta-analytic datasets, conduct spatial homogeneity tests at the voxel level, and compare the results to those generated by existing kernel-based and model-based approaches. Keywords: generalized linear models; meta-analysis; spatial statistics; statistical modeling.
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The number of runners and the incidence of running-related injuries (RRIs) are on the rise. Real-time biofeedback gait retraining offers a promising approach to RRIs prevention. However, due to the diversity in study designs and reported outcomes, there remains uncertainty regarding the efficacy of different forms of feedback on running gait biomechanics. Three databases: MEDLINE, PUBMED, and SPORTDiscus were searched to identify relevant studies published up to March 2024, yielding 4646 articles for review. The quality of the included studies was assessed using the Downs and Black Quality checklist. Primary outcomes, including Peak Tibial Acceleration (PTA), Vertical Average Loading Rate (VALR), and Vertical Instantaneous Loading Rate (VILR), were analysed through meta-analysis. 24 studies met the inclusion criteria and were analysed in this review.17 used visual biofeedback (VB) while 14 chose auditory biofeedback (AB). The meta-analysis revealed a reduction in loading variables both immediately following the intervention and after extended training, with both visual and auditory feedback. Notably, the decrease in loading variables was more pronounced post-training and VB proved to be more effective than AB. Real-time biofeedback interventions are effective in lowering loading variables associated with RRIs. The impact is more substantial with sustained training, and VB outperforms AB in terms of effectiveness.
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Rétroaction biologique (psychologie) , Démarche , Course à pied , Humains , Course à pied/traumatismes , Course à pied/physiologie , Démarche/physiologie , Phénomènes biomécaniques , Traumatismes sportifs/prévention et contrôle , AccélérationRÉSUMÉ
The plant MADS-box transcription factor family is a major regulator of plant flower development and reproduction, and the AGAMOUS-LIKE11/SEEDSTICK (AGL11/STK) subfamily plays conserved functions in the seed development of flowering plants. Camellia japonica is a world-famous ornamental flower, and its seed kernels are rich in highly valuable fatty acids. Seed abortion has been found to be common in C. japonica, but little is known about how it is regulated during seed development. In this study, we performed a genome-wide analysis of the MADS-box gene the in C. japonica genome and identified 126 MADS-box genes. Through gene expression profiling in various tissue types, we revealed the C/D-class MADS-box genes were preferentially expressed in seed-related tissues. We identified the AGL11/STK-like gene, CjSTK, and showed that it contained a typical STK motif and exclusively expressed during seed development. We found a significant increase in the CjSTK expression level in aborted seeds compared with normally developing seeds. Furthermore, overexpression of CjSTK in Arabidopsis thaliana caused shorter pods and smaller seeds. Taken together, we concluded that the fine regulation of the CjSTK expression at different stages of seed development is critical for ovule formation and seed abortion in C. japonica. The present study provides evidence revealing the regulation of seed development in Camellia.
