Search

Objective: The ayu or sweetfish Plecoglossus altivelis is ray-finned fish that is widely distributed in East Asia. The genome size of ayu was estimated at approximately 420 Mb. Previously, we reported on ayu draft genome assembly by whole-genome shotgun using Illumina short reads and PacBio long reads; however, the assembly was not to chromosome level. Therefore, to improve the draft genome sequence of ayu to chromosome level, we performed in situ Hi-C sequencing as a source of linkage information., Results: The ayu genome assembly yielded 28 large scaffolds that corresponded to the karyotype of ayu (n = 28). The resulting ayu genome assembly has a N50 scaffold length of 17.0 Mb, improved from 4.3 Mb. The high-quality reference genome will be helpful for phylogenetic research on bony fishes and for breeding programs in ayu aquaculture., (© 2023. The Author(s).)

Background: Phosphaturic mesenchymal tumors (PMTs) are rare neoplasms that are often associated with tumor-induced osteomalacia (TIO) due to excessive serum levels of fibroblast growth factor 23 (FGF23). PMTs share overlapping histologic features with other types of tumors; thus, accurate pathological diagnosis may be challenging. We performed an immunohistochemical examination of FGF23 expression in PMTs and other types of tumors, together with pertinent molecular analyses., Methods: Seven PMTs (5 with TIO and 2 without TIO) and 46 other types of bone and soft tissue tumors were retrieved, and immunohistochemistry was performed using a commercially available anti-FGF23 antibody. In addition, FGF23 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR), using RNA extracted from formalin-fixed, paraffin-embedded tissues., Results: Immunohistochemical analysis of FGF23 expression showed distinct, punctate staining in the cytoplasm in 5 PMTs with TIO, whereas FGF23 expression was negative in the 2 PMTs without TIO and the other 46 tumors. FGF23 mRNA expression was detected in all 4 PMTs examined, as well as in 1 chondromyxoid fibroma and 1 myxoid liposarcoma. The real-time RT-PCR data showed that the relative expression levels of the FGF23 mRNA tended to be higher in PMTs with TIO than in PMTs without TIO, or in the chondromyxoid fibroma specimen., Conclusions: Our data suggested that the feasibility of immunohistochemical detection of FGF23 may depend on the level of secreted FGF23 from tumor cells. Thus, immunohistochemistry for FGF23 is an useful diagnostic adjunct for PMT, although its utility appears to be limited in cases without TIO.

Background: For renal hilar angiomyolipoma, general surgical resection is often quite challenging. The aim of this study is to evaluate the safety and efficacy of an innovative robot-assisted laparoscopic strategy that combines tumor enucleation with tumor aspiration in the treatment of renal hilar angiomyolipoma. Methods: The clinical data of 38 patients with renal hilar angiomyolipoma who went through robotic tumor enucleation combined with tumor aspiration in the Department of Urology, the Affiliated Hospital of Nanjing University Medical School, from December 2019 to December 2022 were retrospectively analyzed. The basic characteristics, the perioperative variables, intraoperative procedures, and postoperative complications were all recorded. Patients were followed up to evaluate the angiomyolipoma recurrence and the renal function by urologic CT or ultrasound and renal function tests. Results: All surgeries were successfully completed without conversion to radical nephrectomy or open surgery. One patient developed urinary extravasation 10 days after surgery, and was readmitted to the hospital for transurethral ureteral stenting considering the injury of the renal collecting system. The median operative time was 181.5 (123.8-206.3) min, the warm ischemia time was 20.0 (17.3–24.0) min, the blood loss was 125 (100.0-262.5) ml, and no patients received blood transfusion during and after surgery. The median hospitalization time was 7.0 (6.0–9.0) days, and the duration of indwelling drainage tube was 2.0 (2.0–3.0) days. The serum creatinine (Scr) on the first day, 3 months, and 6 months after surgery were 55.5 (50.8–62.8) µmol/L, 55.5 (48.0–62.0) µmol/L and 54.0 (51.8–63.5) µmol/L, respectively, and there was no significant difference compared with the preoperative level 56.0 (47.8–60.3) µmol/L. All patients were followed up after surgery, and the urinary CT scan or renal color doppler ultrasound, and renal function were reexamined. The median follow-up time of all patients was 19.0 (14.75-33.0) months, and no local recurrence of angiomyolipoma was seen in all patients. Conclusions: The surgical strategy of robot-assisted laparoscopic tumor enucleation combined with tumor aspiration is safe and effective in the treatment of renal hilar angiomyolipoma. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported that periderm (the outer ectodermal layer) in zebrafish partially expands into the mouth and pharyngeal pouches, but does not reach the medial endoderm, where the pharyngeal teeth develop. Instead, periderm-like cells, arising independently from the outer periderm, cover prospective tooth-forming epithelia and are crucial for tooth germ initiation. Here we test the hypothesis that restricted expansion of periderm is a teleost-specific character possibly related to the derived way of early embryonic development. To this end, we performed lineage tracing of the periderm in a non-teleost actinopterygian species possessing pharyngeal teeth, the sterlet sturgeon (Acipenser ruthenus), and a sarcopterygian species lacking pharyngeal teeth, the axolotl (Ambystoma mexicanum). Results: In sturgeon, a stratified ectoderm is firmly established at the end of gastrulation, with minimally a basal ectodermal layer and a surface layer that can be homologized to a periderm. Periderm expands to a limited extent into the mouth and remains restricted to the distal parts of the pouches. It does not reach the medial pharyngeal endoderm, where pharyngeal teeth are located. Thus, periderm in sturgeon covers prospective odontogenic epithelium in the jaw region (oral teeth) but not in the pharyngeal region. In axolotl, like in sturgeon, periderm expansion in the oropharynx is restricted to the distal parts of the opening pouches. Oral teeth in axolotl develop long before mouth opening and possible expansion of the periderm into the mouth cavity. Conclusions: Restricted periderm expansion into the oropharynx appears to be an ancestral feature for osteichthyans, as it is found in sturgeon, zebrafish and axolotl. Periderm behavior does not correlate with presence or absence of oral or pharyngeal teeth, whose induction may depend on 'ectodermalized' endoderm. It is proposed that periderm assists in lumenization of the pouches to create an open gill slit. Comparison of basal and advanced actinopterygians with sarcopterygians (axolotl) shows that different trajectories of embryonic development converge on similar dynamics of the periderm: a restricted expansion into the mouth and prospective gill slits. [ABSTRACT FROM AUTHOR]

Background: Human T-cell leukemia virus type 1 (HTLV-1) is a well-known retrovirus, particularly prevalent in northeastern Iran, where it is associated with a range of disorders, including liver dysfunction. Previous studies have demonstrated that HTLV-1 infection can alter lipid profiles, yet no research has examined lipid indices and liver function tests in these patients in the long term. Methods: This data is part of the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study. A total of 1116 participants were randomly selected, including 837 healthy individuals and 279 HTLV-1-infected patients. Following a 10-year follow-up period, Serum levels of liver enzymes were measured. Lipid indices such as the Atherogenic Index of Plasma (AIP), Body Adiposity Index (BAC), Castelli risk index (CRI-I, CRI-II), Lipid Accumulation Product (LAP), Visceral Adiposity Index (VAI), Triglyceride-glucose index (TyG), and Triglyceride and HDL-C Ratio (THR) were calculated. Results: Multivariable-adjusted regression analysis demonstrated a significant coefficient for the Visceral Adiposity Index (VAI) in HTLV-infected patients compared to healthy controls (B: -0.014, 95% CI: -0.02, 0.00, p = 0.046). However, no significant differences were observed in other lipid indices between HTLV-infected patients and healthy individuals. Regarding liver enzymes, significant variations were noted in HTLV-infected patients compared to healthy controls: Aspartate Aminotransferase (AST) (B: 2.978, 95% CI: 1.34, 4.61, p < 0.001), Alanine Aminotransferase (ALT) (B: 3.687, 95% CI: 1.59, 5.78, p = 0.001), Alkaline Phosphatase (ALP) (B: 18.232, 95% CI: 6.81, 29.65, p = 0.002), and Gamma-Glutamyl Transferase (GGT) (B: 3.714, 95% CI: 0.18, 7.24, p = 0.039). Conclusion: Individuals with HTLV-1 infection exhibit reduced VAI but elevated levels of liver enzymes such as AST, ALT, ALP, and GGT, indicating liver damage. These findings emphasize the virus's involvement in liver pathology. Also, HTLV-I is associated with reduced visceral fat tissue. [ABSTRACT FROM AUTHOR]

Introduction: The occurrence of cytomegalovirus colitis is well known in immunosuppressed patients, such as neoplastic patients following chemotherapy, although its exact etiology remains unclear., Case Presentation: We present a case of cytomegalovirus colitis occurring in a 77-year-old man with vomiting and diarrhea 2 weeks after initial systemic chemotherapy consisting of 5-fluorouracil, leucovorin and irinotecan for a recurrent colorectal cancer. Initial colonoscopy revealed multiple punched-out ulcers in the transverse colon and the diagnosis of cytomegalovirus was based on positive cytomegalovirus antigen detected by indirect enzyme antibody method, although immunohistological examination of tissues biopsied at colonoscopy was negative. The symptoms ceased under ganciclovir and octreotide treatment, and the patient recovered gradually., Conclusion: The most probable cause of the cytomegalovirus colitis in this case was impaired immunity following chemotherapy. Cytomegalovirus infection should be included in the differential diagnosis of gastrointestinal disease in colorectal cancer patients after chemotherapy and, when suspected, the clinician should pursue appropriate diagnostic interventions including colonoscopy.

