Gender Incongruence and Autistic Traits: Cerebral and Behavioral Underpinnings.

Gender dysphoria and autism spectrum disorder (ASD) co-occur at high rates. Yet, it is unknown whether gender dysphoria and ASD are associated with common or distinct neurobiological correlates or how they relate to experiences of gender-related body incongruence. Using the Social Responsiveness Scale, we assessed autistic traits in 99 transgender and 99 cisgender individuals and investigated their associations with gender-related body incongruence, measured via a visually based "Body Morph" test, and with cortical thickness in the brain. Autistic traits were significantly higher among transgender individuals, and those with higher autistic traits had higher body incongruence scoring. Among transgender individuals, higher autistic traits were linked with a thinner cortex bilaterally in the temporal pole and the superior and inferior temporal gyri. Autistic traits were only partly associated with cortical morphology patterns previously reported in transgender individuals; instead, they were primarily linked to temporal lobe areas mediating social cognition. While replicating the previous literature on the increased prevalence of autistic traits among transgender individuals, this study reports specific regions in the brains of transgender individuals where cortical thickness is associated with autistic traits.

Comparative analysis of immunological changes following realgar and arsenic trioxide treatments in a murine model of myelodysplastic syndrome.

BACKGROUND: Myelodysplastic syndrome (MDS) is a prevalent hematological neoplastic disorder in clinics and its immunopathogenesis has garnered growing interest. Oral and intravenous arsenic agents have long been used to treat hematological malignancies. The main component of oral arsenic is realgar (arsenic disulfide), while arsenic trioxide is the main component of intravenous arsenic. METHODS: This study aimed to assess the effects of ATO and Realgar on the enhancement of peripheral blood, drug safety, and T cell immune status in the NUP98-HOXD13 (NHD13) mice model of MDS, specifically in the peripheral blood, spleen, and liver. RESULTS: The study findings indicate that realgar and arsenic trioxide (ATO) can improve peripheral hemogram in mice, whereas realgar promotes higher peripheral blood cell production than ATO. Furthermore, the clinical administration method and dose did not cause significant toxicity or side effects and thus can be considered safe. Coexistence and interconversion of hyperimmune function and immunosuppression in mice were also observed in this study. In addition, there were interactions between immune cells in the peripheral blood, spleen, and liver to regulate the immune balance of the body and activate immunity via T-cell activation. CONCLUSION: In summary, oral and intravenous arsenic agents are beneficial in improving peripheral hemogram and immunity in mice.

Amygdala subfield and prefrontal cortex abnormalities in patients with functional seizures.

BACKGROUND: Functional seizures (FS) are paroxysmal episodes, resembling epileptic seizures, but without underlying epileptic abnormality. The aetiology and neuroanatomic associations are incompletely understood. Recent brain imaging data indicate cerebral changes, however, without clarifying possible pathophysiology. In the present study, we specifically investigated the neuroanatomic changes in subregions of the amygdala and hippocampus in FS. METHODS: T1 MRI scans of 37 female patients with FS and 37 age-matched female seizure naïve controls (SNC) were analyzed retrospectively in FreeSurfer version 7.1. Seizure naïve controls included patients with depression and anxiety disorders. The analysis included whole-brain cortical thickness, subcortical volumes, and subfields of the amygdala and hippocampus. Group comparisons were carried out using multivariable linear models. RESULTS: The FS and SNC groups did not differ in the whole hippocampus and amygdala volumes. However, patients had a significant reduction of the right lateral amygdala volume (p = 0.00041), an increase of the right central amygdala, (p = 0.037), and thinning of the left superior frontal gyrus (p = 0.024). Additional findings in patients were increased volumes of the right medial amygdala (p = 0.031), left anterior amygdala (p = 0.017), and left dentate gyrus of the hippocampus (p = 0.035). CONCLUSIONS: The observations from the amygdala and hippocampus segmentation affirm that there are neuroanatomic associations of FS. The pattern of these changes aligned with some of the cerebral changes described in chronic stress conditions and depression. The pattern of detected changes further study, and may, after validation, provide biomarkers for diagnosis and treatment.

