Identification and genomic characterization of feline calicivirus from a leopard cat (Prionailurus bengalensis) in Taiwan.

The leopard cat (Prionailurus bengalensis) is an endangered wildlife that is protected under Taiwan's regulations. The body of a road-killed leopard cat was found to contain sequences of feline calicivirus (FCV), designated W109-1443. Analysis of the complete genomic sequence revealed that it shared approximately 81% similarity with a Chinese strain of FCV found in a domestic cat. Phylogenetic analysis of the VP1 gene indicated that the W109-1443 isolate belonged to genogroup II. Recombination analysis revealed that the W109-1443 isolate may have resulted from recombination between two FCV strains. Given the potential impact of FCV on the health and survival of wild felids, further investigation is necessary to assess its pathogenicity in the leopard cat population.

Novel variants in TNRC6B cause global developmental delay with speech and behavioral abnormalities, short stature, low body weight, café-au-lait spots, and metabolic abnormality.

BACKGROUND: TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease mainly characterized by facial dysmorphism, developmental delay/intellectual disability (DD/ID), speech and language delay, fine and motor delay, attention deficit and hyperactivity disorder (ADHD), and variable behavioral abnormalities. It is caused by heterozygous variant in the TNRC6B gene (NM_001162501.2, MIM 610740), which encodes the trinucleotide repeat-containing adaptor 6B protein. METHODS: In this study, two Chinese patients with TNRC6B deficiency syndrome were recruited, and genomic DNA extraction from peripheral blood leukocytes of these parents and their family members was extracted for whole-exome sequencing and Sanger sequencing. RESULTS: Here, we report two unrelated Chinese patients diagnosed with TNRC6B deficiency syndrome caused by novel de novo likely pathogenic or pathogenic TNRC6B variants c.335C>T (p.Pro112Leu) and c.1632delC (p.Leu546fs*63), which expands the genetic spectrum of TNRC6B deficiency syndrome. The clinical features of the patients were DD/ID, delayed speech, ADHD, behavioral abnormalities, short stature, low body weight, café-au-lait spots, metabolic abnormalities, and facial dysmorphism including coarse facial features, sparse hair, frontal bossing, hypertelorism, amblyopia, strabismus, and downslanted palpebral fissures, which expands the phenotype spectrum associated with TNRC6B deficiency syndrome. CONCLUSION: This study expands the genotypic and phenotypic spectrum of TNRC6B deficiency syndrome. Our findings indicate that patients with TNRC6B deficiency syndrome should be monitored for growth and metabolic problems and therapeutic strategies should be developed to address these problems. Our report also suggests the clinical diversity of TNRC6B deficiency syndrome.

Epidemiology of Severe Fever with Thrombocytopenia Syndrome in Dogs and Cats in Taiwan.

Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by the SFTS Virus (SFTSV), is a global health threat. SFTSV in Taiwan has only been reported in ruminants and wild animals. Thus, we aimed to investigate the infection statuses of dogs and cats, the animals with closer human interactions. Overall, the SFTSV RNA prevalence was 23% (170/735), with dogs showing a 25.9% (111/429) prevalence and cats at 19.3% (59/306) prevalence. Noticeably, the prevalence in stray animals (39.8% 77/193) was significantly higher than in domesticated ones (17.2%, 93/542). Among the four categories analyzed, the highest SFTSV prevalence was found in the stray dogs at 53.9% (120/193), significantly higher than the 24.2% prevalence noted in stray cats. In contrast, domesticated animals exhibited similar prevalence rates, with 17.1% for dogs and 17.2% for cats. It is noteworthy that in the domesticated animal groups, a significantly elevated prevalence (45%, 9/20) was observed among cats exhibiting thrombocytopenia compared to those platelet counts in the reference range (4.8%, 1/21). The high infection rate in stray animals, especially stray dogs, indicated that exposure to various outdoor environments influences the prevalence of infections. Given the higher human interaction with dogs and cats, there is a need for proactive measures to reduce the risk associated with the infection of SFTSV in both animals and humans.

Clinical Efficacy of Diet Intervention Combined with Bismuth Potassium Citrate in Helicobacter pylori-Related Chronic Atrophic Gastritis.

