Incomplete lineage sorting and phenotypic evolution in marsupials.

Incomplete lineage sorting (ILS) makes ancestral genetic polymorphisms persist during rapid speciation events, inducing incongruences between gene trees and species trees. ILS has complicated phylogenetic inference in many lineages, including hominids. However, we lack empirical evidence that ILS leads to incongruent phenotypic variation. Here, we performed phylogenomic analyses to show that the South American monito del monte is the sister lineage of all Australian marsupials, although over 31% of its genome is closer to the Diprotodontia than to other Australian groups due to ILS during ancient radiation. Pervasive conflicting phylogenetic signals across the whole genome are consistent with some of the morphological variation among extant marsupials. We detected hundreds of genes that experienced stochastic fixation during ILS, encoding the same amino acids in non-sister species. Using functional experiments, we confirm how ILS may have directly contributed to hemiplasy in morphological traits that were established during rapid marsupial speciation ca. 60 mya.

Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has high relapse and low 5-year survival rates. Single-cell profiling in relapsed HCC may aid in the design of effective anticancer therapies, including immunotherapies. We profiled the transcriptomes of ∼17,000 cells from 18 primary or early-relapse HCC cases. Early-relapse tumors have reduced levels of regulatory T cells, increased dendritic cells (DCs), and increased infiltrated CD8+ T cells, compared with primary tumors, in two independent cohorts. Remarkably, CD8+ T cells in recurrent tumors overexpressed KLRB1 (CD161) and displayed an innate-like low cytotoxic state, with low clonal expansion, unlike the classical exhausted state observed in primary HCC. The enrichment of these cells was associated with a worse prognosis. Differential gene expression and interaction analyses revealed potential immune evasion mechanisms in recurrent tumor cells that dampen DC antigen presentation and recruit innate-like CD8+ T cells. Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse.

Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears.

Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans.

Pan-cancer scRNA-seq analysis reveals immunological and diagnostic significance of the peripheral blood mononuclear cells.

Peripheral blood mononuclear cells (PBMCs) reflect systemic immune response during cancer progression. However, a comprehensive understanding of the composition and function of PBMCs in cancer patients is lacking, and the potential of these features to assist cancer diagnosis is also unclear. Here, the compositional and status differences between cancer patients and healthy donors in PBMCs were investigated by single-cell RNA sequencing (scRNA-seq), involving 262,025 PBMCs from 68 cancer samples and 14 healthy samples. We observed an enhanced activation and differentiation of most immune subsets in cancer patients, along with reduction of naïve T cells, expansion of macrophages, impairment of NK cells and myeloid cells, as well as tumor promotion and immunosuppression. Based on characteristics including differential cell type abundances and/or hub genes identified from weight gene co-expression network analysis (WGCNA) modules of each major cell type, we applied logistic regression to construct cancer diagnosis models. Furthermore, we found that the above models can distinguish cancer patients and healthy donors with high sensitivity. Our study provided new insights into using the features of PBMCs in non-invasive cancer diagnosis.

Ion Transport in Multi-Nanochannels Regulated by pH and Ion Concentration.

Nanochannels are a powerful technique for detecting a wide range of biomolecules without labeling. The ion transport phenomena in nanochannel arrays differ from those in single nanochannels and are caused by interchannel communication. This study uses a fully coupled Poisson-Nernst-Planck (PNP) and Navier-Stokes model to investigate ion transport in nanochannel arrays. Instead of being set at a constant value, the surface charge density used in this study is established by the protonation and deprotonation of the silanol groups that are present on the walls of the silicon-based nanochannels. The surface charge density of the nanochannel walls varies with the number of nanochannels, the channel lateral distance, and the background solution properties, which consequently influence the ionic concentration distribution, flow velocity, and electric field strength. For example, in different numbers of nanochannel systems, the ion concentration in nanochannels is not much different, but it is different in reservoirs, especially near the openings of nanochannels. The number of nanochannels and the distance between nanochannels can also affect the formation of electro-convective vortex zones under certain conditions. These findings can aid in optimizing the nanochannel array design by regulating the number and distance of nanochannels and facilitating the construction of solid-state nanochannel arrays with any desired nanochannel dimensions.