Cortical Gyrification in Transgender Individuals.

Gender incongruence (GI) is characterized by a feeling of estrangement from the own body in the context of self. GI is often described in people who identify as transgender. The underlying mechanisms are unknown. Data from MRI measurements and tests of own body perception triggered us to pose a model that GI in transgender persons (TGI) could be associated with a disconnection within the brain circuits mediating the perception of own body as self. This is a departure from a previous model of sex atypical cerebral dimorphism, introducing a concept that better accords with a core feature of TGI. The present MRI study of 54 hormone naive transmen (TrM), 38 transwomen (TrW), 44 cismen and 41 ciswomen show that cortical gyrification, a metric that reflects early maturation of cerebral cortex, is significantly lower in transgender compared with cisgender participants. This reduction is limited to the occipito-parietal cortex and the sensory motor cortex, regions encoding own body image and body ownership. Moreover, the cortical gyrification correlated inversely with own body-self incongruence in these regions. These novel data suggest that GI in TGI may originate in the neurodevelopment of body image encoding regions. The results add potentially to understanding neurobiological contributors to gender identity.

Similarities and differences in the induction and regulation of the negative emotions fear and disgust: A functional near infrared spectroscopy study.

Affective processing, including induction and regulation of emotion, activates neural networks, induces physiological responses, and generates subjective experience. Dysregulation of these processes can lead to maladaptive behavior and even psychiatric morbidity. Multimodal studies of emotion thus not only help elucidate the nature of emotion, but also contribute to important clinical insights. In the present study, we compared the induction (EI) and effortful regulation (ER) with reappraisal of fear and disgust in healthy subjects using functional near infrared spectroscopy (fNIRS) in conjunction with electrodermal activity (EDA). During EI, there was significant activation in medial prefrontal cortex (PFC) for fear and more widespread activation for disgust, with right lateral PFC significantly more active during disgust compared to fear. ER was equally effective for fear and disgust reducing subjective emotion rating by roughly 45%. Compared to baseline, there was no increased PFC activity for fear during ER, while for disgust lateral PFC was significantly more active. Significant differences between the two negative emotions were also observed in sympathetic nerve activity as reflected in EDA during EI, but not during ER. Lastly, compared to men, women had higher emotion rating for both fear and disgust without corresponding differences in EDA. In conclusion, in the present study we show that emotion induction was associated with differential activation in both PFC and sympathetic nerve activity for fear and disgust. These differences were however less prominent during emotion regulation. We discuss the potential interpretation of our results and their implications regarding our understanding of negative emotion processing.

Thermo-Optical Tuning Cascaded Double Ring Sensor with Large Measurement Range.

In this paper, a thermo-optic tuning optical waveguide sensor system based on a cascaded double micro-ring resonator is investigated. The system consists of a micro-ring resonator with the microheater as a reference ring and a micro-ring resonator with removing the upper cladding layers as a sensing ring, combined with a microfluidic control. The refractive index change of the sample is measured by the electric power change of the microheater. The experimental results show that the sensitivity of the thermo-optic tuning is 34.231 W/RIU (refractive index units), and the measurement range is 4.325 × 10-3 RIU, almost eight times larger than that of the cascaded double micro-ring resonator without thermo-optic tuning for the intensity interrogation.

Generation of Human Embryonic Stem Cell Line Expressing zsGreen in Cholinergic Neurons Using CRISPR/Cas9 System.

