Cognitive Phenotype Shifts in Risk Taking: Interplay of Nonsuicidal Self-Injury Behaviors and Intensified Depression.

BACKGROUND: Nonsuicidal self-injury (NSSI) behavior is significantly prevalent in both adolescents and psychiatric populations, particularly in individuals with major depressive disorder. NSSI can be considered a result of risky decision making in response to negative emotions, where individuals choose self-harm over other less harmful alternatives, suggesting a potential decision-making deficit in those engaging in NSSI. This study delves into the complex relationship between NSSI and depression severity in decision making and its cognitive underpinnings. METHODS: We assessed decision behaviors in 57 patients with major depressive disorder and NSSI, 42 patients with major depressive disorder without NSSI, and 142 healthy control participants using the Balloon Analog Risk Task, which involves risk taking, learning, and exploration in uncertain scenarios. Using computational modeling, we dissected the nuanced cognitive dimensions influencing decision behaviors. A novel statistical method was developed to elucidate interaction effects between NSSI and depression severity. RESULTS: Contrary to common perceptions, we found that individuals with NSSI behaviors were typically more risk averse. There was also a complex interaction between NSSI and depression severity in shaping risk-taking behaviors. As depressive symptoms intensified, the individuals with NSSI began to perceive less risk and behave more randomly. CONCLUSIONS: This research provides new insights into the cognitive aspects of NSSI and depression, highlighting the importance of considering the influence of comorbid mental disorders when investigating the cognitive underpinnings of such behaviors, especially in the context of prevalent cross-diagnostic phenomena such as NSSI behaviors.

Biochemical characterization of the Eya and PP2A-B55α interaction.

The eyes absent (Eya) proteins were first identified as co-activators of the six homeobox family of transcription factors and are critical in embryonic development. These proteins are also re-expressed in cancers after development is complete, where they drive tumor progression. We have previously shown that the Eya3 N-terminal domain (NTD) contains Ser/Thr phosphatase activity through an interaction with the protein phosphatase 2A (PP2A)-B55α holoenzyme and that this interaction increases the half-life of Myc through pT58 dephosphorylation. Here, we showed that Eya3 directly interacted with the NTD of Myc, recruiting PP2A-B55α to Myc. We also showed that Eya3 increased the Ser/Thr phosphatase activity of PP2A-B55α but not PP2A-B56α. Furthermore, we demonstrated that the NTD (∼250 amino acids) of Eya3 was completely disordered, and it used a 38-residue segment to interact with B55α. In addition, knockdown and phosphoproteomic analyses demonstrated that Eya3 and B55α affected highly similar phosphosite motifs with a preference for Ser/Thr followed by Pro, consistent with Eya3's apparent Ser/Thr phosphatase activity being mediated through its interaction with PP2A-B55α. Intriguingly, mutating this Pro to other amino acids in a Myc peptide dramatically increased dephosphorylation by PP2A. Not surprisingly, MycP59A, a naturally occurring mutation hotspot in several cancers, enhanced Eya3-PP2A-B55α-mediated dephosphorylation of pT58 on Myc, leading to increased Myc stability and cell proliferation, underscoring the critical role of this phosphosite in regulating Myc stability.

Selected humanization of yeast U1 snRNP leads to global suppression of pre-mRNA splicing and mitochondrial dysfunction in the budding yeast.

The recognition of the 5' splice site (5' ss) is one of the earliest steps of pre-mRNA splicing. To better understand, the mechanism and regulation of 5' ss recognition, we selectively humanized components of the yeast U1 (yU1) snRNP to reveal the function of these components in 5' ss recognition and splicing. We targeted U1C and Luc7, two proteins that interact with and stabilize the yU1 snRNA and the 5' ss RNA duplex. We replaced the zinc-finger (ZnF) domain of yeast U1C (yU1C) with its human counterpart, which resulted in a cold-sensitive growth phenotype and moderate splicing defects. We next added an auxin-inducible degron to yeast Luc7 (yLuc7) protein (to mimic the lack of Luc7Ls in human U1 snRNP). We found that Luc7-depleted yU1 snRNP resulted in the concomitant loss of Prp40 and Snu71 (two other essential yU1 snRNP proteins), and further biochemical analyses suggest a model of how these three proteins interact with each other in the U1 snRNP. The loss of these proteins resulted in a significant growth retardation accompanied by a global suppression of pre-mRNA splicing. The splicing suppression led to mitochondrial dysfunction as revealed by a release of Fe2+ into the growth medium and an induction of mitochondrial reactive oxygen species. Together, these observations indicate that the human U1C ZnF can substitute that of yeast, Luc7 is essential for the incorporation of the Luc7-Prp40-Snu71 trimer into yU1 snRNP, and splicing plays a major role in the regulation of mitochondrial function in yeast.

