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Trace metals such as iron, copper, zinc and manganese play essential roles in various biological processes in fish, including development, energy metabolism and immune response. At embryonic stages, fish obtain essential metals primarily from the yolk, whereas in later life stages (i.e. juvenile and adult), the gastrointestine and the gill are the major sites for the acquisition of trace metals. On a molecular level, the absorption of metals is thought to occur at least in part via specific metal ion transporters, including the divalent metal transporter-1 (DMT1), copper transporter-1 (CTR1), and Zrt- and Irt-like proteins (ZIP). A variety of other proteins are also involved in maintaining cellular and systemic metal homeostasis. Interestingly, the expression and function of these metal transport- and metabolism-related proteins can be influenced by a range of trace metals and major ions. β-Glycerophosphate manufacturer Increasing evidence also demonstrates an interplay between the gastrointestine and the gill for the regulation of trace metal absorption. Therefore, there is a complex network of regulatory and compensatory mechanisms involved in maintaining trace metal balance. Yet, an array of factors is known to influence metal metabolism in fish, such as hormonal status and environmental changes. In this Review, we summarize the physiological significance of iron, copper, zinc and manganese, and discuss the current state of knowledge on the mechanisms underlying transepithelial metal ion transport, metal-metal interactions, and cellular and systemic handling of these metals in fish. Finally, we identify knowledge gaps in the regulation of metal homeostasis and discuss potential future research directions.
Providing frontline support places first responders at a high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

This study was aimed to determine the anti-SARS-CoV-2 seroprevalence in a cohort of first responders (i.e. firefighters/paramedics), to detect the underascertainment rate and to assess risk factors associated with seropositivity.

We conducted a serological survey among 745 first responders in Germany during 27 November and 4 December 2020 to determine the anti-SARS-CoV-2 seroprevalence using Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics, Mannheim, Germany). As part of the examination, participants were asked to provide information on coronavirus disease 2019 (COVID-19)-like-symptoms, information on sociodemographic characteristics and workplace risk factors for a SARS-CoV-2 infection and any prior COVID-19 infection. Descriptive statistics and logistic regression analysis were performed and seroprevalence estimates were adjusted for test sensitivity andrkplace control measures such as increased and regular COVID-19-testing and the prompt vaccination of all personnel are necessary.
The late-onset efavirenz neurotoxicity syndrome (LENS) presents as ataxia and/or encephalopathy with supratherapeutic efavirenz plasma concentrations (>4 µg/mL). link2 Efavirenz is primarily metabolized by cytochrome P450 2B6 (CYP2B6), with CYP2A6 as an accessory pathway. We hypothesized that participants with LENS would predominantly be CYP2B6 slow metabolizers. The aim of our study was to determine the frequency of CYP2B6 slow metabolizers in participants with LENS.

Adult HIV-positive participants on efavirenz-based antiretroviral therapy presenting with LENS were prospectively enrolled. Genetic polymorphisms known to be associated with increased efavirenz plasma concentrations in CYP2B6 (rs3745274, rs28399499, rs4803419) and CYP2A6 (rs28399433) were selected and used to determine proportions of slow metabolizers. Pharmacokinetic analyses were performed using liquid chromatography-tandem mass spectrometry. Median (IQR) plasma efavirenz and 8-hydroxyefavirenz were described.

Fifteen participants were enroment.Genetic code expansion in multicellular organisms is currently limited to the use of repurposed amber stop codons. Here, we introduce a system for the use of quadruplet codons to direct incorporation of non-canonical amino acids in vivo in an animal, the nematode worm Caenorhabditis elegans. We develop hybrid pyrrolysyl tRNA variants to incorporate non-canonical amino acids in response to the quadruplet codon UAGA. We demonstrate the efficiency of the quadruplet decoding system by incorporating photocaged amino acids into two proteins widely used as genetic tools. We use photocaged lysine to express photocaged Cre recombinase for the optical control of gene expression and photocaged cysteine to express photo-activatable caspase for light inducible cell ablation. Our approach will facilitate the routine adoption of quadruplet decoding for genetic code expansion in eukaryotic cells and multicellular organisms.An extensive literature base combined with advances in sequencing technologies demonstrate microRNA levels correlate with various metabolic diseases. Mechanistic studies also establish microRNAs regulate central metabolic pathways and thus play vital roles in maintaining organismal energy balance and metabolic homeostasis. This review highlights research progress on the roles and regulation of microRNAs in the peripheral tissues that confer insulin sensitivity. We discuss sequencing technologies used to comprehensively define the target spectrum of microRNAs in metabolic disease that complement studies reporting physiologic roles for microRNAs in the regulation of glucose and lipid metabolism in animal models. We also discuss the emerging roles of exosomal microRNAs as endocrine signals to regulate lipid and carbohydrate metabolism.
Papillary thyroid cancer (PTC) has an excellent prognosis, and recurrence is rare in patients with no evidence of disease (NED) after initial treatment. Despite this, several guidelines recommend long and costly follow-up, with limited evidence of improved patient outcomes. This study aims to examine the value of follow-up in patients with NED after treatment for PTC, by determining the rate of recurrence, recurrence-associated morbidity, and death, and whether any recurrence was diagnosed through the follow-up programme.

