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Verrucosidins, a methylated α-pyrone class of polyketides rarely reported upon, have been implicated in one or more neurological diseases. Despite the significance of verrucosidins as neurotoxins, the absolute configurations of most of the derivatives have not been accurately characterized yet. In this study, three pairs of C-9 epimeric verrucosidin derivatives, including the known compounds penicyrones A and B (1a/1b) and 9-O-methylpenicyrones A and B (2a/2b), the new compounds 9-O-ethylpenicyrones A and B (3a/3b), together with the related known derivative verrucosidin (4), were isolated and identified from the culture extract of Penicillium cyclopium SD-413, which was obtained from the marine sediment collected from the East China sea. Their structures were established based on an in-depth analysis of nuclear magnetic resonances (NMR) and mass spectroscopic data. Determination of the absolute configurations of these compounds was accomplished by Mosher’s method and time-dependent density functional theory (TDDFT) calculations of electronic circular dichroism (ECD) and optical rotation (OR). The configurational assignment of penicyrone A demonstrated that the previously reported C-6 absolute configuration of verrucosidin derivatives needs to be revised from (6S) to (6R). The 9R/9S epimers of compounds 1–3 were found to exhibit growth inhibition against some pathogenic bacteria, indicating that they have potential as lead compounds for the creation of antimicrobial agents.

Long noncoding RNAs (lncRNAs), widely expressed in mammalian cells, play pivotal roles in osteosarcoma (OS) progression. Nevertheless, the detailed molecular mechanisms of lncRNA KIAA0087 in OS remain obscure. Here, the roles of KIAA0087 in OS tumorigenesis were investigated. KIAA0087 and miR-411-3p levels were detected by RT-qPCR. Malignant properties were assessed by CCK-8, colony formation, flow cytometry, wound healing, and transwell assays. SOCS1, EMT, and JAK2/STAT3 pathway-related protein levels were measured by western blotting. Direct binding between miR-411-3p and KIAA0087/SOCS1 was validated by a dual-luciferase reporter, RIP, and FISH assays. In vivo growth and lung metastasis were evaluated in nude mice. The expression levels of SOCS1, Ki-67, E-cadherin, and N-cadherin in tumor tissues were measured by immunohistochemical staining. Downregulation of KIAA0087 and SOCS1 and upregulation of miR-411-3p were found in OS tissues and cells. Low expression of KIAA0087 was associated with a poor survival rate. Forced expression of KIAA0087 or miR-411-3p inhibition repressed the growth, migration, invasion, EMT, and activation of the JAK2/STAT3 pathway and triggered apoptosis of OS cells. However, the opposite results were found with KIAA0087 knockdown or miR-411-3p overexpression. Mechanistic experiments indicated that KIAA0087 enhanced SOCS1 expression to inactivate the JAK2/STAT3 pathway by sponging miR-411-3p. Rescue experiments revealed that the antitumor effects of KIAA0087 overexpression or miR-411-3p suppression were counteracted by miR-411-3p mimics or SOCS1 inhibition, respectively. Finally, in vivo tumor growth and lung metastasis were inhibited in KIAA0087-overexpressing or miR-411-3p-inhibited OS cells. In summary, the downregulation of KIAA0087 promotes the growth, metastasis, and EMT of OS by targeting the miR-411-3p-mediated SOCS1/JAK2/STAT3 pathway.

The positive response of wetland methane (CH4) emissions to climate change is an important yet uncertain Earth-system feedback that amplifies atmospheric CH4 concentrations. Here, using a wetland model, we report intensified wetland CH4 emissions during 2000–2021, corresponding with 2020 and 2021 being exceptional years of growth. Our results highlight the need for sustained monitoring and observations of global wetland CH4 fluxes to document emerging trends, variability and underlying drivers.

Resilience is the cornerstone to mental health, and entails multiple biological and psychological mechanistic processes. However, the interplay of the psychobiological processes in shaping resilience is unclear. Here we report the results of testing whether an acute cortisol response and positive affectivity traits moderate the relationship between participants’ five-year major life stress and current psychological symptoms. The participants comprised 147 individuals (93 females and 54 males, age = 24–45 years) without clinical diagnosis. Acute stress was induced using the Trier Social Stress Task. We found that both the cortisol response to anticipatory acute stress and positive affectivity moderated the stress–symptom relationship. Specifically, a positive relationship between life stress and current symptoms was only observed at low, but not high, levels of cortisol response and positive affectivity. Moreover, the moderating effect of cortisol response was only observed at a low level of trait positive affectivity. These results unravel how the biological and emotional processes of the stress response interact to shape resilience to major life stress.