Background: Gills monogenean infestation causes significant mortalities in cultured fishes as a result of respiratory manifestation. Medicinal plants are currently being heavily emphasized in aquaculture due to their great nutritional, therapeutic, antimicrobial activities, and financial value. Methods: The current study is designed to assess the effect of garlic (Allium sativum) and onion (Allium cepa) extracts as a water treatment on the hematological profile, innate immunity, and immune cytokines expression besides histopathological features of gills of Nile tilapia (Oreochromis niloticus L.) infected with gills monogenetic trematodes (Dactylogyrus sp.). Firstly, the 96-hour lethal concentration 50 (96 h-LC50) of garlic extract (GE) and onion extract (OE) were estimated to be 0.4 g/ L and 3.54 g/ L for GE and OE, respectively. Moreover, the in-vitro anti-parasitic potential for (GE) was found between 0.02 and 0.18 mg/mL and 0.4 to 1.8 mg/mL for OE. For the therapeutic trial, fish (n = 120; body weight: 40–60 g) were randomly distributed into four groups in triplicates (30 fish/group, 10 fish/replicate) for 3 days. Group1 (G1) was not infected or treated and served as control. G2 was infected with Dactylogyrus spp. and not exposed to any treatment. G3, G4 were infected with Dactylogyrus sp. and treated with 1/10 and 1/5 of 96 h LC50 of OE, respectively. G5, G6 were infected with Dactylogyrus sp. and treated with 1/10 and 1/5 of 96 h LC50 of GE, respectively. Results: No apparent signs or behaviors were noted in the control group. Dactylogyrus spp. infected group suffered from clinical signs as Pale color and damaged tissue. Dactylogyrus spp. infection induced lowering of the hematological (HB, MCH, MCHC and WBCs), and immunological variables (lysozyme, nitric oxide, serum Anti- protease activities, and complement 3). the expression of cytokine genes IL-ß and TNF-α were modulated and improved by treatment with A. sativum and A. cepa extracts. The obtained histopathological alterations of the gills of fish infected with (Dactylogyrus spp.) were hyperplasia leading to fusion of the gill filament, lifting of epithelial tissue, aneurism and edema. The results indecated that G4 and G5 is more regenarated epithelium in compare with the control group. Conclusion: A. sativum and A. cepa extracts enhance the blood profile and nonspecific immune parameters, and down-regulated the expression level of (IL-1β and TNF-α). [ABSTRACT FROM AUTHOR]

Background: Macrophages play important roles in phagocytosing tumor cells. However, tumors escape macrophage phagocytosis in part through the expression of anti-phagocytic signals, most commonly CD47. In Ewing sarcoma (ES), we found that tumor cells utilize dual mechanisms to evade macrophage clearance by simultaneously over-expressing CD47 and down-regulating cell surface calreticulin (csCRT), the pro-phagocytic signal. Here, we investigate the combination of a CD47 blockade (magrolimab, MAG) to inhibit the anti-phagocytic signal and a chemotherapy regimen (doxorubicin, DOX) to enhance the pro-phagocytic signal to induce macrophage phagocytosis of ES cells in vitro and inhibit tumor growth and metastasis in vivo. Methods: Macrophages were derived from human peripheral blood monocytes by granulocyte–macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). Flow cytometry- and microscopy-based in-vitro phagocytosis assays were performed to evaluate macrophage phagocytosis of ES cells. Annexin-V assay was performed to evaluate apoptosis. CD47 was knocked out by CRISPR/Cas9 approach. ES cell-based and patient-derived-xenograft (PDX)-based mouse models were utilized to assess the effects of MAG and/or DOX on ES tumor development and animal survival. RNA-Seq combined with CIBERSORTx analysis was utilized to identify changes in tumor cell transcriptome and tumor infiltrating immune cell profiling in MAG and/or DOX treated xenograft tumors. Results: We found that MAG significantly increased macrophage phagocytosis of ES cells in vitro (p < 0.01) and had significant effect on reducing tumor burden (p < 0.01) and increasing survival in NSG mouse model (p < 0.001). The csCRT level on ES cells was significantly enhanced by DOX in a dose- and time-dependent manner (p < 0.01). Importantly, DOX combined with MAG significantly enhanced macrophage phagocytosis of ES cells in vitro (p < 0.01) and significantly decreased tumor burden (p < 0.01) and lung metastasis (p < 0.0001) and extended animal survival in vivo in two different mouse models of ES (p < 0.0001). Furthermore, we identified CD38, CD209, CD163 and CD206 as potential markers for ES-phagocytic macrophages. Moreover, we found increased M2 macrophage infiltration and decreased expression of Cd209 in the tumor microenvironment of MAG and DOX combinatorial therapy treated tumors. Conclusions: By turning "two keys" simultaneously to reactivate macrophage phagocytic activity, our data demonstrated an effective and highly translatable alternative therapeutic approach utilizing innate (tumor associated macrophages) immunotherapy against high-risk metastatic ES. [ABSTRACT FROM AUTHOR]

Background: The Percidae family comprises many fish species of major importance for aquaculture and fisheries. Based on three new chromosome-scale assemblies in Perca fluviatilis, Perca schrenkii, and Sander vitreus along with additional percid fish reference genomes, we provide an evolutionary and comparative genomic analysis of their sex-determination systems. Results: We explored the fate of a duplicated anti-Mullerian hormone receptor type-2 gene (amhr2bY), previously suggested to be the master sex-determining (MSD) gene in P. flavescens. Phylogenetically related and structurally similar amhr2 duplicates (amhr2b) were found in P. schrenkii and Sander lucioperca, potentially dating this duplication event to their last common ancestor around 19–27 Mya. In P. fluviatilis and S. vitreus, this amhr2b duplicate has been likely lost while it was subject to amplification in S. lucioperca. Analyses of the amhr2b locus in P. schrenkii suggest that this duplication could be also male-specific as it is in P. flavescens. In P. fluviatilis, a relatively small (100 kb) non-recombinant sex-determining region (SDR) was characterized on chromosome 18 using population-genomics approaches. This SDR is characterized by many male-specific single-nucleotide variations (SNVs) and no large duplication/insertion event, suggesting that P. fluviatilis has a male heterogametic sex-determination system (XX/XY), generated by allelic diversification. This SDR contains six annotated genes, including three (c18h1orf198, hsdl1, tbc1d32) with higher expression in the testis than in the ovary. Conclusions: Together, our results provide a new example of the highly dynamic sex chromosome turnover in teleosts and provide new genomic resources for Percidae, including sex-genotyping tools for all three known Perca species. [ABSTRACT FROM AUTHOR]

Eph receptors constitute the largest family of receptor tyrosine kinases, comprising 14 distinct members classified into two subgroups: EphAs and EphBs.. Despite their essential functions in normal physiological processes, accumulating evidence suggests that the involvement of the Eph family in cancer is characterized by a dual and often contradictory nature. Research indicates that Eph/ephrin bidirectional signaling influences cell–cell communication, subsequently regulating cell migration, adhesion, differentiation and proliferation. The contradictory functionalities may arise from the diversity of Eph signaling pathways and the heterogeneity of different cancer microenvironment. In this review, we aim to discuss the dual role of the Eph receptors in tumor development, attempting to elucidate the paradoxical functionality through an exploration of Eph receptor signaling pathways, angiogenesis, immune responses, and more. Our objective is to provide a comprehensive understanding of the molecular mechanisms underlying tumor development. Additionally, we will explore the evolving landscape of utilizing Eph receptors as potential targets for tumor therapy and diagnostic tools. [ABSTRACT FROM AUTHOR]

Introduction: The diagnosis of intestinal tuberculosis is challenging even nowadays. This study aims to report the positivity rates of new diagnostic methods such as immunohistochemistry and Real-Time Polymerase Chain Reaction in patients with intestinal tuberculosis, as well as describe the pathological and endoscopic features of intestinal tuberculosis in our population. Methods: This was a retrospective observational study conducted in patients diagnosed with intestinal tuberculosis, between 2010 to 2023 from the Hospital Nacional Daniel Alcides Carrion and a Private Pathology Center, both located in Peru. Clinical data was obtained, histologic features were independently re-evaluated by three pathologists; and immunohistochemistry and real-time Polymerase Chain Reaction evaluation were performed. The 33 patients with intestinal tuberculosis who fulfilled the inclusion criteria were recruited. Results: Immunohistochemistry was positive in 90.9% of cases, while real-time Polymerase Chain Reaction was positive in 38.7%. The ileocecal region was the most affected area (33.3%), and the most frequent endoscopic appearance was an ulcer (63.6%). Most of the granulomas were composed solely of epithelioid histiocytes (75.8%). Crypt architectural disarray was the second most frequent histologic finding (78.8%) after granulomas, but most of them were mild. Conclusion: Since immunohistochemistry does not require an intact cell wall, it demonstrates higher sensitivity compared to Ziehl–Neelsen staining. Therefore, it could be helpful for the diagnosis of paucibacillary tuberculosis. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome is a cluster of metabolic disorders increasing the risk of cardiovascular disease and diabetes. Dietary patterns are supposed to be important and controllable factors in developing metabolic syndrome. The purpose of this study was to investigate the association of dietary patterns with metabolic syndrome and its components. Subjects/Methods: Cross-sectional data were extracted from the Bandare-Kong cohort study conducted on 4063 people aged 35 to 70. Dietary patterns were extracted using principal component analysis based on thirty-eight pre-defined food groups. Multivariable logistic regression was conducted to investigate the association between metabolic syndrome and its components with quintiles of dietary patterns in crude and adjusted models. Results: Three major dietary patterns were identified (healthy, western, and traditional) in the final analysis of 2823 eligible individuals. After adjusting for covariates, the odds of metabolic syndrome were significantly decreased by 46% in subjects with the highest adherence to the healthy dietary pattern compared to those with the lowest adherence quintile. Results from fully adjusted models on individual metabolic syndrome components showed an inverse association between higher adherence to the healthy dietary pattern and the odds of increased blood glucose, high waist circumference, and elevated blood pressure. However, in fully adjusted models, no significant association was observed between the western and traditional dietary patterns with odds of metabolic syndrome and its components. Conclusions: Adherence to a healthy dietary pattern containing high amounts of fruits, vegetables, nuts, low-fat dairy products, and legumes, could be recommended to prevent and control metabolic syndrome. [ABSTRACT FROM AUTHOR]