Patients operated for PTC at Lund University Hospital between January 2004 and December 2016 were eligible. Patients with T1a N0/NX were excluded as well as patients with any other thyroid malignancy. Data were collected retrospectively by searching the patients' medical records. NED was defined as thyroglobulin less than 1 ng/ml, thyroglobulin antibodies less than 20 kIU/l, and negative imaging. Biochemical recurrence was defined as thyroglobulin greater than 1 ng/ml, and/or thyroglobulin antibodies greater than 20 kIU/l. Structural recurrence was defined as a strong suspicion of recurrence on imaging and/or histological proof of recurrence.

Out of a cohort of 187 patients, there were 90 patients with NED who were followed for a median of 6.3 years. Three patients had biochemical recurrence; none of them had symptoms, nor were they treated for their recurrence. Three had structural recurrence; all were above 75 years old and only one was diagnosed through the follow-up programme. No patient died of PTC; five patients died during the follow-up.

Follow-up as it is designed today cannot identify recurrences accurately and seems to be of questionable benefit in younger patients with NED after treatment for PTC.
Follow-up as it is designed today cannot identify recurrences accurately and seems to be of questionable benefit in younger patients with NED after treatment for PTC.Large-scale phosphoproteome profiling using mass spectrometry (MS) provides functional insight that is crucial for disease biology and drug discovery. However, extracting biological understanding from these data is an arduous task requiring multiple analysis platforms that are not adapted for automated high-dimensional data analysis. Here, we introduce an integrated pipeline that combines several R packages to extract high-level biological understanding from large-scale phosphoproteomic data by seamless integration with existing databases and knowledge resources. In a single run, PhosPiR provides data clean-up, fast data overview, multiple statistical testing, differential expression analysis, phosphosite annotation and translation across species, multilevel enrichment analyses, proteome-wide kinase activity and substrate mapping and network hub analysis. Data output includes graphical formats such as heatmap, box-, volcano- and circos-plots. This resource is designed to assist proteome-wide data mining of pathophysiological mechanism without a need for programming knowledge.Cancer is a leading cause of death worldwide, accounting for an estimated 10 million deaths by 2020. Over the decades, various strategies for tumor therapy have been developed and evaluated. link3 Photodynamic therapy (PDT) has attracted increasing attention due to its unique characteristics, including low systemic toxicity and minimally invasive nature. Despite the excellent clinical promise of PDT, hypoxia is still the Achilles' heel associated with its oxygen-dependent nature related to increased tumor proliferation, angiogenesis, and distant metastases. Moreover, PDT-mediated oxygen consumption further exacerbates the hypoxia condition, which will eventually lead to the poor effect of drug treatment and resistance and irreversible tumor metastasis, even limiting its effective application in the treatment of hypoxic tumors. Hypoxia, with increased oxygen consumption, may occur in acute and chronic hypoxia conditions in developing tumors. Tumor cells farther away from the capillaries have much lower oxygen levels than cells in adjacent areas. However, it is difficult to change the tumor's deep hypoxia state through different ways to reduce the tumor tissue's oxygen consumption. Therefore, it will become more difficult to cure malignant tumors completely. In recent years, numerous investigations have focused on improving PDT therapy's efficacy by providing molecular oxygen directly or indirectly to tumor tissues. In this review, different molecular oxygen supplementation methods are summarized to alleviate tumor hypoxia from the innovative perspective of using supplemental oxygen. Besides, the existing problems, future prospects and potential challenges of this strategy are also discussed.The Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) is a polydiagnostic instrument for substance use and psychiatric disorders. We translated the SSADDA English version into Chinese (SSADDA-Chinese) and report here our examination of the diagnostic reliability and validity of DSM-IV substance dependence (SD) diagnoses in a Mandarin-speaking sample in Taiwan. We recruited 125 subjects who underwent an assessment of lifetime SD diagnoses using both the SSADDA-Chinese and the Structured Clinical Interview for DSM-IV, Clinician Version (SCID-Chinese). Thirty-one subjects were retested with the SSADDA-Chinese. Cohen's κ statistic, which measures chance-corrected agreement, was used to measure the test-retest reliability and concurrent validity of the individual SD diagnoses. There was a high degree of concordance between SD diagnoses made using the SSADDA-Chinese and the SCID-Chinese, including those for dependence on alcohol (κ = 0.83), ketamine (κ = 0.97), methamphetamine (κ = 0.93), and opioids (κ = 0.
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