The roles of dietary cholesterol in fish physiology are currently contradictory. The issue reflects the limited studies on the metabolic consequences of cholesterol intake in fish. The present study investigated the metabolic responses to high cholesterol intake in Nile tilapia (Oreochromis niloticus), which were fed with four cholesterol-contained diets (0.8, 1.6, 2.4 and 3.2%) and a control diet for eight weeks. All fish-fed cholesterol diets showed increased body weight, but accumulated cholesterol (the peak level was in the 1.6% cholesterol group). Then, we selected 1.6% cholesterol and control diets for further analysis. The high cholesterol diet impaired liver function and reduced mitochondria number in fish. Furthermore, high cholesterol intake triggered protective adaptation via (1) inhibiting endogenous cholesterol synthesis, (2) elevating the expression of genes related to cholesterol esterification and efflux, and (3) promoting chenodeoxycholic acid synthesis and efflux. Accordingly, high cholesterol intake reshaped the fish gut microbiome by increasing the abundance of Lactobacillus spp. and Mycobacterium spp., both of which are involved in cholesterol and/or bile acids catabolism. Moreover, high cholesterol intake inhibited lipid catabolic activities through mitochondrial β-oxidation, and lysosome-mediated lipophagy, and depressed insulin signaling sensitivity. Protein catabolism was elevated as a compulsory response to maintain energy homeostasis. Therefore, although high cholesterol intake promoted growth, it led to metabolic disorders in fish. For the first time, this study provides evidence for the systemic metabolic response to high cholesterol intake in fish. This knowledge contributes to an understanding of the metabolic syndromes caused by high cholesterol intake or deposition in fish.

Objective Arterial aneurysms are life-threatening but usually asymptomatic before requiring hospitalization. Oculomics of retinal vascular features (RVFs) extracted from retinal fundus images can reflect systemic vascular properties and therefore were hypothesized to provide valuable information on detecting the risk of aneurysms. By integrating oculomics with genomics, this study aimed to (i) identify predictive RVFs as imaging biomarkers for aneurysms and (ii) evaluate the value of these RVFs in supporting early detection of aneurysms in the context of predictive, preventive and personalized medicine (PPPM). Methods This study involved 51,597 UK Biobank participants who had retinal images available to extract oculomics of RVFs. Phenome-wide association analyses (PheWASs) were conducted to identify RVFs associated with the genetic risks of the main types of aneurysms, including abdominal aortic aneurysm (AAA), thoracic aneurysm (TAA), intracranial aneurysm (ICA) and Marfan syndrome (MFS). An aneurysm-RVF model was then developed to predict future aneurysms. The performance of the model was assessed in both derivation and validation cohorts and was compared with other models employing clinical risk factors. An RVF risk score was derived from our aneurysm-RVF model to identify patients with an increased risk of aneurysms. Results PheWAS identified a total of 32 RVFs that were significantly associated with the genetic risks of aneurysms. Of these, the number of vessels in the optic disc (‘ntreeA’) was associated with both AAA (β = −0.36, P = 6.75e−10) and ICA (β = −0.11, P = 5.51e−06). In addition, the mean angles between each artery branch (‘curveangle_mean_a’) were commonly associated with 4 MFS genes (FBN1: β = −0.10, P = 1.63e−12; COL16A1: β = −0.07, P = 3.14e−09; LOC105373592: β = −0.06, P = 1.89e−05; C8orf81/LOC441376: β = 0.07, P = 1.02e−05). The developed aneurysm-RVF model showed good discrimination ability in predicting the risks of aneurysms. In the derivation cohort, the C-index of the aneurysm-RVF model was 0.809 [95% CI: 0.780–0.838], which was similar to the clinical risk model (0.806 [0.778–0.834]) but higher than the baseline model (0.739 [0.733–0.746]). Similar performance was observed in the validation cohort, with a C-index of 0.798 (0.727–0.869) for the aneurysm-RVF model, 0.795 (0.718–0.871) for the clinical risk model and 0.719 (0.620–0.816) for the baseline model. An aneurysm risk score was derived from the aneurysm-RVF model for each study participant. The individuals in the upper tertile of the aneurysm risk score had a significantly higher risk of aneurysm compared to those in the lower tertile (hazard ratio = 17.8 [6.5–48.8], P = 1.02e−05). Conclusion We identified a significant association between certain RVFs and the risk of aneurysms and revealed the impressive capability of using RVFs to predict the future risk of aneurysms by a PPPM approach. Our finds have great potential to support not only the predictive diagnosis of aneurysms but also a preventive and more personalized screening plan which may benefit both patients and the healthcare system. Graphical abstract