Onset of acute severe autoimmune hepatitis after severe acute respiratory syndrome coronavirus 2 infection: a case report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can trigger autoimmune inflammation in the liver, leading to acute autoimmune hepatitis (AIH). We herein report a case involving a 39-year-old woman with a 23-day history of yellow skin and urine. Using the revised original scoring system of the International AIH Group, we definitively diagnosed the patient with acute severe AIH (AS-AIH). She began treatment with 80 mg/day intravenous methylprednisolone, which was gradually reduced and followed by eventual transition to oral methylprednisolone. The patient finally achieved a biochemical response after 30 days of therapy, and liver transplantation was avoided. Clinicians should be aware that the onset of AS-AIH after SARS-CoV-2 infection differs from the onset of conventional AIH with respect to its clinical and pathological features. Early diagnosis and timely glucocorticoid treatment are crucial in improving outcomes.

Pattern of Brain Parenchymal Damage Related to Cerebral Small Vessel Disease in Carriers of Rare NOTCH3 Variants.

BACKGROUND AND OBJECTIVES: Previous studies reported that carriers of rare NOTCH3 variants comprised more than 10% of the general population and are susceptible to a heavy overall burden of cerebral small vessel disease while the injury patterns remain uncovered. This study aimed to investigate the imaging features in relation to rare NOTCH3 variants and the interaction between cortical atrophy and white matter lesions from a longitudinal view, with respect to spatial and dynamic patterns. METHODS: As part of a community-based cohort, we included participants with complete whole-exome sequencing and brain MRI in the baseline analysis. All participants were invited for a 5-year follow-up MRI, and those who did not complete the follow-up were excluded from the longitudinal analysis. NOTCH3 variants with minor allele frequency <1% in all 4 public population databases were defined as rare variants. We used general linear models to compare the volume of white matter hyperintensity (WMH) volume and brain parenchymal fraction between rare NOTCH3 variant carriers and noncarriers. In addition, we compared the WMH probability map and vertex-wise cortex maps at a voxel/vertex-wise level. RESULTS: A total of 1,054 participants were included in baseline analysis (13.56% carried rare NOTCH3 variants), among whom 661 had a follow-up brain MRI (13.76% carried rare NOTCH3 variants). Rare NOTCH3 variant carriers had a heavier white matter hyperintensity burden (1.65 vs 0.85 mL, p = 0.025) and had more extensive WMH distributed in the periventricular areas. We also found that rare NOTCH3 variant carriers were susceptible to worse cortical atrophy (ß = -0.004, SE = 0.002, p = 0.057, adjusted for age and sex). Cortical atrophy of multiple regions in the frontal and parietal lobes was related to white matter hyperintensity progression. DISCUSSION: Individuals with rare NOTCH3 variants have a distinct pattern of brain parenchymal damage related to CSVD. Our findings uncover the important genetic predisposition in age-related cerebral small vessel disease in the general population.

Clinical outcomes of robotic-assisted and manual total hip arthroplasty in the same patient: A case report.

BACKGROUND: Total hip arthroplasty (THA) is an effective treatment for advanced osteonecrosis of the femoral head, which can significantly relieve pain and improve patients' quality of life. Robotic-assisted THA enhances the accuracy and stability of THA surgery and achieves better clinical outcomes than manual THA. CASE SUMMARY: We report the clinical outcomes of robotic-assisted THA and manual THA in the same patient with osteonecrosis of the femoral head. A 49-year-old male patient attended our hospital due to more than 3 years of pain in both hip joints. The left hip was treated with robotic-assisted THA. The patient underwent manual THA of the right hip 3 mo after robotic-assisted THA. We obtained postoperative radiograph parameters, Harris hip score and forgotten joint score of the patient 1 year after surgery. CONCLUSION: Compared with manual THA, the patient's left hip felt better 1 year after robotic-assisted THA. Robotic-assisted THA resulted in a better Harris hip score and forgotten joint score than manual THA in the same patient with osteonecrosis of the femoral head.

