Unveiling the Ovarian Cell Characteristics and Molecular Mechanism of Prolificacy in Goats via Single-Nucleus Transcriptomics Data Analysis.

Increases in litter size, which are influenced by ovulation, are responsible for between 74% and 96% of the economic value of genetic progress, which influences selection. For the selection and breeding of highly prolific goats, genetic mechanisms underlying variations in litter size should be elucidated. Here, we used single-nucleus RNA sequencing to analyze 44,605 single nuclei from the ovaries of polytocous and monotocous goats during the follicular phase. Utilizing known reference marker genes, we identified 10 ovarian cell types characterized by distinct gene expression profiles, transcription factor networks, and reciprocal interaction signatures. An in-depth analysis of the granulosa cells revealed three subtypes exhibiting distinct gene expression patterns and dynamic regulatory mechanisms. Further investigation of cell-type-specific prolificacy-associated transcriptional changes elucidated that "downregulation of apoptosis", "increased anabolism", and "upstream responsiveness to hormonal stimulation" are associated with prolificacy. This study provides a comprehensive understanding of the cell-type-specific mechanisms and regulatory networks in the goat ovary, providing insights into the molecular mechanisms underlying goat prolificacy. These findings establish a vital foundation for furthering understanding of the molecular mechanisms governing folliculogenesis and for improving the litter size in goats via molecular design breeding.

Loss of BAF (mSWI/SNF) chromatin-remodeling ATPase Brg1 causes multiple malformations of cortical development in mice.

Mutations in genes encoding subunits of the BAF (BRG1/BRM-associated factor) complex cause various neurodevelopmental diseases. However, the underlying pathophysiology remains largely unknown. Here, we analyzed the function of Brahma-related gene 1 (Brg1), a core ATPase of BAF complexes, in the developing cerebral cortex. Loss of Brg1 causes several morphological defects resembling human malformations of cortical developments (MCDs), including microcephaly, cortical dysplasia, cobblestone lissencephaly and periventricular heterotopia. We demonstrated that neural progenitor cell renewal, neuronal differentiation, neuronal migration, apoptotic cell death, pial basement membrane and apical junctional complexes, which are associated with MCD formation, were impaired after Brg1 deletion. Furthermore, transcriptome profiling indicated that a large number of genes were deregulated. The deregulated genes were closely related to MCD formation, and most of these genes were bound by Brg1. Cumulatively, our study indicates an essential role of Brg1 in cortical development and provides a new possible pathogenesis underlying Brg1-based BAF complex-related neurodevelopmental disorders.

Vineyard microclimate alterations induced by black inter-row mulch through transcriptome reshaped the flavoromics of cabernet sauvignon grapes.

BACKGROUND: Weed control is essential for agricultural floor management in vineyards and the inter-row mulching is an eco-friendly practice to inhibit weed growth via filtering out photosynthetically active radiation. Besides weed suppression, inter-row mulching can influence grapevine growth and the accumulation of metabolites in grape berries. However, the complex interaction of multiple factors in the field challenges the understanding of molecular mechanisms on the regulated metabolites. In the current study, black geotextile inter-row mulch (M) was applied for two vintages (2016-2017) from anthesis to harvest. Metabolomics and transcriptomics analysis were conducted in two vintages, aiming to provide insights into metabolic and molecular responses of Cabernet Sauvignon grapes to M in a semi-arid climate. RESULTS: Upregulation of genes related to photosynthesis and heat shock proteins confirmed that M weakened the total light exposure and grapes suffered heat stress, resulting in lower sugar-acid ratio at harvest. Key genes responsible for enhancements in phenylalanine, glutamine, ornithine, arginine, and C6 alcohol concentrations, and the downward trend in ε-viniferin, anthocyanins, flavonols, terpenes, and norisoprenoids in M grapes were identified. In addition, several modules significantly correlated with the metabolic biomarkers through weighted correlation network analysis, and the potential key transcription factors regulating the above metabolites including VviGATA11, VviHSFA6B, and VviWRKY03 were also identified. CONCLUSION: This study provides a valuable overview of metabolic and transcriptomic responses of M grapes in semi-arid climates, which could facilitate understanding the complex regulatory network of metabolites in response to microclimate changes.

Novel algorithm for diagnosis of Arrhythmogenic cardiomyopathy and dilated cardiomyopathy: Key gene expression profiling using machine learning.

