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Abstract Background Mycosporine-like amino acids (MAAs) are a class of strongly UV-absorbing compounds produced by cyanobacteria, algae and corals and are promising candidates for natural sunscreen components. Low MAA yields from natural sources, coupled with difficulties in culturing its native producers, have catalyzed synthetic biology-guided approaches to produce MAAs in tractable microbial hosts like Escherichia coli, Saccharomyces cerevisiae and Corynebacterium glutamicum. However, the MAA titres obtained in these hosts are still low, necessitating a thorough understanding of cellular factors regulating MAA production. Results To delineate factors that regulate MAA production, we constructed a shinorine (mycosporine-glycine-serine) producing yeast strain by expressing the four MAA biosynthetic enzymes from Nostoc punctiforme in Saccharomyces cerevisiae. We show that shinorine is produced from the pentose phosphate pathway intermediate sedoheptulose 7-phosphate (S7P), and not from the shikimate pathway intermediate 3-dehydroquinate (3DHQ) as previously suggested. Deletions of transaldolase (TAL1) and phosphofructokinase (PFK1/PFK2) genes boosted S7P/shinorine production via independent mechanisms. Unexpectedly, the enhanced S7P/shinorine production in the PFK mutants was not entirely due to increased flux towards the pentose phosphate pathway. We provide multiple lines of evidence in support of a reversed pathway between glycolysis and the non-oxidative pentose phosphate pathway (NOPPP) that boosts S7P/shinorine production in the phosphofructokinase mutant cells. Conclusion Reversing the direction of flux between glycolysis and the NOPPP offers a novel metabolic engineering strategy in Saccharomyces cerevisiae.

Abstract Objective To compare the outcomes associated with the use of lasmiditan, rimegepant, ubrogepant, and zavegepant for the acute management of migraine headaches. Methods We searched four electronic databases from database inception to August 31, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the acute treatment of migraine. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of evidence using the CINeMA approach. We conducted frequentist network meta-analyses (NMA) to summarise the evidence. Data were analyzed using R-4.3.1. Results A total of 18 eligible studies including 10 different types of interventions with 22,429 migraine patients were included. NMA results showed that compared to ubrogepant (25 mg and 50 mg) and zavegepant, lasmiditan (100 mg and 200 mg) exhibits an elevated probability of achieving pain relief within a 2-hour interval. Similarly, relative to zavegepant, rimegepant (75 mg) and ubrogepant (50 mg and 100 mg) demonstrate an enhanced likelihood of sustaining pain relief over a 24-hour period. Furthermore, in contrast to ubrogepant (25 mg) and lasmiditan (50 mg), rimegepant (75 mg) presents a heightened probability of achieving freedom from photophobia within 2 h. Regarding safety, lasmiditan carries the highest risk of adverse events, which are associated with an increased incidence of adverse effects, including dizziness, somnolence, asthenia, paresthesia, and fatigue. Conclusions In this NMA, a spectrum of evidence ranging from very low to high levels underscores the favorable efficacy and tolerability of rimegepant 75 mg and ubrogepant 100 mg, positioning them as potential candidates for the acute management of migraine. Concurrently, lasmiditan (100 mg and 200 mg) exhibits notable efficacy, albeit accompanied by an increased susceptibility to adverse events. These findings should still be approached with caution, primarily due to the intrinsic limitations associated with indirect comparisons.

Following an introduction to the nature of fisheries catches and their information content, a new development of CMSY, a data-limited stock assessment method for fishes and invertebrates, is presented. This new version, CMSY++, overcomes several of the deficiencies of CMSY, which itself improved upon the “Catch-MSY” method published by S. Martell and R. Froese in 2013. The catch-only application of CMSY++ uses a Bayesian implementation of a modified Schaefer model, which also allows the fitting of abundance indices should such information be available. In the absence of historical catch time series and abundance indices, CMSY++ depends strongly on the provision of appropriate and informative priors for plausible ranges of initial and final stock depletion. An Artificial Neural Network (ANN) now assists in selecting objective priors for relative stock size based on patterns in 400 catch time series used for training. Regarding the cross-validation of the ANN predictions, of the 400 real stocks used in the training of ANN, 94% of final relative biomass (B/k) Bayesian (BSM) estimates were within the approximate 95% confidence limits of the respective CMSY++ estimate. Also, the equilibrium catch-biomass relations of the modified Schaefer model are compared with those of alternative surplus-production and age-structured models, suggesting that the latter two can be strongly biased towards underestimating the biomass required to sustain catches at low abundance. Numerous independent applications demonstrate how CMSY++ can incorporate, in addition to the required catch time series, both abundance data and a wide variety of ancillary information. We stress, however, the caveats and pitfalls of naively using the built-in prior options, which should instead be evaluated case-by-case and ideally be replaced by independent prior knowledge.