Objective: To investigate the clinical impact of dietary intervention in combination with bismuth potassium citrate in the management of chronic atrophic gastritis (CAG) caused by Helicobacter pylori. Methods: From April 2019 to October 2022, 160 patients with newly identified Helicobacter pylori-related CAG were treated at our facility. They were split into two groups at random: the bismuth potassium citrate medication group (n = 80) and the diet intervention + bismuth potassium citrate experimental groups (n = 80). The bismuth potassium citrate treatment group was given bismuth potassium citrate capsule treatment only, and the diet intervention + bismuth potassium citrate treatment group was given diet intervention based on bismuth potassium citrate capsule. The diet intervention score, symptom score, and pathological score of the two groups were observed at baseline and after treatment, and the relationship between dietary intervention and symptoms and pathology of Helicobacter pylori-related CAG was analyzed. Results: During the baseline period, there was no discernible difference in the diet intervention score, symptom score, or pathology score between the two groups (P > .05); after the diet intervention combination treatment, the diet intervention score, diet intervention + bismuth potassium citrate experimental groups symptom score, and pathology score were considerably lower than those in the bismuth potassium citrate treated group (P < .05). Conclusions: Dietary intervention combined with bismuth potassium citrate exhibited more effective treatment than bismuth potassium citrate-only treatment in Helicobacter pylori-related CAG, which hinted us proper diet has a positive impact on improving the therapeutic efficacy of bismuth potassium citrate.

[Application of flat-sided culture tubes during prenatal diagnosis].

OBJECTIVE: To assess the value of using flat-sided culture tubes for preparing chromosomes through chorionic villi (CV) and amniotic fluid (AF) cell cultures during prenatal diagnosis. METHODS: From February to March 2020, 157 CV samples and 147 AF samples subjected to prenatal diagnosis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region were selected as the study subjects. For each sample, one flat-sided tube and one flask culture were set up by following the standard protocols. The methods were evaluated by comparing the cell growth, experimental process, quality of chromosome preparation and costs. RESULTS: The success rates for the culturing of CV and AF samples by the flat-sided culture tube method were 97.45% (153/157) and 97.96% (144/147), respectively. By contrast, the success rates for the conventional flask method were 98.72% (155/157) for CV and 98.64% (145/147) for AF samples. No significant difference was found between the two methods (P > 0.05). The average harvest time required by the flat-sided culture tube method was 8.45 days for CV and 9.43 days for AF cultures, whilst the average harvest time for conventional flask method was 9.05 days and 9.54 days, respectively. The flat-sided culture tube method for CV had required significantly shorter average harvest time than the conventional method (P < 0.001). No statistical significant difference was found in the average harvest time for AF by the two methods (P > 0.05). The conventional culturing method had required three containers with two sample transfers. By contrast, the flat-sided culture tube method was carried out in one tube without any sample transfer. The average total amount of medium used was 3.91 mL for each flat-sided culture tube and 6.26 mL for each conventional flask. CONCLUSION: The flat-sided culture tube method can provide a simple, cost-effective and error-reducing procedure for the CV and AF samples culture during prenatal diagnosis.

Assessing the causal association of trauma with subsequent psychiatric disorders by a Mendelian randomization study trauma and common psychiatric disorders.

Objective: Trauma has been proposed as a risk factor for the development of psychiatric disorders. This study aimed to determine the causal role of trauma in six common psychiatric disorders. Methods: We obtained summary-level data for genetic variants associated with trauma and the corresponding association with psychiatric disorders from previous genome-wide association studies. Two-sample Mendelian randomization analyzes were performed to estimate the causal association between trauma and psychiatric disorders, with inverse variance weighted used as the main method. Results: Genetically predisposed trauma was associated with an increased risk of psychiatric disorders [odds ratio (OR) =1.24, 95%, confidence interval (CI), 1.09-1.40], anxiety disorder (OR = 1.30, 95% CI, 1.10-1.52) and schizophrenia (OR = 1.48, 95% CI, 1.18-1.84). However, the associations between trauma and sleep disorder (OR = 1.17, 95% CI, 1.01-1.35), as well as depression (OR = 1.09, 95% CI, 1.02-1.16) did not reach a Bonferroni corrected significance level. Besides, no association was observed between trauma and risk of bipolar disorder (OR = 1.21, 95% CI, 0.98-1.48) and eating disorder (OR = 1.28, 95% CI, 0.88-1.86). Conclusion: Trauma might be causally associated with an increased risk of some common psychiatric disorders such as anxiety disorder and schizophrenia. However, little evidence supported an association between trauma and risk of depression, bipolar disorder, sleep disorder, and eating disorder. Our findings offered novel insights into the trauma-mediated development mechanism of psychiatric disorders, and psychological intervention to patients with trauma may be an effective prevention strategy for psychological diseases.