Gut microbial profile of treatment-naive patients with primary biliary cholangitis.

Background and aims: The pathogenesis of primary biliary cholangitis (PBC) is associated with alterations of gut microbiota. We compared the gut microbiota of PBC patients and healthy controls from Zhejiang Province and assessed the use of these data for the diagnosis of PBC. Methods: First, 16S rRNA gene sequencing was used to characterize the gut microbiota of treatment-naive PBC patients (n=25) and matched healthy controls (n=25). Then, the value of gut microbiota composition for the diagnosis of PBC and assessment of PBC severity was determined. Results: The gut microbiota of PBC patients had lower diversity based on three different metrics of alpha-diversity (ace, Chao1, and observed features) and fewer overall genera (all p<0.01). PBC patients had significant enrichment of four genera and significant depletion of eight genera. We identified six amplicon sequence variants (Serratia, Oscillospirales, Ruminococcaceae, Faecalibacterium, Sutterellaceae, and Coprococcus) as optimal biomarkers to distinguish PBC patients from controls based on receiver operating characteristic analysis (area under the curve [AUC] = 0.824). PBC patients who were anti-gp210-positive had lower levels of Oscillospiraceae than those who were anti-gp210-negative. KEGG functional annotation suggested the major changes in the gut microbiota of PBC patients were related to lipid metabolism and biosynthesis of secondary metabolites. Conclusion: We characterized the gut microbiota of treatment-naive PBC patients and healthy controls from Zhejiang Province. The PBC patients had significant alterations in their gut microbiota, suggesting that gut microbiota composition could be useful as a non-invasive tool for the diagnosis of PBC.

Best Practices for Comprehensive Annotation of Neuropeptides of Gryllus bimaculatus.

Genome annotation is critically important data that can support research. Draft genome annotations cover representative genes; however, they often do not include genes that are expressed only in limited tissues and stages, or genes with low expression levels. Neuropeptides are responsible for regulation of various physiological and biological processes. A recent study disclosed the genome draft of the two-spotted cricket Gryllus bimaculatus, which was utilized to understand the intriguing physiology and biology of crickets. Thus far, only two of the nine reported neuropeptides in G. bimaculatus were annotated in the draft genome. Even though de novo assembly using transcriptomic analyses can comprehensively identify neuropeptides, this method does not follow those annotations on the genome locus. In this study, we performed the annotations based on the reference mapping, de novo transcriptome assembly, and manual curation. Consequently, we identified 41 neuropeptides out of 43 neuropeptides, which were reported in the insects. Further, 32 of the identified neuropeptides on the genomic loci in G. bimaculatus were annotated. The present annotation methods can be applicable for the neuropeptide annotation of other insects. Furthermore, the methods will help to generate useful infrastructures for studies relevant to neuropeptides.

Cytochrome P450 Monooxygenases CYP6AY3 and CYP6CW1 Regulate Rice Black-Streaked Dwarf Virus Replication in Laodelphax striatellus (Fallén).

The small brown planthopper, Laodelphax striatellus (Fallén), is an important agricultural pest that causes significant losses by sucking and transmitting multiple plant viruses, such as rice black-streaked dwarf virus (RBSDV). Insecticides are commonly used to control planthoppers and cause the induction or overexpression of cytochrome P450 monooxygenases (P450s) from the CYP3 and CYP4 clades after insecticide application. However, little is known about the roles of insecticides and P450s in the regulation of viral replication in insects. In this study, RBSDV-infected L. striatellus were injected with imidacloprid, deltamethrin, pymetrozine, and buprofezin, respectively. The insecticide treatments caused a significant decrease in RBSDV abundance in L. striatellus. Treatment of piperonyl butoxide (PBO), an effective inhibitor of P450s, significantly increased the RBSDV abundance in L. striatellus. Fourteen P450 candidate genes in the CYP3 clade and 21 in the CYP4 clade were systematically identified in L. striatellus, and their expression patterns were analyzed under RBSDV infection, in different tissues, and at different developmental stages. Among the thirty-five P450 genes, the expression level of CYP6CW1 was the highest, while CYP6AY3 was the lowest after RBSDV infection. Knockdown of CYP6CW1 and CYP6AY3 significantly increased the virus abundance and promoted virus replication in L. striatellus. Overall, our data reveal that CYP6CW1 and CYP6AY3 play a critical role in the regulation of virus replication in L.striatellus.

