Occurrence of black queen cell virus in wild bumble bee communities in China.

Wild bumble bees (Hymenoptera: Apidae) play a vital role in agro-ecosystems as important pollinators. However, they are threatened by virus pathogens that are widespread in honey bees. Previous studies have reported that viruses were able to be transmitted across bee genera and caused potential danger to wild bumble bees. China is a global biodiversity hotspot for bumble bees. However, the impact of viruses on the wild bumble bee communities remains elusive. Black queen cell virus (BQCV) is one of the most common honey bee viruses. Here, a total of 72 wild bumble bee samples from 17 geographic regions of China were tested for BQCV. Thirteen positive samples were identified and sequence comparison of partial capsid genes demonstrated a genetic identity of 99.69% to 100%. A phylogenetic tree analysis also showed a close relationship between 13 BQCV isolates and others from a variety of recorded hosts in China. Meanwhile, a distinct evolutionary branch of China isolates was formed when clustering isolates from worldwide bumble bee species. A correlation between BQCV and their geographic locations were observed (P < 0.05). This study not only provides the first evidence of widespread BQCV in wild bumble bee communities in China but also detects a distinct set of genetically identical or closely related BQCV variants that circulate and evolutionarily differ from other countries.

LncRNA lncMGR regulates skeletal muscle development and regeneration by recruiting CDK9 and sponging miRNAs.

Long non-coding RNAs (lncRNAs) play an essential role in vertebrate myogenesis and muscle diseases. However, the dynamic expression patterns, biological functions, and mechanisms of lncRNAs in skeletal muscle development and regeneration remain largely unknown. In this study, a novel lncRNA (named lncMGR) was differentially expressed during breast muscle development in fast- and slow-growing chickens. Functionally, lncMGR promoted myoblast differentiation, inhibited myoblast proliferation in vitro, and promoted myofiber hypertrophy and injury repair in vivo. Mechanistically, lncMGR increased the mRNA and protein expression of skeletal muscle myosin heavy chain 1 A (MYH1A) via both transcriptional and post-transcriptional regulation. Nuclear lncMGR recruited cyclin-dependent kinase 9 (CDK9) to the core transcriptional activation region of the MYH1A gene to activate MYH1A transcription. Cytoplasmic lncMGR served as a competitive endogenous RNA (ceRNA) to competitively absorb miR-2131-5p away from MYH1A and subsequently protected the MYH1A from miR-2131-5p-mediated degradation. Besides miR-2131-5p, cytoplasmic lncMGR could also sponge miR-143-3p to reconcile the antagonist between the miR-2131-5p/MYH1A-mediated inhibition effects and miR-143-3p-mediated promotion effects on myoblast proliferation, thereby inhibiting myoblast proliferation. Collectively, lncMGR could recruit CDK9 and sponge multiple miRNAs to regulate skeletal muscle development and regeneration, and could be a therapeutic target for muscle diseases.

Dorsoventrally asymmetric expression of miR319/TCP generates dorsal-specific venation patterning in petunia corolla tube.

Vein-associated pigmentation (Venation) is a type of floral coloration adopted by plants to attract pollinators. Several petunia (Petunia hybrida) lines generate dorsoventrally asymmetric venation patterning of the corolla tube, in which venation is only presents in the dorsal tube. The molecular mechanism underlying this trait is unknown. Here, we demonstrate that miR319 is preferentially expressed in the dorsal corolla tube, leading to dorsoventrally asymmetric expression of its target genes. Transgenic lines overexpressing phy-miR319a generated uniform venation patterning of the corolla tube. Knockout of TCP genes targeted by miR319 promoted venation patterning in the ventral and dorsal tube, while overexpression of the miR319 target gene, PhTCP6, wholly inhibited corolla tube venation patterning. In addition, miR319-targeted TCPs negatively regulated venation patterning, likely by repressing the regulator of venation patterning, AN4. Together, our data demonstrate that asymmetric expression of miR319 promotes venation patterning in the petunia dorsal tube alone by repressing the expression of its target TCP genes, which negatively regulate corolla tube venation patterning. These findings provide novel insight into how the dorsoventrally asymmetric distribution of venation patterning is established in zygomorphic flowers.