BACKGROUND: It is difficult to distinguish between arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy (DCM) because of their similar clinical manifestations. This study aimed to develop a novel diagnostic algorithm for distinguishing ACM from DCM. METHODS: Two public datasets containing human ACM and DCM myocardial samples were used. Consensus clustering, non-negative matrix factorization and principal component analysis were applied. Weighted gene co-expression network analysis and machine learning methods, including random forest and the least absolute shrinkage and selection operator, were used to identify candidate genes. Receiver operating characteristic curves and nomograms were performed to estimate diagnostic efficacy, and Spearman's correlation analysis was used to assess the correlation between candidate genes and cardiac function indices. RESULTS: Both ACM and DCM showed highly similar gene expression patterns in the clustering analyses. Hub gene modules associated with cardiomyopathy were obtained using weighted gene co-expression network analysis. Thirteen candidate genes were selected using machine learning algorithms, and their combination showed a high diagnostic value (area under the ROC curve = 0.86) for distinguishing ACM from DCM. In addition, TATA-box binding protein associated factor 15 showed a negative correlation with cardiac index (R = -0.54, p = 0.0054) and left ventricular ejection fraction (R = -0.48, p = 0.0015). CONCLUSIONS: Our study revealed an effective diagnostic model with key gene signatures, which indicates a potential tool to differentiate between ACM and DCM in clinical practice. In addition, we identified several genes that are highly related to cardiac function, which may contribute to our understanding of ACM and DCM.

Postpartum Levothyroxine Adjustment and Its Impact Factors in Women With Hypothyroidism in Pregnancy.

OBJECTIVE: Women with hypothyroidism need to increase exogenous thyroid hormone levels during pregnancy to reduce adverse outcomes. Few studies have reported the effect of gestational levothyroxine (LT4) variations on postpartum LT4 treatment. METHODS: Women were classified as having subclinical hypothyroidism (SCH) (n = 101), overt hypothyroidism (OH) caused by autoimmune thyroiditis (AIT-OH), OH following thyroidectomy for benign thyroid disease (BA-OH) (n = 66), and OH after surgery for papillary thyroid cancer (PTC-OH) (n = 46). Thyroid function was monitored, and LT4 therapy was adjusted accordingly. RESULTS: After delivery, all women with SCH stopped LT4 treatment, and 57.4% of them restarted LT4 treatment in the following 1 year, independently of the gestational LT4 variations. Among patients with OH, after adjusted by gestational body weight, 49.1% of them had LT4 doses less than the prepregnancy dose (baseline) in late pregnancy, leading to LT4 reduction in postpartum. The LT4 dose was reduced to approximately 50% baseline for women with AIT-OH and BA-OH and reduced by 27% for women with PTC-OH. The reduction reasons for AIT-OH and BA-OH were thyroid-stimulating hormone levels of <2.5 mU/L during pregnancy and postpartum thyrotoxicosis occurrence (39.4%), and for PTC-OH, the reason was thyroid-stimulating hormone overinhibition (<1.0 mU/L) before delivery. CONCLUSION: For patients with SCH, postpartum LT4 treatment could initially be suspended. For women with OH, if the LT4 dose in late pregnancy was less than baseline, a prepregnancy dose reduced by 50%, 50%, and 27% should be applied after delivery for women with AIT-OH, BA-OH, and PTC-OH, respectively.

In Vitro and in Vivo RNA Inhibition by CD9-HuR Functionalized Exosomes Encapsulated with miRNA or CRISPR/dCas9.

In vitro and in vivo delivery of RNAs of interest holds promise for gene therapy. Recently, exosomes are considered as a kind of rational vehicle for RNA delivery, especially miRNA and/or siRNA, while the loading efficiency is limited. In this study, we engineered the exosomes for RNA loading by constructing a fusion protein in which the exosomal membrane protein CD9 was fused with RNA binding protein, while the RNA of interest either natively harbors or is engineered to have the elements for the binding. By proof-of-principle experiments, we here fused CD9 with HuR, an RNA binding protein interacting with miR-155 with a relatively high affinity. In the exosome packaging cells, the fused CD9-HuR successfully enriched miR-155 into exosomes when miR-155 was excessively expressed. Moreover, miR-155 encapsulated in the exosomes in turn could be efficiently delivered into the recipient cells and recognized the endogenous targets. In addition, we also revealed that the CD9-HuR exosomes could enrich the functional miRNA inhibitor or CRISPR/dCas9 when the RNAs were engineered to have the AU rich elements. Taken together, we here have established a novel strategy for enhanced RNA cargo encapsulation into engineered exosomes, which in turn functions in the recipient cells.

