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Neurotransmitters are key modulators in neuro-immune circuits and have been linked to tumor progression. Medullary thyroid cancer (MTC), an aggressive neuroendocrine tumor, expresses neurotransmitter calcitonin gene-related peptide (CGRP), is insensitive to chemo- and radiotherapies, and the effectiveness of immunotherapies remains unknown. Thus, a comprehensive analysis of the tumor microenvironment would facilitate effective therapies and provide evidence on CGRP’s function outside the nervous system. Here, we compare the single-cell landscape of MTC and papillary thyroid cancer (PTC) and find that expression of CGRP in MTC is associated with dendritic cell (DC) abnormal development characterized by activation of cAMP related pathways and high levels of Kruppel Like Factor 2 (KLF2), correlated with an impaired activity of tumor infiltrating T cells. A CGRP receptor antagonist could offset CGRP detrimental impact on DC development in vitro. Our study provides insights of the MTC immunosuppressive microenvironment, and proposes CGRP receptor as a potential therapeutic target. Medullary thyroid cancer (MTC) is a neuroendocrine tumor that originates from thyroid parafollicular cells, generally associated with a poor prognosis. By comparing MTC with less aggressive papillary thyroid cancer, here the authors find that the neurotransmitter calcitonin gene-related peptide (CGRP) promotes an immunosuppressive microenvironment in MTC.

ObjectiveThe study investigates the association between oral microbiome diversity and all-cause mortality.DesignPopulation-based cohort study.SettingUS National Health and Nutrition Examination Survey (2009–2010 and 2011–2012).ParticipantsA total of 8224 participants who had valid data on the oral microbiome diversity and survival through 31 December 2019 were included in this study.Primary and secondary outcome measuresOral microbiome diversity was measured using the observed number of amplicon sequence variant (ASV) and grouped into quartiles. Cox proportional hazards regression models were used to estimate the HR and 95% CI for all-cause mortality according to the quartiles of ASV number, adjusted for potential confounders.ResultsAmong the 8224 participants (mean (SD) age: 42.0 (15.1) years; 49.9% male; 37.2% white, 23.8% black, 27.2% Hispanic and 11.8% other race/ethnicity), the median follow-up time was 108 months (IQR, 95–120 months) and 429 (5.2%) deaths were identified. Participants with a higher ASV number were more likely to be poor, non-Hispanic black or Hispanic, uninsured and current smokers, more likely to have poor self-rated oral health and periodontitis and less likely to use dental floss. However, compared with the lowest quartile of the ASV number, a suggestive association was observed for the second quartile (HR=0.80, 95% CI: 0.60 to 1.08), a significant reduction in all-cause mortality was observed for the third (HR=0.55, 95% CI: 0.37 to 0.82) and the fourth (HR=0.58, 95% CI: 0.38 to 0.89) quartile. The dose–response association for all-cause mortality risk was curvilinear; the protective association plateaued when the number of ASVs was larger than 120.ConclusionDespite being linked to greater socioeconomic disadvantages and poorer oral health, higher oral microbiome diversity was significantly associated with a substantial reduction in all-cause mortality.

Solute carrier family members control essential physiological functions and are tightly linked to human diseases. Solute carrier family 35 member F2 (SLC35F2) is aberrantly activated in several malignancies. However, the biological function and molecular mechanism of SLC35F2 in papillary thyroid carcinoma (PTC) are yet to be fully explored. Here, we showed that SLC35F2 was prominently upregulated in PTC tissues at both protein and mRNA expression level compared with matched adjacent normal tissues. Besides, the high expression of SLC35F2 was significantly associated with lymph node metastasis in patients with PTC. CRISPR/Cas9‐mediated knockout of SLC35F2 attenuated the tumorigenic properties of PTC, including cell proliferation, migration and invasion and induced G1 phase arrest. In contrast, ectopic expression of SLC35F2 brought about aggressive malignant phenotypes of PTC cells. Moreover, SLC35F2 expedited the proliferation and migration of PTC cells by targeting transforming growth factor‐β type I receptor (TGFBR1) and phosphorylation of apoptosis signal‐regulating kinase 1 (p‐ASK‐1), thereby activating the mitogen‐activated protein kinase signaling pathway. The malignant behaviors induced by overexpression of SLC35F2 could be abrogated by silencing of TGFBR1 using a specific inhibitor. We conducted the first study on SLC35F2 in thyroid cancer with the aim of elucidating the functional significance and molecular mechanism of SLC35F2. Our findings suggest that SLC35F2 exerts its oncogenic effect on PTC progression through the mitogen‐activated protein kinase pathway, with dependence on activation of TGFBR‐1 and apoptosis signal‐regulating kinase 1. SLC35F2 is an oncoprotein remarkably upregulated in PTC tissues, whose expression is closely associated with lymph node metastasis. Ectopic expression of SLC35F2 brings about aggressive malignant phenotypes of PTC cells, including proliferation, migration and invasion and expedites cell cycle coordinating with some critical cyclin‐dependent kinases.

