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Volume 11 ， Issue 5 ， 2024
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Adipsin inhibits Irak2 mitochondrial translocation and improves fatty acid β-oxidation to alleviate diabetic cardiomyopathy AI Introduction
“In the field of diabetic cardiomyopathy, researchers have made significant progress. They found that Adipsin improves fatty acid β-oxidation and alleviates mitochondrial injury in DCM, with the mechanism related to Irak2 interaction and inhibition of Irak2 mitochondrial translocation.”
Abstract：Background:Diabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid β-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity, which impairs myocardial function. Adipsin may play an important protective role in the pathogenesis of DCM. The aim of this study is to investigate the regulatory effect of Adipsin on DCM lipotoxicity and its molecular mechanism.Methods:A high-fat diet (HFD)-induced type 2 diabetes mellitus model was constructed in mice with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg). Liquid chromatography-tandem mass spectrometry (LC–MS/MS), glutathione-S-transferase (GST) pull-down technique, Co-immunoprecipitation (Co-IP) and immunofluorescence colocalization analyses were used to investigate the molecules which can directly interact with Adipsin. The immunocolloidal gold method was also used to detect the interaction between Adipsin and its downstream modulator.Results:The expression of Adipsin was significantly downregulated in the HFD-induced DCM model (P<0.05). Adipose tissue-specific overexpression of Adipsin significantly improved cardiac function and alleviated cardiac remodeling in DCM (P<0.05). Adipsin overexpression also alleviated mitochondrial oxidative phosphorylation function in diabetic stress (P<0.05). LC–MS/MS analysis, GST pull-down technique and Co-IP studies revealed that interleukin-1 receptor-associated kinase-like 2 (Irak2) was a downstream regulator of Adipsin. Immunofluorescence analysis also revealed that Adipsin was co-localized with Irak2 in cardiomyocytes. Immunocolloidal gold electron microscopy and Western blotting analysis indicated that Adipsin inhibited the mitochondrial translocation of Irak2 in DCM, thus dampening the interaction between Irak2 and prohibitin (Phb)-optic atrophy protein 1 (Opa1) on mitochondria and improving the structural integrity and function of mitochondria (P<0.05). Interestingly, in the presence of Irak2 knockdown, Adipsin overexpression did not further alleviate myocardial mitochondrial destruction and cardiac dysfunction, suggesting a downstream role of Irak2 in Adipsin-induced responses (P<0.05). Consistent with these findings, overexpression of Adipsin after Irak2 knockdown did not further reduce the accumulation of lipids and their metabolites in the cardiac myocardium, nor did it enhance the oxidation capacity of cardiomyocytes expose to palmitate (PA) (P<0.05). These results indicated that Irak2 may be a downstream regulator of Adipsin.Conclusions:Adipsin improves fatty acid β-oxidation and alleviates mitochondrial injury in DCM. The mechanism is related to Irak2 interaction and inhibition of Irak2 mitochondrial translocation.Keywords：Diabetic cardiomyopathy;Mitochondrial translocation;Mitochondrial function;Fatty acid β-oxidation80|0|0Updated：2025-12-13 - “In the field of prostate cancer treatment, researchers have identified ADP-dependent glucokinase (ADPGK) as a crucial target. The study found that high ADPGK expression is associated with poor survival outcomes in prostate cancer patients. ADPGK accelerates cancer glycolysis and progression by activating the ALDOC-AMPK signaling pathway, laying a foundation for the construction of a new treatment and prognosis evaluation system for prostate cancer.”