Effects of gibberellic acid (GA3 ) application before anthesis on rachis elongation and berry quality and aroma and flavour compounds in Vitis vinifera L. 'Cabernet Franc' and 'Cabernet Sauvignon' grapes.

BACKGROUND: Gibberellic acid (GA3 ), a plant-growth regulator, is often used to obtain enlarged table grape berries and induce seedlessness in them. However, the effects of GA3 on rachis elongation and bunch compactness have seldom been reported in wine-grape production. We assessed the effects of GA3 spraying on wine-grape inflorescences and bunches and their practical implications for viticulture in the Jiaodong Peninsula, China. RESULTS: Various GA3 concentrations were sprayed on field-grown Vitis vinifera L. 'Cabernet Franc' (CF) and 'Cabernet Sauvignon' (CS) grapevines before anthesis in the Jiaodong Peninsula, China, in 2015 and 2016. Inflorescence length during berry development was measured, and flavonoids and aroma compounds in the fruit were detected by high-performance liquid chromatography - mass spectrometry (HPLC-MS) and gas chromatography - mass spectrometry (GC-MS), respectively. For both cultivars, 50 and 100 mg L-1 GA3 caused significant elongation of the rachis, whereas there was no significant effect on inflorescence growth and berry seed number. Anthocyanin, flavonol, and flavan-3-ol levels in mature berries were not significantly influenced by GA3 spraying, whereas C13 -norisoprenoids were modified. CONCLUSION: The application of 50-100 mg L-1 GA3 prior to grapevine anthesis caused elongation of inflorescences and bunches, and eased cluster compactness in CF and CS, and no negative effects were observed on the yield and seed numbers. The concentration and composition of flavonoids and most aroma compounds were not influenced, except that the norisoprenoids were increased by 50 mg L-1 GA3 applications. © 2020 Society of Chemical Industry.

Chronic myeloid leukemia-derived exosomes attenuate adipogenesis of adipose derived mesenchymal stem cells via transporting miR-92a-3p.

Cancer-associated cachexia (CAC) has tremendous effects on the patient's tolerance to chemotherapy and the quality of life, especially in the advanced stages, such as the acute and terminal stages of chronic myeloid leukemia (CML). However, the underlying mechanisms and mediators remain unclear. Here, we showed that mice injected with CML-derived exosomes had significant weight loss and great drop of body fat rate. In the meanwhile, we found that CML-derived exosomes could be taken up by adipose tissue, and, in turn, suppressed the adipogenic ability of adipose-derived mesenchymal stem cells (ADSCs). By RNA sequencing, miR-92a-3p was found highly expressed in both CML cells and the derivative exosomes. Mechanistically, miR-92a-3p inhibited adipogenesis of ADSCs via posttranscriptionally decreasing C/EBPα expression when transferred into the ADSCs with the exosomes, and encapsulating miR-92a-3p inhibitor into CML exosomes blocked the antiadipogenic effects of CML exosomes. In addition, we also found that miR-92a-3p was highly expressed in exosomes from some other types of cancers that cause cachexia. These results demonstrate that adipogenesis inhibition by tumor-derived exosomes, mainly exosomal microRNAs like miR-92a-3p, are the main mediators for CAC.

Oocyte-specific deletion of Gsα induces oxidative stress and deteriorates oocyte quality in mice.