Forensic and phylogenetic analyses of populations in the Tibetan-Yi corridor using 41 Y-STRs.

Y-chromosome haplotypes of 527 non-related males (176 Han, 186 Tibetan, and 165 Yi) in the Tibetan-Yi corridor were analyzed using SureID® PathFinder Plus. In the populations of Han, Tibetans, and Yi, the haplotype diversity was 0.9989, 0.9981, and 0.9993, respectively, and the discrimination capacity was 0.9148, 0.8925, and 0.9576, respectively. Phylogenetic relationships among 12 studied ethnic groups and 7 other ethnic groups in the Tibetan-Yi corridor were investigated. Both multi-dimensional scaling analysis and phylogenetic reconstructions indicated that Tibetans appeared separated from the Han and Yi ethnic groups in the Tibetan-Yi corridor. Their genetic homogeneity or heterogeneity has not entirely been affected by their geographical distance and linguistic origin.

Phylogenic analysis and forensic genetic characterization of Guizhou Miao tribes from 58 microareas via autosomal STR.

Genetic polymorphism of 17 autosomal short tandem repeat (STR) loci, included in the PowerPlex®18D amplification kit, were analyzed in Miao tribes from 58 different sampling microareas (N = 5255) of Guizhou as well as two cities (N = 151) of Hunan, China. Allele frequencies and forensic efficiency parameters were calculated. Moreover, comprehensive population genetic comparisons among 91 nationwide populations and 174 Asian populations were conducted based on raw genotype data and allele frequency data, respectively. Our results of forensic efficiency parameters showed that the panel was a robust tool in forensic individual identification and paternity cases for this population. Genetic affinities were observed among most of the Miao tribes revealed by multidimensional scaling plot, principal component analysis, and neighboring-joining tree. The genetic distance between Miao tribes and Han nationalities were varies by different geographical positions. Some of the Miao tribes were genetically closer to the Hmong-Mien populations living in southeastern contiguous regions and even the Indochina. The result coincided with the migration or reverse migration routes for Miao nationality in modern history. This study of the Miao tribes from plenty of microareas in Guizhou would be useful in reconstructing the population history and establishing a more comprehensive forensic reference database.

Pananx notoginseng saponins attenuate CCL2-induced cognitive deficits in rats via anti-inflammation and anti-apoptosis effects that involve suppressing over-activation of NMDA receptors.

HIV-associated neurocognitive disorders (HAND) are characterized by synaptic damage and neuronal loss in the brain, ultimately leading to progressive decline of cognitive abilities and memory. Chemokine CC motif ligand 2 (CCL2) is elevated in cerebrospinal fluid (CSF), and has been believed to contribute to HAND. Previous studies by our research team have shown that CCL2 enhances N-Methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs) and causes nerve cell damage. However, there are few drugs currently available to treat nerve damage that is caused by CCL2. Panax notoginseng saponins (PNS) are isolated from Panax notoginseng and benefit the human body in various ways, including the neuroprotective effect. However, the protective effect of PNS on CCL2-induced neurotoxicity remains unknown. In this study, we found that PNS improved CCL2-induced learning and memory impairment, and inhibited CCL2-induced cell death. These effects may be due to inhibiting over-activation of NMDA receptors by alleviating the dysfunction of glutamate metabolism. Furthermore, PNS-modulated CCL2-inducd intracellular oxidative stress was found to attenuate cell inflammation. Additionally, PNS pretreatment evidently inhibited apoptotic pathways by reducing the Bax/BCL-2 ratio and caspase-3, 8, 9 expressions. In conclusion, this study demonstrates that PNS provides substantial neuroprotection against CCL2-induced neurotoxicity, and may be a novel therapeutic agent in CCL2-induced HAND or other neurodegenerative diseases.