Ratiometric G-quadruplex/hemin DNAzymes with low-dosage associative substrates.

BACKGROUND: G-quadruplex (G4)/hemin DNAzymes with conversion of substrates into colorimetric readouts are well recognized as convenient biocatalysis tools in sensor development. However, the previously developed colorimetric G4/hemin DNAzymes are diffusive substrate-based DNAzymes (DSBDs). The current colorimetric DSBDs have several drawbacks including high dosage (∼mM) of diffusive substrates (DSs), colorimetric product toxicity, and single colorimetric readout without tolerance to fluctuation of experimental factors and background. In addition, the usage of high-dosage DSs can smear the G4 foldings and their discard is more harmful to environment. Therefore, exploring alternative DNAzymes with potential to overcome these drawbacks of DSBDs is urgently needed. RESULTS: We herein developed associative substrate-based DNAzymes (ASBDs). Cyanine dyes were selected as associative substrates (ASs) due to their binding competency with G4/hemin DNAzymes. With respect to DSBDs, ASBDs needed only low dosage (∼10 µM) of ASs to be able to cause a rapid and visible substrate conversion. In addition, since cyanine dyes are NIR dyes with high extinction coefficients and their conversion products have absorption bands at shorter wavelength. Therefore, a colorimetric ratio response can be developed to follow activities of G4/hemin DNAzymes with competency to tolerate fluctuation of experimental factors and background. In particular, herein developed ASBDs can endure somewhat concentration fluctuation of H2O2. ASBDs are able to cowork with other enzymes (for example, glucose oxidase) to realize cascade sensing. SIGNIFICANCE: The developed ASBDs can operate at low dosage of substrates with a colorimetric ratio response and can overcome the drawbacks met in DSBDs. We expect that, by designing ASs with fruitful color panel in the future, our work will inspire more interesting in developing environment-benign and low-carbon G4/hemin DNAzymes and desired colorful high-performance sensors.

Maladaptive cognitive regulation moderates the mediating role of emotion dysregulation on the association between psychosocial factors and non-suicidal self-injury in depression.

Introduction: Non-suicidal self-injury (NSSI) is highly prevalent in depression, and is associated with psychosocial factors, emotion dysregulation, and strategies of cognitive emotion regulation. However, the internal combination and interactions of these risk factors in depression remain unclear. Methods: Data from 122 patients with depression, including 56 with NSSI and 66 without NSSI, were analyzed. Self-rating scales were used to assess psychosocial factors, emotion dysregulation, and cognitive regulation strategies. Sparse partial least squares discriminant analysis (sPLS-DA) was employed to explore internal combinations in each profile. A moderated mediation model was applied to examine their interactional relationship. Results: The results identified an NSSI-related psychosocial profile characterized by high neuroticism, childhood trauma, poor family functioning, and low psychological resilience. Emotion dysregulation, including high levels of alexithymia, anhedonia, and emotion regulation difficulties, mediated the association between this psychosocial profile and NSSI. The mediated effect was further moderated by maladaptive cognitive regulation strategies. Limitations: Lack of sufficient information on NSSI frequency and severity. Relatively small sample size for discussing the impact of gender and age of depressive patients with NSSI. Conclusion: These findings hold important implications for the prevention, treatment, and rehabilitation of NSSI.