The stimulatory heterotrimeric Gs protein alpha subunit (Gsα) is a ubiquitous guanine nucleotide-binding protein that regulates the intracellular cAMP signaling pathway and consequently participates in a wide range of biological events. In the reproductive system, despite Gsα being associated with oocyte meiotic arrest in vitro, the exact role of Gsα in female fertility in vivo remains largely unknown. Here, we generated oocyte-specific Gsα knockout mice by using the Cre/LoxP system. We observed that the deletion of Gsα caused complete female infertility. Exclusion of post-implantation abnormalities, oogenesis, fertilization, and early embryo development was subsequently monitored; meiosis in Gsα-deficient oocytes precociously resumed in only 43% of antral follicles from mutant mice, indicating that alteration of meiotic pause was not the key factor in infertility. Ovulation process and number were normal, but the rate of morphological abnormal oocytes was apparently increased; spindle organization, fertilization, and early embryo development were impaired. Furthermore, the level of ROS (reactive oxygen species) and the mitochondrial aggregation increased, and antioxidant glutathione (GSH) content, ATP level, mtDNA copy number, and mitochondrial membrane potential decreased in Gsα-deficient oocytes. GV oocytes from mutant mice showed early-stage apoptosis. Meanwhile, the Gsα knockout-induced decline in oocyte quality and low developmental potential was partially rescued by antioxidant supplementation. To sum up, our results are the first to reveal that the profile of Gsα oocyte-specific deletion caused female infertility in vivo, and oxidative stress plays an important role in this event.

Targeted blocking of miR328 lysosomal degradation with alkalized exosomes sensitizes the chronic leukemia cells to imatinib.

Imatinib resistance remains the biggest hurdle for the treatment of chronic myeloid leukemia (CML), with the underlying mechanisms not fully understood. In this study, we found that miR328 significantly and strikingly decreased among other miRNA candidates during the induction of imatinib resistance. Overexpression of miR328 sensitized resistant cells to imatinib via post-transcriptionally decreasing ABCG2 expression, while miR328 knockdown conferred imatinib resistance in parental K562 cells. Moreover, miR328 was found selectively degraded in the lysosomes of K562R cells, as inhibition of lysosome with chloroquine restored miR328 expression and increased sensitivity to imatinib. Moreover, delivery of alkalized exosomes increased endogenous miR328 expression. Compared with the corresponding controls, the alkalized exosomes with or without miR328 sensitized the chronic leukemia cells to imatinib. Taken together, our study has revealed that lysosomal clearance of miR328 in imatinib-resistant cells at least partially contributes to the drug resistance, while delivery of alkalized exosomes would sensitize the chromic leukemia cells to imatinib.

Rootstock-Mediated Effects on Cabernet Sauvignon Performance: Vine Growth, Berry Ripening, Flavonoids, and Aromatic Profiles.

Rootstocks are widely used in viticulture due to their resistance to biotic and abiotic stress. Additionally, rootstocks can affect vine growth and berry quality. This study evaluated the effects of eight rootstocks (101-14, 110R, 5A, 5BB, Ganzin 1, Harmony, Riparia Gloire, and SO4) on the vine growth, berry ripening, and flavonoids and aromatic profiles of Cabernet Sauvignon in two consecutive seasons (2015⁻2016). With few exceptions, minor differences were observed among grafted and own-rooted vines. Own-rooted vines produced the least pruning weight but the highest yield. 101-14, 5BB, and SO4 slightly reduced total soluble solids, but increased acidity, showing tendencies for retarding maturation. Ganzin 1 inhibited the accumulation of flavan-3-ols in berry skins. Furthermore, concentrations and proportions of epicatechin-3-O-galate were decreased by rootstocks, except for 110R. 5A, Harmony, and Riparia Gloire enhanced flavonol concentrations. SO4 slightly decreased most of the individual anthocyanin concentrations. With respect to volatile compounds, 110R, Riparia Gloire, and SO4 induced reductions in concentrations of total esters, whilst 101-14, Ganzin 1, 110R, and 5BB led to increases in the concentrations of C13-norisoprenoids. Therefore, with respect to the negative effects of SO4 on berry ripening and the accumulation of anthocyanin and volatile esters, SO4 is not recommended in practice.

Artificial shading of teinturier grape Kolor clusters reveals light-responsive biomarkers: focus on flavonoid profiles and metabolism.