The conservation and diversity of the exons encoding the glycine and arginine rich domain of the fibrillarin gene in vertebrates, with special focus on reptiles and birds.

The nucleolar rRNA 2'-O-methyltransferase fibrillarin (FBL) contains a highly conserved methyltransferase domain at the C-terminus and a diverse glycine arginine-rich (GAR) domain at the N-terminus in eukaryotes. We found that a nine-exon configuration of fbl and exon 2-3 encoded GAR domain are conserved and specific in vertebrates. All internal exons except exon 2 and 3 are of the same lengths in different vertebrate lineages. The lengths of exon 2 and 3 vary in different vertebrate species but the ones with longer exon 2 usually have shorter exon 3 complementarily, limiting lengths of the GAR domain within a certain range. In tetrapods except for reptiles, exon 2 appears to be longer than exon 3. We specifically analyzed different lineages of reptiles for their GAR sequences and exon lengths. The lengths of exon 2 in reptiles are around 80-130-nt shorter and the lengths of exon 3 in reptiles are around 50-90 nt longer than those in other tetrapods, all in the GAR-coding regions. An FSPR sequence is present at the beginning of the GAR domain encoded by exon 2 in all vertebrates, and a specific FXSP/G element (X can be K, R, Q, N, and H) exist in the middle of GAR with phenylalanine as the 3rd exon 3-encoded amino acid residue starting from jawfish. Snakes, turtles, and songbirds contain shorter exon 2 compared with lizards, indicating continuous deletions in exon 2 and insertions/duplications in exon 3 in these lineages. Specifically, we confirmed the presence the fbl gene in chicken and validated the RNA expression. Our analyses of the GAR-encoding exons of fbl in vertebrates and reptiles should provide the basis for further evolutionary analyses of more GAR domain encoding proteins.

The First Nationwide Surveillance of Severe Fever with Thrombocytopenia Syndrome in Ruminants and Wildlife in Taiwan.

Since the first discovery of severe fever with thrombocytopenia syndrome virus (SFTSV) in China in 2009, SFTSV has rapidly spread through other Asian countries, including Japan, Korea, Vietnam and Pakistan, in chronological order. Taiwan reported its first discovery of SFTSV in sheep and humans in 2020. However, the prevalence of SFTSV in domestic and wildlife animals and the geographic distribution of the virus within the island remain unknown. A total of 1324 animal samples, including 803 domestic ruminants, 521 wildlife animals and 47 tick pools, were collected from March 2021 to December 2022 from 12 counties and one terrestrial island. The viral RNA was detected by a one-step real-time reverse transcription polymerase chain reaction (RT-PCR). Overall, 29.9% (240/803) of ruminants showed positive SFTSV RNA. Sheep had the highest viral RNA prevalence of 60% (30/50), followed by beef cattle at 28.4% (44/155), goats at 28.3% (47/166), and dairy cows at 27.5% (119/432). The bovine as a total of dairy cow and beef cattle was 27.8% (163/587). The viral RNA prevalence in ticks (predominantly Rhipicephalus microplus) was similar to those of ruminants at 27.7% (13/47), but wild animals exhibited a much lower prevalence at 1.3% (7/521). Geographically the distribution of positivity was quite even, being 33%, 29.1%, 27.5% and 37.5% for northern, central, southern and eastern Taiwan, respectively. Statistically, the positive rate of beef cattle in the central region (55.6%) and dairy cattle in the eastern region (40.6%) were significantly higher than the other regions; and the prevalence in Autumn (September-November) was significantly higher than in the other seasons (p < 0.001). The nationwide study herein revealed for the first time the wide distribution and high prevalence of SFTSV in both domestic animals and ticks in Taiwan. Considering the high mortality rate in humans, surveillance of other animal species, particularly those in close contact with humans, and instigation of protective measures for farmers, veterinarians, and especially older populations visiting or living near farms or rural areas should be prioritized.