Association between organophosphorus pesticides and obesity among American adults.

OBJECTIVE: To investigate any connections between urinary organophosphorus pesticide (OPP) metabolites and adiposity measures. METHODS: In this study, data from the National Health and Nutrition Examination Survey (NHANES) projects from 2003 to 2008, 2011 to 2012, and 2015 to 2018 were analysed. Obesity was defined as a body mass index (BMI) of 30 kg/m² or higher. Abdominal obesity was defined as a waist circumference (WC) over 102 cm for men and 88 cm for women. Four urinary OPP metabolites (dimethyl phosphate [DMP], diethyl phosphate [DEP], dimethyl phosphorothioate [DMTP], and diethyl phosphorothioate [DETP]) and adiposity measures were examined using multiple linear regression and logistic regression analyses. The correlations between a variety of urinary OPP metabolites and the prevalence of obesity were investigated using weighted quantile sum regression and quantile g-computation regression. RESULTS: In this analysis, a total of 9,505 adults were taken into account. There were 49.81% of male participants, and the average age was 46.00 years old. The median BMI and WC of the subjects were 27.70 kg/m2 and 97.10 cm, respectively. Moreover, 35.60% of the participants were obese, and 54.42% had abdominal obesity. DMP, DMTP, and DETP were discovered to have a negative correlation with WC and BMI in the adjusted models. DMP (OR = 0.93 [95% CI: 0.89-0.98]), DEP (OR = 0.94 [95% CI: 0.90-0.99]), DMTP (OR = 0.91 [95% CI: 0.86-0.95]), and DETP (OR = 0.85 [95% CI: 0.80-0.90]) exhibited negative associations with obesity prevalence. Similar correlations between the prevalence of abdominal obesity and the urine OPP metabolites were discovered. Moreover, the mixture of urinary OPP metabolites showed negative associations with adiposity measures, with DMTP and DETP showing the most significant effects. CONCLUSION: Together, higher levels of urinary OPP metabolites in the urine were linked to a decline in the prevalence of obesity.

Long-term residue returning increased subsoil carbon quality in a rice-wheat cropping system.

Residue returning (RR) was widely implemented to increase soil organic carbon (SOC) in farmland. Extensive studies concentrated on the effects of RR on SOC quantity instead of SOC fractions at aggregate scales. This study investigated the effects of 20-year RR on the distribution of labile (e.g., dissolved, microbial biomass, and permanganate oxidizable organic) and stable (e.g., microbial necromass) carbon fractions at aggregate scales, as well as their contribution to SOC accumulation and mineralization. The findings indicated a synchronized variation in the carbon content of bacterial and fungal necromass. Residue retention (RR) notably elevated the concentration of bacterial and fungal necromass carbon, while it did not amplify the microbial necromass carbon (MNC) contribution to SOC when compared to residue removal (R0) in the topsoil (0-5 cm). In the subsoil (5-15 cm), RR increased the MNC contribution to SOC concentration by 21.2%-33.4% and mitigated SOC mineralization by 12.6% in micro-aggregates (P < 0.05). Besides, RR increased soil ß-glucosidase and peroxidase activities but decreased soil phenol oxidase activity in micro-aggregates (P < 0.05). These indicated that RR might accelerate cellulose degradation and conversion to stable microbial necromass C, and thus RR improved SOC stability because SOC occluded in micro-aggregates were more stable. Interestingly, SOC concentration was mainly regulated by MNC, while SOC mineralization was by dissolved organic carbon under RR, both of which were affected by soil carbon, nitrogen, and phosphorus associated nutrients and enzyme activities. The findings of this study emphasize that the paths of RR-induced SOC accumulation and mineralization were different, and depended on stable and labile C, respectively. Overall, long-term RR increased topsoil carbon quantity and subsoil carbon quality.

bmo-miR-2739 and the novel microRNA miR-167 coordinately regulate the expression of the vitellogenin receptor in Bombyx mori oogenesis.