Left atrial appendage filling defect in exclusive early-phase scanning of dual-phase cardiac computed tomography: An indicator for elevated thromboembolic risk.

BACKGROUND: Dual-phase cardiac computed tomography (CCT) has been applied to detect left atrial appendage (LAA) thrombosis, which is characterized as the presence of left atrial appendage filling defects (LAADF) in both early- and delayed-phase scanning. However, the clinical implication of LAAFD in exclusive early-phase scanning (LAAFD-EEpS) of CCT in patients with atrial fibrillation (AF) is unclear. METHODS: The baseline clinical data and dual-phase CCT findings in 1183 AF patients (62.1 ± 11.6 years, 59.9% male) was collected and analyzed. A further analysis of CCT and transesophageal echocardiography (TEE) data (within 5 days) in a subgroup of 687 patients was performed. LAAFD-EEpS was defined as LAAFD present in early-phase and absent in delayed-phase scanning of dual-phase CCT. RESULTS: A total of 133 (11.2%) patients were detected with LAAFD-EEpS. Patients with LAAFD-EEpS had a higher prevalence of ischemic stroke or transient ischemic attack (TIA) (p < 0.001) and a higher predefined thromboembolic risk (p < 0.001). In multivariate analysis, a history of ischemic stroke or TIA was independently associated with LAAFD-EEpS (odds ratio [OR] 11.412, 95% confidence interval [CI] 6.561-19.851, p < 0.001). When spontaneous echo contrast in TEE was used as the reference standard, the sensitivity, specificity, positive predictive value, and negative predictive value of LAAFD-EEpS was 77.0% (95% CI 66.5-87.6%), 89.0% (95% CI 86.5-91.4%), 40.5% (95% CI 31.6-49.5%), 97.5% (96.3-98.8%), respectively. CONCLUSIONS: In AF patients, LAAFD-EEpS is not an uncommon finding in dual-phase CCT scanning, and is associated with elevated thromboembolic risk.

miR-19b-3p regulated by estrogen controls lipid synthesis through targeting MSMO1 and ELOVL5 in LMH cells.

miR-19b-3p is reported to undertake various biological role, while its function and action mechanism in chicken hepatic lipid metabolism is unclear. Conservation analysis and tissue expression pattern of miR-19b-3p and its target gene were evaluated, respectively. Dual luciferase reporter system and Western blot technologies were adopted to validate miR-19b-3p target gene. Overexpression and knockdown assays were done to explore the biological functions of miR-19b-3p and target gene in Leghorn Male Hepatoma cell line (LMH). Regulatory approaches of estrogen on miR-19b-3p and target gene expressions are analyzed through site-directed mutation combined with estrogen receptors antagonist treatment assays. The results showed that chicken miR-19b-3p mature sequences are highly conserved among Capra hircus, Columba livia, Rattus norvegicus, Mus musculus, Cricetulus griseus, Danio rerio, Danio novaehollandiae, Orycodylus porosus, Crocodylus porosus, Gadus morhua, and widely expressed in lung, ovary, spleen, duodenum, kidney, heart, liver, leg muscle, and pectoral muscle tissues. miR-19b-3p could significantly increase intracellular triglyceride (TG) content and decrease intracellular cholesterol (TC) content via targeting methylsterol monooxygenase 1 (MSMO1) and elongase of very long chain fatty acids 5 (ELOVL5), which are highly conserved among species, in both mRNA and protein levels. Estrogen could inhibit miR-19b-3p expression, but directly promoted MSMO1 transcription via estrogen receptor α (ERα) and indirectly regulated ELOVL5 expression at the transcription level. Meanwhile, estrogen could also upregulate MSMO1 and ELOVL5 expression through inhibiting miR-19b-3p expression at the post-transcription level. Taken together, these results highlight the role and regulatory mechanism of miR-19b-3p in hepatic lipid metabolism in chicken, and might produce useful comparative information for human obesity studies and biomedical research.

Comparative analyses of dynamic transcriptome profiles highlight key response genes and dominant isoforms for muscle development and growth in chicken.