Lineage specific human embryonic stem cell (hESC) reporter cell line is a versatile tool for biological studies on real time monitoring of differentiation, physiological and biochemical features of special cell types and pathological mechanism of disease. Here we report the generation of ChAT-zsGreen reporter hESC line that express zsGreen under the control of the choline acetyltransferase (ChAT) promoter using CRISPR (Clustered Regularly Interspersed Short Palindromic Repeats)/Cas9 system. We show that the ChAT-zsGreen hESC reporter cell lines retain the features of undifferentiated hESC. After cholinergic neuronal differentiation, cholinergic neurons were clearly labeled with green fluorescence protein (zsGreen). The ChAT-zsGreen reporter hESC lines are invaluable not only for the monitoring cholinergic neuronal differentiation but also for study physiological and biochemical hallmarks of cholinergic neurons.

Synthesis of ultrathin TiO2/Ti films with tunable structural color.

A series of ultrathin TiO2/Ti films with iridescent structural colors were fabricated on high-purity titanium sheets via a one-step anodization procedure. Tunable color in the films can be obtained by adjusting the anodization time and can be adjusted across the entire visible range. It was found that all the films displayed highly saturated colors. Trichromatic coordinates of color x, y were delineated, and the color was identified by positioning the x and y values in the Commission International de I'Eclairage chromaticity diagram. Theoretical and experimental results of the changes in the structural color according to the principle of complementary colors are consistent with the experimental results. The TiO2/Ti films may have potential in color displays, decoration, and anticounterfeiting technology.

Computational identification and experimental validation of microRNAs binding to the fragile X syndrome gene Fmr1.

MicroRNAs (miRNAs) usually bind to their target mRNAs through imperfect base pairing in the 3'-untranslated regions (3' UTRs) and regulate target gene expression via post-transcriptional suppression. In recent years, computational approaches to predict miRNA targets have facilitated the identification of potential target sites. In this study, we used three programs TargetScan, miRDB and miRanda to predict potential miRNA binding sites to the fragile X gene Fmr1 and picked out 61 miRNAs which were predicted by all three programs for further investigation. Excitingly, 5 out of these miRNAs, miR-23a, miR-32, miR-124, miR-335-5p and miR-350, were experimentally verified by luciferase reporter assays. Furthermore, overexpression of miR-124 in mouse embryonic neural progenitor cells (eNPC) could not only significantly reduce Fmr1 level, but also increase Cdk4 and cyclin D1 levels which coincidently promoted eNPC proliferation. Our results imply that miR-124 plays an important role in the proliferation of mouse embryonic stem cells by promoting Cdk4 and cyclin D1 expression through directly inhibiting Fmr1 expression.

AI-based selection of individuals for supplemental MRI in population-based breast cancer screening: the randomized ScreenTrustMRI trial.

Screening mammography reduces breast cancer mortality, but studies analyzing interval cancers diagnosed after negative screens have shown that many cancers are missed. Supplemental screening using magnetic resonance imaging (MRI) can reduce the number of missed cancers. However, as qualified MRI staff are lacking, the equipment is expensive to purchase and cost-effectiveness for screening may not be convincing, the utilization of MRI is currently limited. An effective method for triaging individuals to supplemental MRI screening is therefore needed. We conducted a randomized clinical trial, ScreenTrustMRI, using a recently developed artificial intelligence (AI) tool to score each mammogram. We offered trial participation to individuals with a negative screening mammogram and a high AI score (top 6.9%). Upon agreeing to participate, individuals were assigned randomly to one of two groups: those receiving supplemental MRI and those not receiving MRI. The primary endpoint of ScreenTrustMRI is advanced breast cancer defined as either interval cancer, invasive component larger than 15 mm or lymph node positive cancer, based on a 27-month follow-up time from the initial screening. Secondary endpoints, prespecified in the study protocol to be reported before the primary outcome, include cancer detected by supplemental MRI, which is the focus of the current paper. Compared with traditional breast density measures used in a previous clinical trial, the current AI method was nearly four times more efficient in terms of cancers detected per 1,000 MRI examinations (64 versus 16.5). Most additional cancers detected were invasive and several were multifocal, suggesting that their detection was timely. Altogether, our results show that using an AI-based score to select a small proportion (6.9%) of individuals for supplemental MRI after negative mammography detects many missed cancers, making the cost per cancer detected comparable with screening mammography. ClinicalTrials.gov registration: NCT04832594 .