Kolor is a teinturier grape cultivar, that accumulates flavonoids in the skin and pulp. However, the concentrations and proportions of flavonoids in Kolor skin and pulp differ, suggesting tissue specificity in teinturier grapes. Light conditions significantly influence the evolution of flavonoids. Moreover, studies on the mechanisms governing flavonoid accumulation in light response sensitivity of teinturier grapes are limited. In the three consecutive years of study, the exposure of Kolor clusters was altered by bagging from pre-veraison to harvest. QqQ/MS and RT‒qPCR wereused to determine the individual anthocyanin contents and the relative gene expression. There was a significant decrease in the total anthocyanins and flavonols in the Kolor berries, with flavonols showing greater sensitivity to bagging. Bagging did not exert a consistent impact on the flavan-3-ols in Kolor berries. The sensitivities of anthocyanins in Kolor skin and pulp differed under light exclusion conditions. The concentration of trihydroxy-substituted anthocyanins in the skin decreased, while the proportion of dihydroxy-substituted anthocyanins in the pulp significantly increased, but the anthocyanin concentration in the pulp did not change significantly after bagging. The contents of malvidins and quercetins in the skin, and myricetins and quercetins in the pulp, were significantly reduced after bagging. The expression of flavonoid synthesis genes in Kolor skin and pulp was tissue-specific. After bagging, UFGT expression increased in the pulp and decreased in the skin. In addition, LDOX, FLS-1, CHI-1, CHI-2, F3H-1, F3H-2, and MYB4a exhibited sensitive light responses in both the skin and pulp. This study offers new insights into the regulation of flavonoids in Kolor grapes under light exclusion conditions.

Association between the triglyceride-glucose index and thyroid disorders: a cross-sectional survey and Mendelian randomization analysis.

BACKGROUND: Metabolic diseases are associated with thyroid disorders. Insulin resistance is the common pathological basis of metabolic diseases. We explored the relationship between the triglyceride-glucose (TyG) index, a simple insulin-resistance marker, and thyroid disorders. METHODS: Eligible TIDE (Thyroid Diseases, Iodine Status and Diabetes Epidemiology) subjects (n = 47,710) were screened with inclusion/exclusion criteria. Thyroid disorder prevalence among different TyG index groups was stratified by sex. Logistic regression evaluated the correlation between the TyG index and thyroid disorders. Multiple linear regression evaluated the association between the TyG index and TSH. Additionally, two-sample Mendelian randomization (MR) using published genome-wide association study data evaluated causality in the association between the TyG index and TSH. RESULTS: Men and women with greater TyG indices had a significantly greater prevalence of thyroid disorders than individuals with the lowest quartile (Q1) of TyG index (p < 0.05). Following adjustment for confounding factors, we observed that a greater TyG index significantly increased the risk of subclinical hypothyroidism in men and women (men: Q2: odds ratio (OR) [95% confidence interval (CI)] = 1.22 [1.07-1.38], p = 0.002; Q3: OR [95% CI] = 1.28 [1.12-1.45], p < 0.001; Q4: OR [95% CI] = 1.29 [1.12-1.50], p = 0.001; women: Q2: OR [95% CI] = 1.25 [1.12-1.39], p < 0.001; Q3: OR [95% CI] = 1.47 [1.31-1.64], p < 0.001; Q4: OR [95% CI] = 1.61 [1.43-1.82], p < 0.001). Only among women was the highest TyG index quartile associated with hypothyroidism (OR [95% CI] = 1.70 [1.15-2.50], p = 0.007). Additionally, in men, the association exists only in the more than adequate iodine intake population. In women, the relationship between the TyG index and thyroid disorders disappears after menopause. Furthermore, the TyG index exhibited a linear positive correlation with TSH levels. The MR analysis results revealed a causal relationship between a genetically determined greater TyG index and increased TSH (inverse-variance weighting (IVW): OR [95% CI] = 1.14 [1.02-1.28], p = 0.020); however, this causal relationship disappeared after adjusting for BMI in multivariable MR (MVMR) analysis (MVMR-IVW: OR 1.03, 95% CI 0.87-1.22, p = 0.739). CONCLUSIONS: A greater TyG index is associated with hypothyroidism and subclinical hypothyroidism and varies by sex and menopausal status. MR analysis demonstrated that the causal relationship between a genetically determined greater TyG index and elevated TSH levels is confounded or mediated by BMI.

Analyzing inclusive green growth in China: a perspective of relative efficiency.