NS2 is a key determinant of compatibility in reassortant avian influenza virus with heterologous H7N9-derived NS segment.

Influenza A viruses are common pathogens with high prevalence worldwide and potential for pandemic spread. While influenza A infections typically elicit robust cellular innate immune responses, the non-structural protein 1 (NS1) antagonizes host anti-viral responses and is critical for efficient virus replication and virulence. The avian influenza virus (AIV) H7N9 initially emerged in China in 2013 and has since crossed the avian-human barrier, causing severe disease in humans. To investigate the influence of the H7N9 NS gene (NS079) on viral replication and innate immune response, we generated several recombinant AIVs bearing various NS079 segments on the backbone of H6N1 (strain 0702). Intriguingly, the recombinant virus bearing the heterologous NS079 gene was highly attenuated compared with virus carrying the homologous NS gene (NS0702). Furthermore, we generated a NS079-0702R virus that expresses a chimeric NS gene in which part of the NS079 effector domain was replaced with the sequence from NS0702. The NS079-0702R virus exhibited significantly enhanced viral yield, approximately 100-fold more than virus bearing NS079. The high infection rate of NS079-0702R virus was reflected by strong induction of IFN and Mx expression in human A549 cells. Intriguingly, our in vitro comparative analysis suggested that the increased NS079-0702R infection capacity was independent of the ability of NS1 to interact with cellular partners, such as PKR and CPSF30. Since partial substitution of the effector domain from NS0702 altered the coding sequence of NS2, we further generated another recombinant virus with NS2 derived from H7N9. Surprisingly, the virus with H7N9-derived NS2 exhibited growth characteristics similar to NS079. Our data demonstrate that swapping NS2 components changes infection efficiency, suggesting a key role for NS2 as a determinant of viral compatibility upon reassortment. These findings warrant further investigation into the precise mechanisms by which NS2 contributes to viral replication and host immunity.1.

A variant NS1 protein from H5N2 avian influenza virus suppresses PKR activation and promotes replication and virulence in mammals.

Highly pathogenic avian influenza viruses (HPAIVs) frequently receive global attention as threats to public health. The NS1 protein is a key virulence factor known to impair host antiviral responses. The study herein revealed HPAIV H5N2 NS gene encoded additional protein; a truncated NS1 variant, designated NS3, produced by alternative splicing of the NS transcript. To examine the function of NS3 during infection, we generated recombinant viruses expressing either full-length NS1 (RG-AIV-T375G) or NS3 (RG-AIV-NS3). Interestingly, RG-AIV-NS3 virus produced higher titres than RG-AIV-T375G in multiple mammalian cell lines. However, RG-AIV-T375G exhibited a replication advantage over RG-AIV-NS3 in chicken DF-1 cells, indicating that host cell identity dictates the effect of NS3 on viral replication. In mice and mammalian cells, RG-AIV-NS3 infection elicited higher level of cytokines, including IFN-ß, MX and TNF-α, potentially due to its higher replication activity. Based on mini-genome assay, NS3 had pronounced effects on viral replication machinery. Surprisingly, NS3 retained an interaction with PKR and suppressed PKR activation despite its lack of amino-acid residues 126-167. The poor replication ability of RG-AIV-T375G was partially restored in cells deficient in PKR suggesting that full-length NS1 may be insufficient to suppress PKR function. Notably, virulence of the full-length NS1-expressing RG-AIV-T375G virus was highly attenuated in mice when compared to RG-AIV-NS3. In summary, our study reveals the existence and function of a previously unidentified H5N2 viral protein, NS3. We found that NS3 is functionally distinct from NS1 protein, as it enhances viral replication and pathogenicity in mammalian systems, potentially via suppression of PKR activity.

Surface-Enhanced Raman Spectroscopy Analysis of Astragalus Saponins and Identification of Metabolites After Oral Administration in Rats by Ultrahigh-Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry Analysis.