MicroRNA-130b targets Fmr1 and regulates embryonic neural progenitor cell proliferation and differentiation.

Fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by expansion of the CGG repeat in the 5'-untranslated region of the X-linked Fmr1 gene, which results in transcriptional silencing and loss of expression of its encoded protein FMRP. The loss of FMRP increases proliferation and alters fate specification in adult neural progenitor cells (aNPCs). However, little is known about Fmr1 mRNA regulation at the transcriptional and post-transcriptional levels. In the present study, we report that miR-130b regulated Fmr1 expression by directly targeting its 3'-untranslated region (3' UTR). Up-regulation of miR-130b in mouse embryonic neural progenitor cells (eNPCs) decreased Fmr1 expression, markedly increased eNPC proliferation and altered the differentiation tendency of eNPCs, suggesting that antagonizing miR-130b may be a new therapeutic entry point for treating Fragile X syndrome.

Determination of Cuproptosis-related Subtypes, Development of a Prognostic Model, and Characterization of Tumor Microenvironment Infiltration in Acute Myeloid Leukemia.

BACKGROUND/AIM: Acute myeloid leukemia (AML) is a severe malignancy of the bone marrow marked by an abnormal accumulation of bone marrow precursors. Cuproptosis is a recently identified type of copper-dependent regulatory cell apoptosis that relies on mitochondrial respiration. However, its participation in the development of AML remains unclear. This study analyzed the association between cuproptosis-related genes and the prognosis of AML patients. MATERIALS AND METHODS: Cases of AML were acquired from TCGA, GEO, and TARGET and the molecular subgroups characterized by genes associated with cuproptosis, besides the associated cell infiltration of the tumor microenvironment (TME) were investigated. The cuproptosis score was developed using the minor absolute shrinkage and selection operator (LASSO) tool to evaluate the cuproptosis features of a single tumor sample. RESULTS: Two distinct molecular subgroups related to cuproptosis were discovered in AML with different prognoses. The cellular infiltration assay of TME showed immunological heterogeneity between the two subtypes. The cuproptosis score predicted tumor subgroups, immunity, and prognosis. A small cuproptosis value was marked by a good prognosis, whereas the anti-PD-1/PD-L1 immunotherapy group suggested the same cuproptosis group was related to an elevated immunotherapy potency. CONCLUSION: The cuproptosis score is a biomarker important for determining the molecular subgroups, prognosis, TME cell infiltration features, and immunotherapeutic efficacy of individuals with leukemia.

Exploring underlying mechanism of artesunate in treatment of acute myeloid leukemia using network pharmacology and molecular docking.

BACKGROUND: Acute myeloid leukemia (AML) is a highly heterogeneous hematological cancer. The current diagnosis and therapy model of AML has gradually shifted to personalization and accuracy. Artesunate, a member of the artemisinin family, has anti-tumor impacts on AML. This research uses network pharmacology and molecular docking to anticipate artesunate potential mechanisms of action in the therapy of AML. METHODS: Screening the action targets of artesunate through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PubChem, and Swiss Target Prediction databases; The databases of Online Mendelian Inheritance in Man (OMIM), Disgenet, GeneCards, and Drugbank were utilized to identify target genes of AML, and an effective target of artesunate for AML treatment was obtained through cross-analysis. Protein-protein interaction (PPI) networks are built on the Cytoscape platform. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the relevant targets using R software. Finally, using molecular docking technology and Pymol, we performed verification of the effects of active components and essential targets. RESULTS: Artesunate 30 effective targets for treating AML include CASP3, EGFR, MAPK1, and STAT3, four targeted genes that may have a crucial function in disease management. The virus infection-related pathway (HeptatisB (HBV), Human papillomavirus (HPV), Epstein-Barr virus (EBV) infection and etc.), FoxO, viral carcinogenesis, and proteoglycans in cancer signaling pathways have all been hypothesized to be involved in the action mechanism of GO, which is enriched in 2044 biological processes, 125 molecular functions, 209 cellular components, and 106 KEGG pathways. Molecular docking findings revealed that artesunate was critically important in the therapy of AML due to its high affinity for the four primary disease targets. Molecular docking with a low binding energy yields helpful information for developing medicines against AML. CONCLUSIONS: Consequently, artesunate may play a role in multi-targeted, multi-signaling pathways in treating AML, suggesting that artesunate may have therapeutic potential for AML.

