Extrafacial Acquired Dermal Melanocytosis: An Exceptionally Rare Example With Bilateral Multifocal Disease.

Dermal melanocytoses are a group of cutaneous disorders characterized by the presence of ectopic melanocytes in the dermis; the most well-known example is the Mongolian spot. Acquired dermal melanocytosis (ADM) is a term used to describe the onset of dermal melanocytosis occurring after its usual age of presentation (i.e., birth and infancy). ADMs usually occur on the face and can less commonly affect extrafacial sites, such as the back and limbs. Purely extrafacial ADM is extremely uncommon and, when present, is usually unifocal. Herein, we present an exceptionally rare example of purely extrafacial ADM with extensive bilateral involvement in a 44-year-old female originally from the Philippines.

Complete chloroplast genomes of the hemiparasitic genus Cymbaria: Insights into comparative analysis, development of molecular markers, and phylogenetic relationships.

The hemiparasitic tribe Cymbarieae (Orobanchaceae) plays a crucial role in elucidating the initial stage of the transition from autotrophism to heterotrophism. However, the complete chloroplast genome of the type genus Cymbaria has yet to be reported. In addition, the traditional Mongolian medicine Cymbaria daurica is frequently subjected to adulteration or substitution because of the minor morphological differences with Cymbaria mongolica. In this study, the complete chloroplast genomes of the two Cymbaria species were assembled and annotated, and those of other published 52 Orobanchaceae species were retrieved for comparative analyses. We found that the Cymbaria chloroplast genomes are characterized by pseudogenization or loss of stress-relevant genes (ndh) and a unique rbcL-matK inversion. Unlike the high variability observed in holoparasites, Cymbaria and other hemiparasites exhibit high similarity to autotrophs in genome size, guanine-cytosine (GC) content, and intact genes. Notably, four pairs of specific DNA barcodes were developed and validated to distinguish the medicinal herb from its adulterants. Phylogenetic analyses revealed that the genus Cymbaria and the Schwalbea-Siphonostegia clade are grouped into the tribe Cymbarieae, which forms a sister clade to the remaining Orobanchaceae parasitic lineages. Moreover, the diversification of monophyletic Cymbaria occurred during the late Miocene (6.72 Mya) in the Mongol-Chinese steppe region. Our findings provide valuable genetic resources for studying the phylogeny of Orobanchaceae and plant parasitism, and genetic tools to validate the authenticity of the traditional Mongolian medicine "Xinba.".

Integration of Gut Microbiota, Serum Metabolomic, and Network Pharmacology to Reveal the Anti Insomnia Mechanism of Mongolian Medicine Sugemule-4 Decoction on Insomnia Model Rats.

Objective: To explored the potential molecular mechanism of Sugemule-4 decoction (MMS-4D) in treating insomnia. Methods: DL-4-chlorophenylalanine (PCPA) + chronic unpredictable mild stress stimulation (CUMS) was used to induce an insomnia model in rats. After the model was successfully established, MMS-4D was intervened at low, medium, and high doses for 7 days. The open-field test (OFT) was used to preliminarily evaluate the efficacy. The potential mechanism of MMS-4D in treating insomnia was investigated using gut microbiota, serum metabolomics, and network pharmacology (NP). Experimental validation of the main components of the key pathways was carried out using ELISA and Western blot. Results: The weights of the insomnia-model rats were significantly raised (p ≤ 0.05), the total exercise distance in the OFT increased (p ≤ 0.05), the rest time shortened, and the number of standing times increased (p ≤ 0.05), after treatment with MMS-4D. Moreover, there was a substantial recovery in the 5-HT, DA, GABA, and Glu levels in the hypothalamus tissue and the 5-HT and GABA levels in the colon tissue of rats. The expression of DAT and DRD1 proteins in the hippocampus of insomnia rats reduced after drug treatment. MMS-4D may treat insomnia by regulating different crucial pathways including 5-HT -, DA -, GABA -, and Glu-mediated neuroactive light receiver interaction, cAMP signaling pathway, serotonergic, glutamatergic, dopaminergic, and GABAergic synapses. Conclusion: This study revealed that MMS-4D can improve the general state and behavioral changes of insomnia model rats. Its mechanism may be related to the reversal of abnormal pathways mediated by 5-HT, DA, GABA, and Glu, such as Serotonergic synapse, Dopaminergic synapse, Glutamatergic synapse, and GABAergic synapse.