Abstract：Background:Cell metabolism plays a pivotal role in tumor progression, and targeting cancer metabolism might effectively kill cancer cells. We aimed to investigate the role of hexokinases in prostate cancer (PCa) and identify a crucial target for PCa treatment.Methods:The Cancer Genome Atlas (TCGA) database, online tools and clinical samples were used to assess the expression and prognostic role of ADP-dependent glucokinase (ADPGK) in PCa. The effect of ADPGK expression on PCa cell malignant phenotypes was validated in vitro and in vivo. Quantitative proteomics, metabolomics, and extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) tests were performed to evaluate the impact of ADPGK on PCa metabolism. The underlying mechanisms were explored through ADPGK overexpression and knockdown, co-immunoprecipitation (Co-IP), ECAR analysis and cell counting kit-8 (CCK-8) assays.Results:ADPGK was the only glucokinase that was both upregulated and predicted worse overall survival (OS) in prostate adenocarcinoma (PRAD). Clinical sample analysis demonstrated that ADPGK was markedly upregulated in PCa tissues vs. non-PCa tissues. High ADPGK expression indicates worse survival outcomes, and ADPGK serves as an independent factor of biochemical recurrence. In vitro and in vivo experiments showed that ADPGK overexpression promoted PCa cell proliferation and migration, and ADPGK inhibition suppressed malignant phenotypes. Metabolomics, proteomics, and ECAR and OCR tests revealed that ADPGK significantly accelerated glycolysis in PCa. Mechanistically, ADPGK binds aldolase C (ALDOC) to promote glycolysis via AMP-activated protein kinase (AMPK) phosphorylation. ALDOC was positively correlated with ADPGK, and high ALDOC expression was associated with worse survival outcomes in PCa.Conclusions:In summary, ADPGK is a driving factor in PCa progression, and its high expression contributes to a poor prognosis in PCa patients. ADPGK accelerates PCa glycolysis and progression by activating ALDOC-AMPK signaling, suggesting that ADPGK might be an effective target and marker for PCa treatment and prognosis evaluation.Keywords：Prostate cancer (PCa);ADP-dependent glucokinase (ADPGK);Aldolase C (ALDOC);AMPK;Glycolysis56|0|1Updated：2025-12-13
RESEARCH
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Regulatory T cells in skin regeneration and wound healing AI Introduction
“Reporting on the latest advancements in skin wound healing, the study delves into the pivotal role of regulatory T cells in balancing immune responses and facilitating skin regeneration. Expert insights reveal the multifaceted activity of Tregs, offering new avenues for understanding wound pathologies and developing innovative treatment strategies.”
Abstract：As the body’s integumentary system, the skin is vulnerable to injuries. The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality. To this end, multiple tissue-resident cells and recruited immune cells cooperate to efficiently repair the injured tissue. Such temporally- and spatially-coordinated interplay necessitates tight regulation to prevent collateral damage such as overshooting immune responses and excessive inflammation. In this context, regulatory T cells (Tregs) hold a key role in balancing immune homeostasis and mediating cutaneous wound healing. A comprehensive understanding of Tregs’ multifaceted field of activity may help decipher wound pathologies and, ultimately, establish new treatment modalities. Herein, we review the role of Tregs in orchestrating the regeneration of skin adnexa and catalyzing healthy wound repair. Further, we discuss how Tregs operate during fibrosis, keloidosis, and scarring.Keywords：Regulatory T cells (Tregs);Wound healing;Wound repair;Skin injury;Skin regeneration34|1|0Updated：2025-12-13 -
Abstract：In the United States (US), the Surveillance, Epidemiology, and End Results (SEER) program is the only comprehensive source of population-based information that includes stage of cancer at the time of diagnosis and patient survival data. This program aims to provide a database about cancer incidence and survival for studies of surveillance and the development of analytical and methodological tools in the cancer field. Currently, the SEER program covers approximately half of the total cancer patients in the US. A growing number of clinical studies have applied the SEER database in various aspects. However, the intrinsic features of the SEER database, such as the huge data volume and complexity of data types, have hindered its application. In this review, we provided a systematic overview of the commonly used methodologies and study designs for retrospective epidemiological research in order to illustrate the application of the SEER database. Therefore, the goal of this review is to assist researchers in the selection of appropriate methods and study designs for enhancing the robustness and reliability of clinical studies by mining the SEER database.Keywords：Surveillance;epidemiology;and End results (SEER);Big data;Methodologies;Study design37|1|0Updated：2025-12-13 -
Abstract：Regulation of gut microbiota and its impact on human health is the theme of intensive research. The incidence and prevalence of atrial fibrillation (AF) are continuously escalating as the global population ages and chronic disease survival rates increase; however, the mechanisms are not entirely clarified. It is gaining awareness that alterations in the assembly, structure, and dynamics of gut microbiota are intimately engaged in the AF progression. Owing to advancements in next-generation sequencing technologies and computational strategies, researchers can explore novel linkages with the genomes, transcriptomes, proteomes, and metabolomes through parallel meta-omics approaches, rendering a panoramic view of the culture-independent microbial investigation. In this review, we summarized the evidence for a bidirectional correlation between AF and the gut microbiome. Furthermore, we proposed the concept of "gut-immune-heart" axis and addressed the direct and indirect causal roots between the gut microbiome and AF. The intricate relationship was unveiled to generate innovative microbiota-based preventive and therapeutic interventions, which shed light on a definite direction for future experiments.Keywords：atrial fibrillation;Gut microbiome;Meta-omics;Metabolites;Immunity26|1|0Updated：2025-12-13 -
Insights gained from single-cell analysis of chimeric antigen receptor T-cell immunotherapy in cancer AI Introduction
“Advances in chimeric antigen receptor (CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies. However, progress is still hindered as clinical benefit is only available for a fraction of patients. In this review, we discuss the reasons why CAR-T immunotherapy fails in clinical practice and what this field has learned since the milestone of single-cell sequencing technologies. Expert xx established the xx system/explored the xx topic/verified the xx conjecture, which provides solutions to solve xx problems/open up a new direction for xx research/lay a foundation for the construction of xx system.”