Black flounder (Paralichthys orbignyanus, Pleuronectiformes) is a commercially significant marine fish with promising aquaculture potential in Argentina. Despite extensive studies on Black flounder aquaculture, its limited genetic information available hampers the crucial role genetics plays in the development of this activity. In this study, we first employed Illumina sequencing technology to sequence the entire genome of Black flounder. Utilizing two independent libraries—one from a female and another from a male—with 150 bp paired-end reads, a mean insert length of 350 bp, and over 35 X-fold coverage, we achieved assemblies resulting in a genome size of ~ 538 Mbp. Analysis of the assemblies revealed that more than 98% of the core genes were present, with more than 78% of them having more than 50% coverage. This indicates a somehow complete and accurate genome at the coding sequence level. This genome contains 25,231 protein-coding genes, 445 tRNAs, 3 rRNAs, and more than 1,500 non-coding RNAs of other types. Black flounder, along with pufferfishes, seahorses, pipefishes, and anabantid fish, displays a smaller genome compared to most other teleost groups. In vertebrates, the number of transposable elements (TEs) is often correlated with genome size. However, it remains unclear whether the sizes of introns and exons also play a role in determining genome size. Hence, to elucidate the potential factors contributing to this reduced genome size, we conducted a comparative genomic analysis between Black flounder and other teleost orders to determine if the small genomic size could be explained by repetitive elements or gene features, including the whole genome genes and introns sizes. We show that the smaller genome size of flounders can be attributed to several factors, including changes in the number of repetitive elements, and decreased gene size, particularly due to lower amount of very large and small introns. Thus, these components appear to be involved in the genome reduction in Black flounder. Despite these insights, the full implications and potential benefits of genome reduction in Black flounder for reproduction and aquaculture remain incompletely understood, necessitating further research. [ABSTRACT FROM AUTHOR]

Breast cancer is significantly influenced by endoplasmic reticulum (ER) stress, impacting both its initiation and progression. When cells experience an accumulation of misfolded or unfolded proteins, they activate the unfolded protein response (UPR) to restore cellular balance. In breast cancer, the UPR is frequently triggered due to challenging conditions within tumors. The UPR has a dual impact on breast cancer. On one hand, it can contribute to tumor growth by enhancing cell survival and resistance to programmed cell death in unfavorable environments. On the other hand, prolonged and severe ER stress can trigger cell death mechanisms, limiting tumor progression. Furthermore, ER stress has been linked to the regulation of non-coding RNAs (ncRNAs) in breast cancer cells. These ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play essential roles in cancer development by influencing gene expression and cellular processes. An improved understanding of how ER stress and ncRNAs interact in breast cancer can potentially lead to new treatment approaches. Modifying specific ncRNAs involved in the ER stress response might interfere with cancer cell survival and induce cell death. Additionally, focusing on UPR-associated proteins that interact with ncRNAs could offer novel therapeutic possibilities. Therefore, this review provides a concise overview of the interconnection between ER stress and ncRNAs in breast cancer, elucidating the nuanced effects of the UPR on cell fate and emphasizing the regulatory roles of ncRNAs in breast cancer progression. [ABSTRACT FROM AUTHOR]

Background: Dietary diversity is an indicator of nutrient intake among the elderly. Previous researches have primarily examined dietary diversity and the risks with chronic and infectious disease and cognitive impairment, limited evidence shows the association between dietary diversity and the overall health status of specific populations with a heterogeneity analysis. This study aimed to probe the effects of dietary diversity on health status among Chinese older adults. Methods: There were 5740 sample participants aged 65 and above selected from the Chinese Longitudinal Healthy Longevity Survey, among which 3334 samples in 2018 wave and 2406 samples in 2011 wave. Dietary diversity was assessed by Dietary Diversity Score ranged from 0 to 9, the higher the score, the better dietary diversity. Health status was assessed into healthy, impaired and dysfunctional state by three indicators: Activities of Daily Living, Instrument Activities of Daily Living and Mini-Mental State Examination. Multinomial logistic regression was employed to assess the effects of dietary diversity on the health status among the elderly. Heterogeneity analysis between different groups by age was further discussed. Results: Older adults with better dietary diversity are in better health status, the mean dietary diversity score for healthy group was higher than that of impaired and dysfunctional groups (In 2018 wave, the scores were 6.54, 6.26 and 5.92, respectively; and in 2011 wave, they were 6.38, 5.93 and 5.71, respectively). Heterogeneity analysis shows that the younger groups tend to have more diversified dietary and be in better health status. Dietary diversity was more significantly associated with health status of the younger elderly (OR, 1.22, 95% CI, 1.04–1.44, p < 0.05) than the older elderly (OR, 1.01, 95% CI, 0.37–2.78, p > 0.05) in 2018 wave; and in 2011 wave, dietary diversity was more significantly related to health status among the younger elderly (OR, 1.62, 95% CI, 1.26–2.08, p < 0.001) than the older elderly (OR, 0.08, 95%CI, 0.31–1.94, p > 0.05). Conclusions: Better dietary diversity has positive effects on health status and is more significantly related to the younger elderly than the older elderly. So interventions including available dietary diversity assessment, variety of dietary assistance services in daily life, keeping nutrient digestion and absorption capacity for the venerable age might benefit to ensure the effects of dietary diversity on health status among older adults especially in maintaining intrinsic ability and physical function. In addition, healthy lifestyle should also be recommended. [ABSTRACT FROM AUTHOR]

The cuttlefish, Sepia pharaonis, is characterized by rapid growth and strong disease resistance, making it an important commercially farmed cephalopod species in the southeastern coastal regions of China. However, in the reproductive process of S. pharaonis, there are challenges such as a low output of eggs, poor quality, and low survival rates of newly hatched juveniles. Therefore, there is an urgent need to study the molecular mechanisms underlying ovarian development in this species. In this study, we conducted the first transcriptomic analysis of the ovary at four developmental stages: the undeveloped stage, developing stage, nearly-ripe stage, and ripe stage, and compared the transcriptomics among these four stages using Illumina sequencing technology. The total numbers of clean reads of the four stages ranged from 40,890,772 to 52,055,714 reads. A total of 136,829 DEGs were obtained, GC base ratios of raw data were between 38.44 and 44.59%, and the number of uniquely mapped reads spanned from 88.08 to 95.90%. The Pearson correlation coefficient demonstrated a strong correlation among different samples within the same group, PCA and Anosim analysis also revealed that the grouping of these four stages was feasible, and each stage could be distinguished from the others. GO enrichment analysis demonstrated that ovarian follicle growth, sex differentiation, and transforming growth factor beta receptor, played a foreshadowing role at the early ovarian development stage, and the terms of small molecule metabolic process, peptide metabolic process, and catalytic activity were prominent at the mature stage. Meanwhile, KEGG analysis showed that the early ovarian development of S. pharaonis was mainly associated with the cell cycle, DNA replication, and carbon metabolism, while the mid-late ovarian development was involved with the signal transduction, endocrine system, and reproduction pathway. RT-qPCR further confirmed the consistent expression patterns of genes such as 17β-HSD, GH, VGS, NFR, and NYR in the ovaries of S. pharaonis, exhibiting elevated levels of expression during the maturation stage. Conversely, ER and OM exhibited high expression levels during the early stages of ovarian development. These transcriptomic data provide insights into the molecular mechanisms of S. pharaonis ovarian development. The findings of this study will contribute to improving the reproduction and development of cuttlefish and enriching the bioinformatics knowledge of cephalopods. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence supports the significant role of human microbiome in development and therapeutic response of tumors. Circulating microbial DNA is non-invasive and could show a general view of the microbiome of host, making it a promising biomarker for cancers. However, whether circulating microbiome is associated with prognosis of non-small cell lung cancer (NSCLC) and its potential mechanisms on tumor immune microenvironment still remains unknown. Methods: The blood microbiome data and matching tumor RNA-seq data of TCGA NSCLC patients were obtained from Poore's study and UCSC Xena. Univariate and multivariate Cox regression analysis were used to identify circulating microbiome signatures associated with overall survival (OS) and construct the circulating microbial abundance prognostic scoring (MAPS) model. Nomograms integrating clinical characteristics and circulating MAPS scores were established to predict OS rate of NSCLC patients. Joint analysis of blood microbiome data and matching tumor RNA-seq data was used to deciphered the tumor microenvironment landscape of patients in circulating MAPS-high and MAPS-low groups. Finally, the predictive value of circulating MAPS on the efficacy of immunotherapy and chemotherapy were assessed. Results: A circulating MAPS prediction model consisting of 14 circulating microbes was constructed and had an independent prognostic value for NSCLC. The integration of circulating MAPS into nomograms may improve the prognosis predictive power. Joint analysis revealed potential interactions between prognostic circulating microbiome and tumor immune microenvironment. Especially, intratumor plasma cells and humoral immune response were enriched in circulating MAPS-low group, while intratumor CD4 + Th2 cells and proliferative related pathways were enriched in MAPS-high group. Finally, drug sensitivity analysis indicated the potential of circulating MAPS as a predictor of chemotherapy efficacy. Conclusion: A circulating MAPS prediction model was constructed successfully and showed great prognostic value for NSCLC. Our study provides new insights of interactions between microbes, tumors and immunity, and may further contribute to precision medicine for NSCLC. [ABSTRACT FROM AUTHOR]