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Camellia , Régulation de l'expression des gènes végétaux , Protéines à domaine MADS , Protéines végétales , Graines , Camellia/génétique , Camellia/métabolisme , Camellia/croissance et développement , Graines/génétique , Graines/croissance et développement , Protéines à domaine MADS/génétique , Protéines à domaine MADS/métabolisme , Protéines végétales/génétique , Protéines végétales/métabolisme , Phylogenèse , Arabidopsis/génétique , Arabidopsis/métabolisme , Analyse de profil d'expression de gènes , Famille multigénique , Génome végétal , Étude d'association pangénomiqueRÉSUMÉ
Rationale: Idiopathic pulmonary fibrosis (IPF) is an irreversible, fatal interstitial lung disease lacking specific therapeutics. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the nicotinamide adenine dinucleotide (NAD) salvage biosynthesis pathway and a cytokine, has been previously reported as a biomarker for lung diseases; however, the role of NAMPT in pulmonary fibrosis has not been elucidated. Methods: We identified the NAMPT level changes in pulmonary fibrosis by analyzing public RNA-Seq databases, verified in collected clinical samples and mice pulmonary fibrosis model by Western blotting, qRT-PCR, ELISA and Immunohistochemical staining. We investigated the role and mechanism of NAMPT in lung fibrosis by using pharmacological inhibition on NAMPT and Nampt transgenic mice. In vivo macrophage depletion by clodronate liposomes and reinfusion of IL-4-induced M2 bone marrow-derived macrophages (BMDMs) from wild-type mice, combined with in vitro cell experiments, were performed to further validate the mechanism underlying NAMPT involving lung fibrosis. Results: We found that NAMPT increased in the lungs of patients with IPF and mice with bleomycin (BLM)-induced pulmonary fibrosis. NAMPT inhibitor FK866 alleviated BLM-induced pulmonary fibrosis in mice and significantly reduced NAMPT levels in bronchoalveolar lavage fluid (BALF). The lung single-cell RNA sequencing showed that NAMPT expression in monocytes/macrophages of IPF patients was much higher than in other lung cells. Knocking out NAMPT in mouse monocytes/macrophages (Namptfl/fl;Cx3cr1CreER) significantly alleviated BLM-induced pulmonary fibrosis in mice, decreased NAMPT levels in BALF, reduced the infiltration of M2 macrophages in the lungs and improved mice survival. Depleting monocytes/macrophages in Namptfl/fl;Cx3cr1CreER mice by clodronate liposomes and subsequent pulmonary reinfusion of IL-4-induced M2 BMDMs from wild-type mice, reversed the protective effect of monocyte/macrophage NAMPT-deletion on lung fibrosis. In vitro experiments confirmed that the mechanism of NAMPT engaged in pulmonary fibrosis is related to the released NAMPT by macrophages promoting M2 polarization in a non-enzyme-dependent manner by activating the STAT6 signal pathway. Conclusions: NAMPT prompts bleomycin-induced pulmonary fibrosis by driving macrophage M2 polarization in mice. Targeting the NAMPT of monocytes/macrophages is a promising strategy for treating pulmonary fibrosis.
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Bléomycine , Cytokines , Fibrose pulmonaire idiopathique , Macrophages , Nicotinamide phosphoribosyltransferase , Animaux , Femelle , Humains , Mâle , Souris , Acrylamides , Cytokines/métabolisme , Modèles animaux de maladie humaine , Fibrose pulmonaire idiopathique/métabolisme , Fibrose pulmonaire idiopathique/induit chimiquement , Poumon/anatomopathologie , Poumon/métabolisme , Macrophages/métabolisme , Souris de lignée C57BL , Souris transgéniques , Nicotinamide phosphoribosyltransferase/métabolisme , Pipéridines/pharmacologieRÉSUMÉ
Extracellular vesicles (EVs) have been the subject of an exponentially growing number of studies covering their biogenesis mechanisms, isolation and analysis techniques, physiological and pathological roles, and clinical applications, such as biomarker and therapeutic uses. Nevertheless, the heterogeneity of EVs both challenges our understanding of them and presents new opportunities for their potential application. Recently, the EV field experienced a wide range of advances. However, the challenges also remain huge. This review focuses on the recent progress and difficulties encountered in the practical use of EVs in clinical settings. In addition, we also explored the concept of EV heterogeneity to acquire a more thorough understanding of EVs and their involvement in cancer, specifically focusing on the fundamental nature of EVs.
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Marqueurs biologiques tumoraux , Vésicules extracellulaires , Tumeurs , Humains , Vésicules extracellulaires/métabolisme , Tumeurs/anatomopathologie , Tumeurs/thérapie , Tumeurs/métabolisme , Marqueurs biologiques tumoraux/métabolisme , Marqueurs biologiques tumoraux/génétique , AnimauxRÉSUMÉ
Authors' Response to Letter to Editor from Hinpetch Daungsupawong and Viroj Wiwanitkit.