Garbractin A, a Polycyclic Polyprenylated Acylphloroglucinol with a 4,11-dioxatricyclo[4.4.2.01,5]Dodecane Skeleton from Garcinia bracteata Fruits.

Garbractin A (1), a structurally complicated polycyclic polyprenylated acylphloroglucinol (PPAP) with an unprecedented 4,11-dioxatricyclo[4.4.2.01,5] dodecane skeleton, was isolated from the fruits of Garcinia bracteata, along with five new biosynthetic analogues named garcibracteatones A-E (2-6). Their structures containing absolute configurations were revealed using spectroscopic data, the residual dipolar coupling-enhanced NMR approach, and quantum chemical calculations. The antihyperglycemic effect of these PPAPs (1-6) was evaluated using insulin-resistant HepG2 cells (IR-HepG2 cells) induced through palmitic acid (PA). Compounds 1, 3, and 4 were found to significantly promote glucose consumption in the IR-HepG2 cells and, therefore, may hold potential as candidates for treating hyperglycemia.

Isolation and antihyperglycemic effects of garcibractinols A-H, intricate polycyclic polyprenylated acylphloroglucinols from the fruits of Garcinia bracteata.

Eight previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) were isolated from the fruits of Garcinia bracteata and named garcibractinols A-H. Garcibractinols A-F (compounds 1-6) were bicyclic polyprenylated acylphloroglucinols (BPAPs) sharing a rare bicyclo[4.3.1]decane core. On the other hand, garcibractinols G and H (compounds 7 and 8) shared an unprecedented BPAP skeleton bearing a 9-oxabicyclo[6.2.1]undecane core. The structures andabsolute configurations of compounds 1-8 were determined by spectroscopic analysis,single-crystal X-ray diffraction analysis, and quantum chemical calculation. The breakage of the C-3/C-4 linkage through the retro-Claisen reaction was a key step in the biosynthesis of compounds 7 and 8. The antihyperglycemic effects of the eight compounds were evaluated in insulin-resistant HepG2 cells. At a concentration of 10 µM, compounds 2 and 5-8 significantly increased the glucose consumption in the HepG2 cells. Furthermore, compound 7 was more effective than metformin (which was used as a positive control) in promoting glucose consumption in the cells. The findings of this study suggest that compounds 2 and 5-8 have anti-diabetic effects.

Scalemic diacetylenic spiroacetal enol ethers from the flowers of Tanacetum tatsienense.

Six scalemic mixtures of previously undescribed diacetylenic spiroacetal enol ethers (DSEEs) and six scalemic mixtures of known DSEEs were isolated from the flowers of Tanacetum tatsienense. Except for E-epidendranthemenol, Z-O-acetyl-epi dendranthemenol, and Z-O-isovaleryl-epidendranthemenol, the remaining scalemic mixtures of DSEEs were resolved by chiral HPLC, and their structures were determined through an analysis of HR-ESI-MS and NMR data. The absolute configurations of seven pairs of enantiomers and one pair of epimers were determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectra. In addition, the inhibitory effects of all of the DSEEs on nitric oxide (NO) production were evaluated in LPS-stimulated RAW264.7 cells. The results showed that (+)-tatsienenol B had a weak inhibitory effect on NO production. The IC50 value of the compound was 19.78 ±â€¯0.78 µM. This study is the first to report that DSEEs are isolable from plants as scalemic mixtures. Moreover, this study is the first to determine the absolute configurations of DSEEs by chiral resolution and ECD calculations.