Gut microbiome signatures associated with type 2 diabetes in obesity in Mongolia.

Mongolian people possess a unique dietary habit characterized by high consumption of meat and dairy products and fewer vegetables, resulting in the highest obesity rate in East Asia. Although obesity is a known cause of type 2 diabetes (T2D), the T2D rate is moderate in this population; this is known as the "Mongolian paradox." Since the gut microbiota plays a key role in energy and metabolic homeostasis as an interface between food and body, we investigated gut microbial factors involved in the prevention of the co-occurrence of T2D with obesity in Mongolians. We compared the gut microbiome and metabolome of Mongolian adults with obesity with T2D (DO: n = 31) or without T2D (NDO: n = 35). Dysbiotic signatures were found in the gut microbiome of the DO group; lower levels of Faecalibacterium and Anaerostipes which are known as short-chain fatty acid (SCFA) producers and higher levels of Methanobrevibacter, Desulfovibrio, and Solobacterium which are known to be associated with certain diseases. On the other hand, the NDO group exhibited a higher level of fecal SCFA concentration, particularly acetate. This is consistent with the results of the whole shotgun metagenomic analysis, which revealed a higher relative abundance of SCFA biosynthesis-related genes encoded largely by Anaerostipes hadrus in the NDO group. Multiple logistic regression analysis including host demographic parameters indicated that acetate had the highest negative contribution to the onset of T2D. These findings suggest that SCFAs produced by the gut microbial community participate in preventing the development of T2D in obesity in Mongolians.

[Clinical effect of the warm acupuncture of Mongolian medicine on insomnia in the elderly and its brain-gut peptide mechanism: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect and safety of the warm acupuncture of Mongolian medicine in treatment of insomnia in the elderly, and to explore its underlying brain-gut peptide mechanism. METHODS: Sixty elderly patients with insomnia were randomly divided into a warm acupuncture group and a western medication group, 30 cases in each group. In the warm acupuncture group, the warm acupuncture of Mongolian medicine was operated at Dinghuixue (at the center of the vertex, the crossing site of the anterior midline and the line connected the upper edges of two ear apexes), Heyixue (at the depression of the spinous process of the 7th cervical vertebra) or Xinxue (at the depression of the spinous process of the 6th thoracic vertebra) in each treatment. Only one of the above points was selected and stimulated for 20 min one treatment and the three points were used alternatively. The treatment was given once every day or every other day, 3 times a week, and for a total of 3 weeks. In the western medication group, estazolam tablets were administered orally, once a day, 1 mg before bedtime, consecutively for 3 weeks. Before and after treatment, as well as in 1-month follow-up visit after the treatment completion, the scores of the Pittsburgh sleep quality index (PSQI) and the insomnia severity index (ISI) were observed in the two groups. The serum brain-related peptide markers (substance P [SP], neuropeptide Y [NPY], 5-hydroxytryptamine 1A [5-HT1A] and 5-hydroxytryptamine 2A [5-HT2A]) were measured before and after treatment, and the clinical efficacy and safety was evaluated in the two groups. RESULTS: After treatment and in follow-up, the scores of sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance and daytime dysfunction, as well as the total scores of PSQI, and ISI scores were all reduced in the two groups (P<0.05, P<0.01); and the scores in the warm acupuncture group were lower than those of the western medication group (P<0.05, P<0.01). After treatment, the levels of serum SP and 5-HT2A were decreased (P<0.01) and the levels of serum NPY and 5-HT1A were increased (P<0.01) when compared with those before treatment in the two groups. The levels of serum SP and 5-HT2A in the warm acupuncture group were lower than those of the western medication group (P<0.05), and the levels of serum NPY and 5-HT1A were higher than those of the western medication group (P<0.05). After treatment, the total effective rate was 93.3% (28/30) in the warm acupuncture group, which was higher than 83.3% (25/30) of the western medication group (P<0.05). No serious adverse reactions were found in the two groups. CONCLUSION: Warm acupuncture of Mongolian medicine can effectively improve the sleep quality of the elderly patients with insomnia, and its mechanism may be related to the regulation of the levels of serum SP, NPY, 5-HT1A and 5-HT2A.