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MAIN CONCLUSION: Transcription factors MhMYB1 and MhMYB2 correlate with monoterpenoid biosynthesis pathway in l-menthol chemotype of Mentha haplocalyx Briq, which could affect the contents of ( -)-menthol and ( -)-menthone. Mentha haplocalyx Briq., a plant with traditional medicinal and edible uses, is renowned for its rich essential oil content. The distinct functional activities and aromatic flavors of mint essential oils arise from various chemotypes. While the biosynthetic pathways of the main monoterpenes in mint are well understood, the regulatory mechanisms governing different chemotypes remain inadequately explored. In this investigation, we identified and cloned two transcription factor genes from the M. haplocalyx MYB family, namely MhMYB1 (PP236792) and MhMYB2 (PP236793), previously identified by our research group. Bioinformatics analysis revealed that MhMYB1 possesses two conserved MYB domains, while MhMYB2 contains a conserved SANT domain. Yeast one-hybrid (Y1H) analysis results demonstrated that both MhMYB1 and MhMYB2 interacted with the promoter regions of MhMD and MhPR, critical enzymes in the monoterpenoid biosynthesis pathway of M. haplocalyx. Subsequent virus-induced gene silencing (VIGS) of MhMYB1 and MhMYB2 led to a significant reduction (P < 0.01) in the relative expression levels of MhMD and MhPR genes in the VIGS groups of M. haplocalyx. In addition, there was a noteworthy decrease (P < 0.05) in the contents of ( -)-menthol and ( -)-menthone in the essential oil of M. haplocalyx. These findings suggest that MhMYB1 and MhMYB2 transcription factors play a positive regulatory role in ( -)-menthol biosynthesis, consequently influencing the essential oil composition in the l-menthol chemotype of M. haplocalyx. This study serves as a pivotal foundation for unraveling the regulatory mechanisms governing monoterpenoid biosynthesis in different chemotypes of M. haplocalyx.
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Régulation de l'expression des gènes végétaux , Mentha , Menthol , Monoterpènes , Protéines végétales , Facteurs de transcription , Facteurs de transcription/génétique , Facteurs de transcription/métabolisme , Mentha/génétique , Mentha/métabolisme , Monoterpènes/métabolisme , Protéines végétales/génétique , Protéines végétales/métabolisme , Menthol/métabolisme , Huile essentielle/métabolisme , Voies de biosynthèse/génétique , Régions promotrices (génétique)/génétiqueRÉSUMÉ
The development of simple methods for the isolation and quantification of exosomes in biological samples is important. By using the typical two-dimensional (2D) nanomaterials, graphene oxide (GO), the present work first studied the interaction of liposomes with the nanocomposites formed by adsorbing HRP on the GO surface and found the presence of liposomes led to the release of HRP from the GO surface to the solution phase triggering the luminol-H2O2 chemiluminescence (CL) reaction to emit light. Benefiting from the similarity of exosomes to liposomes in both composition and morphology aspects, the GO-HRP nanocomposites with a mass ratio of 120:1 and 160:1 were employed for the quantitative detection of exosomes in 100-fold diluted serum samples. The whole detection process took about 15 min and as low as 3.2 × 102 particles µL-1 of exosomes could be sensitively detected. In addition to GO-HRP nanocomposites, the CL responses of other nanocomposites obtained from adsorbing HRP on other 2D nanomaterials such as layered MoS2 for exosomes were also tested. MoS2-HRP exhibited similar behavior and the LODs for the detection of exosomes were 5.8 × 102 particles µL-1. The proposed assays were a biomarker-independent quantitative method that achieved the quantification of exosomes in serum samples directly without an isolation process.