In recent years, the role of nobiletin in neuronal disorders has received extensive attention. However, the study of nobiletin in the peripheral nervous system is limited. Nobiletin, as a compound with high fat solubility, high bioavailability and low toxicity, has been extensively studied. Accumulating scientific evidence has shown that nobiletin has a variety of biological functions in the nervous system, such as inhibiting the expression of inflammatory factors, reducing the neurotoxic response, improving the antioxidant capacity, promoting the survival of nerve cells, promoting axon growth, reducing blood‒brain barrier permeability, reducing brain oedema, promoting cAMP response element binding protein expression, improving memory, and promoting mild depolarization of nerve cell mitochondria to improve antioxidative stress capacity. Accumulating studies have shown that nobiletin also protects enteric nervous system, spinal cord and sciatic nerve. To explore the new therapeutic potential of nobiletin in the nervous system, recent and relevant research progress is reviewed in this article. This will provide a new research idea for nobiletin in the nervous system. [ABSTRACT FROM AUTHOR]

Background: Trypanosomatids are parasitic flagellates well known because of some representatives infecting humans, domestic animals, and cultural plants. Many trypanosomatid species bear RNA viruses, which, in the case of human pathogens Leishmania spp., influence the course of the disease. One of the close relatives of leishmaniae, Leptomonas pyrrhocoris, has been previously shown to harbor viruses of the groups not documented in other trypanosomatids. At the same time, this species has a worldwide distribution and high prevalence in the natural populations of its cosmopolitan firebug host. It therefore represents an attractive model to study the diversity of RNA viruses. Results: We surveyed 106 axenic cultures of L. pyrrhocoris and found that 64 (60%) of these displayed 2–12 double-stranded RNA fragments. The analysis of next-generation sequencing data revealed four viral groups with seven species, of which up to five were simultaneously detected in a single trypanosomatid isolate. Only two of these species, a tombus-like virus and an Ostravirus, were earlier documented in L. pyrrhocoris. In addition, there were four new species of Leishbuviridae, the family encompassing trypanosomatid-specific viruses, and a new species of Qinviridae, the family previously known only from metatranscriptomes of invertebrates. Currently, this is the only qinvirus with an unambiguously determined host. Our phylogenetic inferences suggest reassortment in the tombus-like virus owing to the interaction of different trypanosomatid strains. Two of the new Leishbuviridae members branch early on the phylogenetic tree of this family and display intermediate stages of genomic segment reduction between insect Phenuiviridae and crown Leishbuviridae. Conclusions: The unprecedented wide range of viruses in one protist species and the simultaneous presence of up to five viral species in a single Leptomonas pyrrhocoris isolate indicate the uniqueness of this flagellate. This is likely determined by the peculiarity of its firebug host, a highly abundant cosmopolitan species with several habits ensuring wide distribution and profuseness of L. pyrrhocoris, as well as its exposure to a wider spectrum of viruses compared to other trypanosomatids combined with a limited ability to transmit these viruses to its relatives. Thus, L. pyrrhocoris represents a suitable model to study the adoption of new viruses and their relationships with a protist host. [ABSTRACT FROM AUTHOR]

Background: The impact of consuming soybean and its products on cardiovascular events (CVEs), cardiovascular mortality, and all-cause mortality remains unclear. This study aimed to examine the prospective association of soybean consumption with CVEs, cardiovascular mortality, and all-cause mortality among the elderly population in rural China. Methods: The Northeast China Rural Cardiovascular Health Study included 2477 elderly individuals (mean age 67 ± 6 years, 49.97% men) in the initial phase of the study from 2012 to 2013, with a follow-up period between 2015 and 2017. Soybean consumption was categorized as follows: low-frequency consumption: rare consumption; moderate-frequency consumption: two to three times/week; high-frequency consumption: ≥ four times/week. Cox proportional hazard analysis assessed the potential relationship of soybean consumption with CVEs, cardiovascular mortality, and all-cause mortality. Results: The prevalence of soybean and its product consumption was as follows: 38.3% for low-frequency consumption (43.8% for women; 32.8% for men), 49.7% for moderate-frequency consumption (45.8% for women; 53.7% for men), and 11.9% for high-frequency consumption (10.4% for women; 13.5% for men). After adjusting for possible confounders, Cox proportional hazard analysis revealed that the frequency of soybean consumption was an effective predictor of CVEs [Hazard ratio (HR) high (95% CI): 0.555 (0.348, 0.883)], stroke [HR moderate (95% CI): 0.672 (0.494, 0.913); HR high (95% CI): 0.483 (0.276, 0.842)], and all-cause mortality [HR high (95% CI): 0.540 (0.310, 0.942)] in the overall older population. High-frequency consumption of soybean [HR (95% CI): 0.467 (0.225, 0.968)] and moderate-frequency consumption [HR (95% CI): 0.458 (0.270, 0.779)] were associated with stroke events in older men and women, respectively. In addition, high-frequency consumption of soybean [HR (95% CI): 0.437 (0.197, 0.968)] decreased the risk of CVEs in older women. Conclusion: Soybean consumption is closely associated with CVEs and all-cause mortality in older individuals residing in rural areas, with a significant gender discrepancy in this relationship. These findings provide new insights into the impact of soybean consumption on cardiovascular well-being in the elderly rural population, thus enhancing our understanding of this field of interest. [ABSTRACT FROM AUTHOR]

Depression is a common mood disorder characterized by a range of clinical symptoms, including prolonged low mood and diminished interest. Although many clinical and animal studies have provided significant insights into the pathophysiology of depression, current treatment strategies are not sufficient to manage this disorder. It has been suggested that connexin (Cx)-based hemichannels are candidates for depression intervention by modifying the state of neuroinflammation. In this study, we investigated the antidepressant-like effect of a recently discovered selective Cx hemichannel inhibitor, a small organic molecule called D4. We first showed that D4 reduced hemichannel activity following systemic inflammation after LPS injections. Next, we found that D4 treatment prevented LPS-induced inflammatory response and depressive-like behaviors. These behavioral effects were accompanied by reduced astrocytic activation and hemichannel activity in depressive-like mice induced by repeated low-dose LPS challenges. D4 treatment also reverses depressive-like symptoms in mice subjected to chronic restraint stress (CRS). To test whether D4 broadly affected neural activity, we measured c-Fos expression in depression-related brain regions and found a reduction in c-Fos+ cells in different brain regions. D4 significantly normalized CRS-induced hypoactivation in several brain regions, including the hippocampus, entorhinal cortex, and lateral septum. Together, these results indicate that blocking Cx hemichannels using D4 can normalize neuronal activity and reduce depressive-like symptoms in mice by reducing neuroinflammation. Our work provides evidence of the antidepressant-like effect of D4 and supports glial Cx hemichannels as potential therapeutic targets for depression. [ABSTRACT FROM AUTHOR]

Blood flow and pressure calculated using the currently available methods have shown the potential to predict the progression of pathology, guide treatment strategies and help with postoperative recovery. However, the conspicuous disadvantage of these methods might be the time-consuming nature due to the simulation of virtual interventional treatment. The purpose of this study is to propose a fast novel physics-based model, called FAST, for the prediction of blood flow and pressure. More specifically, blood flow in a vessel is discretized into a number of micro-flow elements along the centerline of the artery, so that when using the equation of viscous fluid motion, the complex blood flow in the artery is simplified into a one-dimensional (1D) steady-state flow. We demonstrate that this method can compute the fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA). 345 patients with 402 lesions are used to evaluate the feasibility of the FAST simulation through a comparison with three-dimensional (3D) computational fluid dynamics (CFD) simulation. Invasive FFR is also introduced to validate the diagnostic performance of the FAST method as a reference standard. The performance of the FAST method is comparable with the 3D CFD method. Compared with invasive FFR, the accuracy, sensitivity and specificity of FAST is 88.6%, 83.2% and 91.3%, respectively. The AUC of FFRFAST is 0.906. This demonstrates that the FAST algorithm and 3D CFD method show high consistency in predicting steady-state blood flow and pressure. Meanwhile, the FAST method also shows the potential in detecting lesion-specific ischemia. [ABSTRACT FROM AUTHOR]

Aim: Few studies considered the association between snack patterns and metabolic abnormalities. Here we aimed to characterize the major snack patterns among Iranian adults and determine their association with the risk of metabolic syndrome (MetS). Methods: This study was conducted on 1713 MetS-free adults who participated in the third phase of the Tehran Lipid and Glucose Study (TLGS). At baseline, dietary intake of snack was assessed using a validated 168-items food frequency questionnaire, and snack patterns were obtained by principal component analysis (PCA). Adjusted Hazard Ratios (HRs) and 95% confidence intervals (CIs) were calculated for the association of incident MetS with the extracted snack patterns. Results: PCA identified five major snack patterns, defined as "healthy pattern", "low-fructose pattern", "high-trans pattern", "high-caffeine pattern" and "high-fructose pattern". Participants in the highest tertile of the "high-caffeine pattern" had lower risk of MetS (HR = 0.80, 95% CI = 0.65–0.99, P for trend = 0.032). Other snack patterns have not shown any significant association with MetS incidence. Conclusions: Our findings suggest that consuming a snack pattern with high loads of caffeine, defined as "High-caffeine pattern" in the present study, could reduce the risk of MetS in healthy adults. Further prospective studies are needed to more fully determine the association between snack patterns and MetS incidence. [ABSTRACT FROM AUTHOR]