BACKGROUND: Modern breeding strategies have resulted in significant differences in muscle mass between indigenous chicken and specialized broiler. However, the molecular regulatory mechanisms that underlie these differences remain elusive. The aim of this study was to identify key genes and regulatory mechanisms underlying differences in breast muscle development between indigenous chicken and specialized broiler. RESULTS: Two time-series RNA-sequencing profiles of breast muscles were generated from commercial Arbor Acres (AA) broiler (fast-growing) and Chinese indigenous Lushi blue-shelled-egg (LS) chicken (slow-growing) at embryonic days 10, 14, and 18, and post-hatching day 1 and weeks 1, 3, and 5. Principal component analysis of the transcriptome profiles showed that the top four principal components accounted for more than 80% of the total variance in each breed. The developmental axes between the AA and LS chicken overlapped at the embryonic stages but gradually separated at the adult stages. Integrative investigation of differentially-expressed transcripts contained in the top four principal components identified 44 genes that formed a molecular network associated with differences in breast muscle mass between the two breeds. In addition, alternative splicing analysis revealed that genes with multiple isoforms always had one dominant transcript that exhibited a significantly higher expression level than the others. Among the 44 genes, the TNFRSF6B gene, a mediator of signal transduction pathways and cell proliferation, harbored two alternative splicing isoforms, TNFRSF6B-X1 and TNFRSF6B-X2. TNFRSF6B-X1 was the dominant isoform in both breeds before the age of one week. A switching event of the dominant isoform occurred at one week of age, resulting in TNFRSF6B-X2 being the dominant isoform in AA broiler, whereas TNFRSF6B-X1 remained the dominant isoform in LS chicken. Gain-of-function assays demonstrated that both isoforms promoted the proliferation of chicken primary myoblasts, but only TNFRSF6B-X2 augmented the differentiation and intracellular protein content of chicken primary myoblasts. CONCLUSIONS: For the first time, we identified several key genes and dominant isoforms that may be responsible for differences in muscle mass between slow-growing indigenous chicken and fast-growing commercial broiler. These findings provide new insights into the regulatory mechanisms underlying breast muscle development in chicken.

Association between atherosclerosis and primary Sjogren's syndrome: A cross-sectional study.

Background and Aims: Atherosclerosis (AS) risk increases in patients with systemic autoimmune diseases. The association and mechanism between primary Sjogren's syndrome (pSS) and AS haven't been explained for now. We did this cross-sectional study to clarify the prevalence and risk factors of AS in patients with pSS, and to further explore how immune cells and inflammatory cytokines work in the process. Methods: Patients with pSS were enrolled. General information, AS events, immune cells, inflammatory cytokines, and related clinical data were recorded. Prevalence of AS events was calculated. Correlation analysis between immune factors and AS quantitative parameters were conducted by SPSS v20.0. Results: A total of 155 pSS patients were included with a median Framingham 10-year risk of 7%. Sixty-four AS events were recorded, with a prevalence of 41.3%. Carotid intima-media thickness was positively correlated to immunoglobulin (Ig) A (r = 0.245, p = 0.030) and negatively correlated to IgM (r = -0.227, p = 0.045). Left ankle-brachial pulse wave velocity (baPWV) was positively correlated to the course of disease (r = 0.352, p = 0.004), B cells (r = 0.410, p = 0.001), and T helper (Th) cells (r = 0.284, p = 0.029), while negatively correlated to IgM (r = -0.257, p = 0.042). Right baPWV was positively correlated to the course of pSS (r = 0.319, p = 0.010), B cells (r = 0.453, p < 0.001), Th cells (r = 0.302, p = 0.020), and C-reactive protein (CRP) (r = 0.286, p = 0.042). Use of hydroxychloroquine, cyclophosphamide, and glucocorticoids had no impact on AS events. Conclusion: The prevalence of AS in patients with pSS is reported to be 41.3%. Several risk factors have been associated with AS in these patients, including the duration of the disease, levels of Th cells, B lymphocytes, and CRP. Interestingly, IgM appears to have a protective effect against AS. It is worth noting that traditional therapy for pSS does not seem to have any effect in preventing AS events.

Untargeted Lipidomics Analysis Unravels the Different Metabolites in the Fat Body of Mated Bumblebee (Bombus terrestris) Queens.