Molecular insight into the specific interactions of the SARS-Coronavirus-2 nucleocapsid with RNA and host protein.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid protein is the most abundantly expressed viral protein during infection where it targets both RNA and host proteins. However, identifying how a single viral protein interacts with so many different targets remains a challenge, providing the impetus here for identifying the interaction sites through multiple methods. Through a combination of nuclear magnetic resonance (NMR), electron microscopy, and biochemical methods, we have characterized nucleocapsid interactions with RNA and with three host proteins, which include human cyclophilin-A, Pin1, and 14-3-3τ. Regarding RNA interactions, the nucleocapsid protein N-terminal folded domain preferentially interacts with smaller RNA fragments relative to the C-terminal region, suggesting an initial RNA engagement is largely dictated by this N-terminal region followed by weaker interactions to the C-terminal region. The nucleocapsid protein forms 10 nm ribonuclear complexes with larger RNA fragments that include 200 and 354 nucleic acids, revealing its potential diversity in sequestering different viral genomic regions during viral packaging. Regarding host protein interactions, while the nucleocapsid targets all three host proteins through its serine-arginine-rich region, unstructured termini of the nucleocapsid protein also engage host cyclophilin-A and host 14-3-3τ. Considering these host proteins play roles in innate immunity, the SARS-CoV-2 nucleocapsid protein may block the host response by competing interactions. Finally, phosphorylation of the nucleocapsid protein quenches an inherent dynamic exchange process within its serine-arginine-rich region. Our studies identify many of the diverse interactions that may be important for SARS-CoV-2 pathology during infection.

Selected humanization of yeast U1 snRNP leads to global suppression of pre-mRNA splicing and mitochondrial dysfunction in the budding yeast.

The recognition of 5' splice site (5' ss) is one of the earliest steps of pre-mRNA splicing. To better understand the mechanism and regulation of 5' ss recognition, we selectively humanized components of the yeast U1 snRNP to reveal the function of these components in 5' ss recognition and splicing. We targeted U1C and Luc7, two proteins that interact with and stabilize the yeast U1 (yU1) snRNA and the 5' ss RNA duplex. We replaced the Zinc-Finger (ZnF) domain of yU1C with its human counterpart, which resulted in cold-sensitive growth phenotype and moderate splicing defects. Next, we added an auxin-inducible degron to yLuc7 protein and found that Luc7-depleted yU1 snRNP resulted in the concomitant loss of PRP40 and Snu71 (two other essential yeast U1 snRNP proteins), and further biochemical analyses suggest a model of how these three proteins interact with each other in the U1 snRNP. The loss of these proteins resulted in a significant growth retardation accompanied by a global suppression of pre-mRNA splicing. The splicing suppression led to mitochondrial dysfunction as revealed by a release of Fe 2+ into the growth medium and an induction of mitochondrial reactive oxygen species. Together, these observations indicate that the human U1C ZnF can substitute that of yeast, Luc7 is essential for the incorporation of the Luc7-Prp40-Snu71 trimer into yeast U1 snRNP, and splicing plays a major role in the regulation of mitochondria function in yeast.

Human PRPF39 is an alternative splicing factor recruiting U1 snRNP to weak 5' splice sites.

Human PRPF39 is a homolog of the yeast Prp39 and Prp42 paralogs. We have previously shown that human PRPF39 forms a homodimer that interacts with the CTD of U1C, mirroring the yeast Prp39/Prp42 heterodimer. We demonstrate here that PRPF39 knockdown in HEK293 cells affects many alternative splicing events primarily by reducing the usage of weak 5'ss. Additionally, PRPF39 preferentially binds to a GC-rich RNA, likely at the interface between its NTD and CTD. These data indicate that PRPF39 potentially recruits U1 snRNP to a weak 5' ss, serving as a previously unrecognized alternative splicing factor. We further demonstrate that human TIA1 binds to U1C through its RRM1 and RRM3+Q domains but has no significant binding to PRPF39. Finally, all three human LUC7L isoforms directly interact with U1C. These results reveal significant parallels to the yeast U1 snRNP structure and support the use of yeast U1 snRNP as a model for understanding the mechanism of human alternative splicing.