Background: Red-tail catfish (Hemibagrus wyckioides) is an important commercially farmed catfish in southern China. Males of red-tail catfish grow faster than females, suggesting that all-male catfish will produce more significant economic benefits in aquaculture practice. However, little research has been reported on sex determination and gonadal development in red-tail catfish. Results: In this study, we performed the first transcriptomic analysis of male and female gonads at four developmental stages at 10, 18, 30, and 48 days post hatching (dph) using RNA-seq technology. A total of 23,588 genes were screened in 24 sequenced samples, of which 28, 213, 636, and 1381 differentially expressed genes (DEGs) were detected at four developmental stages, respectively. Seven candidate genes of sex determination and differentiation were further identified. Real-time quantitative PCR (RT-qPCR) further confirmed that anti-Mullerian hormone (amh), growth differentiation factor 6a (gdf6a), testis-specific gene antigen 10 (tsga10), and cytochrome P450 family 17 subfamily A (cyp17a) were highly expressed mainly in the male, while cytochrome P450 family 19 subfamily A polypeptide 1b (cyp19a1b), forkhead box L2 (foxl2), and hydroxysteroid 17-beta dehydrogenase 1 (hsd17b1) were highly expressed in the female. The KEGG pathway enrichment data showed that these identified DEGs were mainly involved in steroid hormone biosynthesis and TGF-β signaling pathways. Conclusions: Based on RNA-seq data of gonads at the early developmental stages, seven DEGs shared by the four developmental stages were identified, among which amh and gdf6a may be the male-biased expression genes, while foxl2, cyp19a1b and hsd17b1 may be the female-biased expression genes in red-tail catfish. Our study will provide crucial genetic information for the research on sex control in red-tail catfish, as well as for exploring the evolutionary processes of sex determination mechanisms in fish. [ABSTRACT FROM AUTHOR]

Background: Frailty has emerged as a global health burden with increased population aging. A diverse diet is essential for an adequate and balanced supply of nutrients. However, limited evidence supports the relationship between dietary diversity and frailty. We therefore assessed the associations of dietary diversity with the risk of frailty. Methods: We used the Chinese Longitudinal Healthy Longevity Survey to analyze a prospective cohort of Chinese older adults. A total of 1948 non-frail older adults were included in the final sample. Participants were categorized into groups with high or low dietary diversity scores (DDSs) using a food frequency questionnaire. A Generalized Estimating Equation were used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for determining frailty incidence. Results: Among 1,948 participants, 381 had frailty with the prevalence of 19.56% during the 3-year follow-up period. Compared with the low DDS group, the high DDS group exhibited a lower risk of frailty (RR, 0.72; 95% CI: 0.57–0.91). Compared with those with a consistently low DDS, the RR of participants with a consistently high DDS for frailty was 0.56 (95% CI: 0.42–0.74). Moreover, meat, beans, fish, nuts, fresh fruits, and fresh vegetables were inversely associated with frailty. In stratified analysis, a consistently high DDS, compared with a consistently low DDS, reduced the risk of frailty for people aged 65-79 years and those living in town and rural areas. Conclusion: This study found a prospective association between dietary diversity and frailty among Chinese older adults. These findings stressed that it is important to improve dietary diversity for older adults to promote healthy ageing, particularly for young older adults and in town and rural areas. [ABSTRACT FROM AUTHOR]

Background: If the bony region indicating the ilioischial line is established on the preoperative axial computed tomography (CT) image, the distance between the simulated cup and the ilioischial line can be measured on this image so that the surgeon can use these data to define a more accurate preoperative two-dimensional (2D) template of total hip arthroplasty (THA). This study aimed to verify the hypothesis that on the CT axial image, the cortical bone area, indicated by the superimposition of a line (line α) with a perspective projection angle to the ilioischial line on radiography and tangent to the medial acetabular wall, is the cortical bone that represents the ilioischial line on radiography.Methods: Study 1: If the two measured distances (distance A' and distance B) are sufficiently equal, then the hypothesis can be supported. Distance A' was calculated by multiplying the distance A, between the ilioischial line and the medial margin of the metal cup after THA measured at the level of the hip joint center on the pelvic radiograph, by 0.91 to correct for radiographic magnification. Distance B was defined as the distance between the medial margin of the metal cup and line α on the axial CT image at the level of the hip joint center. These two distances were measured for all 51 hip joints included in the study. Study 2: The difference between distance A and distance A# (distance A on the 2D template) was compared between the group containing 59 primary THAs in which distance B' was measured (distance B in the simulation) and the control group containing 59 primary THAs.Results: Study 1: The average distance for A' was 4.5 ± 2 mm, and the average distance for B was 4.7 ± 2.1 mm. The difference between distances A and B was 0.2 ± 0.2 mm. Study 2: The mean difference between distance A and distance A# for the measurement and control groups was 1.8 ± 1.3 mm and 3.7 ± 2.4 mm, respectively (P < 0.001).Conclusions: The ilioischial line is located in the bony region where line α intersects the medial acetabular wall with a maximum overlap on axial CT images. [ABSTRACT FROM AUTHOR]

The Greek Society of Migraine and Headache Patients (GSMHP), maintaining a strong commitment to research and information, conducted its second web-based online survey named "Migraine in Greece-2020", following its first one conducted in 2018. The 2020 study included 2,105 migraine patients who were called to answer 151 questions. The purposes of the current research were to record the demographic and clinical characteristics of migraine patients in Greece, including the severity and effects of migraine on respondents' quality of life, as well as to survey the effects of the coronavirus pandemic on the course of migraine. Our population, internet-based study provides data that will hopefully contribute to better comprehend the clinical phenotype and course of migraine during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Progesterone receptor (PGR) is a master regulator of uterine function through antagonistic and synergistic interplays with oestrogen receptors. PGR action is primarily mediated by activation functions AF1 and AF2, but their physiological significance is unknown. Results: We report the first study of AF1 function in mice. The AF1 mutant mice are infertile with impaired implantation and decidualization. This is associated with a delay in the cessation of epithelial proliferation and in the initiation of stromal proliferation at preimplantation. Despite tissue selective effect on PGR target genes, AF1 mutations caused global loss of the antioestrogenic activity of progesterone in both pregnant and ovariectomized models. Importantly, the study provides evidence that PGR can exert an antioestrogenic effect by genomic inhibition of Esr1 and Greb1 expression. ChIP-Seq data mining reveals intermingled PGR and ESR1 binding on Esr1 and Greb1 gene enhancers. Chromatin conformation analysis shows reduced interactions in these genes' loci in the mutant, coinciding with their upregulations. Conclusion: AF1 mediates genomic inhibition of ESR1 action globally whilst it also has tissue-selective effect on PGR target genes. [ABSTRACT FROM AUTHOR]

Background: Diet and physical activity are key components of healthy aging. Current interventions that promote healthy eating and physical activity among the elderly have limitations and evidence of French interventions' effectiveness is lacking. We aim to assess (i) the effectiveness of a combined diet/physical activity intervention (the "ALAPAGE" program) on older peoples' eating behaviors, physical activity and fitness levels, quality of life, and feelings of loneliness; (ii) the intervention's process and (iii) its cost effectiveness.Methods: We performed a pragmatic cluster randomized controlled trial with two parallel arms (2:1 ratio) among people ≥60 years old who live at home in southeastern France. A cluster consists of 10 people participating in a "workshop" (i.e., a collective intervention conducted at a local organization). We aim to include 45 workshops randomized into two groups: the intervention group (including 30 workshops) in the ALAPAGE program; and the waiting-list control group (including 15 workshops). Participants (expected total sample size: 450) will be recruited through both local organizations' usual practices and an innovative active recruitment strategy that targets hard-to-reach people. We developed the ALAPAGE program based on existing workshops, combining a participatory and a theory-based approach. It includes a 7-week period with weekly collective sessions supported by a dietician and/or an adapted physical activity professional, followed by a 12-week period of post-session activities without professional supervision. Primary outcomes are dietary diversity (calculated using two 24-hour diet recalls and one Food Frequency Questionnaire) and lower-limb muscle strength (assessed by the 30-second chair stand test from the Senior Fitness Test battery). Secondary outcomes include consumption frequencies of main food groups and water/hot drinks, other physical fitness measures, overall level of physical activity, quality of life, and feelings of loneliness. Outcomes are assessed before the intervention, at 6 weeks and 3 months later. The process evaluation assesses the fidelity, dose, and reach of the intervention as its causal mechanisms (quantitative and qualitative data).Discussion: This study aims to improve healthy aging while limiting social inequalities. We developed and evaluated the ALAPAGE program in partnership with major healthy aging organizations, providing a unique opportunity to expand its reach.Trial Registration: ClinicalTrials.gov Identifier: NCT05140330 , December 1, 2021.Protocol Version: Version 3.0 (November 5, 2021). [ABSTRACT FROM AUTHOR]

Background: The expression and biological functions of circular RNAs (circRNAs) in reproductive organs have been extensively reported. However, it is still unclear whether circRNAs are involved in sex change. To this end, RNA sequencing (RNA-seq) was performed in gonads at 5 sexual stages (ovary, early intersexual stage gonad, middle intersexual stage gonad, late intersexual stage gonad, and testis) of ricefield eel, and the expression profiles and potential functions of circRNAs were studied. Results: Seven hundred twenty-one circRNAs were identified, and the expression levels of 10 circRNAs were verified by quantitative real-time PCR (qRT–PCR) and found to be in accordance with the RNA-seq data, suggesting that the RNA-seq data were reliable. Then, the sequence length, category, sequence composition and the relationship between the parent genes of the circRNAs were explored. A total of 147 circRNAs were differentially expressed in the sex change process, and GO and KEGG analyses revealed that some differentially expressed (such as novel_circ_0000659, novel_circ_0004005 and novel_circ_0005865) circRNAs were closely involved in sex change. Furthermore, expression pattern analysis demonstrated that both circSnd1 and foxl2 were downregulated in the process of sex change, which was contrary to mal-miR-135b. Finally, dual-luciferase reporter assay and RNA immunoprecipitation showed that circSnd1 and foxl2 can combine with mal-miR-135b and mal-miR-135c. These data revealed that circSnd1 regulates foxl2 expression in the sex change of ricefield eel by acting as a sponge of mal-miR-135b/c. Conclusion: Our results are the first to demonstrate that circRNAs have potential effects on sex change in ricefield eel; and circSnd1 could regulate foxl2 expression in the sex change of ricefield eel by acting as a sponge of mal-miR-135b/c. These data will be useful for enhancing our understanding of sequential hermaphroditism and sex change in ricefield eel or other teleosts. [ABSTRACT FROM AUTHOR]