Establishment and Application of a Novel Genetic Detection Panel for SNPs in Mongolian Gerbils.

The Mongolian gerbil is a distinctive experimental animal in China, as its genetic qualities possess significant value in the field of medical biology research. Here, we aimed to establish an economical and efficient panel for genetic quality detection in Mongolian gerbils using single-nucleotide polymorphism (SNP) markers. To search for SNPs, we conducted whole-genome sequencing (WGS) in 40 Mongolian gerbils from outbred populations. Reliable screening criteria were established to preliminarily select SNPs with a wide genome distribution and high levels of polymorphism. Subsequently, a multiple-target regional capture detection system based on second-generation sequencing was developed for SNP genotyping. Based on the results of WGS, 219 SNPs were preliminarily selected, and they were established and optimized in a multiple-amplification system that included 206 SNP loci by genotyping three outbred populations. PopGen.32 analysis revealed that the average effective allele number, Shannon index, observed heterozygosity, expected heterozygosity, average heterozygosity, polymorphism information content, and other population genetic parameters of the Capital Medical University (CMU) gerbils were the highest, followed by those of Zhejiang gerbils and Dalian gerbils. Through scientific screening and optimization, we successfully established a novel, robust, and cost-effective genetic detection system for Mongolian gerbils by utilizing SNP markers for the first time.

Atypical localized Mongolian spots in dark pigmented skin - a challenge for forensic medical examination.

The assessment of skin changes in the context of possible child abuse is an important task in forensic medicine. This requires knowledge of pigmentation variants and pigmentation disorders such as congenital dermal melanocytosis, which includes Mongolian spots. Particularly in the case of atypical localization and dark pigmented skin, the differentiation from hematomas can be challenging. A case of two Nigerian siblings with extensive and atypically localized Mongolian spots is reported. The 1.5-year-old girl showed Mongolian spots on her back and the right side of her trunk. The 8-year-old boy showed Mongolian spots only on the back of his thighs. The authors are not aware of any case in which so called Mongolian spots were present exclusively on the back of the thighs and this case is all the more noteworthy as the back of the thigh is a common localization of blunt force trauma.

Comparative Analysis of mRNA and lncRNA Expression Profiles in Testicular Tissue of Sexually Immature and Sexually Mature Mongolian Horses.

Testicular development and spermatogenesis are tightly regulated by both coding and non-coding genes, with mRNA and lncRNA playing crucial roles in post-transcriptional gene expression regulation. However, there are significant differences in regulatory mechanisms before and after sexual maturity. Nevertheless, the mRNAs and lncRNAs in the testes of Mongolian horses have not been systematically identified. In this study, we first identified the testicular tissues of sexually immature and sexually mature Mongolian horses at the tissue and protein levels, and comprehensively analyzed the expression profiles of mRNA and lncRNA in the testes of 1-year-old (12 months, n = 3) and 10-year-old (n = 3) Mongolian horses using RNA sequencing technology. Through gene expression analysis, we identified 16,582 mRNAs and 2128 unknown lncRNAs that are commonly expressed in both sexually immature and sexually mature Mongolian horses. Meanwhile, 9217 mRNAs (p < 0.05) and 2191 unknown lncRNAs (p < 0.05) were identified as differentially expressed between the two stages, which were further validated by real-time fluorescent quantitative PCR and analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The analysis results showed that genes in the sexually immature stage were mainly enriched in terms related to cellular infrastructure, while genes in the sexually mature stage were enriched in terms associated with hormones, metabolism, and spermatogenesis. In summary, the findings of this study provide valuable resources for a deeper understanding of the molecular mechanisms underlying testicular development and spermatogenesis in Mongolian horses and offer new perspectives for future related research.

The Metabolic Functional Feature of Gut Microbiota in Mongolian Patients with Type 2 Diabetes.