Vitellogenin receptors (VgRs) play crucial roles in oogenesis by mediating endocytosis of vitellogenin and other nutrients in ovipara. We conducted small RNA sequencing and screening with a luciferase reporter system, and found that bmo-miR-2739 and a novel miRNA (novel-miR-167) coordinately regulate the expression of VgR in Bombyx mori (BmVgR). Further analyses suggested that these two miRNAs direct target repression by binding directly to the BmVgR 3' untranslated region. Forced expression of either miRNA using the piggyBac system blocked vitellogenin (Vg) transport and retarded ovariole development. Antagomir silencing of bmo-miR-2739 or novel-miR-167 resulted in increased amounts of BmVgR protein in the ovaries and BmVgR mRNA in the fat body. This evidence, combined with spatiotemporal expression profiles, revealed that these two miRNAs function together to fine-tune the amount of BmVgR protein for ovarian development. Additionally, novel-miR-167 was mainly responsible for the post-transcriptional repression of BmVgR in non-ovarian tissues. The results of this study contribute to our understanding of the function of miRNAs during ovarian development of a lepidopteran and suggest a new strategy for controlling insect reproduction.

The FASTQ+ format and PISA.

SUMMARY: The FASTQ+ format is designed for single-cell experiments. It extends various optional tags, including cell barcodes and unique molecular identifiers, to the sequence identifier and is fully compatible with the FASTQ format. In addition, PISA implements various utilities for processing sequences in the FASTQ format and alignments in the SAM/BAM/CRAM format from single-cell experiments, such as converting FASTQ format to FASTQ+, annotating alignments, PCR deduplication, feature counting and barcodes correction. The software is open-source and written in C language. AVAILABILITY AND IMPLEMENTATION: https://doi.org/10.5281/zenodo.7007056 or https://github.com/shiquan/PISA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The correlation between prenatal maternal active smoking and neurodevelopmental disorders in children: a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the association between maternal active smoking during pregnancy and Tourette syndrome (TS), chronic tic disorder (CTD), and developmental coordination disorder (DCD) in children, and to provide evidence-based medical references to reduce the incidence of neurodevelopmental disorders in children. METHOD: We searched PubMed, Web of Science, Embase, and Cochrane Library to obtain relevant articles published before 4 August 2021. Two reviewers independently assessed the articles for eligibility and extracted data. RESULTS: We included eight studies involving a total of 50,317 participants (3 cohort, 3 case-control, and 2 cross-sectional studies). The pooled effect estimates suggested that prenatal maternal active smoking is related to an increased risk of neurodevelopmental disorders (OR = 1.91, 95% CI: 1.30-2.80), especially DCD (OR = 2.25, 95% CI: 1.35-3.75). Maternal active smoking during pregnancy is not associated with TS (OR = 1.07, 95% CI: 0.66-1.73) in children. CONCLUSION: In this meta-analysis, we found evidence for a correlation between active smoking exposure in pregnant women and neurodevelopmental disorders in children. Owing to the differences in sample size, smoking categories and diagnostic methods, further research is needed to validate our results.

The evolutionary history of extinct and living lions.

Lions are one of the world's most iconic megafauna, yet little is known about their temporal and spatial demographic history and population differentiation. We analyzed a genomic dataset of 20 specimens: two ca. 30,000-y-old cave lions (Panthera leo spelaea), 12 historic lions (Panthera leo leo/Panthera leo melanochaita) that lived between the 15th and 20th centuries outside the current geographic distribution of lions, and 6 present-day lions from Africa and India. We found that cave and modern lions shared an ancestor ca. 500,000 y ago and that the 2 lineages likely did not hybridize following their divergence. Within modern lions, we found 2 main lineages that diverged ca. 70,000 y ago, with clear evidence of subsequent gene flow. Our data also reveal a nearly complete absence of genetic diversity within Indian lions, probably due to well-documented extremely low effective population sizes in the recent past. Our results contribute toward the understanding of the evolutionary history of lions and complement conservation efforts to protect the diversity of this vulnerable species.