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Exosomes , Graphite , Horseradish peroxidase , Mesures de luminescence , Nanostructures , Exosomes/composition chimique , Graphite/composition chimique , Horseradish peroxidase/composition chimique , Mesures de luminescence/méthodes , Adsorption , Humains , Nanostructures/composition chimique , Luminol/composition chimique , Molybdène/composition chimique , Disulfures/composition chimique , Peroxyde d'hydrogène/composition chimique , Limite de détection , Liposomes/composition chimique , Nanocomposites/composition chimiqueRÉSUMÉ
To enhance the operability of the rat orthotopic left lung transplantation model, we implemented several improvements and meticulously detailed the procedure. One hundred and thirty-one healthy male Sprague Dawley rats, weighing between 250 and 300 g, were utilized, with 64 serving as donors, 64 as recipients, and 3 as sham controls. We employed a modified three-cuff technique for the orthotopic left lung transplantation. Notably, our modified perfusion method could prevent donor lung edema, while waist-shaped cuffs minimized suture slippage during anastomosis. Additionally, positioning the recipient rat in a slightly left-elevated supine position during anastomosis reduced tension on the lung hilum, thus mitigating the risk of vascular laceration. The introduction of a unique two-person anastomosis technique significantly reduced operation time and substantially improved success rates. Furthermore, maximizing inflation of donor lungs both during preservation and surgery minimized the occurrence of postoperative atelectasis. Various other procedural refinements contributed to the enhanced operability of our model. Sixty-four rat orthotopic left lung transplantations were performed with only one surgical failure observed. The acquisition time for donor lungs averaged (19 ± 4) minutes, while (11 ± 1) minutes were allocated for donor lung hilum anatomy and cuff installation. Recipient thoracotomy and left lung hilar anatomy before anastomosis required (24 ± 8) minutes, with anastomosis itself taking (31 ± 6) minutes. Remarkably, the survival rate at the 4-h postoperative mark stood at 96.7 %. Even six months post-operation, transplanted left rat lungs continued to exhibit proper inflation and contraction rhythms, displaying signs of chronic pathological changes. In summary, our modified rat model of orthotopic left lung transplantation demonstrates robust operability, significantly reducing surgical duration, improving operation success rates, and enhancing postoperative survival rates. Furthermore, its long-term survival capacity enables the simulation of acute and chronic disease processes following lung transplantation.
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The finite periodic arrangement of functional nanomaterials on the two-dimensional scale enables the integration and enhancement of individual properties, making them an important research topic in the field of tuneable nanodevices. Although layer-controllable lattices such as graphene have been successfully synthesized, achieving similar control over colloidal nanoparticles remains a challenge. DNA origami technology has achieved remarkable breakthroughs in programmed nanoparticle assembly. Based on this technology, we proposed a hierarchical assembly strategy to construct a universal DNA origami platform with customized layer properties, which we called 2.5-dimensional (2.5D) DNA origami crystals. Methodologically, this strategy divides the assembly procedure into two steps: 1) array synthesis, and 2) lattice synthesis, which means that the layer properties, including layer number, interlayer distance, and surface morphology, can be flexibly customized based on the independent designs in each step. In practice, these synthesized 2.5D crystals not only pioneer the expansion of the DNA origami crystal library to a wider range of dimensions, but also highlight the technological potential for templating 2.5D colloidal nanomaterial lattices.
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ADN , ADN/composition chimique , Nanostructures/composition chimique , Taille de particule , Cristallisation , Propriétés de surface , Conformation d'acide nucléiqueRÉSUMÉ
The belief in online news has become a topical issue. Previous studies demonstrated the role emotion plays in fake news vulnerability. However, few studies have explored the effect of empathy on online news belief. This study investigated the relationship between trait empathy, state empathy, belief in online news, and the potential moderating effect of news type. One hundred and forty undergraduates evaluated 50 online news pieces (25 real, 25 fake) regarding their belief, state empathy, valence, arousal, and familiarity. Trait empathy data were collected using the Chinese version of the Interpersonal Reactivity Index. State empathy was positively correlated with affective empathy in trait empathy and believability, and affective empathy was positively correlated with believability. The influence of affective empathy on news belief was partially mediated by state empathy and regulated by news type (fake, real). We discuss the influence of empathy on online news belief and its internal processes. This study shares some unique insights for researchers, practitioners, social media users, and social media platform providers.