Abstract：Advances in chimeric antigen receptor (CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies. However, progress is still hindered as clinical benefit is only available for a fraction of patients. A lack of understanding of CAR-T cell behaviors in vivo at the single-cell level impedes their more extensive application in clinical practice. Mounting evidence suggests that single-cell sequencing techniques can help perfect the receptor design, guide gene-based T cell modification, and optimize the CAR-T manufacturing conditions, and all of them are essential for long-term immunosurveillance and more favorable clinical outcomes. The information generated by employing these methods also potentially informs our understanding of the numerous complex factors that dictate therapeutic efficacy and toxicities. In this review, we discuss the reasons why CAR-T immunotherapy fails in clinical practice and what this field has learned since the milestone of single-cell sequencing technologies. We further outline recent advances in the application of single-cell analyses in CAR-T immunotherapy. Specifically, we provide an overview of single-cell studies focusing on target antigens, CAR-transgene integration, and preclinical research and clinical applications, and then discuss how it will affect the future of CAR-T cell therapy.Keywords：Single-cell sequencing;Cancer immunotherapy;Chimeric antigen receptor-T therapy;Cell heterogeneity;Trajectory inference;Tumor microenvironment22|0|0Updated：2025-12-13 -
Abstract：Latent tuberculosis infection (LTBI) has become a major source of active tuberculosis (ATB). Although the tuberculin skin test and interferon-gamma release assay can be used to diagnose LTBI, these methods can only differentiate infected individuals from healthy ones but cannot discriminate between LTBI and ATB. Thus, the diagnosis of LTBI faces many challenges, such as the lack of effective biomarkers from Mycobacterium tuberculosis (MTB) for distinguishing LTBI, the low diagnostic efficacy of biomarkers derived from the human host, and the absence of a gold standard to differentiate between LTBI and ATB. Sputum culture, as the gold standard for diagnosing tuberculosis, is time-consuming and cannot distinguish between ATB and LTBI. In this article, we review the pathogenesis of MTB and the immune mechanisms of the host in LTBI, including the innate and adaptive immune responses, multiple immune evasion mechanisms of MTB, and epigenetic regulation. Based on this knowledge, we summarize the current status and challenges in diagnosing LTBI and present the application of machine learning (ML) in LTBI diagnosis, as well as the advantages and limitations of ML in this context. Finally, we discuss the future development directions of ML applied to LTBI diagnosis.Keywords：Tuberculosis (TB);Latent tuberculosis infection (LTBI);Machine learning (ML);Biomarkers;Differential diagnosis34|0|0Updated：2025-12-13
REVIEW
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White-light-induced synthesis of injectable alginate- based composite hydrogels for rapid hemostasis AI Introduction
“In the field of xxx, expert xx has made significant research progress. By establishing the xx system/exploring the xx topic/verifying the xx conjecture, xx has provided solutions to address xx problems/open up a new direction for xx research/lay a foundation for the construction of the xx system.”
Keywords：Photoinitiator;Photopolymerization;Alginate;Hydrogel;Hemostasis31|0|0Updated：2025-12-13 - “In the field of artificial intelligence, expert Dr. Smith established the AI system, which provides solutions to solve complex decision-making problems.”
Keywords：Resuscitative endovascular balloon occlusion of the aorta (REBOA);Pre-hospital;Endovascular;Aortic balloon occlusion;Trauma;Hemorrhage;Shock24|0|0Updated：2025-12-13
LETTER TO THE EDITOR
- “In the field of xxx, expert xx has made significant research progress. By establishing the xx system/exploring the xx topic/verifying the xx conjecture, xx has provided solutions to solve xx problems/open up a new direction for xx research/lay a foundation for the construction of the xx system.”Keywords：Cell therapy;Inflammaging;Secretome;Senescence23|1|0Updated：2025-12-13
- “In the field of artificial intelligence, expert Dr. Smith established the AI decision-making system, which provides solutions to solve complex decision-making problems.”
Keywords：Adipsin;Complement factor D;interleukin-1;Interleukin-1 receptor-associated kinase like 2 (Irak2);Opa1;Prohibitin (PHB)23|0|0Updated：2025-12-13
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