Dietary Guanidine Acetic Acid Addition Improved Carcass Quality with Less Back-Fat Thickness and Remarkably Increased Meat Protein Deposition in Rapid-Growing Lambs Fed Different Forage Types.

The aim of this study was to investigate whether guanidine acetic acid (GAA) yields a response in rapid-growing lambs depending on forage type. In this study, seventy-two small-tailed Han lambs (initial body weights = 12 ± 1.6 kg) were used in a 120-d feeding experiment after a 7-d adaptation period. A 2 × 3 factorial experimental feeding design was applied to the lambs, which were fed a total mixed ration with two forage types (OH: oaten hay; OHWS: oaten hay plus wheat silage) and three forms of additional GAA (GAA: 0 g/kg; UGAA: Uncoated GAA, 1 g/kg; CGAA: Coated GAA, 1 g/kg). The OH diet had a greater dry matter intake, average daily gain, and hot carcass weight than the OHWS diet. The GAA supplementation increased the final body weight, hot carcass weight, dressing percentage, and ribeye area in the longissimus lumborum. Meanwhile, it decreased backfat thickness and serum triglycerides. Dietary GAA decreased the acidity of the meat and elevated the water-holding capacity in mutton. In addition, the crude protein content in mutton increased with GAA addition. Dietary GAA (UGAA or CGAA) might be an effective additive in lamb fed by different forage types, as it has potential to improve growth performance and meat quality.

Behavioral, cortical and autonomic effects of single-dose escitalopram on the induction and regulation of fear and disgust: Comparison with single-session psychological emotion regulation with reappraisal.

Introduction: Adaptive and successful emotion regulation, the ability to flexibly exert voluntary control over emotional experience and the ensuing behavior, is vital for optimal daily functioning and good mental health. In clinical settings, pharmacological and psychological interventions are widely employed to modify pathological emotion processing and ameliorate its deleterious consequences. Methods: In this study, we investigated the acute effects of single-dose escitalopram on the induction and regulation of fear and disgust in healthy subjects. Furthermore, we compared these pharmacological effects with psychological emotion regulation that utilized a cognitive strategy with reappraisal. Emotion induction and regulation tasks were performed before and 4 h after ingestion of placebo or 10 mg escitalopram in a randomized, double-blind design. The International Affective Picture System (IAPS) was used as a source of images, with threat-related pictures selected for fear and disease and contamination-related pictures for disgust. Behavioral data, electrodermal activity (EDA), and functional near-infrared spectroscopy (fNIRS) recordings were collected. Results: Escitalopram significantly reduced emotion intensity for both fear and disgust during emotion induction, albeit with differing electrodermal and hemodynamic activity patterns for the two negative emotions. At rest, i.e., in the absence of emotive stimuli, escitalopram increased sympathetic activity during the fear but not during the disgust experiments. For both fear and disgust, emotion regulation with reappraisal was more effective in reducing emotion intensity compared to pharmacological intervention with escitalopram or placebo. Discussion: We concluded that emotion regulation with reappraisal and acute administration of escitalopram, but not placebo, reduce emotion intensity for both fear and disgust, with cognitive regulation being significantly more efficient compared to pharmacological regulation under the conditions of this study. Results from the fNIRS and EDA recordings support the concept of differential mechanisms of emotion regulation that could be emotion-specific.

The release and catabolism of ferulic acid in plant cell wall by rumen microbes: A review.