The fat body has important functions in energy, fertility, and immunity. In female insects, mating stimulates physiological, behavioral, and gene expression changes. However, it remains unclear whether the metabolites in the fat body are affected after the bumblebee (Bombus terrestris) queen mates. Here, the ultrastructure and lipid metabolites in fat body of mated queens were compared with those of virgins. The fat body weight of mated bumblebee queens was significantly increased, and the adipocytes were filled with lipid droplets. Using LC-MS/MS-based untargeted lipidomics, 949 and 748 differential metabolites were identified in the fat body of virgin and mated bumblebee queens, respectively, in positive and negative ion modes. Most lipid metabolites were decreased, especially some biomembrane components. In order to explore the relationship between the structures of lipid droplets and metabolite accumulation, transmission electron microscopy and fluorescence microscopy were used to observe the fat body ultrastructure. The size/area of lipid droplets was larger, and the fusion of lipid droplets was increased in the mated queen's fat body. These enlarged lipid droplets may store more energy and nutrients. The observed differences in lipid metabolites in the fat body of queens contribute to understanding the regulatory network of bumblebees post mating.

LncHLEF promotes hepatic lipid synthesis through miR-2188-3p/GATA6 axis and encoding peptides and enhances intramuscular fat deposition via exosome.

Long noncoding RNAs (lncRNAs) have emergingly been implicated in mammalian lipid metabolism. However, their biological functions and regulatory mechanisms underlying adipogenesis remain largely elusive in chicken. Here, we systematically characterized the genome-wide full-length lncRNAs in the livers of pre- and peak-laying hens, and identified a novel intergenic lncRNA, lncHLEF, an RNA macromolecule with a calculated molecular weight of 433 kDa. lncHLEF was primarily distributed in cytoplasm of chicken hepatocyte and significantly up-regulated in livers of peak-laying hens. Functionally, lncHLEF could promote hepatocyte lipid droplet formation, triglycerides and total cholesterol contents. Mechanistically, lncHLEF could not only serve as a competitive endogenous RNA to modulate miR-2188-3p/GATA6 axis, but also encode three small functional polypeptides that directly interact with ACLY protein to enable its stabilization. Importantly, adeno-associated virus-mediated liver-specific lncHLEF overexpression resulted in increased hepatic lipid synthesis and intramuscular fat (IMF) deposition, but did not alter abdominal fat (AbF) deposition. Furthermore, hepatocyte lncHLEF could be delivered into intramuscular and abdominal preadipocytes via hepatocyte-secreted exosome to enhance intramuscular preadipocytes differentiation without altering abdominal preadipocytes differentiation. In conclusion, this study revealed that the lncHLEF could promote hepatic lipid synthesis through two independent regulatory mechanisms, and could enhance IMF deposition via hepatocyte-adipocyte communications mediated by exosome.

Unexpected worker mating and colony-founding in a superorganism.

The emergence of caste-differentiated colonies, which have been defined as 'superorganisms', in ants, bees, and wasps represents a major transition in evolution. Lifetime mating commitment by queens, pre-imaginal caste determination and lifetime unmatedness of workers are key features of these animal societies. Workers in superorganismal species like honey bees and many ants have consequently lost, or retain only vestigial spermathecal structures. However, bumble bee workers retain complete spermathecae despite 25-40 million years since their origin of superorganismality, which remains an evolutionary mystery. Here, we show (i) that bumble bee workers retain queen-like reproductive traits, being able to mate and produce colonies, underlain by queen-like gene expression, (ii) the social conditions required for worker mating, and (iii) that these abilities may be selected for by early queen-loss in these annual species. These results challenge the idea of lifetime worker unmatedness in superorganisms, and provide an exciting new tool for the conservation of endangered bumble bee species.

A semi-analytical model to estimate Chlorophyll-a spatial-temporal patterns from Orbita Hyperspectral image in inland eutrophic waters.