Studies have documented that per- and polyfluoroalkyl substance (PFAS) exposures are associated with thyroid hormones (TH) and lipid levels. This study investigates whether these effects interfere with each other. We analyzed data on 3954 adults in the US National Health and Nutrition Examination Survey (NHANES; 2007–2012). TH disorder was defined using thyroid hormones. Serum high-density lipoprotein (HDL) cholesterol, total cholesterol, and six types of PFAS were included. Weighted quantile sum (WQS) regression was used to estimate the overall effect of PFAS mixture on TH disorder and cholesterols, respectively. Potential confounders, including age, race, gender, education, household poverty, smoking, and alcohol drinking, were adjusted. PFAS mixture was associated increased risk for TH disorder (odds ratio = 1.21, 95% confidence interval (CI): 1.02, 1.43), higher HDL cholesterol (linear coefficient = 1.31, 95% CI: 0.50, 2.11), and higher total cholesterol (linear coefficient = 5.30, 95% CI: 3.40, 7.21). TH disorder was associated with higher HDL cholesterol (linear coefficient = 2.30, 95% CI: 0.50, 2.11), but not total cholesterol. When adjusted for TH disorder, the effect estimates of PFAS mixture remain roughly unchanged on HDL cholesterol (linear coefficient = 1.13, 95% CI: 0.28, 1.98) and total cholesterol (linear coefficient = 5.61, 95% CI: 3.58, 7.63). Sex modified the effect of PFAS mixture on HDL cholesterol (P for interaction: 0.04) but did not change the interaction between PFAS and TH disorder on cholesterols. We corroborated the adverse health effects of PFAS exposure on TH and lipids; however, these two effects appear to be independent of and not interfere with each other.

Abstract Objective To investigate the association between thyroid functions and the oral microbiome diversity. Method Data from the US National Health and Nutrition Examination Survey (NHANES; 2009-2012) were analyzed. Thyroid functions were defined using thyroid hormones and related biomarkers. Oral microbiome was measured using the observed number of amplicon sequence variants (ASVs) and the Bray-Curtis dissimilarity. Linear regression was used to estimate the average change (β) and 95% CI for the number of ASVs against thyroid functions, adjusted for sociodemographic variables, health conditions, urinary iodine status, and periodontitis. Non-metric multidimensional scaling (NMDS) was used to analyze the Bray-Curtis dissimilarity. Results A total of 2943 participants were analyzed. The observed number of ASVs has a weighted mean of 128.9. Self-reported thyroid disease was associated with reduced number of ASVs (β = −9.2, 95% CI: −17.2, −1.2), if only adjusted for sociodemographic variables and health conditions. In the fully adjusted model, compared to normal thyroid function, both subclinical and clinical hyperthyroidism were associated with reduced number of ASVs (β = −59.6, 95% CI: −73.2, −46.0; β = −28.2, 95% CI: −50.0, −6.5, respectively). Thyroid peroxidase antibody level higher than the reference range was associated with higher observed ASV (β= 9.0, 95% CI: 1.2, 16.9). NMDS analysis suggested significant difference in oral microbiome composition between free triiodothyronine groups (P = .002), between free thyroxine groups (P = .015), and between thyroglobulin groups (P = .035). Conclusion Hyperthyroidism was associated with reduced oral microbiome diversity. Free triiodothyronine, free thyroxine, and thyroglobulin levels may alter the oral microbiome composition.

During the processes of primary and secondary endosymbiosis, different microalgae evolved to synthesis different storage polysaccharides. In stramenopiles, the main storage polysaccharides are β-1,3-glucan, or laminarin, in vacuoles. Currently, laminarin is gaining considerable attention due to its application in the food, cosmetic and pharmaceuticals industries, and also its importance in global biogeochemical cycles (especially in the ocean carbon cycle). In this review, the structures, composition, contents, and bioactivity of laminarin were summarized in different algae. It was shown that the general features of laminarin are species-dependence. Furthermore, the proposed biosynthesis and catabolism pathways of laminarin, functions of key genes, and diel regulation of laminarin were also depicted and comprehensively discussed for the first time. However, the complete pathways, functions of genes, and diel regulatory mechanisms of laminarin require more biomolecular studies. This review provides more useful information and identifies the knowledge gap regarding the future studies of laminarin and its applications.

