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.

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.

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 (AU)

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.

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.

In Situ Rumen Degradation Characteristics and Bacterial Colonization of Corn Silages Differing in Ferulic and p-Coumaric Acid Contents.

In plant cell wall, ferulic acid (FA) and p-coumaric acid (pCA) are commonly linked with arabinoxylans and lignin through ester and ether bonds. These linkages were deemed to hinder the access of rumen microbes to cell wall polysaccharides. The attachment of rumen microbes to plant cell wall was believed to have profound effects on the rate and the extent of forage digestion in rumen. The objective of this study was to evaluate the effect of bound phenolic acid content and their composition in corn silages on the nutrient degradability, and the composition of the attached bacteria. Following an in situ rumen degradation method, eight representative corn silages with different FA and pCA contents were placed into nylon bags and incubated in the rumens of three matured lactating Holstein cows for 0, 6, 12, 24, 36, 48, and 72 h, respectively. Corn silage digestibility was assessed by in situ degradation methods. As a result, the effective degradability of dry matter, neutral detergent fibre, and acid detergent fibre were negatively related to the ether-linked FA and pCA, and their ratio in corn silages, suggesting that not only the content and but also the composition of phenolic acids significantly affected the degradation characteristics of corn silages. After 24 h rumen fermentation, Firmicutes, Actinobacteria, and Bacteroidota were observed as the dominant phyla in the bacterial communities attached to the corn silages. After 72 h rumen fermentation, the rumen degradation of ester-linked FA was much greater than that of ester-linked pCA. The correlation analysis noted that Erysipelotrichaceae_UCG-002, Olsenella, Ruminococcus_gauvreauii_group, Acetitomaculum, and Bifidobacterium were negatively related to the initial ether-linked FA content while Prevotella was positively related to the ether-linked FA content and the ratio of pCA to FA. In summary, the present results suggested that the content of ether-linked phenolic acids in plant cell walls exhibited a more profound effect on the pattern of microbial colonization than the fibre content.

Guanidine acetic acid exhibited greater growth performance in younger (13-30 kg) than in older (30-50 kg) lambs under high-concentrate feedlotting pattern.

Guanidine acetic acid (GAA) is increasingly considered as a nutritional growth promoter in monogastric animals. Whether or not such response would exist in rapid-growing lambs is unclear yet. The objective of this study was to investigate whether dietary supplementation with uncoated GAA (UGAA) and coated GAA (CGAA) could alter growth performance, nutrient digestion, serum metabolites, and antioxidant capacity in lambs. Seventy-two small-tailed Han lambs initially weighed 12 ± 1.6 kg were randomly allocated into six groups in a 2 × 3 factorial experimental design including two forage-type rations [Oaten hay (OH) vs. its combination with wheat silage (OHWS)] and three GAA treatment per ration: no GAA, 1 g UGAA, and 1 g CGAA per kg dry matter. The whole experiment was completed in two consecutive growing stages (stage 1, 13-30 kg; stage 2, 30-50 kg). Under high-concentrate feeding pattern (Stage 1, 25: 75; Stage 2, 20: 80), UGAA or CGAA supplementation in young lambs presented greater dry matter intake (DMI) in stage 1 and average daily gain (ADG) in the whole experimental period; lambs in OH group had higher ADG and DMI than that in OHWS group in stage 1 and whole experimental period, but this phenomenon was not observed in stage 2. Both UCGA and CGAA addition increased dietary DM, organic matter (OM), neutral detergent fiber (NDF), and acid detergent fiber (ADF) digestion in both stages. In blood metabolism, UCGA and CGAA addition resulted in a greater total protein (TP) and insulin-like growth factor 1(IGF-1) levels, as well as antioxidant capacity; at the same time, UCGA and CGAA addition increased GAA metabolism-creatine kinase and decreased guanidinoacetate N-methyltransferase (GAMT) and L-Arginine glycine amidine transferase catalyzes (AGAT) activity. In a brief, the results obtained in the present study suggested that GAA (UGAA and CGAA; 1 g/kg DM) could be applied to improve growth performance in younger (13-30 kg) instead of older (30-50 kg) lambs in high-concentrate feedlotting practice.

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.

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.

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.

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.

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.

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.

Isolation and Identification of a Rumen Lactobacillus Bacteria and Its Degradation Potential of Gossypol in Cottonseed Meal during Solid-State Fermentation.

Cottonseed meal (CSM) is an important protein feed source for dairy cows. Its inclusion in ruminant diets is limited due to the presence of the highly toxic gossypol though rumen microorganisms are believed to be capable of gossypol degrading and transforming. The objective of the present study was to isolate the gossypol-degrading bacteria from the rumen contents and to assess its potential for gossypol degradation in vitro. A strain named Lactobacillus agilis WWK129 was anaerobically isolated from dairy cows after mixed rumen microorganisms were grown on a substrate with gossypol as the sole carbon source. Furthermore, the strain was applied at 5% inoculum concentration in vitro to continuously ferment CSM at 39 °C for five days, and it presented gossypol degradability as high as 83%. Meanwhile, the CSM contents of crude protein, essential amino acids increased significantly along with the increase of lactic acid yield (p < 0.01). Compared with the original CSM, the fermented CSM contents of neutral detergent fiber and acid detergent fiber was remarkably decreased after the anaerobic fermentation (p < 0.01). In brief, the Lactobacillus strain isolated from the rumen is not only of great importance for gossypol biodegradation of CSM, but it could also be used to further explore the role of rumen microorganisms in gossypol degradation by the ruminants.