Inclusive Green Growth (IGG) has important reference value for China's ecological civilization construction and transformation of economic development. Therefore, this study assesses China's IGG level from the perspective of relative efficiency. The IGG efficiency (IGGE) was measured at the provincial level in China from 2000 to 2020 by using Super-Epsilon-Based Measure (EBM) model that considers undesirable outputs. The spatiotemporal pattern of IGGE was analyzed by kernel density estimation and spatial autocorrelation. The results indicate a fluctuating trend from 2000 to 2020 for the IGGE of China, and significant differences between regional and interprovincial IGGE were observed. On average, the eastern region presented the highest efficiency, while the level in the central regions was lowest. There is a positive spatial autocorrelation in the IGGE distribution, and the agglomeration of spatial distribution fluctuated during the study period. The IGGE has spatial spillover effects at the provincial level according to the spatial Durbin model. Among the influencing factors, the spatial spillover effects of industrial structure, government administrative capability, and industrialization level are significant. The regression results also confirm the Environmental Kuznets Curve effect between IGG and economic growth in China. Finally, some implicit policies can be established based on the empirical analysis.

Digital economy impact on inclusive green growth: intermediary and spatial spillover effects in China.

As a new economic form that has emerged from the technological and digital revolution, the digital economy has great benefits to the green development of the economy, protection of the ecological environment, and improvement in social well-being. This study examines whether the digital economy affects the inclusive green growth (IGG). Measurement index system for the digital economy and IGG from 2013 to 2020 in China was constructed and the entropy evaluation method and super-efficiency epsilon-based measure (Super-EBM) model was used to evaluate them. We examined the direct effect, mediation effect, and spatial spillover effect of the digital economy on IGG using the basic regression model, mediating effect model, and the spatial Durbin model. Our results revealed that the development of the digital economy has clear regional differences. The role of digital economy on IGG has positive direct effects and positive spatial spillover effects. The digital economy affects IGG through industrial structure upgrading, so industrial structure upgrading has a significant intermediary effect. By comparing the coefficients, we found that the spatial spillover effects are stronger than the direct effects. Absorbing the spillover of the digital economy in surrounding areas is particularly important for promoting IGG. Heterogeneity analysis revealed that the digital economy is better for IGG and releases more digital dividends in eastern China. Finally, the research conclusions of this paper provide reference for the Chinese government to formulate relevant policies to deepen the integration of digital information technology and IGG, and promote the coordinated development of regional digital economy and IGG.

The evaluation of active transcriptional repressor domain for CRISPRi in plants.

With the development of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) system in gene editing, the catalytic site in Cas9 has been mutated to dead Cas9 (dCas9) to regulate target gene's expression with the guidance of single guide RNA (sgRNA) in many organisms. When dCas9 was navigated to the region close to the transcription start site, duo to sterical hindrance, it could downregulate the expression level of target gene specifically without genomic alteration. Furthermore, the fusion of synthetic transcriptional repressor domain (TRD) to dCas9 could improve the gene silencing efficiency dramatically, the above all was also known as CRISPR interference system (CRISPRi). Till now, SRDX repressor domain was the most frequently used TRD in plant. Nevertheless, its incomplete repression limited the application of CRISPRi system. Hereafter, in this study, we identified three more effective TRDs, DLN144, DLS and MIX in plant. To dissect the transcriptional repressing activity of DLN144, DLS and MIX in plant, first and foremost, we proved their transcriptional repression efficiency in transient transformed Nicotiana benthamiana leaves. Then, their intrinsic transcriptional repressing activity was corroborated in stable transgenic wheat and N. benthamiana. These three functional TRDs, DLN144, DLS and MIX, provide more options for the application of CRISPRi in plant and shed new light on the advancement of more robust TRDs by combining different individual effective repressor domain in plant which will facilitate the application of CRISPRi when higher repression efficiency is required.

A Highly Stereoselective Redox Isomerization-Reductive Deuteration Sequence of Propargyl Amines to α-Deuterated Amino Acids.

Herein, we report a Cu-catalyzed redox isomerization-reductive deuteration sequence, providing facile access to a range of α-deuterated amino acid esters featuring an Z-configured alkene moiety with high yields. The advantages of this sequence include mild conditions, broad substrate scope, and excellent stereoselectivity. This research also represents a rare example of the Z-selective redox isomerization of propargyl amines.

A Systematic Review and Meta-Analysis Examining the Risk of Adverse Pregnancy and Neonatal Outcomes in Women with Isolated Hypothyroxinemia in Pregnancy.