Tanshinone IIA Alleviates CCL2-Induced Leaning memory and Cognition Impairment in Rats: A Potential Therapeutic Approach for HIV-Associated Neurocognitive Disorder.

Chemokine CC motif ligand 2 (CCL2) is one of the most recognized proinflammatory chemokines, and the expression of CCL2 in the cerebrospinal fluid of patients infected with HIV-1 is significantly higher than that of healthy people. As such, it is seen as an important cause of HIV-associated neurocognitive disorder (HAND). Our previous investigation has confirmed the pathological role of CCL2 in mediating brain damage leading to cognitive dysfunction. Currently, however, research on therapeutic drugs for the central nervous system targeting CCL2 is very limited. Our present study used brain stereotactic technology to induce cognitive impairment in rats by injecting CCL2 (5 ng) into the bilateral hippocampus. To investigate the protective effect and mechanism of Tanshinone IIA (25, 50, 75 mg/kg/d) on CCL2-induced learning memory and cognitive impairment in rats, we performed the Morris water maze (MWM) and novel object recognition tests (NORT) on the rats. The results showed that Tanshinone IIA significantly alleviated CCL2-induced learning memory and cognitive dysfunction. Further studies on the hippocampal tissue of the rats revealed that Tanshinone IIA treatment significantly increased the activity of SOD and GSH-Px while the level of MDA decreased compared to the model group. Additionally, the relative expression of apoptosis-associated genes caspase-3, caspase-8, and caspase-9 and inflammation-associated genes IL-1ß and IL-6 in Tanshinone IIA-treated rats was lower than that in model rats. Finally, we confirmed hippocampal neuron loss and apoptosis by Nissl staining and TdT-mediated dUTP Nick end labeling (TUNEL). Taken together, these data imply that Tanshinone IIA can ameliorate CCL2-induced learning memory and cognitive impairment by impacting oxidative stress, inflammation, and apoptosis. Tanshinone IIA may be a potential therapeutic agent for the treatment of HAND.

Naringin provides neuroprotection in CCL2-induced cognition impairment by attenuating neuronal apoptosis in the hippocampus.

BACKGROUND: Chemokine C-C motif ligand 2 (CCL2) is one of the most widely recognised proinflammatory chemokines in cognitive disorders. Currently, CCL2-targeting drugs are extremely limited. Thus, this study aimed to explore the neuroprotection afforded by naringin in CCL2-induced cognitive impairment in rats. METHODS: Before the CCL2 intra-hippocampal injection, rats were treated with naringin for 3 consecutive days via intraperitoneal injection. Two days post-surgery, the Morris water maze (MWM) and novel object recognition (NORT) tests were performed to detect spatial learning and memory and object cognition, respectively. Nissl staining and dUTP nick-end labelling (TUNEL) staining were performed to assess histopathological changes in the hippocampus. Commercial kits were used to measure the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the relative mRNA expression of interleukin 1ß, (IL-1ß), interleukin 6 (IL-6), glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), phosphate-activated glutaminase (PAG), cysteine aspartic acid-specific protease 8 (caspase-8), cysteine aspartic acid-specific protease 3 (caspase-3), cell lymphoma/leukaemia-2 (Bcl-2), and Bcl-2 associated X protein (Bax). RESULTS: In the MWM, the average escape latency and average swimming distance were significantly reduced and the crossing times were increased in the naringin-treated groups, compared with the CCL2 group. The NORT results revealed that, compared with the CCL2 rats, the discrimination index in the naringin-treated rats increased significantly. Nissl and TUNEL staining revealed that naringin protected the structure and survival of the neurons in the CA1 zone of the hippocampus. In the naringin-treated groups, the SOD and GSH-Px activities were increased, whereas the MDA levels were decreased. Furthermore, in the naringin-treated groups, the relative mRNA expression of IL-1ß and IL-6 was significantly decreased; GLAST and GLT-1 mRNA expression levels were increased, whereas PAG was decreased. In the naringin-treated groups, the relative mRNA expression levels of caspase-8, caspase-3, and Bax were decreased, whereas that of Bcl-2 was increased. CONCLUSION: Collectively, these data indicated that naringin alleviated the CCL2-induced cognitive impairment. The underlying mechanisms could be associated with the inhibition of neuroinflammation, oxidative stress, apoptosis, and the regulation of glutamate metabolism.