Gossypol detoxification in the rumen and Helicoverpa armigera larvae: A review.

Gossypol, a phenolic compound found in the cotton plant, is widely distributed in cottonseed by-products. Although ruminant animals are believed to be more tolerant of gossypol toxicity than monogastric animals due to rumen microbial fermentation, the actual mechanisms of detoxification remain unclear. In contrast, the metabolic detoxification of gossypol by Helicoverpa armigera (Lepidoptera: Noctuidae) larvae has achieved great advances. The present review discusses the clinical signs of gossypol in ruminant animals, as well as summarizing advances in the study of gossypol detoxification in the rumen. It also examines the regulatory roles of several key enzymes in gossypol detoxification and transformation known in H. armigera. With the rapid development of modern molecular biotechnology and -omics technology strategies, evidence increasingly indicates that research into the biological degradation of gossypol in H. armigera larvae and some microbes, in terms of these key enzymes, could provide scientific insights that would underpin future work on microbial gossypol detoxification in the rumen, with the ultimate aim of further alleviating gossypol toxicity in ruminant animals.

In situ rumen degradation characteristics and bacterial colonization of whole cottonseed, cottonseed hull and cottonseed meal with different gossypol content.

Regarding whole cottonseed (WCS), cottonseed meal (CSM), and cottonseed hull (CSH), in situ rumen incubation was applied to determine their nutrient and gossypol degradation characteristics and bacterial colonization profile in lactating Holstein cows. Nylon bags containing the cotton by-products were incubated for 0, 6, 12, 24, 36, 48 and 72 h in the rumen, respectively. The relationship between nutrient degradability and free gossypol (FG) content were examined, and the differences in the composition and inferred gene function of the colonized microbiota were studied. As a result, CSM presented highest effective degradability of dry matter, neutral detergent fibre and acid detergent fibre, but the highest effective degradability of crude protein was found in WCS. Free gossypol disappearance rate increased significantly in the first 6 h, and it reached approximately 94% at 72 h of incubation among all samples. The level of FG did not affect nutrient degradability of cotton by-products. Significant differences were noted in attached bacterial community structure among cotton by-products after 24 h rumen incubation. Among the most abundant taxa at genus level, a greater abundance of Cercis gigantea and Succiniclasticum was observed in WCS samples, whereas the CSH and CSM samples contained a greater proportion of Prevotella 1 and Rikenellaceae RC9 gut group. The redundancy analysis revealed that the level of neutral detergent fibre, ether extract, and FG in cotton by-products were significantly positive related with the composition of the attached bacteria. Collectively, our results revealed the dynamics of degradation characteristics, and the difference in the composition of bacterial colonization. These findings are of importance for the targeted improvement of cotton by-products nutrient use efficiency in ruminants and further understanding of the gossypol degradation mechanism in the rumen.

Gossypol Exhibited Higher Detrimental Effect on Ruminal Fermentation Characteristics of Low-Forage in Comparison with High-Forage Mixed Feeds.

Gossypol is a key anti-nutritional factor which limits the feeding application of cottonseed by-products in animal production. A 2 × 4 factorial in vitro experiment was conducted to determine the effect of gossypol addition levels of 0, 0.25, 0.5, and 0.75 mg/g on ruminal fermentation of a high-forage feed (HF, Chinese wildrye hay/corn meal = 3:2) in comparison with a low-forage feed (LF, Chinese wildrye hay/corn meal = 2:3). After 48 h of incubation, in vitro dry matter disappearance was greater in the LF than the HF group, while the cumulative gas production and asymptotic gas production were greater in the HF than the LF group (p < 0.05). Regardless of whatever ration type was incubated, the increasing gossypol addition did not alter in vitro dry matter disappearance. The asymptotic gas production, cumulative gas production, molar percentage of CO2 and H2 in fermentation gases, and microbial protein in cultural fluids decreased with the increase in the gossypol addition. Conversely, the gossypol addition increased the molar percentage of CH4, ammonia N, and total volatile fatty acid production. More than 95% of the gossypol addition disappeared after 48 h of in vitro incubation. Regardless of whatever ration type was incubated, the real-time PCR analysis showed that the gossypol addition decreased the populations of Fibrobactersuccinogenes, Ruminococcus albus, Butyrivibrio fibrisolvens, Prevotella ruminicola, Selenomonas ruminantium, and fungi but increased Ruminococcus flavefaciens, protozoa, and total bacteria in culture fluids in comparison with the control (p < 0.01). Additionally, the tendency of a smaller population was observed for R. albus, B. fibrisolvens, and fungi with greater inclusion of gossypol, but a greater population was observed for F. succinogenes, R. flavefaciens, S. ruminantium, protozoa, and total bacteria. In summary, the present results suggest that rumen microorganisms indeed presented a high ability to degrade gossypol, but there was an obvious detrimental effect of the gossypol addition on rumen fermentation by decreasing microbial activity when the gossypol inclusion exceeded 0.5 mg/g, and such inhibitory effect was more pronounced in the low-forage than the high-forage group.