It can be challenging to accurately estimate the Chlorophyll-a (Chl-a) concentration in inland eutrophic lakes due to lakes' extremely complex optical properties. The Orbita Hyperspectral (OHS) satellite, with its high spatial resolution (10 m), high spectral resolution (2.5 nm), and high temporal resolution (2.5 d), has great potential for estimating the Chl-a concentration in inland eutrophic waters. However, the estimation capability and radiometric performance of OHS have received limited examination. In this study, we developed a new quasi-analytical algorithm (QAA716) for estimating Chl-a using OHS images. Based on the optical properties in Dianchi Lake, the ability of OHS to remotely estimate Chl-a was evaluated by comparing the signal-to-noise ratio (SNR) and the noise equivalent of Chl-a (NEChl-a). The main findings are as follows: (1) QAA716 achieved significantly better results than those of the other three QAA models, and the Chl-a estimation model, using QAA716, produced robust results with a mean absolute percentage difference (MAPD) of 11.54 %, which was better than existing Chl-a estimation models; (2) The FLAASH (Fast Line-of-sight Atmospheric Analysis of Spectral Hypercubes) atmospheric correction model (MAPD = 22.22 %) was more suitable for OHS image compared to the other three atmospheric correction models we tested; (3) OHS had relatively moderate SNR and NEChl-a, improving its ability to accurately detect Chl-a concentration and resulting in an average SNR of 59.47 and average NEChl-a of 72.86 µg/L; (4) The increased Chl-a concentration in Dianchi Lake was primarily related to the nutrients input, and this had a significant positive correlation with total nitrogen. These findings expand existing knowledge of the capabilities and limitations of OHS in remotely estimating Chl-a, thereby facilitating effective water quality management in eutrophic lake environments.

Integrated LC/MS-based lipidomics and transcriptomics analyses revealed lipid composition heterogeneity between pectoralis intramuscular fat and abdominal fat and its regulatory mechanism in chicken.

Intramuscular fat (IMF) content is conducive to multiple meat quality properties, while abdominal fat (AF) is treated as waste product in chicken industry. However, the heterogeneity and distinct regulatory mechanisms of lipid composition between the IMF and AF are still unclear. In this study, we carried out non-targeted lipidomics analyses of pectoralis IMF and AF, and detected a total of 423 differential lipid molecules (DLMs) between chicken IMF and AF, including 307 up-regulated and 116 down-regulated DLMs in pectoral IMF. These DLMs exhibited the definite alteration of lipid composition. The up-reglated DLMs in IMF were mainly glycerophospholipids (GPs), including the bulk of phosphatidylcholines (PC, PC (P) and PC (O)), phosphatidylethanolamines (PE, PE (P) and PE (O)), phosphatidylglycerols (PG) and phosphatidylinositol (PI), while the up-reglated DLMs in AF were mainly glycerolipids (GLs), including most of triacylglycerols (TG) and diacylglycerols (DG). We further identified 28 main DLMs contributing to the heterogeneous deposition of IMF and AF, including 11 TGs common to IMF and AF, 12 PCs/PC (P)s specific to IMF and 5 DGs specific to AF. Further integration of transcriptome with the main DLMs by weighted gene co-expression network analysis (WGCNA), we found five key gene sets that included 386 unique genes promoting IMF deposition in pectoralis, 213 unique genes promoting AF deposition, 6 unique genes detrimental to AF deposition, 7 common genes that promote IMF deposition in pectoralis while adversely affect AF deposition, and 28 genes that only promoted IMF deposition in pectoralis but had no effect on AF deposition. In addition, we also observed the expression characteristics of key genes in vivo and in vitro, and found that transmembrane protein family gene TMEM164 might be mainly involved in the positive regulation of intramuscular fat deposition in pectoralis and zinc finger protein family gene ZNF488 had a potential unique positive regulatory function on abdominal fat deposition. These findings provide new perspectives for understanding IMF and AF heterodeposition and will serve as a valuable information resource for improving meat quality via breeding selection in chicken.

Adiponectin inhibits GnRH secretion via activating AMPK and PI3K signaling pathways in chicken hypothalamic neuron cells.