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This paper uses green innovation and environmental pollution as the mediating variables to construct a mediating effect model to investigate whether China's carbon emission trading policy can improve regional eco-efficiency by reducing regional environmental pollution and stimulating green innovation. This study is based on panel data from 30 provinces and municipalities directly under China's central government and autonomous regions from 2003 to 2019. The eco-efficiency of these provinces is measured using the super-efficiency DEA model and the difference-in-difference method (DID). The results show that (1) China's emission trading policy significantly improves regional ecological efficiency and the per capita GDP. The improvement can effectively improve regional ecological efficiency. (2) The mediating effect of green innovation and environmental pollution is significant. That is, China's carbon emission trading policy further improves regional ecological efficiency by stimulating more green innovation and reducing the synergy brought by environmental pollution. (3) There are differences in the feedback of this impact mechanism between different regions: It shows the characteristics of the western region being more significant than the eastern region. The central region has no significant effect. The research conclusion can provide a policy reference for the subsequent unified promotion of the construction of a carbon emission trading market nationwide and a theoretical basis for helping to achieve the "dual carbon" goal.
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Carbone , Pollution de l'environnement , Chine , Politique de l'environnementRÉSUMÉ
Liver hepatocellular carcinoma (LIHC) is a significant global health issue with limited treatment options. In this study, single-cell RNA sequencing (scRNA-seq) data were used to explore the molecular mechanisms of LIHC development and identify potential targets for therapy. The expression of peroxisome proliferator-activated receptors (PPAR)-related genes was analysed in LIHC samples, and primary cell populations, including natural killer cells, T cells, B cells, myeloid cells, endothelial cells, fibroblasts and hepatocytes, were identified. Analysis of the differentially expressed genes (DEGs) between normal and tumour tissues revealed significant changes in gene expression in various cell populations. PPAR activity was evaluated using the 'AUCell' R software, which indicated higher scores in the normal versus the malignant hepatocytes. Furthermore, the DEGs showed significant enrichment of pathways related to lipid and glucose metabolism, cell development, differentiation and inflammation. A prognostic model was then constructed using 8 PPARs-related genes, including FABP5, LPL, ACAA1, PPARD, FABP4, PLIN1, HMGCS2 and CYP7A1, identified using least absolute shrinkage and selection operator-Cox regression analysis, and validated in the TCGA-LIHC, ICGI-LIRI and GSE14520 datasets. Patients with low-risk scores had better prognosis in all cohorts. Based on the expression of the eight model genes, two clusters of patients were identified by ConsensusCluster analysis. We also predicted small-molecule drugs targeting the model genes, and identified perfluorohexanesulfonic acid, triflumizole and perfluorononanoic acid as potential candidates. Finally, wound healing assay confirmed that PPARD can promote the migration of liver cancer cells. Overall, our study offers novel perspectives on the molecular mechanisms of LIHC and potential areas for therapeutic intervention, which may facilitate the development of more effective treatment regimens.