Ferulic acid (FA) is one of the most abundant hydroxycinnamic acids in the plant world, especially in the cell wall of grain bran, in comparison with forage and crop residues. Previous studies noted that FA was mainly linked with arabinoxylans and lignin in plant cell walls in ester and ether covalent forms. After forages were ingested by ruminant animals or encountered rumen microbial fermentation in vitro, these cross-linkages form physical and chemical barriers to protect cell-wall carbohydrates from microbial attack and enzymatic hydrolysis. Additionally, increasing studies noted that FA presented some toxic effect on microbial growth in the rumen. In recent decades, many studies have addressed the relationships of ester and/or ether-linked FA with rumen nutrient digestibility, and there is still some controversy whether these linkages could be used as a predicator of forage digestibility in ruminants. The authors in this review summarized the possible relationships between ester and/or ether-linked FA and fiber digestion in ruminants. Rumen microbes, especially bacteria and fungi, were found capable of breaking down the ester linkages within plant cell walls by secreting feruloyl and p-coumaroyl esterase, resulting in the release of free FA and improvement of cell wall digestibility. The increasing evidence noted that these esterases secreted by rumen microbes presented synergistic effects with xylanase and cellulase to effectively hydrolyze forage cell walls. Some released FA were absorbed through the rumen wall directly and entered into blood circulation and presented antioxidant effects on host animals. The others were partially catabolized into volatile fatty acids by rumen microbes, and the possible catabolic pathways discussed. To better understand plant cell wall degradation in the rumen, the metabolic fate of FA along with lignin decomposition mechanisms are needed to be explored via future microbial isolation and incubation studies with aims to maximize dietary fiber intake and enhance fiber digestion in ruminant animals.

Reduced prefrontal cortex and sympathetic nervous system activity correlate with fatigue after aHSCT.

Long-term fatigue and cognitive dysfunction affects 35% of allogeneic haematopoietic stem cell transplantation (aHSCT) survivors, suggesting a dysfunctional prefrontal cortex. In this study, we assessed prefrontal cortex and sympathetic nervous system activity in aHSCT patients with fatigue (n = 12), non-fatigued patients (n = 12) and healthy controls (n = 27). Measurement of near-infrared spectroscopy and electrodermal activity was carried out at rest and during cognitive performance (Stroop, verbal fluency and emotion regulation tasks). Prefrontal cortex and sympathetic nervous system activity were also analyzed in response to dopamine and noradrenaline increase after a single dose of methylphenidate. Baseline cognitive performance was similar in the two patient groups. However, after methylphenidate, only non-fatigued patients improved in Stroop accuracy and had better verbal fluency task performance compared to the fatigued group. Task-related activation of prefrontal cortex in fatigued patients was lower compared to non-fatigued patients during all cognitive tests, both before and after methylphenidate administration. During the Stroop task, reaction time, prefrontal cortex activation, and sympathetic nervous system activity were all lower in fatigued patients compared to healthy controls, but similar in non-fatigued patients and healthy controls.Reduced prefrontal cortex activity and sympathetic arousal suggests novel treatment targets to improve fatigue after aHSCT.