Generally, successful testis transplantation has been considered to require immune suppression in the recipient to avoid rejection of the transplanted tissue. In the present study, we demonstrate in medaka that allogeneic adult testicular tissue will engraft in adult recipients immediately after partial castration without the use of immunosuppressive drugs. The allografted testes are retained in the recipient's body for at least 3 months and are able to produce viable sperm that yield offspring after natural mating. Some recipients showed a high frequency (over 60%) of offspring derived from spermatozoa produced by the transplanted testicular tissue. Histological analyses showed that allografted testicular tissues included both germ cells and somatic cells that had become established within an immunocompetent recipient testis. The relative simplicity of this testis transplantation approach will benefit investigations of the basic processes of reproductive immunology and will improve the technique of gonadal tissue transplantation. [ABSTRACT FROM AUTHOR]

Background: The protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway regulates early follicular activation and follicular pool maintenance in female germline cells. Fragile X mental retardation 1 (FMR1) regulates folliculogenesis and it is variably expressed in patients with Premature Ovary Insufficiency. FMR1 expression is supposed to be linked to AKT/mTOR signaling in an ovarian response dependent manner as demonstrated in recent invitro and invivo studies in the female germline invitro and invivo. Methods: We evaluated changes in the expression of AKT/mTOR signaling pathway genes by real time PCR in the peripheral blood of 74 patients with Premature Ovarian Insufficiency and 56 fertile controls and correlated their expression with FMR1 expression. Results: Expression of the genes AKT1, TSC2, mTOR, and S6K was significantly more abundant in patients with POI than in the controls. For AKT1, TSC2 and mTOR, gene expression was not affected by FMR1-CGG repeat number in the 5´-untranslated region. FMR1 and S6K expression levels, however, were significantly upregulated in patients with POI and an FMR1 premutation. Independent of a premutation, expression of mTOR, S6K, and TSC2 was significantly correlated with that of FMR1 in all patients. Furthermore, when grouped according to ovarian reserve, this effect remained significant only for mTOR and S6K, with higher significance note in patients with Premature Ovarian Insufficiency than in the controls. Conclusions: In Premature ovarian insufficiency patients, activation of AKT/mTOR signaling pathway is remarkable and putatively pathognomonic. Additionally, it seems to be triggered by an FMR1/mTOR/S6K linkage mechanism, most relevant in premutation carriers. [ABSTRACT FROM AUTHOR]

Background: Hypercalcemic hyperparathyroidism has been associated with poor outcomes after kidney transplantation (KTx). However, the clinical implications of normocalcemic hyperparathyroidism after KTx are unclear. This retrospective cohort study attempted to identify these implications.Methods: Normocalcemic recipients who underwent KTx between 2000 and 2016 without a history of parathyroidectomy were included in the study. Those who lost their graft within 1 year posttransplant were excluded. Normocalcemia was defined as total serum calcium levels of 8.5-10.5 mg/dL, while hyperparathyroidism was defined as when intact parathyroid hormone levels exceeded 80 pg/mL. The patients were divided into two groups based on the presence of hyperparathyroidism 1 year after KTx. The primary outcome was the risk of graft loss.Results: Among the 892 consecutive patients, 493 did not have hyperparathyroidism (HPT-free group), and 399 had normocalcemic hyperparathyroidism (NC-HPT group). Ninety-five patients lost their grafts. Death-censored graft survival after KTx was significantly lower in the NC-HPT group than in the HPT-free group (96.7% vs. 99.6% after 5 years, respectively, P < 0.001). Cox hazard analysis revealed that normocalcemic hyperparathyroidism was an independent risk factor for graft loss (P = 0.002; hazard ratio, 1.94; 95% confidence interval, 1.27-2.98).Conclusions: Normocalcemic hyperparathyroidism 1 year after KTx was an independent risk factor for death-censored graft loss. Early intervention of elevated parathyroid hormone levels may lead to better graft outcomes, even without overt hypercalcemia. [ABSTRACT FROM AUTHOR]

Background: The adoption of teleconsultation for outpatient neurology services was limited until the onset of the COVID-19 pandemic which forced many outpatient neurology services to rapidly switch to virtual models. However, it remains unclear how this change has impacted patients' and clinicians' perceptions of service quality. The purpose of this scoping review is to identify process factors that influence patients' and clinicians' experiences of outpatient teleconsultation services during COVID-19. Methods: Arksey and O'Malley scoping review framework was used to search PubMed, Scopus, CINAHL, and PsycInfo for original peer-reviewed research studies that examined the experiences of synchronous teleconsultation between a clinician and patient in a home-setting since the World Health Organization announced the COVID-19 global pandemic. The service quality model SERVQUAL was used to conduct a deductive thematic analysis to identify the key factors that impacted the patients' and clinicians' perception of teleconsultation services. Results: A total of nineteen studies published between January 1, 2020, and April 17, 2021, were identified. The most common service process factors affecting the patients' and clinicians' experiences of teleconsultation were technical issues, addressing logistical needs, communication, ability to perform clinical activities, appropriate triage, and administrative support. Conclusions: Our findings identified six key service process factors affecting the patients' and clinicians' teleconsultation experiences in outpatient neurology services. The need for improvement of triage process and standardizing administrative virtual care pathway are identified as important steps to improve patients and clinicians' teleconsultation experiences compared to pre-COVID era. More research is needed to assess outpatient neurology teleconsultation service quality from patients' and clinicians' perspectives. [ABSTRACT FROM AUTHOR]

Background: Several microorganisms inhabit the mammalian gastrointestinal tract and are associated with the pathogenesis of various diseases, including cancer. Recent studies have indicated that several probiotics produce antitumor molecules and inhibit host tumor progression. We demonstrated that heptelidic acid (HA), a sesquiterpene lactone derived from the probiotic Aspergillus oryzae, exerts antitumor effects against pancreatic cancer in vitro and in vivo. In this study, the antitumor effects of HA against extraintestinal melanoma were assessed in vitro and in vivo. Results: Sulforhodamine B (SRB) assay revealed that the growth of B16F10 cells was significantly inhibited by HA in a concentration-dependent manner. The enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) decreased in proportion with the growth inhibition effect of HA. Moreover, oral HA administration significantly suppressed the growth of transplanted B16F10 tumors without any significant changes in biochemical test values. Moreover, GAPDH activity in the transplanted tumor tissues in the HA group significantly decreased compared with that in the PBS group. Conclusion: This study suggests that orally administered HA was absorbed in the gastrointestinal tract, reached the cancer cells transplanted in the skin, and inhibited GAPDH activity, thereby inhibiting the growth of extraintestinal melanoma cells. Thus, this study proposes a novel system for extraintestinal tumor regulation via gut bacteria-derived bioactive mediators. [ABSTRACT FROM AUTHOR]

Background: Despite the morphological diversity of animals, their basic anatomical patterns—the body plans in each animal phylum—have remained highly conserved over hundreds of millions of evolutionary years. This is attributed to conservation of the body plan-establishing developmental period (the phylotypic period) in each lineage. However, the evolutionary mechanism behind this phylotypic period conservation remains under debate. A variety of hypotheses based on the concept of modern synthesis have been proposed, such as negative selection in the phylotypic period through its vulnerability to embryonic lethality. Here we tested a new hypothesis that the phylotypic period is developmentally stable; it has less potential to produce phenotypic variations than the other stages, and this has most likely led to the evolutionary conservation of body plans. Results: By analyzing the embryos of inbred Japanese medaka embryos raised under the same laboratory conditions and measuring the whole embryonic transcriptome as a phenotype, we found that the phylotypic period has greater developmental stability than other stages. Comparison of phenotypic differences between two wild medaka populations indicated that the phylotypic period and its genes in this period remained less variational, even after environmental and mutational modifications accumulated during intraspecies evolution. Genes with stable expression levels were enriched with those involved in cell-cell signalling and morphological specification such as Wnt and Hox, implying possible involvement in body plan development of these genes. Conclusions: This study demonstrated the correspondence between the developmental stage with low potential to produce phenotypic variations and that with low diversity in micro- and macroevolution, namely the phylotypic period. Whereas modern synthesis explains evolution as a process of shaping of phenotypic variations caused by mutations, our results highlight the possibility that phenotypic variations are readily limited by the intrinsic nature of organisms, namely developmental stability, thus biasing evolutionary outcomes. [ABSTRACT FROM AUTHOR]