AIM: To analyze the correlation between SLC52A2 and uveal melanoma(UM)based on the cancer genome atlas(TCGA)database, and preliminarily explore the influence of SLC52A2 on the prognosis of UM patients and potential mechanism.METHODS: The clinical information on 80 patients with UM and mRNA expression data of SLC52A2 were collected from TCGA database. According to the expression level of SLC52A2, 80 patients were divided into high and low expression groups by median method. The relationship between the expression of SLC52A2 and clinical pathological features, as well as the prognosis was analyzed. The age, sex, clinical stage, pathological stage, and mRNA expression of SLC52A2 were analyzed by univariate and multivariate Cox analysis to search the prognostic factors of UM. Enrichment analyses were used to predict the possible regulatory pathway of SLC52A2 in UM.RESULTS: The survival prognosis of patients with low expression of SLC52A2 was better than that of patients with high expression of SLC52A2(P0.05). Multivariate Cox analysis showed that the high expression of SLC52A2 was a risk factor for poor prognosis. The nomogram prediction model developed by combining the expression of SLC52A2 with clinical pathological features could accurately predict the survival probability of UM patients. The infiltration abundance of Th2 and Treg cells in both groups has difference(all P

To date, the intricacies and efficacy of how periodic seasonal environmental fluctuations affect fish populations in biogeography in the context of profound climate change remain to be elucidated. Collected monitoring data on fish resources in the temperate estuary provide an excellent opportunity to assess the effects of seasonal environmental fluctuations on populations and functional assemblages under climate change. We first developed a framework for predicting habitat suitability under different climate change scenarios (SSP1-2.6 and SSP5-8.5) for 12 fish populations in the Yangtze estuary by examining the seasonal environmental affinities of temperate estuarine fishes. We then summarized the multidimensional habitat suitability responses (HSRs) of populations and functional assemblages and discussed the possible drivers and mechanisms underlying these changes. The results suggest that the acidity of the Yangtze estuary may decline in the future as the climate warms, endangering the ecosystem that many fish species depend on. Prospective climate change may have an impact on fish population HSRs through redistribution, area changes, and centroid migration of suitable habitats; nevertheless, affinity for environmental factors may be limited to distinguishing patterns of population response in the spring. Fish (5 populations) and functional assemblages (11 assemblages) may exhibit robust adaptations or non-adaptations to climate change when seasons change, given their suitable habitat area. Furthermore, projections indicate that the majority of fish habitat centroids exhibit seasonal responses, migrating northeast in the spring and southeast in the autumn. By decentralizing climate risk to seasonal scales, seasonal resilience in the multidimensional HSRs of several fish populations (5/12) and their functional assemblages (11/16) is revealed for the first time. Efforts to mitigate climate risks and safeguard resources should take these seasonal forecasts and indicative information into account.

Endothelial-to-mesenchymal transition (EndMT) is the process by which endothelial cells lose their endothelial properties and acquire mesenchymal characteristics. Dual-specific protein phosphatase 22 (DUSP22) inactivates various protein kinases and transcription factors by dephosphorylating serine/threonine residues: hence, it plays a key role in many diseases. The aim of this study was to explore the functional role of DUSP22 in EndMT. In the transforming growth factor-β-induced EndMT model in human umbilical vein endothelial cells (HUVECs), we observed a downregulation of DUSP22 expression. This DUSP22 deficiency could aggravate EndMT. Conversely, the overexpression of DUSP22 could ameliorate EndMT. We used signaling pathway inhibitors to verify our results and found that DUSP22 could regulate EndMT through the smad2/3 and the mitogen-activated protein kinase (MAPK) signaling pathways. In summary, DUSP22 ameliorates EndMT in HUVECs in vitro through the smad2/3 and MAPK signaling pathways.

Background Cardiac hypertrophy (CH) is a well‐established risk factor for many cardiovascular diseases and a primary cause of mortality and morbidity among older adults. Currently, no pharmacological interventions have been specifically tailored to treat CH. OTUD7B (ovarian tumor domain‐containing 7B) is a member of the ovarian tumor‐related protease (OTU) family that regulates many important cell signaling pathways. However, the role of OTUD7B in the development of CH is unclear. Therefore, we investigated the role of OTUD7B in CH. Methods and Results OTUD7B knockout mice were used to assay the role of OTUD7B in CH after transverse aortic coarctation surgery. We further assayed the specific functions of OTUD7B in isolated neonatal rat cardiomyocytes. We found that OTUD7B expression decreased in hypertrophic mice hearts and phenylephrine‐stimulated neonatal rat cardiomyocytes. Furthermore, OTUD7B deficiency exacerbated transverse aortic coarctation surgery‐induced myocardial hypertrophy, abnormal cardiac function, and fibrosis. In cardiac myocytes, OTUD7B knockdown promoted phenylephrine stimulation‐induced myocardial hypertrophy, whereas OTUD7B overexpression had the opposite effect. An immunoprecipitation–mass spectrometry analysis showed that OTUD7B directly binds to KLF4 (Krüppel‐like factor 4). Additional molecular experiments showed that OTUD7B impedes KLF4 degradation by inhibiting lysine residue at 48 site‐linked ubiquitination and suppressing myocardial hypertrophy by activating the serine/threonine kinase pathway. Conclusions These results demonstrate that the OTUD7B‐KLF4 axis is a novel molecular target for CH treatment.