Effects of physical exercise on blood pressure during pregnancy.

OBJECTIVE: Effect of physical exercise on pregnant women currently has become a hot topic in prenatal health care. In this study, A meta-analysis was conducted on account of Randomized Controlled Trial (RCT). It focused on evaluating the effect of physical exercise intervention on blood pressure so that could provide certain evidence for health care during pregnancy. METHODS: Results of relevant studies were retrieved from PubMed, Embase, Web of Science and the Cochrane Library, and all of these included studies were evaluated according to the Cochrane collaboration's tool for assessing the risk of bias. Stata 15.1 was used for meta-analysis, and mean difference (MD) was used as statistic for pooled analysis. The effect values were combined by conventional meta-analysis and Bayesian meta-analysis respectively, and the consistency of pooled results was considered as well. RESULTS: A total of 18 RCT studies were included in the quantitative analysis. The conventional meta-analysis showed differences in blood pressure between intervention group and control group (P < 0.05). Systolic and diastolic blood pressures of intervention group were 3.19 mmHg (95% CI: -5.13, -1.25) and 2.14 mmHg (95% CI: -4.26, -0.03) lower than that of control group, respectively. Bayesian meta-analysis showed that both systolic and diastolic pressure among intervention group decreased by 3.34 mmHg (95% CrI: -5.15, -1.56) and 2.14 mmHg (95% CrI: -3.79, - 0.50), respectively. Subgroup analysis supported that as long as healthy pregnant women participated in exercises, their blood pressure could be slightly regulated, while hypertension susceptible pregnant women significantly lowered blood pressure. CONCLUSION: Exercise intervention during pregnancy is beneficial to lower or normalize blood pressure, and this research provides clues for follow-up studies.

Isolation, structure identification and hepatoprotective activity of a polysaccharide from Sabia parviflora.

The extraction, purification, structure and hepatoprotective activity of a homogenous polysaccharide (SPS60) from Sabia parviflora were investigated. SPS60 was screened after purification with Sephadex G-100 and showed the excellent hepatoprotective activity. Its structural characteristics were investigated by Time of flight mass spectrometry (TOF-MS), PMP Pre-column derivatization-HPLC (PMP-HPLC), nuclear magnetic resonance (NMR) spectroscopy and Atomic Force Microscopy (AFM). The results showed that SPS60 possessed the molecular weight of 16900 Da and the monosaccharide component was glucose, as well as a 1 â†’ 6 glycosidic bond. The results of atomic force microscopy (AFM) show that SPS60 is a blocky sphere in solution. Furthermore, the SPS60 could significantly improve the survival rate of LO2 hepatocytes which were damaged by CCl4. Therefore, SPS60 may be an active substance of S. parviflora as a local functional tea.

20-Hydroxyecdysone-responsive microRNAs of insects.

20-Hydroxyecdysone (20-HE) plays essential roles in coordinating developmental transitions of insects through responsive protein-coding genes and microRNAs (miRNAs). The involvement of single miRNAs in the ecdysone-signalling pathways has been extensively explored, but the interplay between ecdysone and the majority of miRNAs still remains largely unknown. Here, by small RNA sequencing, we systematically investigated the genome-wide responses of miRNAs to 20-HE in the embryogenic cell lines of Bombyx mori and Drosophila melanogaster. Over 60 and 70 20-HE-responsive miRNAs were identified in the BmE cell line and S2 cell line, respectively. The response of miRNAs to ecdysone exhibited a time-dependent pattern, and the response intensity increased with extending exposure to 20-HE. The relationship between ecdysone and the miRNAs was further explored through knockdown of ecdysone-signalling pathway genes. Specifically, ecdysone regulated the cluster miR-275 and miR-305 through the coordination of BmEcR-B and downstream BmE75B, and the interaction between BmEcR and miR-275 cluster was strengthened by the feedback regulation of BmE75B. Ecdysone induced miR-275-3p and miR-305-5p through the ecdysone response effectors (EcREs) at the upstream of the pre-miR-275 cluster. Overall, the results might help us further understand the relationship between ecdysone signalling pathways and small RNAs in the development and metamorphosis of insects.