Astragalus mongholicus Bunge (Fabaceae) is an ancient Chinese herbal medicine, and Astragalus saponins are the main active components, which have a wide range of biological activities, such as immunomodulation, antioxidation, and neuroprotection. In this study, silver nanoparticles obtained by sodium borohydride reduction were used as the enhanced substrate to detect astragaloside I (1), astragaloside II (2), astragaloside III (3), astragaloside IV (4), isoastragaloside I (5), and isoastragaloside II (6) in the phloem, xylem, and cork by surface-enhanced Raman spectroscopy (SERS). In the SERS spectrum of Astragalus slices, the characteristic peaks were observed at 562, 671, 732, 801, 836, 950, 1,026, 1,391, and 1,584 cm-1, among which 950 cm-1 and 1,391 cm-1 were strong SERS signals. Subsequently, the metabolites of the six kinds of Astragalus saponins were identified by UPLC/ESI/Q-TOF-MS. Totally, 80, 89, and 90 metabolites were identified in rat plasma, urine, and feces, respectively. The metabolism of saponins mainly involves dehydration, deacetylation, dihydroxylation, dexylose reaction, deglycosylation, methylation, deacetylation, and glycol dehydration. Ten metabolites (1-M2, 1-M11, 2-M3, 2-M12, 3-M14, 4-M9, 5-M2, 5-M17, 6-M3, and 6-M12) were identified by comparison with reference standards. Interestingly, Astragalus saponins 1, 2, 5, and 6 were deacetylated to form astragaloside IV (4), which has been reported to have good pharmacological neuroprotective, liver protective, anticancer, and antidiabetic effects. Six kinds of active Astragalus saponins from different parts of Astragalus mongholicus were identified by SERS spectroscopy. Six kinds of active Astragalus saponins from different parts of Astragalus mongholicus were identified by SERS spectrum, and the metabolites were characterized by UPLC/ESI/Q-TOF-MS, which not only provided a new method for the identification of traditional Chinese medicine but also provided a theoretical basis for the study of the pharmacodynamic substance basis of Astragalus mongholicus saponins.

Traumatic Brain Injury and Risk of Dementia and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Previous studies have investigated the potential role of traumatic brain injury (TBI) in subsequent development of dementia and Alzheimer's disease (AD) but reported inconsistent results. We aimed to determine the association between TBI and subsequent occurrence of dementia and AD. METHODS: We performed a systematic search in PubMed and Web of Science for studies that quantitatively investigated the association between TBI and risk of dementia and AD and were published on or before September 21, 2021. A random-effects model was used to combine the estimates. RESULTS: Twenty-five eligible articles were included in this meta-analysis. The results suggested that TBI was associated with an increased risk of dementia (pooled odds ratio [OR] = 1.81, 95% confidence interval [CI] = 1.53-2.14). However, no association was observed between TBI and AD (pooled OR = 1.02, 95% CI = 0.91-1.15). In the subgroup analysis, TBI with loss of consciousness was not associated with risk of dementia (pooled OR = 0.96, 95% CI = 0.84-1.09). Besides, Asian ethnicity, male gender, and mean age of the participants less than 65 years were associated with a higher risk of dementia. CONCLUSION: Our study suggests an increased risk of dementia among individuals with TBI, highlighting the need for more intensive medical monitoring and health education in individuals with TBI. Biological mechanisms linking TBI and the development of dementia are needed in future studies.

Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Molecular Characterization and Pathogenicity of the Novel Recombinant Muscovy Duck Parvovirus Isolated from Geese.

Goose parvovirus (GPV) and Muscovy duck parvovirus (MDPV) are the main agents associated with waterfowl parvovirus infections that caused great economic losses in the waterfowl industry. In 2020, a recombinant waterfowl parvovirus, 20-0910G, was isolated in a goose flock in Taiwan that experienced high morbidity and mortality. The whole genome of 20-0910G was sequenced to investigate the genomic characteristics of this isolate. Recombination analysis revealed that, like Chinese rMDPVs, 20-0910G had a classical MDPV genomic backbone and underwent two recombination events with classical GPVs at the P9 promoter and partial VP3 gene regions. Phylogenetic analysis of the genomic sequence found that this goose-origin parvovirus was highly similar to the circulating recombinant MDPVs (rMDPVs) isolated from duck flocks in China. The results of experimental challenge tests showed that 20-0910G caused 100% mortality in goose embryos and in 1-day-old goslings by 11 and 12 days post-inoculation, respectively. Taken together, the results indicated that this goose-origin rMDPV was closely related to the duck-origin rMDPVs and was highly pathogenic to young geese.

