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Potassium (K) isotopic compositions for a suite of crustal rocks (plutonic unit, sheeted dike complex, and volcanic sequence) in the Troodos ophiolite, Cyprus, were determined to investigate fluid-transport processes during subduction inception. The gabbros and plagiogranites in the plutonic unit have restricted K isotopic compositions (0.01–0.20 ‰ and −0.17 to 0.02 ‰, respectively), whereas diabases in the sheeted dike complex have variable δ41K values from −0.24 to 1.13 ‰. The δ41K values of the volcanic sequence range from −0.26 to −0.07 ‰ in the lower pillow lavas, and from −0.71 to 0.34 ‰ in the upper pillow lavas. These δ41K values are clearly distinct from those of subducting sediments and altered oceanic crust, ruling out direct crustal input as the cause of the unusually heavy K isotopic compositions. Rather, the high K/Th, K/U, and Sr/Th ratios of the investigated samples, together with binary mixing modelling, reveal that the anomalously heavy K isotopic compositions in Troodos rocks are attributed to the influx of fluids during subduction inception. Notably, the δ41K values in the crustal rocks of the Troodos ophiolite are more variable and extend to higher values than those of arc-front and rear-arc lavas of the Izu arc and arc lavas of Martinique in the Lesser Antilles, indicating continuous K isotope fractionation during slab dehydration. Thus, the heavy K isotopic compositions of the Troodos ophiolite reflect K isotope fractionation during dehydration of a shallow slab within a newly formed subduction system, where heavy K isotopes preferentially enter into the aqueous fluids. Later, progressive breakdown of K-bearing phases at deeper levels results in isotopically lighter hydrous melts, which can be delivered to the arc. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common gastrointestinal malignancies, characterized by insidious onset and high propensity for metastasis and recurrence. Apart from surgical resection, there are no effective curative methods for HCC in recent years, due to resistance to radiotherapy and chemotherapy. Heat shock proteins (HSP) play a crucial role in maintaining cellular homeostasis and normal organism development as molecular chaperones for intracellular proteins. Both basic research and clinical data have shown that HSPs are crucial participants in the HCC microenvironment, as well as the occurrence, development, metastasis, and resistance to radiotherapy and chemotherapy in various malignancies, particularly liver cancer. This review aims to discuss the molecular mechanisms and potential clinical value of HSPs in HCC, which may provide new insights for HSP-based therapeutic interventions for HCC. [Display omitted] • Heat shock proteins (HSP) plays an important role in the tumor microenvironment of Hepatocellular carcinoma. • In highly suspicious cases, HSP helps in differential diagnosis. • HSP related inhibitors and HSP based tumor vaccines have broad prospects in the treatment of HCC. [ABSTRACT FROM AUTHOR]

• What is the key question? In adults, is treatment with GLP-1RAs (as compared with placebo or other glucose-lowering drugs) effective against depressive symptoms? • What are the new findings? In adults, GLP-1RAs induced significant reductions in the depression rating scales compared to control treatments. GLP-1RAs alleviate depressive symptoms in Type 2 diabetes patients. When only RCTs were included, GLP-1RAs showed a significant positive effect on depressive symptoms in adults. • How might this impact on clinical practice in the foreseeable future? GLP-1RAs may be a potential treatment for alleviating depressive symptoms in humans. Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may exert positive effects in patients with depression. Our aim was to conduct a systematic review and meta-analysis to examine the antidepressant effects of GLP-1RAs. Randomized controlled trials and prospective cohort studies investigating the effects of GLP-1RAs versus placebo or other antidiabetic therapies on depressive symptoms were searched for using multiple electronic sources (CENTRAL, PubMed, EMBASE, PsycINFO, World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, China Network Knowledge Infrastructure, China Biomedical Database, Wan Fang data, and Chinese Scientific Journals Database) from inception to February 16, 2023. We utilized a random effects model to analyze standardized mean differences for the change in depression rating scales comparing GLP-1RA treated groups with control treated groups. The meta-analysis comprising 2,071 participants included 5 randomized controlled trials and 1 prospective cohort study. The meta-analysis indicated that the change from baseline in depression rating scale scores decreased significantly when patients received treatment with GLP-1RAs compared to control treatments (SMD = −0.12, 95% CI [−0.21, −0.03], p SMD <0.01, I 2 = 0%, p Q = 0.52). The subgroup analysis showed that the effects of GLP-1RAs on depressive symptoms were consistent in patients with Type 2 diabetes mellitus (SMD = −0.12, 95% CI [−0.21, −0.03], p SMD <0.01, I 2 = 2%, p Q = 0.40). Adults treated with GLP-1RAs showed significant reductions in the depression rating scale scores compared to those treated with control substances. Our findings suggest that GLP-1RAs may be a potential treatment for alleviating depressive symptoms in humans. [ABSTRACT FROM AUTHOR]

Extracellular nucleotides are widely recognized as crucial modulators of immune responses in peripheral tissues. Adenosine triphosphate (ATP) and adenosine are key components of extracellular nucleotides, the balance of which contributes to immune homeostasis. Under tissue injury, ATP exerts its pro-inflammatory function, while the adenosinergic pathway rapidly degrades ATP to immunosuppressive adenosine, thus inhibiting excessive and uncontrolled inflammatory responses. Previous reviews have explored the immunoregulatory role of extracellular adenosine in various pathological conditions, especially inflammation and malignancy. However, current knowledge regarding adenosine and adenosinergic metabolism in the context of solid organ transplantation remains fragmented. In this review, we summarize the latest information on adenosine metabolism and the mechanisms by which it suppresses the effector function of immune cells, as well as highlight the protective role of adenosine in all stages of solid organ transplantation, including reducing ischemia reperfusion injury during organ procurement, alleviating rejection, and promoting graft regeneration after transplantation. Finally, we discuss the potential for future clinical translation of adenosinergic pathway in solid organ transplantation. [ABSTRACT FROM AUTHOR]