Let-7 microRNA is a critical regulator in controlling the growth and function of silk gland in the silkworm.

The silk gland is characterized by high protein synthesis. However, the molecular mechanisms controlling silk gland growth and silk protein synthesis remain undetermined. Here we demonstrated that CRISPR/Cas9-based knockdown of let-7 or the whole cluster promoted endoreduplication and enlargement of the silk gland, accompanied by changing silk yield, whereas transgenic overexpression of let-7 led to atrophy and degeneration of the silk gland. Mechanistically, let-7 controls cell growth in the silk gland through coordinating nutrient metabolism processes and energy signalling pathways. Transgenic overexpression of pyruvate carboxylase, a novel target of let-7, resulted in enlargement of the silk glands, which is consistent with the abnormal phenotype of the let-7 knockdown. Overall, our data reveal a previously unknown miRNA-mediated regulation of silk gland growth and physiology and shed light on involvement of let-7 as a critical stabilizer and booster in carbohydrate metabolism, which may have important implications for understanding of the molecular mechanism and physiological function of specialized organs in other species.

Genome sequence of a diabetes-prone rodent reveals a mutation hotspot around the ParaHox gene cluster.

The sand rat Psammomys obesus is a gerbil species native to deserts of North Africa and the Middle East, and is constrained in its ecology because high carbohydrate diets induce obesity and type II diabetes that, in extreme cases, can lead to pancreatic failure and death. We report the sequencing of the sand rat genome and discovery of an unusual, extensive, and mutationally biased GC-rich genomic domain. This highly divergent genomic region encompasses several functionally essential genes, and spans the ParaHox cluster which includes the insulin-regulating homeobox gene Pdx1. The sequence of sand rat Pdx1 has been grossly affected by GC-biased mutation, leading to the highest divergence observed for this gene across the Bilateria. In addition to genomic insights into restricted caloric intake in a desert species, the discovery of a localized chromosomal region subject to elevated mutation suggests that mutational heterogeneity within genomes could influence the course of evolution.

Genetic Manipulation of MicroRNAs in the Silk Gland of Silkworm, Bombyx Mori.

BACKGROUND: MicroRNAs (miRNAs) are a class of non-coding RNAs with important post-transcriptional regulatory functions. To reveal the function of miRNAs in vivo, the critical step is to change their expression levels in the tissues or organs. In this work, we explored the application of several important genetic techniques in altering the expression of silk gland-specific miR-274 of silkworm (Bombyx mori). RESULTS: Injection of synthesized microRNA mimics and antagomirs exerted no effect on the expression of miR-274 in the silk gland, miR-274 sponge specifically absorbed miR-274 and down-regulated its expression, transgenic overexpression of miR-274 precursor significantly up-regulated miR-274, and finally tissue-specific CRISPR/Cas9 system achieved deletion of miR-274. CONCLUSIONS: A practical technical system was established for studying the functions of miRNAs in silk gland of Bombyx mori. Our research provides methodological support for the functional study of miRNAs and other noncoding RNAs in the silk gland and more organs in other species.

A coumarin analogue NFA from endophytic Aspergillus fumigatus improves drought resistance in rice as an antioxidant.