Background: Both early detection and severity assessment of liver trauma are critical for optimal triage and management of trauma patients. Current trauma protocols utilize computed tomography (CT) assessment of injuries in a subjective and qualitative (v.s. quantitative) fashion, shortcomings which could both be addressed by automated computer-aided systems that are capable of generating real-time reproducible and quantitative information. This study outlines an end-to-end pipeline to calculate the percentage of the liver parenchyma disrupted by trauma, an important component of the American Association for the Surgery of Trauma (AAST) liver injury scale, the primary tool to assess liver trauma severity at CT. Methods: This framework comprises deep convolutional neural networks that first generate initial masks of both liver parenchyma (including normal and affected liver) and regions affected by trauma using three dimensional contrast-enhanced CT scans. Next, during the post-processing step, human domain knowledge about the location and intensity distribution of liver trauma is integrated into the model to avoid false positive regions. After generating the liver parenchyma and trauma masks, the corresponding volumes are calculated. Liver parenchymal disruption is then computed as the volume of the liver parenchyma that is disrupted by trauma. Results: The proposed model was trained and validated on an internal dataset from the University of Michigan Health System (UMHS) including 77 CT scans (34 with and 43 without liver parenchymal trauma). The Dice/recall/precision coefficients of the proposed segmentation models are 96.13/96.00/96.35% and 51.21/53.20/56.76%, respectively, in segmenting liver parenchyma and liver trauma regions. In volume-based severity analysis, the proposed model yields a linear regression relation of 0.95 in estimating the percentage of liver parenchyma disrupted by trauma. The model shows an accurate performance in avoiding false positives for patients without any liver parenchymal trauma. These results indicate that the model is generalizable on patients with pre-existing liver conditions, including fatty livers and congestive hepatopathy. Conclusion: The proposed algorithms are able to accurately segment the liver and the regions affected by trauma. This pipeline demonstrates an accurate performance in estimating the percentage of liver parenchyma that is affected by trauma. Such a system can aid critical care medical personnel by providing a reproducible quantitative assessment of liver trauma as an alternative to the sometimes subjective AAST grading system that is used currently. [ABSTRACT FROM AUTHOR]

Background: Dietary diversity (DD) is an indicator of nutrient intake and is related to health outcomes in older people. Currently, limited research exists regarding factors associated with DD in older people in developing countries, such as Thailand, despite rapid growth in this population. Therefore, this study aims to examine the association between socio-demographic characteristics and DD in Thai older people. Methods: A cross-sectional study based on the fifth Thai National Health Examination Survey (NHES-V) conducted between 2013 and 2015 was performed. A total of 7,300 nationally representative older participants aged ≥ 60 years were included. The individual-level dietary diversity score (DDS) was assessed as the frequency of consumption of eight food groups using food frequency questionnaires. Each food group was scored from 0 to 4 according to the frequency of consumption. The DDS was calculated as the sum of the scores, ranging from 0 to 32. Socio-demographic characteristics, including age, sex, highest education level, wealth index, living conditions, and residential area, were assessed. Data were analyzed using multiple linear regression and adjusted for complex survey design. Results: The participants had a mean age of 69.7 (SD 7.6) years. The mean DDS of participants was 18.4 (SD 3.9). In the adjusted model, a higher educational level, a higher wealth index, and living in an urban area were positively associated with DDS, with adjusted β (95% CI) values of 1.37 (1.04, 1.70) for secondary education or higher, 0.81 (0.55, 1.06) for the richest group, and 0.24 (0.10, 0.44) for living in an urban area. Nevertheless, living alone had negative associations with DDS, with a β (95% CI) of - 0.27 (- 0.53, - 0.00). Conclusions: This study showed that a higher educational level, a higher wealth index, and living in an urban area had a positive association, whereas living alone had a negative association with DD among Thai older participants. Interventions aiming to improve dietary diversity among older people might benefit from targeting more vulnerable groups, particularly those with less education and wealth, those living alone, or those in rural areas. [ABSTRACT FROM AUTHOR]

Background: Fishes are the one of the most diverse groups of animals with respect to their modes of sex determination, providing unique models for uncovering the evolutionary and molecular mechanisms underlying sex determination and reversal. Here, we have investigated how sex is determined in a species of both commercial and ecological importance, the Siamese fighting fish Betta splendens. Results: We conducted association mapping on four commercial and two wild populations of B. splendens. In three of the four commercial populations, the master sex determining (MSD) locus was found to be located in a region of ~ 80 kb on LG2 which harbours five protein coding genes, including dmrt1, a gene involved in male sex determination in different animal taxa. In these fish, dmrt1 shows a male-biased gonadal expression from undifferentiated stages to adult organs and the knockout of this gene resulted in ovarian development in XY genotypes. Genome sequencing of XX and YY genotypes identified a transposon, drbx1, inserted into the fourth intron of the X-linked dmrt1 allele. Methylation assays revealed that epigenetic changes induced by drbx1 spread out to the promoter region of dmrt1. In addition, drbx1 being inserted between two closely linked cis-regulatory elements reduced their enhancer activities. Thus, epigenetic changes, induced by drbx1, contribute to the reduced expression of the X-linked dmrt1 allele, leading to female development. This represents a previously undescribed solution in animals relying on dmrt1 function for sex determination. Differentiation between the X and Y chromosomes is limited to a small region of ~ 200 kb surrounding the MSD gene. Recombination suppression spread slightly out of the SD locus. However, this mechanism was not found in the fourth commercial stock we studied, or in the two wild populations analysed, suggesting that it originated recently during domestication. Conclusions: Taken together, our data provide novel insights into the role of epigenetic regulation of dmrt1 in sex determination and turnover of SD systems and suggest that fighting fish are a suitable model to study the initial stages of sex chromosome evolution. [ABSTRACT FROM AUTHOR]

Background: The effect of tea consumption on metabolic syndrome (MetS) remains controversial. The objective of this study is to examine the prospective association of tea consumption with 5-year incident MetS among aged population in China. Methods: This analysis included 3005 Chinese adults aged 60 years or older who were free of MetS at baseline examination. MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III. Information regarding tea consumption was collected via an interviewer-administrated questionnaire. The prospective associations between tea consumption at baseline and 5-year incident MetS, as well as its individual components, were assessed by multiple logistic regression models. Results: Of the 3005 participants free of MetS at baseline, 406 participants (cumulative incidence: 13.5%) developed MetS at the 5-year follow-up examination. In multiple logistic regressions, 5-year cumulative incidence of MetS was found to be higher in those who drank tea more than 5 times per week as compared with non-habitual drinkers (OR = 1.38, 95% CI: 1.05-1.82; P = 0.02). This relationship still existed in men (OR = 1.43, 95%CI: 1.00-2.01; P = 0.05) when stratified by gender. Among the five major components of MetS, low high-density lipoprotein cholesterol was observed in men, while high body mass index, elevated blood pressure and the presence of diabetes mellitus were significant in women. Conclusions: High-frequent tea consumption increased the risk of MetS among older Chinese adults. These findings may add novel knowledge to the current studies regarding the controversial effect of tea consumption on cardiovascular and metabolic health among the aged population. [ABSTRACT FROM AUTHOR]

Background: Locomotive syndrome (LS) is a condition of reduced mobility due to a disorder of the locomotive system. Increasing moderate to vigorous physical activity (MVPA) has been recommended to prevent LS. However, to increase daily MVPA is difficult for older people with LS. The MVPA consists of not only locomotive activities such as walking but also non-locomotive activities such as household activities. The aim of this study was to examine the associations between locomotive/non-locomotive MVPA and physical performance in older females with and without LS. Methods: Participants of this cross-sectional study were 143 older community-dwelling Japanese females. The participants were divided into two groups based on the results of the stand-up test: the normal group (NL) (n = 86) and the LS group (n = 57). Both the locomotive and non-locomotive PA seperately measured with its intensity. The intensity of physical activity (PA) was calculated as METs and classified as sedentary behavior (SB 1–1.5 metabolic equivalent tasks (METs)), low-intensity physical activity (LPA 1.6–2.9 METs), and MVPA (≥ 3 METs). For example, locomotive LPA is slow walking speed of 54 m/min, and locomotive MVPA is walking speed of 67 m/min. While non-locomotive LPA is office work and cooking, non-locomotive MVPA is housecleaning. Physical function was evaluated by handgrip strength, walking speed, and 2-step test. Results: Walking speed, hand-grip strength, 2-step test, daily step counts, and all PA measurements were not significantly different between two groups. In the LS, locomotive MVPA (r = 0.293, p < 0.05) and total MVPA (r = 0.299, p < 0.05) was significantly correlated with walking speed, but not in the NL. Conclusions: Walking speed was positively correlated with locomotive MVPA and total MVPA in the LS group, but not in NL group. This result suggests that slow walking speed in older people with LS occur in connection with lower locomotive MVPA and total MVPA. [ABSTRACT FROM AUTHOR]

Background: The genetic control of sex determination in teleost species is poorly understood. This is partly because of the diversity of mechanisms that determine sex in this large group of vertebrates, including constitutive genes linked to sex chromosomes, polygenic constitutive mechanisms, environmental factors, hermaphroditism, and unisexuality. Here we use a de novo genome assembly of New Zealand silver trevally (Pseudocaranx georgianus) together with sex-specific whole genome sequencing data to detect sexually divergent genomic regions, identify candidate genes and develop molecular makers. Results: The de novo assembly of an unsexed trevally (Trevally_v1) resulted in a final assembly of 579.4 Mb in length, with a N50 of 25.2 Mb. Of the assembled scaffolds, 24 were of chromosome scale, ranging from 11 to 31 Mb in length. A total of 28,416 genes were annotated after 12.8 % of the assembly was masked with repetitive elements. Whole genome re-sequencing of 13 wild sexed trevally (seven males and six females) identified two sexually divergent regions located on two scaffolds, including a 6 kb region at the proximal end of chromosome 21. Blast analyses revealed similarity between one region and the aromatase genes cyp19 (a1a/b) (E-value < 1.00E-25, identity > 78.8 %). Males contained higher numbers of heterozygous variants in both regions, while females showed regions of very low read-depth, indicative of male-specificity of this genomic region. Molecular markers were developed and subsequently tested on 96 histologically-sexed fish (42 males and 54 females). Three markers amplified in absolute correspondence with sex (positive in males, negative in females). Conclusions: The higher number of heterozygous variants in males combined with the absence of these regions in females support a XY sex-determination model, indicating that the trevally_v1 genome assembly was developed from a male specimen. This sex system contrasts with the ZW sex-determination model documented in closely related carangid species. Our results indicate a sex-determining function of a cyp19a1a-like gene, suggesting the molecular pathway of sex determination is somewhat conserved in this family. The genomic resources developed here will facilitate future comparative work, and enable improved insights into the varied sex determination pathways in teleosts. The sex marker developed in this study will be a valuable resource for aquaculture selective breeding programmes, and for determining sex ratios in wild populations. [ABSTRACT FROM AUTHOR]