Effects of propofol and inhalational anesthetics on the optic nerve sheath diameter in patients undergoing surgery in the steep Trendelenburg position: a systematic review and meta-analysis.

BACKGROUND: Optic nerve sheath diameter (ONSD) is recognized as a surrogate indicator of intracranial pressure (ICP) during surgery. Due to the requirements of surgery, the adjustment to the steep Trendelenburg position and the establishment of CO2 pneumoperitoneum can lead to an increase in ICP, resulting in an increase in the ONSD. Anesthetic agents have different impacts on cerebral blood volume and ICP. The aim of this study was to evaluate the effects of propofol and inhalational anesthetics on the ONSD based on data from randomized controlled trials (RCTs). METHODS: The electronic databases of PubMed, EMBASE, Ovid MEDLINE, the Cochrane Library, and other databases were searched systematically using specified keywords from their inception to June 2021. The Chi-square test and I2 test were used to evaluate the heterogeneity across the studies. The weighted mean difference (WMD) with 95% confidence interval (CI) were adopted to analyze continuous data. RESULTS: A total of 379 patients from 7 studies were involved in this meta-analysis. There were borderline significant differences in the ONSD atT2 between propofol and the control group: T2 (WMD =-0.15, 95% CI: -0.31, -0.00, P=0.005). There were significant differences at T3 (WMD =-0.23,95% CI: -0.42, -0.05, P =0.013) and T4 (WMD  =-0.18, 95% CI: -0.29, -0.07, P =0 .001). After statistical verification, there was no significant difference in the ONSD at T1 between the 2 groups: T1 (WMD =-0.08, 95% CI: -0.26, 0.10, P =0 .368). There were also no significant differences in mean arterial pressure (MAP) (P=0.654, 0.445, 0.698, and 0.562, respectively) and end tidal CO2 (ETCO2) (P=0.081, 0.506, 0.126, and 0.983, respectively) at T1, T2, T3 and T4 between propofol and inhalational anesthetics. DISCUSSION: The findings in the present study indicated that the ONSD during propofol anesthesia was significantly lower than that during inhalational anesthesia after adopting the Trendelenburg position and CO2 pneumoperitoneum. These analysis results suggest that propofol anesthesia may help to minimize changes in ICP compared to inhalational anesthetics.

Metabolites Identification of Chemical Constituents From the Eggplant (Solanum melongena L.) Calyx in Rats by UPLC/ESI/qTOF-MS Analysis and Their Cytotoxic Activities.

Eggplant (Solanum melongena L.) Calyx is a medicinal and edible traditional Chinese medicine with anti-inflammatory, anti-oxidant, and anti-cancer properties. However, the pharmacodynamic components and metabolic characteristics remain unclear. Amide and phenylpropanoid were the two main constituents, and four amides, including n-trans-p-coumaroyltyramine (1), n-trans-p-coumaroyloctopamine (2), n-trans-p-coumaroylnoradrenline (3), n-trans-feruloyloctopamine (4), and a phenylpropanoid neochlorogenic acid (5) were selected. In this study, these five representative compounds showed cytotoxic activities on A549, HCT116, and MCF7 cells. In addition, the metabolites of 1-5 from the eggplant calyx in rats were identified. In total, 23, 37, 29, and 17 metabolites were separately characterized in rat plasma, urine, feces, and livers, by UPLC/ESI/qTOF-MS analysis. The metabolism of amides and phenylpropanoid was mainly involved in hydroxylation, methylation, glucuronidation, or sulfation reactions. Two hydroxylated metabolites (1-M2 and 2-M3) were clearly identified by comparison with reference standards. Rat liver microsome incubation experiments indicated that P450 enzymes could hydroxylate 1-5, and the methylation reaction of the 7-hydroxyl was also observed. This is the first study on the in vivo metabolism of these compounds, which lays a foundation for follow-up studies on pharmacodynamic evaluations and mechanisms.

Head Injury and Amyotrophic Lateral Sclerosis: A Meta-Analysis.