BACKGROUND: Drought and its resulting oxidative damage are the major yield limiting factors for crops in arid and semi-arid regions. Recent studies have found that endophytic fungi coexisting in plants can alleviate biotic or abiotic damage to plant growth and development. In order to screen for the endophytes associated with drought stress, 12 strains of endophytic fungi with high antioxidant activity isolated from riparian plants Myricaria laxiflora were evaluated for their effects in rice by the crude extracts. RESULTS: Of the 12 endophytic fungi, Aspergillus fumigatus SG-17 functioned most effectively, with the crude extract exhibiting relatively higher antioxidant capacity both in vivo and in vitro. The subsequent MS and NMR analysis showed that the primary substance responsible for the antioxidant activity in the extract was (Z)-N-(4-hydroxystyryl) formamide (NFA), an analogue of coumarin. Enzyme activity assay in nerve cells SH-SY5Y showed that NFA could maintain the membrane integrity and regulate the antioxidase activity under oxidative stress. In rice suffering drought stress, NFA effectively alleviated the harm by regulating the contents of NADPH oxidases, antioxidants and heat shock proteins, all of which are closely related with the reactive oxygen species pathway. CONCLUSION: These findings indicated that some endophytes from plants often subjected to flooding and oxidative stress could enhance drought resistance by producing compounds such as NFA to regulate the oxidative pathway.

Body mass index and C-peptide are important for the promptly differential diagnosis of maturity-onset diabetes from familial type 2 diabetes in outpatient clinic.

Type 2 diabetic patients are becoming younger and having a tendency to family aggregation, they are easily suspected as maturity-onset diabetes of young (MODY) in the outpatient clinic and send to genetic testing. 9 diabetic families were compared in our outpatient clinic who met the primary diagnosis criteria of MODY. Detailed clinical features and laboratory data including gene sequence were collected and analyzed. The patients met the primary clinical diagnostic criteria of MODY for genetic testing at the first look. However, members of families A1 to A3 had normal Body mass index (BMI) and a lower C-peptide level which indicated impaired pancreatic islet function. In contrast, the members with diabetes of families B1 to B6 had normal or increased C-peptide level which indicated insulin resistance and were overweight with BMI. Genetic testing showed that the mutations in HNF1A, INS, KCNJ11 and so on in families A were consistent with the diagnosis of MODY. No pathogenic mutation was found in the members of families B which were diagnosed with familial T2D. Before the clinical laboratory testing and the further gene test, BMI and the concentration of C-peptide are important for the promptly differential diagnosis of MODY from familial type 2 diabetes and medication instruction in the outpatient clinic which could help to alleviate the burden of genetic testing for them.

Influence of prenatal and early-life exposures on food allergy and eczema in infancy: a birth cohort study.

BACKGROUND: Few prospective birth cohort studies are available on the effects of prenatal and early-life exposures on food allergy and eczema among Chinese children. The aim of this study was to evaluate the influence of prenatal and early-life exposures on food allergy and eczema during the first year of life in a prospective birth cohort study. METHODS: This study was based on a prospective, observational birth cohort of 976 mother-child pairs in three Streets in Changsha, China from January to December 2015. Data on prenatal, early-life exposures and allergic outcomes were obtained from questionnaires collected at birth, and 1, 3, 6, 8, and 12 months of age. Multivariate logistic regression models were performed to estimate the effects of prenatal and early-life exposures on food allergy and eczema. RESULTS: Common risk factors for food allergy and eczema in infancy were parental history of allergy, while moderate eggs consumption (3-4 times/week) during pregnancy was protective for both of them compared with low consumption (≤ 2 times/week). Factors only associated with food allergy were maternal aquatic products consumption during pregnancy, number of older siblings and age of solid food introduction, whereas factors only associated with eczema were maternal milk or milk products consumption during pregnancy, maternal antibiotic exposure during pregnancy, season of birth and antibiotic exposure through medication during the first year of life. CONCLUSION: Our study suggests that factors associated with food allergy and eczema are multifaceted, which involving hereditary, environmental and nutritional exposures. Furthermore, differential factors influence the development of food allergy and eczema in infants.