Background: The relationship between isolated hypothyroxinemia (IH) in pregnancy and adverse pregnancy outcomes is controversial, with no consensus on the need for treatment. Summary: We conducted a systematic review and meta-analysis examining adverse pregnancy and neonatal outcomes in women with IH in pregnancy. We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials for publications from inception to December 2022. Randomized clinical trials and cohort studies were included. Random-effects meta-analyses were used to estimate pooled relative risks (RRs) for each outcome. We included 21 articles, of which 19 investigated the relationship between IH and maternal and neonatal outcomes and 4 investigated the efficacy of levothyroxine (LT4) treatment. Compared with euthyroid pregnancies, IH pregnancies were associated with an increased risk of preterm birth (RR 1.35 [confidence interval, CI, 1.16-1.56]; I2 = 9%), premature rupture of membranes (RR 1.41 [CI 1.08-1.84]; I2 = 0%), gestational diabetes (RR 1.34 [CI 1.07-1.67]; I2 = 76%), macrosomia (RR 1.62 [CI 1.31-2.02]; I2 = 42%), and fetal distress (RR 1.72 [CI 1.15-2.56]; I2 = 0%). However, no statistically significant differences were noted in adverse outcomes according to LT4 treatment status. Conclusions: There is evidence suggesting that IH in pregnancy may be associated with an increased risk of adverse pregnancy and neonatal outcomes. However, it is unclear whether LT4 may mitigate the risk of these adverse outcomes.

Resveratrol inhibits the formation and accumulation of lipid droplets through AdipoQ signal pathway and lipid metabolism lncRNAs.

Resveratrol (RES) is one of the best-known bioactive polyphenols that has received much attention in recent years because of its importance to anti-obesity. However, the exact mechanism underlying this effect and whether it can improve lipid metabolism by regulating the long-chain noncoding RNA (lncRNA) remains unclear. In this study, 24 healthy crossbred castrated boars were fed a basal diet (control) and a basal diet supplemented with 200 mg, 400 mg or 600 mg RES per Kilogram (kg) of feed for 41 d, respectively. We found that 400 mg/kg and 600 mg/kg RES-supplemented diet did not affect growth rate, but reduced significantly subcutaneous adipose thickness, carcass fat rate, greater dramatically the serum concentration of adiponectin and high-density lipoprotein in pigs. Further, we verified that RES could inhibit the formation and accumulation of lipid droplets by AdipoQ-AdipoR1-AMPKα and AdipoQ-AdipoR2-PPARα signal pathway in vivo and vitro (3T3-L1 preadipocytes). Transcriptome analyses found that 5 differently expressed (DE) lncRNAs and 77 mRNAs in subcutaneous adipose between control group and 400 mg/kg RES group, which mainly involved in "adipocytokine signaling pathway," "Wnt signaling pathway," "PI3K-Akt signaling pathway" and "MAPK signaling pathway." In conclusion, RES can inhibit the formation and accumulation of lipid droplets through AdipoQ signal pathway and lipid metabolism-related lncRNAs. Our results provide a new insight on the molecular mechanism of RES as a nutritional agents to the prevention and treatment for obesity.

Comparative and Functional Analysis of miRNAs and mRNAs Involved in Muscle Fiber Hypertrophy of Juvenile and Adult Goats.

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate several pathway intermediates and affect the skeletal muscle development in mice, pigs, sheep, and cattle. However, to date, only a small number of miRNAs have been reported in the muscle development of goats. In this report, the longissimus dorsi transcripts of one- and ten-month-old goats were analyzed by sequencing RNAs and miRNAs. The results showed that the ten-month-old Longlin goats had 327 up- and 419 down-regulated differentially expressed genes (DEGs) compared with the one-month-old. In addition, 20 co-up-regulated and 55 co-down-regulated miRNAs involved in the muscle fiber hypertrophy of goats were identified in ten-month-old Longlin and Nubian goats compared with one-month-old. Five miRNA-mRNA pairs (chi-let-7b-3p-MIRLET7A, chi-miR193b-3p-MMP14, chi-miR-355-5p-DGAT2, novel_128-LOC102178119, novel_140-SOD3) involved in the goat skeletal muscle development were identified by miRNA-mRNA negative correlation network analysis. Our results provided new insight into the functional roles of goat muscle-associated miRNAs, allowing a deeper understanding of the transformation of miRNA roles during mammalian muscle development.