Corrigendum to "Tanshinone IIA Alleviates CCL2-Induced Leaning memory and Cognition Impairment in Rats: A Potential Therapeutic Approach for HIV-Associated Neurocognitive Disorder".

[This corrects the article DOI: 10.1155/2020/2702175.].

Biological functions of Arabidopsis thaliana MBP-1-like protein encoded by ENO2 in the response to drought and salt stresses.

Arabidopsis thaliana ENO2 (AtENO2) plays an important role in plant growth and development. It encodes two proteins, a full-length AtENO2 and a truncated version, AtMBP-1, alternatively translated from the second start codon of the mRNA. The AtENO2 mutant (eno2- ) exhibited reduced leaf size, shortened siliques, a dwarf phenotype and higher sensitivity to abiotic stress. The objectives of this study were to analyze the regulatory network of the ENO2 gene in plant growth development and understand the function of AtENO2/AtMBP-1 to abiotic stresses. An eno2- /35S:AtENO2-GFP line and an eno2- /35S:AtMBP-1-GFP line of Arabidopsis were obtained. Results of sequencing by 454 GS FLX identified 578 upregulated and 720 downregulated differential expressed genes (DEGs) in a pairwise comparison (WT-VS-eno2- ). All the high-quality reads were annotated using the Gene Ontology (GO) terms. The DEGs with KEGG pathway annotations occurred in 110 pathways. The metabolic pathways and biosynthesis of secondary metabolites contained more DEGs. Moreover, the eno2- /35S:AtENO2-GFP line returned to the wild-type (WT) phenotype and was tolerant to drought and salt stresses. However, the eno2- /35S:AtMBP-1-GFP line was not able to recover the WT phenotype but it has a higher tolerance to drought and salt stresses. Results from this study demonstrate that AtENO2 is critical for the growth and development, and the AtMBP-1 coded by AtENO2 is important in tolerance of Arabidopsis to abiotic stresses.

Specific distribution of expression and enzymatic activity of cholesterol biosynthetic enzyme DHCR24 orthologs in the phytophagous insect.

Insects must intake sterol compounds because of their inability to synthesize cholesterol de novo. In phytophagous insects, enzymatic conversion of phytosterols to cholesterol involving 24-dehydrocholesterol reductase (DHCR24) exerts to acquire cholesterol. Here, we reported the presence of two DHCR24 homologs in the silkworm Bombyx mori, BmDHCR24-1 and -2, with several transcript variants. Consistent with the data of spatial expression analyses by RT-PCR, predominant enzymatic activity of DHCR24 was observed in B. mori larval midgut whereas weak activity was observed in the other tissues examined. In addition, BmDHCR24-1 expression in HEK293 cells showed an enzymatic activity, but BmDHCR24-2 did not, although both BmDHCR24s were localized in the endoplasmic reticulum, where the mammalian DHCR24s are located to exert their enzymatic activities. The present data indicated that BmDHCR24-1 but not BmDHCR24-2 contributes to conversion of phytosterols to cholesterol mainly in the midgut of the phytophagous lepidopteran larvae.

[Polarity of ameloblasts and odontoblasts and their related regulators].

The polarity of ameloblasts and odontoblasts is crucial for their differentiation and function. Polarity-related molecules play an important role in this process. This review summarizes the process of polarity formation of ameloblasts and odontoblasts and their related regulators.