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Carcinome hépatocellulaire , Régulation de l'expression des gènes tumoraux , Tumeurs du foie , Simulation de docking moléculaire , Récepteurs activés par les proliférateurs de peroxysomes , Humains , Carcinome hépatocellulaire/génétique , Carcinome hépatocellulaire/métabolisme , Carcinome hépatocellulaire/anatomopathologie , Tumeurs du foie/génétique , Tumeurs du foie/métabolisme , Tumeurs du foie/anatomopathologie , Pronostic , Récepteurs activés par les proliférateurs de peroxysomes/métabolisme , Récepteurs activés par les proliférateurs de peroxysomes/génétique , Analyse de profil d'expression de gènes , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolismeRÉSUMÉ
To assess ChatGPT 4.0 (ChatGPT) and Gemini Ultra 1.0 (Gemini) large language models on NONMEM coding tasks relevant to pharmacometrics and clinical pharmacology. ChatGPT and Gemini were assessed on tasks mimicking real-world applications of NONMEM. The tasks ranged from providing a curriculum for learning NONMEM, an overview of NONMEM code structure to generating code. Prompts in lay language to elicit NONMEM code for a linear pharmacokinetic (PK) model with oral administration and a more complex model with two parallel first-order absorption mechanisms were investigated. Reproducibility and the impact of "temperature" hyperparameter settings were assessed. The code was reviewed by two NONMEM experts. ChatGPT and Gemini provided NONMEM curriculum structures combining foundational knowledge with advanced concepts (e.g., covariate modeling and Bayesian approaches) and practical skills including NONMEM code structure and syntax. ChatGPT provided an informative summary of the NONMEM control stream structure and outlined the key NONMEM Translator (NM-TRAN) records needed. ChatGPT and Gemini were able to generate code blocks for the NONMEM control stream from the lay language prompts for the two coding tasks. The control streams contained focal structural and syntax errors that required revision before they could be executed without errors and warnings. The code output from ChatGPT and Gemini was not reproducible, and varying the temperature hyperparameter did not reduce the errors and omissions substantively. Large language models may be useful in pharmacometrics for efficiently generating an initial coding template for modeling projects. However, the output can contain errors and omissions that require correction.
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Théorème de Bayes , Humains , Pharmacocinétique , Modèles biologiques , Reproductibilité des résultats , Logiciel , Pharmacologie clinique/méthodes , Dynamique non linéaire , Simulation numériqueRÉSUMÉ
BACKGROUND: Obtaining high-quality chloroplast genome sequences requires chloroplast DNA (cpDNA) samples that meet the sequencing requirements. The quality of extracted cpDNA directly impacts the efficiency and accuracy of sequencing analysis. Currently, there are no reported methods for extracting cpDNA from Erigeron breviscapus. Therefore, we developed a suitable method for extracting cpDNA from E. breviscapus and further verified its applicability to other medicinal plants. RESULTS: We conducted a comparative analysis of chloroplast isolation and cpDNA extraction using modified high-salt low-pH method, the high-salt method, and the NaOH low-salt method, respectively. Subsequently, the number of cpDNA copies relative to the nuclear DNA (nDNA ) was quantified via qPCR. As anticipated, chloroplasts isolated from E. breviscapus using the modified high-salt low-pH method exhibited intact structures with minimal cell debris. Moreover, the concentration, purity, and quality of E. breviscapus cpDNA extracted through this method surpassed those obtained from the other two methods. Furthermore, qPCR analysis confirmed that the modified high-salt low-pH method effectively minimized nDNA contamination in the extracted cpDNA. We then applied the developed modified high-salt low-pH method to other medicinal plant species, including Mentha haplocalyx, Taraxacum mongolicum, and Portulaca oleracea. The resultant effect on chloroplast isolation and cpDNA extraction further validated the generalizability and efficacy of this method across different plant species. CONCLUSIONS: The modified high-salt low-pH method represents a reliable approach for obtaining high-quality cpDNA from E. breviscapus. Its universal applicability establishes a solid foundation for chloroplast genome sequencing and analysis of this species. Moreover, it serves as a benchmark for developing similar methods to extract chloroplast genomes from other medicinal plants.
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Génome de chloroplaste , Plantes médicinales , ADN des chloroplastes/génétique , Plantes médicinales/génétique , Chloroplastes/génétique , Cartographie chromosomique , PhylogenèseRÉSUMÉ
What is already known about this topic?: Brucellosis, mainly caused by Brucella melitensis (B. melitensis), is regarded as a significant zoonotic disease in China. In Weihai, located at the eastern end of the Shandong Peninsula, brucellosis has been in a low epidemic phase for the past five years. What is added by this report?: This was the initial report of a brucellosis outbreak in the last five years. Strains of B. melitensis bv. 3 from Weihai and other cities showed a close genetic relationship, suggesting a potential common ancestry. What are the implications for public health practice?: Epidemiological investigations depend on standardized and effective molecular typing methods and analysis tools for public health laboratories to identify and trace outbreaks. Understanding the circulation patterns of livestock in free-range households in heavily affected areas is essential for controlling the spread of brucellosis.