The accumulating evidence substantiates the indispensable role of gut microbiota in modulating the pathogenesis of type 2 diabetes. Uncovering the intricacies of the mechanism is imperative in aiding disease control efforts. Revealing key bacterial species, their metabolites and/or metabolic pathways from the vast array of gut microorganisms can significantly contribute to precise treatment of the disease. With a high prevalence of type 2 diabetes in Inner Mongolia, China, we recruited volunteers from among the Mongolian population to investigate the relationship between gut microbiota and the disease. Fecal samples were collected from the Volunteers of Mongolia with Type 2 Diabetes group and a Control group, and detected by metagenomic analysis and untargeted metabolomics analysis. The findings suggest that Firmicutes and Bacteroidetes phyla are the predominant gut microorganisms that exert significant influence on the pathogenesis of type 2 diabetes in the Mongolian population. In the disease group, despite an increase in the quantity of most gut microbial metabolic enzymes, there was a concomitant weakening of gut metabolic function, suggesting that the gut microbiota may be in a compensatory state during the disease stage. ß-Tocotrienol may serve as a pivotal gut metabolite produced by gut microorganisms and a potential biomarker for type 2 diabetes. The metabolic biosynthesis pathways of ubiquinone and other terpenoid quinones could be the crucial mechanism through which the gut microbiota regulates type 2 diabetes. Additionally, certain Clostridium gut species may play a pivotal role in the progression of the disease.

Single-Cell Transcriptome Sequencing Reveals Molecular Expression Differences and Marker Genes in Testes during the Sexual Maturation of Mongolian Horses.

This study aimed to investigate differences in testicular tissue morphology, gene expression, and marker genes between sexually immature (1-year-old) and sexually mature (10-year-old) Mongolian horses. The purposes of our research were to provide insights into the reproductive physiology of male Mongolian horses and to identify potential markers for sexual maturity. The methods we applied included the transcriptomic profiling of testicular cells using single-cell sequencing techniques. Our results revealed significant differences in tissue morphology and gene expression patterns between the two age groups. Specifically, 25 cell clusters and 10 cell types were identified, including spermatogonial and somatic cells. Differential gene expression analysis highlighted distinct patterns related to cellular infrastructure in sexually immature horses and spermatogenesis in sexually mature horses. Marker genes specific to each stage were also identified, including APOA1, AMH, TAC3, INHA, SPARC, and SOX9 for the sexually immature stage, and PRM1, PRM2, LOC100051500, PRSS37, HMGB4, and H1-9 for the sexually mature stage. These findings contribute to a deeper understanding of testicular development and spermatogenesis in Mongolian horses and have potential applications in equine reproductive biology and breeding programs. In conclusion, this study provides valuable insights into the molecular mechanisms underlying sexual maturity in Mongolian horses.

Atypical Mongolian Spots With Hurler's Disease: A Case Report.

Mongolian spots are bluish-grey, irregular, hyperpigmented macules present at birth or that appear in the first few weeks of life. They are classified as atypical if they occur in unusual locations without spontaneous disappearance after infancy; or if new lesions continue to appear beyond early infancy. Although they are generally considered benign, recent studies have shown that atypical Mongolian spots may be associated with inborn errors of metabolism, such as lysosomal storage disorders and neurocristopathies. An 11-month-old male presented with multiple aberrant Mongolian spots on the abdomen, back, buttocks, arms, and legs, with the largest patch measuring 10x10 cm. Additionally, the child exhibited coarse facial features, a high-arched palate, low-set ears, and a depressed nasal bridge. Systemic examination revealed hepatosplenomegaly, fundus examination showed a hazy cornea, and the urine glycosaminoglycan test was positive, prompting us to conduct further research prioritising lysosomal storage disorders. The mucopolysaccharidosis (MPS) spot test was positive, and electrophoresis for MPS revealed bands for chondroitin sulfate and dermatan sulfate, confirming the diagnosis of MPS. Enzyme assay revealed no alpha-iduronidase activity and normal beta-galactosidase activity, thus confirming Hurler's disease. This case report highlights the importance of considering atypical Mongolian spots as a potential indicator of underlying storage disorders, enabling early intervention.

Melatonin promotes proliferation of Inner Mongolia cashmere goat hair follicle papilla cells through Wnt10b.

The study demonstrated that melatonin (MT) can induce the development of secondary hair follicles in Inner Mongolian cashmere goats through the Wnt10b gene, leading to secondary dehairing. However, the mechanisms underlying the expression and molecular function of Wnt10b in dermal papilla cells (DPC) remain unknown. This research aimed to investigate the impact of MT on DPC and the regulation of Wnt10b expression, function, and molecular mechanisms in DPC. The findings revealed that MT promotes DPC proliferation and enhances DPC activity. Co-culturing DPC with overexpressed Wnt10b and MT showed a significant growth promotion. Subsequent RNA sequencing (RNA-seq) of overexpressed Wnt10b and control groups unveiled the regulatory role of Wnt10b in DPC. Numerous genes and pathways, including developmental pathways such as Wnt and MAPK, as well as processes like hair follicle morphogenesis and hair cycle, were identified. These results suggest that Wnt10b promotes the growth of secondary hair follicles in Inner Mongolian cashmere goats by regulating crucial factors and pathways in DPC proliferation.