Transcriptome sequencing reveals Gastrodia elata Blume could increase the cell viability of eNPCs under hypoxic condition by improving DNA damage repair ability.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Blume (GEB), known as Tianma in China, is a traditional medicinal herb that has been reported to have various pharmacological effects and neuroprotection, has long been used for treating dizziness, epilepsy, stroke. However, explanation of its underlying mechanisms remains a great challenge. AIM OF THE STUDY: The neuroprotective mechanism of GEB on hypoxia-induced neuronal injury in cultured mouse embryonic neural progenitor cells (eNPCs) was investigated, with emphasis on the eNPCs proliferation and DNA damage repair. MATERIALS AND METHODS: In this study, hypoxia was focused, which may be caused by stroke or acute cerebral ischemia and is considered as one of the important factors contributing to the Central Nervous System diseases. CoCl2 was adopted to construct a hypoxic/ischemic condition in eNPCs. eNPCs proliferation analysis validated GEB neuroprotective effect under hypoxic/ischemic condition. Transcriptome and weighted gene co-expression network analysis (WGCNA) screened the special gene-network module correlated with what appeared to have significant positive correlation with GEB. Then, Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed to explore the biological functions of selected genes in the modules that had high correlation with GEB. RESULTS: GEB has neuroprotective effect and could rescue eNPCs proliferation under hypoxic/ischemic condition induced by CoCl2. Transcriptome and WGCNA unveil the neuroprotective mechanism of GEB on improving DNA damage repair ability by increasing the expression of genes associated with DNA repair and replication. Western blotting and qPCR showed that GEB could improve DNA damage repair ability by increasing the expression of Mcm2, Mcm6, Pold2, Pole, Pole2, Rfc1, Pole4, Dna2 and Rpa2, which were associated with DNA damage and replication. CONCLUSION: Through transcriptome and WGCNA, this study unveiled Gastrodia elata Blume could increase the cell viability of eNPCs under hypoxic condition by improving DNA damage repair ability.

Single-Cell Transcriptomics Reveals Splicing Features of Adult Neural Stem Cells in the Subventricular Zone.

The central nervous system has enormously complex cellular diversity with hundreds of distinct cell types, yet alternative splicing features in single cells of important cell types at neurogenic regions are not well understood. By employing in silico analysis, we systematically identified 3,611 alternative splicing events from 1,908 genes in 28 single-cell transcriptomic data of adult mouse ependymal and subependymal regions, and found that single-cell RNA-seq has the advantage in uncovering rare splicing isoforms compared to bulk RNA-seq at the population level. We uncovered that the simultaneous presence of multiple isoforms from the same gene in a single cell is prevalent, and quiescent stem cells, activated stem cells, and neuroblast cells exhibit high heterogeneity of splicing variants. Furthermore, we also demonstrated the existence of novel bicistronic transcripts in quiescent stem cells.

Dietary Cysteamine Supplementation Remarkably Increased Feed Efficiency and Shifted Rumen Fermentation toward Glucogenic Propionate Production via Enrichment of Prevotella in Feedlot Lambs.

Cysteamine (CS) is an essential nutritional regulator that improves the productive performance of animals by regulating somatotropic hormone secretion. To investigate the fattening potential and effects of CS on rumen microbial fermentation, 48 feedlot lambs were randomly assigned to four groups and fed diets supplemented with different CS concentrations (0, 20, 40, and 60 mg/kg BW). An increase in dietary CS concentrations linearly increased the average daily gain (ADG) and dry matter intake (p < 0.05) but decreased the feed-to-gain ratio (p < 0.01). For the serum hormone, increasing the dietary CS concentration linearly decreased somatostatin and leptin concentration (p < 0.01) but linearly increased the concentration of growth hormone and insulin-like growth factor 1 (p < 0.01). Regarding rumen fermentation, ruminal pH, ammonia-N, and butyrate content did not differ among the four treatments, although dietary CS supplementation linearly increased microbial protein and propionate and decreased the amount of acetate (p < 0.05). Furthermore, an increase in dietary CS concentrations quadratically decreased the estimated methane production and methane production per kg ADG (p < 0.05). High-throughput sequencing revealed that increased dietary CS concentrations quadratically increased Prevotella (p < 0.05), and Prevotella and norank_f__norank_o__Clostridia_UCG-014 were positively correlated with growth performance and rumen fermentation in a Spearman correlation analysis (r > 0.55, p < 0.05). Overall, a CS concentration higher than 20 mg/kg BW produced growth-promoting effects by inhibiting somatostatin concentrations and shifting the rumen toward glucogenic propionate fermentation by enriching Prevotella. In addition, Prevotella and norank_f__norank_o__Clostridia_UCG-014 were positively correlated with growth performance in lambs.