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Background: Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular carcinoma (HCC) are currently lacking. This systematic review and meta-analysis aims to investigate the reliability of neoadjuvant immunotherapy's efficacy and safety in the context of HCC. Methods: A systematic search was conducted across PubMed (MEDLINE), EMBASE, the Web of Science, the Cochrane Library, and conference proceedings to identify clinical trials involving resectable HCC and neoadjuvant immunotherapy. Single-arm meta-analyses were employed to compute odds ratios and 95% confidence intervals (CIs). Heterogeneity analysis, data quality assessment, and subgroup analyses based on the type of immunotherapy drugs and combination therapies were performed. This meta-analysis is registered in PROSPERO (identifier CRD42023474276). Results: This meta-analysis included 255 patients from 11 studies. Among resectable HCC patients, neoadjuvant immunotherapy exhibited an overall major pathological response (MPR) rate of 0.47 (95% CI 0.31-0.70) and a pathological complete response (pCR) rate of 0.22 (95% CI 0.14-0.36). The overall objective response rate (ORR) was 0.37 (95% CI 0.20-0.69), with a grade 3-4 treatment-related adverse event (TRAE) incidence rate of 0.35 (95% CI 0.24-0.51). Furthermore, the combined surgical resection rate was 3.08 (95% CI 1.66-5.72). Subgroup analysis shows no significant differences in the efficacy and safety of different single-agent immunotherapies; the efficacy of dual ICIs (Immune Checkpoint Inhibitors) combination therapy is superior to targeted combined immunotherapy and monotherapy, while the reverse is observed in terms of safety. Discussion: Neoadjuvant immunotherapy presents beneficial outcomes in the treatment of resectable HCC. However, large-scale, high-quality experiments are warranted in the future to provide robust data support.
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Carcinome hépatocellulaire , Inhibiteurs de points de contrôle immunitaires , Tumeurs du foie , Humains , Carcinome hépatocellulaire/traitement médicamenteux , Inhibiteurs de points de contrôle immunitaires/usage thérapeutique , Tumeurs du foie/traitement médicamenteux , Traitement néoadjuvant , Reproductibilité des résultatsRÉSUMÉ
Cardiomyocyte survival is a critical contributing process of host adaptive responses to cardiovascular diseases (CVD). Cells of the cardiovascular endothelium have recently been reported to promote cardiomyocyte survival through exosome-loading cargos. Sphingosylphosphorylcholine (SPC), an intermediate metabolite of sphingolipids, mediates protection against myocardial infarction (MI). Nevertheless, the mechanism of SPC delivery by vascular endothelial cell (VEC)-derived exosomes (VEC-Exos) remains uncharacterized at the time of this writing. The present study utilized a mice model of ischemia/reperfusion (I/R) to demonstrate that the administration of exosomes via tail vein injection significantly diminished the severity of I/R-induced cardiac damage and prevented apoptosis of cardiomyocytes. Moreover, SPC was here identified as the primary mediator of the observed protective effects of VEC-Exos. In addition, within this investigation, in vitro experiments using cardiomyocytes showed that SPC counteracted myocardial I/R injury by activating the Parkin and nuclear receptor subfamily group A member 2/optineurin (NR4A2/OPTN) pathways, in turn resulting in increased levels of mitophagy within I/R-affected myocardium. The present study highlights the potential therapeutic effects of SPC-rich exosomes secreted by VECs on alleviating I/R-induced apoptosis in cardiomyocytes, thereby providing strong experimental evidence to support the application of SPC as a potential therapeutic target in the prevention and treatment of myocardial infarction.