It has been reported that adiponectin (AdipoQ), an adipokine secreted by white adipose tissue, plays an important role in the control of animal reproduction in addition to its function in energy homeostasis by binding to its receptors AdipoR1/2. However, the molecular mechanisms of AdipoQ in the regulation of animal reproduction remain elusive. In this study, we investigated the effects of AdipoQ on hypothalamic reproductive hormone (GnRH) secretion and reproduction-related receptor gene (estrogen receptor [ER] and progesterone receptor [PR]) expression in hypothalamic neuronal cells (HNCs) of chickens by using real-time fluorescent quantitative PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), Western blot (WB) and cell counting kit-8 (CCK-8) assays and found that overexpression of AdipoQ could increase the expression levels of AdipoR1/2 and reproduction-related receptor genes (P < 0.05) while decreasing the expression level of GnRH. In contrast, interference with AdipoQ mRNA showed the opposite results in HNCs. Furthermore, we demonstrated that AdipoQ exerts its functions through the AMPK and PI3K signaling pathways. Finally, our in vitro experiments found that AdipoRon (a synthetic substitute for AdipoQ) treatment and AdipoR1/2 RNAi interference co-treatment resulted in no effect on GnRH secretion, suggesting that the inhibition of GnRH secretion by AdipoQ is mediated by the AdipoR1/2 signaling axis. In summary, we uncovered, for the first time, the molecular mechanism of AdipoQ in the regulation of reproductive hormone secretion in hypothalamic neurons in chickens.

Potential role of the gut microbiota of bumblebee Bombus pyrosoma in adaptation to high-altitude habitats.

The gut microbiota affects the health and overall fitness of bumblebees. It can enhance the host's ecological range by leveraging their metabolic capacities. However, the diversity of the gut microbiota and adaptive functional evolution in high-altitude regions remain unclear. To explore how the gut microbiota helps the host adapt to high-altitude environments, we analyzed the differences in diversity and function of the gut microbiota between high- and low-altitude regions through full-length 16S rRNA sequencing. Our results show that high-altitude regions have a lower abundance of Fructobacillus and Saccharibacter compared to low-altitude regions. Additionally, some individuals in low-altitude regions were invaded by opportunistic pathogens. The gut microbiota in high-altitude regions has a greater number of pathways involved in "Protein digestion and absorption" and "Biosynthesis of amino acids," while fewer carbohydrate pathways are involved in "digestion and absorption" and "Salmonella infection." Our finding suggests that plateau hosts typically reduce energy metabolism and enhance immunity in response to adverse environments. Correspondingly, the gut microbiota also makes changes, such as reducing carbohydrate degradation and increasing protein utilization in response to the host. Additionally, the gut microbiota regulates their abundance and function to help the host adapt to adverse high-altitude environments.

NosP Detection of Heme Modulates Burkholderia thailandensis Biofilm Formation.

Aggregated bacteria embedded within self-secreted extracellular polymeric substances, or biofilms, are resistant to antibiotics and cause chronic infections. As such, they are a significant public health threat. Heme is an abundant iron source for pathogenic bacteria during infection; many bacteria have systems to detect heme assimilated from host cells, which is correlated with the transition between acute and chronic infection states. Here, we investigate the heme-sensing function of a newly discovered multifactorial sensory hemoprotein called NosP and its role in biofilm regulation in the soil-dwelling bacterium Burkholderia thailandensis, the close surrogate of Bio-Safety-Level-3 pathogen Burkholderia pseudomallei. The NosP family protein has previously been shown to exhibit both nitric oxide (NO)- and heme-sensing functions and to regulate biofilms through NosP-associated histidine kinases and two-component systems. Our in vitro studies suggest that BtNosP exhibits heme-binding kinetics and thermodynamics consistent with a labile heme-responsive protein and that the holo-form of BtNosP acts as an inhibitor of its associated histidine kinase BtNahK. Furthermore, our in vivo studies suggest that increasing the concentration of extracellular heme decreases B. thailandensis biofilm formation, and deletion of nosP and nahK abolishes this phenotype, consistent with a model that BtNosP detects heme and exerts an inhibitory effect on BtNahK to decrease the biofilm.

Divergence and convergence of gut microbiomes of wild insect pollinators.