Features of gut microbiota in patients with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a psychological disorder, which is characterized by the misunderstanding of body image, food restriction, and low body weight. An increasing number of studies have reported that the pathophysiological mechanism of AN might be associated with the dysbiosis of gut microbiota. The purpose of our study was to explore the features of gut microbiota in patients with AN, hoping to provide valuable information on its pathogenesis and treatment. METHODS: In this cross-sectional study, from August 2020 to June 2021, patients with AN who were admitted into Peking University Third Hospital and Peking University Sixth Hospital ( n   =  30) were recruited as the AN group, and healthy controls (HC) were recruited from a middle school and a university in Beijing ( n   =  30). Demographic data, Hamilton Depression Scale (HAMD) scores of the two groups, and length of stay of the AN group were recorded. Microbial diversity analysis of gut microbiota in stool samples from the two groups was analyzed by 16S ribosomal RNA (rRNA) gene sequencing. RESULTS: The weight (AN vs. HC, [39.31 ±â€Š7.90] kg vs. [56.47 ±â€Š8.88] kg, P  < 0.001) and body mass index (BMI, AN vs. HC, [14.92 ±â€Š2.54] kg/m 2vs. [20.89 ±â€Š2.14] kg/m 2 , P  < 0.001) of patients with AN were statistically significantly lower than those of HC, and HAMD scores in AN group were statistically significantly higher than those of HC. For alpha diversity, there were no statistically significant differences between the two groups; for beta diversity, the two groups differed obviously regarding community composition. Compared to HC, the proportion of Lachnospiraceae in patients with AN was statistically significantly higher (AN vs. HC, 40.50% vs. 31.21%, Z  = -1.981, P  = 0.048), while that of Ruminococcaceae was lower (AN vs. HC, 12.17% vs. 19.15%, Z  = -2.728, P  = 0.007); the proportion of Faecalibacterium (AN vs. HC, 3.97% vs. 9.40%, Z  = -3.638, P  < 0.001) and Subdoligranulum (AN vs. HC, 4.60% vs. 7.02%, Z  = -2.369, P  = 0.018) were statistically significantly lower, while that of Eubacterium_hallii_group was significantly higher (AN vs. HC, 7.63% vs. 3.43%, Z  = -2.115, P  = 0.035). Linear discriminant effect (LEfSe) analysis (LDA score >3.5) showed that o_Lachnospirales, f_Lachnospiraceae, and g_Eubacterium_hallii_group (o, f and g represents order, family and genus respectively) were enriched in patients with AN. Microbial function of nutrient transport and metabolism in AN group were more abundant ( P  > 0.05). In AN group, weight and BMI were significantly negatively correlated with the abundance of Bacteroidota and Bacteroides , while positively correlated with Subdoligranulum . BMI was significantly positively correlated with Firmicutes; HAMD scores were significantly negatively correlated with Faecalibacterium. CONCLUSIONS: The composition of gut microbiota in patients with AN was different from that of healthy people. Clinical indicators have correlations with the abundance of gut microbiota in patients with AN.

Chemical constituents from the seeds of Nigella glandulifera and their hypoglycemic activities.

The seeds of Nigella glandulifera Freyn et Sint. are traditional Uygur medicine used for the treatment of diabetes. However, the active anti-diabetic constituents in the seeds of N. glandulifera remain unclear. In the present study, a new delabellane-type diterpene, 8-denicotinoylnigellamine A1 (1), and a new acyclic sesquiterpene, 2,6,10-trimethyl-6,7,12-trihydroxy-dodec-2-ene (3), together with eight known compounds including alkaloids (2 and 7), triterpenoid saponins (4-6), and phenolic compounds (8-10), were isolated from the seeds of N. glandulifera. Their structures were determined by extensive spectroscopic analyses and quantum chemical calculations. We evaluated the potential protective effects of the isolated compounds on an insulin resistant HepG2 (IR-HepG2) cell model. The results showed that compounds 2, 4-8, and 10 could promote the consumption of glucose in IR-HepG2 cells. Those compounds might be responsible for the anti-diabetic effects of the seeds of N. glandulifera.

Phenolic Compounds From the Stems and Leaves of Berchemia lineata (L.) DC.