Study on preparation and properties of silver alloy for Mongolian medicine acupuncture.

The Mongolian medical silver needles often encounter issues of bending, fracturing, and blunting in clinical applications. Similarly, Mongolian warm needles can cause burns on patients due to inaccurate temperature control. In this study, we developed an Ag85Cu15 alloy specifically for acupuncture needles based on material preparation. By incorporating appropriate amounts of Mn and Ti elements, we were able to enhance the mechanical properties and biocompatibility of the acupuncture needles. Compared to commercially available silver needles, this alloy exhibited a significant increase in microhardness up to 210.2 Hv0.2 and an improved tensile strength of 880.2 MPa. Furthermore, we designed a thermoelectric effect-based temperature measurement model for precise control of the warm needle's temperature, enhancing the therapeutic effectiveness of the treatment.

Immunocytochemical localization of nitric oxide synthase-containing neurons in the visual cortex of the Mongolian gerbil.

INTRODUCTION: Nitric oxide (NO) is present in various cell types in the central nervous system and plays a crucial role in the control of various cellular functions. The diurnal Mongolian gerbil is a member of the rodent family Muridae that exhibits unique physiological, anatomical, and behavioral differences from the nocturnal rat and mouse, which render it a useful model for studying the visual system. The purpose of this study was to confirm the distribution and morphology of neurons that contain nitric oxide synthase (NOS) and their pattern of co-expressing NOS with neuropeptide Y (NPY), somatostatin (SST), and gamma-aminobutyric acid (GABA) in the visual cortex of Mongolian gerbils. MATERIALS AND METHODS: Mongolian gerbils were used in the study. We confirmed the localization of NOS in the visual cortex of Mongolian gerbils using horseradish peroxidase immunocytochemistry, fluorescent immunocytochemistry, and conventional confocal microscopy. RESULTS: NOS-immunoreactive (IR) neurons were present in all layers of the visual cortex of the Mongolian gerbil, with the exception of layer I, with the highest density observed in layer V (50.00%). The predominant type of NOS-IR neurons was multipolar round/oval cells (60.96%). Two-color immunofluorescence revealed that 100% NOS-IR neurons were co-labeled with NPY and SST and 34.55% were co-labeled with GABA. CONCLUSIONS: Our findings of the laminar distribution and morphological characteristics of NOS-IR neurons, as well as the colocalization patterns of NOS-IR neurons with NPY, SST, and GABA, indicated the presence of species-specific differences, suggesting the functional diversity of NO in the visual cortex. This study provides valuable data on the anatomical organization of NOS-IR neurons and, consequently, a better understanding of the functional aspects of NO and species diversity.

Gut microbiome changes in mouse, Mongolian gerbil, and hamster models following Clostridioides difficile challenge.

Introduction: Clostridioides difficile infection (CDI), as well as its etiology and pathogenesis, have been extensively investigated. However, the absence of suitable CDI animal models that reflect CDI symptoms and the associated gut microbiome changes in humans has limited research progress in this field. Thus, we aimed to investigate whether Mongolian gerbils, which present a range of human pathological conditions, can been used in studies on CDI. Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing. Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing. Results: The results obtained showed that C. difficile colonized the gastrointestinal tracts of the three rodents, and after the C. difficile challenge, C57BL/6J mice did not manifest CDI symptoms and their intestines showed no significant pathological changes. However, the hamsters showed explosive intestinal bleeding and inflammation and the Mongolian gerbils presented diarrhea as well as increased infiltration of inflammatory cells, mucus secretion, and epithelial cell shedding in their intestinal tissue. Further, intestinal microbiome analysis revealed significant differences with respect to intestinal flora abundance and diversity. Specifically, after C. difficile challenge, the Firmicutes/Bacteroidetes ratio decreased for C57BL/6J mice, but increased significantly for Mongolian gerbils and hamsters. Furthermore, the abundance of Proteobacteria increased in all three models, especially in hamsters, while that of Verrucomicrobia only increased significantly in C57BL/6J mice and Mongolian gerbils. Our results also indicated that differences in the relative abundances of Lactobacillaceae and Akkermansia were primarily responsible for the observed differences in response to C. difficile challenge. Conclusion: Based on the observed responses to C. difficile challenge, we concluded for the first time that the Mongolian gerbil could be used as an animal model for CDI. Additionally, the taxa identified in this study may be used as biomarkers for further studies on CDI and to improve understanding regarding changes in gut microbiome in CDI-related diseases.