Pollination services provided by wild insect pollinators are critical to natural ecosystems and crops around the world. There is an increasing appreciation that the gut microbiota of these insects influences their health and consequently their services. However, pollinator gut microbiota studies have focused on well-described social bees, but rarely include other, more phylogenetically divergent insect pollinators. To expand our understanding, we explored the insect pollinator microbiomes across three insect orders through two DNA sequencing approaches. First, in an exploratory 16S amplicon sequencing analysis of taxonomic community assemblages, we found lineage-specific divergences of dominant microbial genera and microbiota community composition across divergent insect pollinator genera. However, we found no evidence for a strong broad-scale phylogenetic signal, which we see for community relatedness at finer scales. Subsequently, we utilized metagenomic shotgun sequencing to obtain metagenome-assembled genomes and assess the functionality of the microbiota from pollinating flies and social wasps. We uncover a novel gut microbe from pollinating flies in the family Orbaceae that is closely related to Gilliamella spp. from social bees but with divergent functions. We propose this novel species be named Candidatus Gilliamella eristali. Further metagenomes of dominant fly and wasp microbiome members suggest that they are largely not host-insect adapted and instead may be environmentally derived. Overall, this study suggests selective processes involving ecology or physiology, or neutral processes determining microbe colonization may predominate in the turnover of lineages in insect pollinators broadly, while evolution with hosts may occur only under certain circumstances and on smaller phylogenetic scales. IMPORTANCE Wild insect pollinators provide many key ecosystem services, and the microbes associated with these insect pollinators may influence their health. Therefore, understanding the diversity in microbiota structure and function, along with the potential mechanisms shaping the microbiota across diverse insect pollinators, is critical. Our study expands beyond existing knowledge of well-studied social bees, like honey bees, including members from other bee, wasp, butterfly, and fly pollinators. We infer ecological and evolutionary factors that may influence microbiome structure across diverse insect pollinator hosts and the functions that microbiota members may play. We highlight significant differentiation of microbiomes among diverse pollinators. Closer analysis suggests that dominant members may show varying levels of host association and functions, even in a comparison of closely related microbes found in bees and flies. This work suggests varied importance of ecological, physiological, and non-evolutionary filters in determining structure and function across largely divergent wild insect pollinator microbiomes.

Hypertrophic cardiomyopathy caused by a heterozygous variant in TTR gene: A case report.

RATIONALE: We report a rare case of hypertrophic cardiomyopathy (HCM) caused by a heterozygous variant in TTR gene. PATIENT CONCERNS: The proband had been vomiting without obvious inducement since the age of 27, accompanied by the expulsion of stomach contents. At the age of 28, she began to suddenly syncope. DIAGNOSIS: Cardiac magnetic resonance showed thickening of the right ventricular lateral wall and ventricular septum. The left ventricular diastolic function was limited. Targeted Sanger sequencing validates the presence of mutation p.Leu75Pro in TTR gene. INTERVENTIONS AND OUTCOMES: After admission to hospital for syncope, she was given metoprolol tablets 25 mg bid, spironolactone tablets 20 mg qd, and trimetazidine 20 mg tid. Her symptoms improved after taking the medicine. LESSONS: The results of this case show that HCM caused by TTR mutation is not easy to be identified and treatment is easy to be delayed. Therefore, high-risk patients with amyloidosis should be evaluated as soon as possible. Timely diagnosis of HCM caused by TTR mutation before irreversible organ damage is essential for proper treatment and better outcomes.

An Observational Study: Clinical Manifestations and Prognosis of Left Atrial Thrombosis in Atrial Fibrillation.

We did this study to find out the clinical manifestations and prognosis of left atrial thrombosis in different types of atrial fibrillation and the relationship with systemic thromboembolism, hoping to find a better therapy strategy. A single-center retrospective study enrolled patients with definite diagnosis of atrial fibrillation complicated with left atrial thrombosis. Data of general clinical information, anticoagulation medications, thromboembolism events, and thrombosis prognosis were recorded and analyzed. A total of 103 patients were enrolled. Compared with non-valvular atrial fibrillation (NVAF), thrombosis outside the left atrial appendage (LAA) was much more common in valvular atrial fibrillation (VAF) with p=0.003. Total prevalence of systemic thromboembolism was 33.0%. Thrombi disappeared in 78 cases (75.7%) under anticoagulation treatment within 2 years. There was no significant difference between warfarin, dabigatran, and rivaroxaban on thromboembolism events and thrombosis prognosis in NVAF, with p=0.740 and 0.493, respectively. Atrial fibrillation patients with LA thrombosis have a high risk of systemic thromboembolism events. Compared with NVAF, patients with VAF had higher incidence of thrombosis outside the LAA. Standard stroke-preventing doses of anticoagulants might not be sufficient to deplete all LA thrombi. There was no statistically difference between warfarin, dabigatran, and rivaroxaban for depleting LA thrombi in NVAF patients.