Eight new phenolic compounds, named bercheminols A-H (1-8), and eleven known analogues were isolated from the stems and leaves of Berchemia lineata (L.) DC. Their structures including the absolute configurations were elucidated by extensive spectroscopic analysis, chemical method, and quantum chemical calculations. Compound 1 possesses an unprecedented 3,4-dihydro-11H-benzo[b]pyrano[4,3-e] oxepin-11-one skeleton. The other new compounds belong to three structural types of natural products, including naphthopyrones (2-5), flavonoids (6-7), and bibenzyl (8). The α-glucosidase inhibitory activities of the isolated compounds were assayed. As a result, vittarin-B (9), rubrofusarin-6-O-ß-D-glucopyranoside (11), quercetin (14), kaempferol (15), and dihydrokaempferol (17) showed moderate inhibitory activities against α-glucosidase with IC50 values of 22.5, 28.0, 36.5, 32.7, and 31.9 µM, respectively.

Polyprenylated Acylphloroglucinols With Different Carbon Skeletons From the Fruits of Garcinia multiflora.

Eleven new polycyclic polyprenylated acylphloroglucinols (PPAPs, 1-11) and three new monocyclic polyprenylated acylphloroglucinols (MPAPs, 12-14), together with ten known analogues were isolated from the fruits of Garcinia multiflora. These PPAPs belong to three types including the bicyclic polyprenylated acylphloroglucinols (BPAPs), the caged PPAPs, and the complicated PPAPs. Their structures and absolute configurations were determined through HRESIMS, NMR spectroscopy data, electronic circular dichroism (ECD) calculations, and gauge-independent atomic orbital (GIAO) NMR calculations with DP4+ analyses. Moreover, compounds 2 and 7 exhibited moderate cytotoxicity against three human cancer lines (MCF-7, T98, and HepG2) with IC50 values ranging from 9.81 ± 1.56 to 17.00 ± 2.75 µM.

Detecting circRNA in purified spliceosomal P complex.

Circular RNAs (circRNAs) generated from back-splicing of exons have been found in a wide range of eukaryotic species and exert a variety of biological functions. Unlike canonical splicing, the mechanism of back-splicing has long remained elusive. We recently determined the cryo-EM structure of the yeast spliceosomal E complex assembled on introns, leading us to hypothesize that the same E complex can assemble across an exon forming the exon-definition complex. This complex, when assembled on long exons, goes through the splicing cycle and catalyzes back-splicing to generate circRNAs. Supporting this hypothesis, we purified the yeast post-catalytic spliceosomal P complex (the best complex in the splicing cycle to trap splicing products and intermediates) and detected canonical and back-splicing products as well as splicing intermediates. Here we describe in detail this procedure, which may be applied to other organisms to facilitate research on the biogenesis and regulation of circRNA.

Disturbed Resting-State Whole-Brain Functional Connectivity of Striatal Subregions in Bulimia Nervosa.

BACKGROUND: Disturbed self-regulation, taste reward, as well as somatosensory and visuospatial processes were thought to drive binge eating and purging behaviors that characterize bulimia nervosa. Although studies have implicated a central role of the striatum in these dysfunctions, there have been no direct investigations on striatal functional connectivity in bulimia nervosa from a network perspective. METHODS: We calculated the functional connectivity of striatal subregions based on the resting-state functional Magnetic Resonance Imaging data of 51 bulimia nervosa patients and 53 healthy women. RESULTS: Compared with the healthy women, bulimia nervosa patients showed increased positive functional connectivity in bilateral striatal nuclei and thalamus for nearly all of the striatal subregions, and increased negative functional connectivity in bilateral primary sensorimotor cortex and occipital areas for both ventral striatum and putamen subregions. Only for the putamen subregions, we observed reduced negative functional connectivity in the prefrontal (bilateral superior and middle frontal gyri) and parietal (right inferior parietal lobe and precuneus) areas. Several striatal connectivities with occipital and primary sensorimotor cortex significantly correlated with the severity of bulimia. CONCLUSIONS: The findings indicate bulimia nervosa-related alterations in striatal functional connectivity with the dorsolateral prefrontal cortex supporting self-regulation, the subcortical striatum and thalamus involved in taste reward, as well as the visual occipital and sensorimotor regions mediating body image, which contribute to our understanding of neural circuitry of bulimia nervosa and encourage future therapeutic developments for bulimia nervosa by modulating striatal pathway.

Impact of N-Acetylcysteine on the Gut Microbiota in the Piglets Infected With Porcine Epidemic Diarrhea Virus.