CSF1R inhibitor PLX3397 depletes microglia in Mongolian gerbil Meriones unguiculatus, but not in syrian hamster Mesocricetus auratus.

Microglia are the residential immune cells in the central nervous system. Their roles as innate immune cells and regulators of synaptic remodeling are critical to the development and the maintenance of the brain. Numerous studies have depleted microglia to elucidate their involvement in healthy and pathological conditions. PLX3397, a blocker of colony stimulating factor 1 receptor (CSF1R), is widely used to deplete mouse microglia due to its non-invasiveness and convenience. Recently, other small rodents, including Syrian hamsters (Mesocricetus auratus) and Mongolian gerbils (Meriones unguiculatus), have been recognized as valuable animal models for studying brain functions and diseases. However, whether microglia depletion via PLX3397 is feasible in these species remains unclear. Here, we administered PLX3397 orally via food pellets to hamsters and gerbils. PLX3397 successfully depleted gerbil microglia but had no effect on microglial density in hamsters. Comparative analysis of the CSF1R amino acid sequence in different species hints that amino acid substitutions in the juxtamembrane domain may potentially contribute to the inefficacy of PLX3397 in hamsters.

An Immunocompetent Mongolian Gerbil Model for Hepatitis E Virus Genotype 1 Infection.

BACKGROUND AND AIMS: Hepatitis E virus (HEV), primarily genotype 1 (HEV-1), causes approximately 20.1 million infections, 44,000 deaths, and 3000 stillbirths annually. Current evidence indicates that HEV-1 is only transmitted in humans. Here, we evaluated whether Mongolian gerbils can serve as animal models for HEV-1 infection. METHODS: Mongolian gerbils were used for HEV-1 and hepatitis E virus genotype 3 infection experiments. HEV infection parameters, including detection of HEV RNA and HEV antigen, liver function assessment, and histopathology, were evaluated. RESULTS: We adapted a clinical isolate of HEV-1 for Mongolian gerbils by serial passaging in feces of aged male gerbils. The gerbil-adapted strain obtained at passage 3 induced a robust, acute HEV infection, characterized by stable fecal virus shedding, elevated liver enzymes, histopathologic changes in the liver, and seroconversion to anti-HEV. An infectious complementary DNA clone of the adapted virus was generated. HEV-1-infected pregnant gerbils showed a high rate of maternal mortality and vertical transmission. HEV RNA or antigens were detected in the liver, kidney, intestine, placenta, testis, and fetus liver. Liver and placental transcriptomic analyses indicated activation of host immunity. Tacrolimus prolonged HEV-1 infection, whereas ribavirin cleared infection. The protective efficacy of a licensed HEV vaccine was validated using this model. CONCLUSIONS: HEV-1 efficiently infected Mongolian gerbils. This HEV-1 infection model will be valuable for investigating hepatitis E immunopathogenesis and evaluating vaccines and antivirals against HEV.

Integration of transcriptomics and metabolomics reveals toxicological mechanisms of ZhuRiHeng drop pill in the 180-day repeated oral toxicity study.