BACKGROUND: Prior studies have suggested that head injury might be a potential risk factor of amyotrophic lateral sclerosis (ALS). However, the association has not been well established. We aimed to provide a synopsis of the current understanding of head injury's role in ALS. METHODS: We performed a systematic search in PubMed for observational studies that quantitatively investigated the association between head injury and ALS risk published before April 10, 2020. We used a random-effects model to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Fourteen eligible articles including 10,703 cases and 2,159,324 controls were selected in current meta-analysis. We found that head injury was associated with an increased risk of ALS (OR = 1.38, 95% CI: 1.20-1.60) and the association was slightly stronger concerning severe head injury and ALS risk (OR = 1.69, 95% CI: 1.27-2.23). Considering the number of head injuries (N) and ALS risk, the association was weak (OR = 1.23, 95% CI: 1.10-1.37, N = 1; OR = 1.29, 95% CI: 0.89-1.86, N ≥ 2). In addition, a strong association with ALS risk was found in individuals who suffered head injury <1 year (OR = 4.05, 95% CI: 2.79-5.89), and when the time lag was set at 1-5, 5-10, and >10 years, the pooled OR was 1.13, 1.35, and 1.10, respectively. CONCLUSION: This meta-analysis indicates that head injury, especially severe head injury, could increase ALS risk. Although a strong association is found between head injury <1 year and ALS risk in the current study, this result suggests a possibility of reverse causation.

Trauma and amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Background: Trauma especially head trauma is considered a potential risk factor of amyotrophic lateral sclerosis (ALS), but their association has not been well established. We aimed to determine the association of prior trauma with ALS risk. Methods: This study was performed according to the Meta-Analysis of Observational Studies in Epidemiology guideline to assess related literatures, and a random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Twenty-nine eligible articles involving 18,390 cases and 6,519,391 controls were included in this meta-analysis. The results showed that trauma was associated with an increased risk of ALS (pooled OR = 1.51, 95% CI: 1.32-1.73). Besides, patients with trunk trauma, head trauma and lower limb trauma had an increased risk of ALS, whereas no evidence suggested that upper limb trauma and spine trauma could increase ALS risk. Considering the number of traumatic events, the association between trauma and ALS risk was significant for patients with repeated trauma events (pooled OR = 1.21, 95% CI: 1.07-1.38). The results showed that individuals with a history of trauma within 5 years were more likely to be diagnosed with ALS (pooled OR = 1.84, 95% CI: 1.56-2.17). Importantly, both old trauma and very old trauma were found to be associated with an increased risk of ALS (pooled OR = 1.24, 95% CI: 1.12-1.38; pooled OR = 1.28, 95% CI: 1.10-1.49; respectively). Conclusions: This meta-analysis indicated that trauma could increase ALS risk, which may be applied for the clinicians to tailor targeted treatment regimens and make prophylactic strategies for ALS in traumatic patients.

SNHG10 Promotes Cell Proliferation and Migration in Gastric Cancer by Targeting miR-495-3p/CTNNB1 Axis.

BACKGROUND: Long non-coding RNAs have been acknowledged as the crucial regulators in the progression of human cancers, including gastric cancer (GC). Small nucleolar RNA host gene 10 (SNHG10) has been identified as an oncogene in several cancer types. Nonetheless, it is unclear whether SNHG10 exerts functions in GC cells. AIMS: The aims of the current study were to explore the function and underlying mechanism of SNHG10 in GC. METHODS: The expression levels of SNHG10, miR-495-3p and catenin beta 1 (CTNNB1) were detected by RT-qPCR. Loss-of-function assays, including CCK-8, colony formation assay, flow cytometry analysis and transwell assays, were conducted to verify the effect of SHNG10 on the proliferation, apoptosis, migration and invasion of GC cells. Mechanism experiments were performed to identify the downstream molecular mechanism of SNHG10. RESULTS: SNHG10 was expressed at a high level in GC cells. Knockdown of SNHG10 inhibited the proliferation, migration and invasion of GC cells. Silencing of SNHG10 led to the downregulation of core factors of WNT signaling pathway. Knockdown of SNHG10 could decline the expression of CTNNB1 through sequestering miR-495-3p. CONCLUSIONS: SNHG10 promotes the procession of GC through targeting miR-495-3p/CTNNB1 and activating WNT signaling pathway.