Prevalence, predictors and management of left atrial appendage thrombogenic milieu in atrial fibrillation with low thromboembolic risk.

BACKGROUND: The present study aimed to investigate the prevalence, predictors, and management of left atrial appendage (LAA) thrombogenic milieu (TM) identified with transesophageal echocardiography (TEE) in non-valvular atrial fibrillation (NVAF) patients with low to moderate thromboembolic (TE) risk. METHODS: We retrospectively analyzed the baseline clinical data and TEE findings in 391 NVAF patients (54.7 ± 8.9 years, 69.1% male) with low to moderate TE risk according to the CHA2DS2-VASc score. LAA TM was defined as LAA thrombus (LAAT), sludge or spontaneous echo contrast (SEC). Management of LAA TM was at the discretion of the treating physician. RESULTS: A total of 43 patients (11.0%) were detected with LAA TM, including 5 with LAAT (11.6%), 4 with LAAT + Sect. (9.3%), 3 with sludge (7.0%), and 31 with Sect. (72.1%). In multivariate model, non-paroxysmal AF (OR 3.121; 95% CI 1.205-8.083, p = 0.019), and a larger left atrial diameter (LAD) (OR 1.134; 95% CI 1.060-1.213, p < 0.001) were significantly associated with the presence of LAA TM. All LAATs or sludges effectively resolved after mean duration of 117.5 ± 20.0 days for oral anticoagulant (OAC) medication. TE events occurred in 3 patients (18.8%) among those discontinuing OAC over a mean follow-up of 26.2 ± 8.8 months, while no TE events occurred in patients with continuous OAC. CONCLUSIONS: LAA TM could be identified in 11.0% in NVAF patients with low to moderate TE risk, especially in those with non-paroxysmal AF and enlarged LAD. Short-term OAC medication could effectively resolve the LAAT or sludge.

Evolutionary analysis and functional characterization reveal the role of the insulin-like growth factor system in a diversified selection of chickens (Gallus gallus).

The insulin-like growth factor (IGF) system plays an indispensable role in embryonic and postnatal development in mammals. However, the effects of the system on growth, carcass, and egg-laying traits, and diversified selection have not been systematically studied in chickens. In the present study, firstly the composition and gene structures of the chicken IGF system were investigated using phylogenetic tree and conserved synteny analysis. Then the effects of the genetic variations in the IGF system genes on breeding of specialized varieties were explored by principal component analysis. In addition, the spatiotemporal expression properties of the genes in this system were analyzed by RT-qPCR and the functions of the genes in egg production performance and growth were explored by association study. Moreover, the effects of IGF-binding proteins 3 (IGFBP3) on skeletal muscle development in chicken were investigated by cell cycle analysis, 5-ethynyl-2'-deoxyuridine (EdU) and Cell Counting Kit-8 (CCK-8) assays. The results showed that the chicken IGF system included 13 members which could be classified into 3 groups based on their amino acid sequences: IGF binding proteins 1 to 5 and 7 (IGFBP1-5 and 7) belonged to the first group; IGF 1 and 2 (IGF1 and IGF2), and IGF 1 and 2 receptor (IGF1R and IGF2R) belonged to the second group; and IGF2 binding proteins 1-3 (IGF2BP1-3) belonged to the third group. The IGF2BP1 and 3, and IGFBP2, 3, and 7 genes likely contributed more to the formation of both the specialized meat-type and egg-type lines, whereas IGFBP1 and 5 likely contributed more to the formation of the egg-type lines. The SNPs in the IGF2BP3 and IGFBP2 and 5 genes were significantly associated with egg number, and SNPs in the IGFBP3 promoter region were significantly associated with body weight, breast muscle weight and leg muscle weight. The IGFBP3 inhibited proliferation but promoted differentiation of chicken primary myoblasts (CPMs). These results provide insights into the roles of the IGF system in the diversified selection of chickens. The SNPs associated with egg-laying performance, growth, and carcass traits could be used as genetic markers for breeding selection of chickens in the future.