Background: Mosquito-borne dengue virus (DENV) causes major disease worldwide, impacting 50–100 million people every year, and is spread by the major mosquito vector Aedes aegypti. Understanding mosquito physiology, including antiviral mechanisms, and developing new control strategies have become an important step towards the elimination of DENV disease. In the study reported here, we focused on autophagy, a pathway suggested as having a positive influence on virus replication in humans, as a potential antiviral target in the mosquito. Methods: To understand the role played by autophagy in Ae. aegypti, we examined the activation of this pathway in Aag-2 cells, an Ae. aegypti-derived cell line, infected with DENV. Rapamycin and 3-methyladenine, two small molecules that have been shown to affect the function of the autophagy pathway, were used to activate or suppress, respectively, the autophagy pathway. Results: At 1-day post-DENV infection in Aag-2 cells, transcript levels of both the microtubule-associated protein light chain 3-phosphatidylethanolamine conjugate (LC3-II) and autophagy-related protein 1 (ATG1) increased. Rapamycin treatment activated the autophagy pathway as early as 1-h post-treatment, and the virus titer had decreased in the Aag-2 cells at 2 days post-infection; in contrast, the 3-methyladenine treatment did not significantly affect the DENV titer. Treatment with these small molecules also impacted the ATG12 transcript levels in DENV-infected cells. Conclusions: Our studies revealed that activation of the autophagy pathway through rapamycin treatment altered DENV infection in the mosquito cells, suggesting that this pathway could be a possible antiviral mechanism in the mosquito system. Here we provide fundamental information needed to proceed with future experiments and to improve our understanding of the mosquito's immune response against DENV. [ABSTRACT FROM AUTHOR]

Background: The number of total hip arthroplasties (THAs) performed for patients undergoing dialysis is increasing. However, there are few reports of cementless THA for patients undergoing dialysis. This study investigated the mid-term to long-term results of hydroxyapatite (HA)-coated cementless THA for dialysis patients.Methods: This single-center, retrospective study enrolled dialysis patients undergoing primary HA-coated cementless THA. A total of 24 patients (30 hips) were included in the final analyses. The Harris hip score and radiographic results were assessed preoperatively and during the final follow-up examination. Postoperative complications and mortality rates were recorded. The mean follow-up period was 109 months (range, 60-216 months).Results: The total Harris hip score significantly improved from 40 to 84 points. The overall cumulative survival rates with revision as the endpoint were 100% at 5 years and 90.4% at both 10 and 15 years. Stress shielding was observed in 24 hips (80%). No deaths were related to the primary THA. Complications included periprosthetic fracture for one patient (3.3%), blood transfusion for nine patients (30%), shunt blockage for two patients (6.7%), deep infection for one patient (3.3%), and dislocation for two patients (6.7%).Conclusions: HA-coated cementless THA resulted in good mid-term outcomes for patients undergoing dialysis with no mortality risk. However, the procedure involved a relatively high perioperative risk of blood transfusion. [ABSTRACT FROM AUTHOR]

Background: Cell invasion is a hallmark of metastatic cancer, leading to unfavorable clinical outcomes. In this study, we established two highly invasive lung cancer cell models (A549-i8 and H1299-i8) and identified mesoderm-specific transcript (MEST) as a novel invasive regulator of lung cancer. We aim to characterize its biological function and clinical significance in lung cancer metastasis. Methods: Transwell invasion assay was performed to establish high-invasive lung cancer cell model. Immunohistochemistry (IHC) was used to detect MEST expression in tumor tissues. Mass spectrometry and bioinformatic analyses were used to identify MEST-regulated proteins and binding partners. Co-immunoprecipitation assay was performed to detect the interaction of MEST and VCP. The biological functions of MEST were investigated in vitro and in vivo. Immunofluorescence staining was conducted to explore the colocalization of MEST and VCP. Results: MEST overexpression promoted metastasis of lung cancer cells in vivo and in vitro by activating NF-κB signaling. MEST increased the interaction between VCP and IκBα, which accelerated IκBα degradation and NF-κB activation. Such acceleration was abrogated by VCP silencing, indicating that MEST is an upstream activator of the VCP/IκBα/NF-κB signaling pathway. Furthermore, high expressions of MEST and VCP were associated with poor survival of lung cancer patients. Conclusion: Collectively, these results demonstrate that MEST plays an important role in driving invasion and metastasis of lung cancer by interacting with VCP to coordinate the IκBα/NF-κB pathway. Targeting the MEST/VCP/IκBα/NF-κB signaling pathway may be a promising strategy to treat lung cancer. [ABSTRACT FROM AUTHOR]

Background: A phosphaturic mesenchymal tumor (PMT) is classified into four histological subtypes: mixed connective tissue, osteoblast-like, non-ossifying fibroma-like, and ossifying fibroma-like. The ossifying fibroma-like subtype being extremely rare. Most PMTs are benign, with a minimal number becoming malignant after recurrence. In this study, we report a case of recurrence and malignant transformation of PMT-ossifying fibroma-like subtype in the left hip bone.Case Presentation: Here, we report the clinical manifestations, histology, pathological features, and treatment of a 57-year-old Chinese woman with a recurrent and malignant ossifying fibroma-like subtype PMT of the left iliac bone. The tumor was first discovered 3 years ago when the patient underwent surgery to remove the tumor. Precisely 2 years and 6 months after the operation, the pain in the left hip reappeared. After 6 months, the patient went to our hospital for treatment. After the tumor resection, the postoperative symptoms improved significantly, and the serum alkaline phosphatase level returned to normal. Based on clinical manifestations, evaluation of serum biochemical indicators, X-ray examination, computerized tomography scan of the pelvis, and histopathological examination of the two operations, the patient was finally diagnosed with a recurring and malignant transformation of the left iliac bone phosphaturic mesenchymal tumor-ossifying fibroma-like subtype. No tumor recurrence was found during the follow-up 15 months after the operation.Conclusions: This case increases the awareness of a rare malignant subtype of PMT and provides a valuable reference for the diagnosis of this disease. [ABSTRACT FROM AUTHOR]

Background: Arthropoda, the most numerous and diverse metazoan phylum, has species in many habitats where they encounter various microorganisms and, as a result, mechanisms for pathogen recognition and elimination have evolved. The Toll pathway, involved in the innate immune system, was first described as part of the developmental pathway for dorsal-ventral differentiation in Drosophila. Its later discovery in vertebrates suggested that this system was extremely conserved. However, there is variation in presence/absence, copy number and sequence divergence in various genes along the pathway. As most studies have only focused on Diptera, for a comprehensive and accurate homology-based approach it is important to understand gene function in a number of different species and, in a group as diverse as insects, the use of species belonging to different taxonomic groups is essential. Results: We evaluated the diversity of Toll pathway gene families in 39 Arthropod genomes, encompassing 13 different Insect Orders. Through computational methods, we shed some light into the evolution and functional annotation of protein families involved in the Toll pathway innate immune response. Our data indicates that: 1) intracellular proteins of the Toll pathway show mostly species-specific expansions; 2) the different Toll subfamilies seem to have distinct evolutionary backgrounds; 3) patterns of gene expansion observed in the Toll phylogenetic tree indicate that homology based methods of functional inference might not be accurate for some subfamilies; 4) Spatzle subfamilies are highly divergent and also pose a problem for homology based inference; 5) Spatzle subfamilies should not be analyzed together in the same phylogenetic framework; 6) network analyses seem to be a good first step in inferring functional groups in these cases. We specifically show that understanding Drosophila's Toll functions might not indicate the same function in other species. Conclusions: Our results show the importance of using species representing the different orders to better understand insect gene content, origin and evolution. More specifically, in intracellular Toll pathway gene families the presence of orthologues has important implications for homology based functional inference. Also, the different evolutionary backgrounds of Toll gene subfamilies should be taken into consideration when functional studies are performed, especially for TOLL9, TOLL, TOLL2_7, and the new TOLL10 clade. The presence of Diptera specific clades or the ones lacking Diptera species show the importance of overcoming the Diptera bias when performing functional characterization of Toll pathways. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is having a tremendous impact on humanity. Although COVID-19 vaccines are showing promising results, they are not 100% effective and resistant mutant SARS-CoV-2 strains are on the rise. To successfully fight against SARS-CoV-2 and prepare for future coronavirus outbreaks, it is essential to understand SARS-CoV-2 protein functions, their host interactions, and how these processes convey pathogenicity at host tissue, organ and systemic levels. In vitro models are valuable but lack the physiological context of a whole organism. Current animal models for SARS-CoV-2 research are exclusively mammals, with the intrinsic limitations of long reproduction times, few progeny, ethical concerns and high maintenance costs. These limitations make them unsuitable for rapid functional investigations of virus proteins as well as genetic and pharmacological screens. Remarkably, 90% of the SARS-CoV-2 virus-host interacting proteins are conserved between Drosophila and humans. As a well-established model system for studying human diseases, the fruit fly offers a highly complementary alternative to current mammalian models for SARS-CoV-2 research, from investigating virus protein function to developing targeted drugs. Herein, we review Drosophila's track record in studying human viruses and discuss the advantages and limitations of using fruit flies for SARS-CoV-2 research. We also review studies that already used Drosophila to investigate SARS-CoV-2 protein pathogenicity and their damaging effects in COVID-19 relevant tissues, as well as studies in which the fly was used as an efficient whole animal drug testing platform for targeted therapeutics against SARS-CoV-2 proteins or their host interacting pathways. [ABSTRACT FROM AUTHOR]