This study was to investigate the impact of N-acetylcysteine (NAC) on the gut microbiota in the healthy piglets and the piglets infected with porcine epidemic diarrhea virus (PEDV). Forty seven-day-old piglets were allocated into four groups: control group, NAC group (supplemented with 50 mg/kg body weight NAC), PEDV group (inoculated with 104.5 TCID50 PEDV), and PEDV+NAC group (PEDV infection + NAC supplementation). The intestinal content was collected for DNA extraction and Illumina sequencing. The PEDV-infected piglets displayed distinct bacterial communities compared to the healthy piglets. PEDV infection decreased the abundance of Shigella and increased the abundance of Lactobacillus, Odoribacter, Anaerovibrio, Helicobacter, unclassified Lachnospiraceae, and Sutterella; affected several functions associated with metabolism, barrier, and immune. NAC supplementation decreased the abundance of unclassified Rikenellaceae and increased the abundance of Lactobacillus, Streptococcus, and Enterococcus in the healthy piglets, decreased the abundance of Oscillospira and Prevotella and increased the abundance of Lactobacillus in the PEDV-infected piglets; altered multiple functions involving in amino acid metabolism, cell signaling, cellular community, disease-related pathways, endocrine, and excretory system. In conclusion, PEDV infection caused severe dysbiosis of gut microbiome, whereas NAC supplementation played a positive role in regulating the gut microbiome during PEDV infection. Therefore, substances that can regulate gut microbiota could be ideal candidates to prevent or treat PEDV infection.

A unified mechanism for intron and exon definition and back-splicing.

The molecular mechanisms of exon definition and back-splicing are fundamental unanswered questions in pre-mRNA splicing. Here we report cryo-electron microscopy structures of the yeast spliceosomal E complex assembled on introns, providing a view of the earliest event in the splicing cycle that commits pre-mRNAs to splicing. The E complex architecture suggests that the same spliceosome can assemble across an exon, and that it either remodels to span an intron for canonical linear splicing (typically on short exons) or catalyses back-splicing to generate circular RNA (on long exons). The model is supported by our experiments, which show that an E complex assembled on the middle exon of yeast EFM5 or HMRA1 can be chased into circular RNA when the exon is sufficiently long. This simple model unifies intron definition, exon definition, and back-splicing through the same spliceosome in all eukaryotes and should inspire experiments in many other systems to understand the mechanism and regulation of these processes.

Abnormal structural brain network and hemisphere-specific changes in bulimia nervosa.

Bulimia nervosa (BN) is characterized by episodic binge eating and purging behaviors. Disrupted neural processes of self-regulation, taste-rewarding, and body image has been associated with the pathogenesis of BN. However, the structural basis for these behavioral and functional deficits remains largely unknown. We employed diffusion tensor imaging and graph theory approaches (including the nodal properties and network-based statistics (NBS)) to characterize the whole-brain structural network of 48 BN and 44 healthy women. For nodal measures of strength, local efficiency, and betweenness centrality, BN patients displayed abnormal increases in multiple left-lateralized nodes within the mesocorticolimbic reward circuitry (including the orbitofrontal cortex, anterior cingulate, insular, medial temporal, and subcortical areas), lateral temporal-occipital cortex, and precuneus, while reduced global efficiency was observed in the right-lateralized nodes within the dorsolateral prefrontal cortex, mesocorticolimbic circuitry, somatosensory and visuospatial system. Several mesocorticolimbic nodes significantly correlated with BN symptoms. At a network level, we found increased left-lateralized connections primarily within the orbitofrontal cortex and its connections to mesocorticolimbic and lateral temporal-occipital areas, but reduced right-lateralized connections across the inferior frontal gyrus and insula, as well as their connections to the lateral temporal cortex. This study revealed BN-related changes in white-matter connections across the prefrontal control, mesocorticolimbic reward, somatosensory and visuospatial systems. The hemispheric-specific change could be an important aspect of the pathophysiology of BN. By characterizing whole-brain structural network changes of BN, our study provides novel evidence for understanding the behavioral and functional deficits of the disorder.