Background The genome of rye, Secale cereale , is distinguished by large repetitive regions including subtelomeric heterochromatin and retrotransposon-dominant centromeres, which contrast with the satellite-repeat-based centromeres in most characterized plant genome assemblies. This study aims to decode the architecture and evolution of these elusive regions through high-resolution genome assembly, with a focus on centromere dynamics and chromatin regulation. Results Using PacBio HiFi and Nanopore sequencing, we generate a chromosome-scale assembly encompassing three complete centromeres and resolving subtelomeric heterochromatin. We identify terminal tandem repeat arrays as key determinants in establishing specialized chromatin environments linked to retrotransposon deposition. Notably, rye centromeres exhibit an unconventional epigenetic signature depleted of conventional activation and repression marks but displaying unique DNA hypomethylation patterns. This retrotransposon-enriched landscape promotes both the integration of young LTR retrotransposons and the recruitment of CENH3. Cross-species CENH3 ChIP-seq analyses reveal that Cereba retrotransposons are associated with enhanced CENH3 loading in cultivated and wild rye lineages, particularly through their conserved protease and integrase domains, suggesting a potential positive feedback loop for centromere evolution. Conclusions Our findings establish retrotransposons as autonomous organizers of centromere chromatin and identity in rye, challenging the paradigm of satellite-dependent centromere specification. The dual role of retrotransposons in maintaining CENH3 recruitment while facilitating genomic innovation provides a mechanistic basis for centromere plasticity. This work advances functional genomics of Triticeae crops and opens new avenues for centromere engineering to manipulate meiotic stability and chromosome transmission in crop breeding.

Recent evidence suggests that athletes have microbial features distinct from those of sedentary individuals. However, the characteristics of the gut microbiota in athletes competing at different levels have not been assessed. The aim of this study was to investigate whether the gut microbiome is significantly different between higher-level and lower-level athletes. Faecal microbiota communities were analysed with hypervariable tag sequencing of the V3-V4 region of the 16S rRNA gene among 28 professional martial arts athletes, including 12 higher-level and 16 lower-level athletes. The gut microbial richness and diversity (the Shannon diversity index (p = 0.019) and Simpson diversity index (p = 0.001)) were significantly higher in the higher-level athletes than in the lower-level athletes. Moreover, the genera Parabacteroides, Phascolarctobacterium, Oscillibacter and Bilophila were enriched in the higher-level athletes, whereas Megasphaera was abundant in the lower-level athletes. Interestingly, the abundance of the genus Parabacteroides was positively correlated with the amount of time participants exercised during an average week. Further analysis of the functional prediction revealed that histidine metabolism and carbohydrate metabolism pathways were markedly over-represented in the gut microbiota of the higher-level athletes. Collectively, this study provides the first insight into the gut microbiota characteristics of professional martial arts athletes. The higher-level athletes had increased diversity and higher metabolic capacity of the gut microbiome for it may positively influence athletic performance.

Group B Streptococcus (GBS) is a major human and animal pathogen that threatens public health and food security. Spill-over and spill-back between host species is possible due to adaptation and amplification of GBS in new niches but the evolutionary and functional mechanisms underpinning those phenomena are poorly known. Based on analysis of 1,254 curated genomes from all major GBS host species and six continents, we found that the global GBS population comprises host-generalist, host-adapted and host-restricted sublineages, which are found across host groups, preferentially within one host group, or exclusively within one host group, respectively, and show distinct levels of recombination. Strikingly, the association of GBS genomes with the three major host groups (humans, cattle, fish) is driven by a single accessory gene cluster per host, regardless of sublineage or the breadth of host spectrum. Moreover, those gene clusters are shared with other streptococcal species occupying the same niche and are functionally relevant for host tropism. Our findings demonstrate (1) the heterogeneity of genome plasticity within a bacterial species of public health importance, enabling the identification of high-risk clones; (2) the contribution of inter-species gene transmission to the evolution of GBS; and (3) the importance of considering the role of animal hosts, and the accessory gene pool associated with their microbiota, in the evolution of multi-host bacterial pathogens. Collectively, these phenomena may explain the adaptation and clonal expansion of GBS in animal reservoirs and the risk of spill-over and spill-back between animals and humans.