Background: ZhuRiHeng Drop Pill (ZRH) is a traditional Mongolian medicinal preparation. Despite its long history of use for the treatment of coronary heart disease, there have been few toxicological studies of the safety profile of ZRH. Purpose: In order to comprehensively elucidate the underlying mechanisms behind the observed toxicity of ZRH on rat livers in the 180-day repeated oral toxicity study, we conducted a comprehensive analysis by integrating transcriptomic and metabolomic data. Methods: High-resolution mass spectrometry was conducted to evaluate the constituents of ZRH. For the acute oral toxicity study, mice were administered a dose of 32 g/(kg·d) of ZRH, while rats were instead orally administered 0.934, 1.868, or 3.736 g/(kg·d) of ZRH over a 180-day period in a 180-day repeated oral toxicity study. Conventional index and organ weights/histology were then monitored to detect any potential ZRH treatment-related toxicity. To identify key genes and metabolites involved in ZRH toxicological processes, we performed transcriptomic and metabolomic analyses of liver tissue upon ZRH treatment using RNA-seq techniques, qPCR and liquid chromatography-mass spectrometry analyses. Results: A total of 60 compounds in ZRH were identified and speculated in positive and negative ion modes. Mice in the acute toxicity study exhibited no signs of ZRH-related toxicity. In a protracted oral toxicity investigation spanning 180 days, discernible elevations in liver ratios were noted in both male and female rats across all three dose cohorts, relative to the control group (p < 0.05 or p < 0.01). Upon subjecting to ZRH treatment, our transcriptomic and qPCR analyses unveiled notable upregulation of crucial genes, exemplified by Abcb1b and Cyp2b2, known for theirs involvement in liver drug transport and metabolism function. Furthermore, our untargeted metabolomic analysis provided supplementary insights, revealing significant regulation in pyrimidine metabolism, as well as alanine, aspartate, and glutamate metabolism pathways. Conclusion: Our study unveils a panoramic understanding of the temporal, dosage-specific, and gene dimensions surrounding the metabolic and transcriptional shifts induced by ZRH exposure. As we peer into the future, recommendations emerge for further exploration, encompassing aspects such as time dynamics, dosage considerations, and gene-centric avenues to enhance therapeutic efficacy.

Systematical explorations of forensic feature and population genetic diversity of the Chinese Mongolian group from northwest China via a self-constructed Multi-InDel panel.

This study aimed to investigate the genetic polymorphisms and population characteristics of Chinese Mongolian group from northwest China (NCM) through a self-developed panel including 43 autosomal insertion/deletion (A-InDel) polymorphism genetic markers. Herein, 288 unrelated healthy individuals from the NCM group were employed to obtain the genetic data of 43 A-InDels through multiplex PCR amplification and InDel genotyping using capillary electrophoresis platform. In addition, multiplex population genetic analyses were performed between the NCM group and 27 reference populations. There were no deviations at 43 loci from Hardy-Weinberg equilibrium in the NCM group. The observed heterozygosity (Ho) values ranged from 0.312 8 to 0.559 2, and the combined power of discrimination (CPD) and cumulative probability of exclusion (CPE) values in the NCM group were 0.999 999 999 999 999 998 77 and 0.999 814, respectively. The forensic parameter values indicated that this panel was polymorphic and informative in the NCM group and could be used as an effective tool for forensic personal identification. Furthermore, the results of pairwise genetic distances, principal component analysis, multidimensional scaling analysis, phylogenetic tree construction, and admixture analysis among the NCM group and 27 reference populations revealed that there were closer genetic relationships between the NCM group and East Asian populations, especially Chinese Hui group (CHH) from the northwest China, which is consistent with the geographical location. These present findings contributed to the ongoing genetic explorations and insights into the genetic architecture of the NCM group.

Toxicity prediction and classification of Gunqile-7 with small sample based on transfer learning method.

Drug-induced diseases are the most important component of iatrogenic disease. It is the duty of doctors to provide a reasonable and safe dose of medication. Gunqile-7 is a Mongolian medicine with analgesic and anti-inflammatory effects. As a foreign substance in the body, even with reasonable medication, it may produce varying degrees of adverse reactions or toxic side effects. Since the cost of collecting Gunqile-7 for pharmacological animal trials is high and the data sample is small, this paper employs transfer learning and data augmentation methods to study the toxicity of Gunqile-7. More specifically, to reduce the necessary number of training samples, the data augmentation approach is employed to extend the data set. Then, the transfer learning method and one-dimensional convolutional neural network are utilized to train the network. In addition, we use the support vector machine-recursive feature elimination method for feature selection to reduce features that have adverse effects on model predictions. Furthermore, due to the important role of the pre-trained model of transfer learning, we select a quantitative toxicity prediction model as the pre-trained model, which is consistent with the purpose of this paper. Lastly, the experimental results demonstrate the efficiency of the proposed method. Our method can improve accuracy by up to 9 percentage points compared to the method without transfer learning on a small sample set.