Antagonistic Effect of Short Neuropeptide F on Allatotropin-Inhibited Feeding Motivation of the Silkworm Larva, Bombyx mori.

Here, we demonstrated an antagonistic effect of short neuropeptide F (sNPF) in modulating feeding motivation in the silkworm Bombyx mori; sNPF reduced the feeding-delaying effects caused by administration of an inhibitory peptide, allatotropin (AT). In situ hybridization and MALDI-TOF MS analysis revealed the presence of three subtypes of sNPFs (sNPF-1, -2, and -3) in the midgut enteroendocrine cells. Ca2+-imaging analyses revealed that three subtypes of sNPF receptors (sNPFRs) (BNGR-A7, -A10, and -A11) showed different affinities with the three subtypes of sNPFs. In addition, sNPF activated its signaling via ERK phosphorylation in the midgut, while mixture of sNPF and AT reduced the phosphorylation level, agreeing with the results of behavioral assay. Together, our current findings suggest that intestinal sNPF positively modulates the feeding motivation by reducing the inhibitory effects by AT within the midgut.

Function of myosuppressin in regulating digestive function in the two-spotted cricket, Gryllus bimaculatus.

Myosuppressin is one of essential peptides controlling biological processes including feeding behavior. Here we identified and characterized the cDNAs that encode myosuppressin precursor and its receptor in the two-spotted cricket Gryllus bimaculatus. The presence of the mature peptide (Grybi-MS) was confirmed by direct measurement of adult brain. RT-PCR revealed the tissue distribution of these transcripts; myosuppressin is expressed predominantly in the brain and central nervous system, whereas its receptor is ubiquitously expressed in the cricket body. To address the function of Grybi-MS, we performed several bioassays to test concerning feeding behavior and digestive function upon exposure to Grybi-MS. Administration of synthetic Grybi-MS resulted in increased feeding motivation, accompanied by an increase in food intake. Meanwhile, the hemolymph lipid and carbohydrate titers were both elevated after Grybi-MS injection. As the intestinal contraction is significantly inhibited by the exposure to Grybi-MS, the upregulating feeding index might be complicated in the cricket body. The current data indicate that Grybi-MS modulates feeding behavior to control the physiological processes in the cricket.

lnc TINCR induced by NOD1 mediates inflammatory response in 3T3-L1 adipocytes.

OBJECTIVE: Investigating the expression of the lnc RNAs screened above between normal and insulin resistant 3T3-L1 adipocytes. Addressing the mechanism underlying the regulation of inflammation response by lnc TINCR. METHODS: 3T3-L1 preadipocytes were induced to differentiate into mature adipocytes. Oil red O staining was used to find the fat droplets in mature adipocytes. Mature adipocytes were randomized to normal control group and Tri-DAP (NOD1 ligand) group. After the establishment of insulin resistance model, we used deep RNA sequencing(RNA-Seq) to identify lncRNAs that are regulated during NODI activation in mouse adipocytes. Real-time PCR was used to analyze the expression of lnc TINCR, proinflammatory IL-6, TNF-α, Cxcl1 and RIPK2 in the presence or absence of Tri-DAP(10 µg/ml). We employed siRNA against lnc TINCR to confirm its effects in inflammatory response. RESULTS: Deep RNA sequencing identified 81 lncRNAs and 167 coding genes that were significantly up-related while 78 lncRNAs and 82 coding genes that were significantly down-related greater than twofold during NOD1 activation in adipocytes. We discovered that lnc TINCR, termed lnc TINCR(Tri-DAP-inducible non-protein coding RNA) is greatly upregulated in Tri-DAP activated adipocytes. Moreover knockdown of lnc TINCR dampens the proinflammatory response (P < 0.05; in adipocytes). CONCLUSIONS: lnc TINCR is a positive regulator of inflammation-induced insulin resistance presumably via activation of NOD1 signaling pathways.