High-Quality Genomes of Pangolins: Insights into the Molecular Basis of Scale Formation and Adaption to Myrmecophagous Diet.

Pangolins are one of nature's most fascinating species being scales covered and myrmecophagous diet, yet relatively little is known about the molecular basis. Here, we combine the multi-omics, evolution, and fundamental proteins feature analysis of both Chinese and Malayan pangolins, highlighting the molecular mechanism of both myrmecophagous diet and scale formation, representing a fascinating evolutionary strategy to occupy the unique ecological niches. In contrast to conserved organization of epidermal differentiation complex, pangolin has undergone large scale variation and gene loss events causing expression pattern and function conversion that contribute to cornified epithelium structures on stomach to adapt myrmecophagous diet. Our assemblies also enable us to discover large copies number of high glycine-tyrosine keratin-associated proteins (HGT-KRTAPs). In addition, highly homogenized tandem array, amino content, and the specific expression pattern further validate the strong connection between the molecular mechanism of scale hardness and HGT-KRTAPs.

Regulatory Roles of Peroxisomal Metabolic Pathways Involved in Musk Secretion in Muskrats.

In this study, we analyzed the main components of muskrat musk by gas chromatography-mass spectrometry, the results showed that muskrat musk contained fatty acids (29.32%), esters (31.89%), cholesterol (4.38%), cyclic ketones (16.31%), alcohols (6.42%) and other compounds, among which 9-octadecenoic acid accounted for 4.89%. We also analyzed the genes of the metabolic pathway in the scent gland at the transcriptomic level during musk-secreting and non-secreting seasons by RNA-seq (RNA sequencing). We detected 21 genes in the peroxisomal metabolic pathways, including PEX14(peroxin-14) and ACOX3(acyl-CoA oxidase), which exhibited significant differential expression between the musk-secreting season and the non-secreting season (p < 0.05). The RNA-seq results for these genes were validated by reverse transcription PCR(RT-PCR) for both seasons. In addition, we examined changes in the composition of muskrat musk from the glandular cells of scent glands cultured in vitro after RNA interference-mediated silencing of 2 differentially expressed genes, ACOX3 and HSD17B4(D-bifunctional protein, DBP). The 9-Octadecenoic acid content in muskrat musk decreased significantly following the silencing of ACOX3 and HSD17B4(D-bifunctional protein, DBP). These results suggest that peroxisomal metabolic pathways play important roles in the regulation of musk secretion in scent glands in the muskrat.

Epicardial ganglionated plexi ablation increases the inducibility of ventricular tachyarrhythmias in a canine postmyocardial infarction model.

INTRODUCTION: Previous studies have shown that epicardial ganglionated plexi ablation (EGPA) could increase the risk of ventricular arrhythmias induced by acute myocardial ischemia. However, the long-term effect of EGPA in a canine postmyocardial infarction (MI) model is not well established. MATERIALS AND METHODS: Twenty mongrel dogs were randomly divided into two groups: an MI group (n = 10) and an EGPA group (EGPA plus MI, n = 10). EGPA was achieved by ablation of four major ganglion plexi and the ligament of Marshall. The electrocardiograph (ECG) parameters, ventricular effective refractory period (ERP), inducibility of tachyarrhythmias, and ventricular fibrillation threshold (VFT) were measured at baseline and after 8 weeks. Tyrosine hydroxylase (TH) and nerve growth factor (NGF) expression levels in the peri-infarcted zone were also determined by immunohistochemistry in both groups at the end of the study. RESULTS: No significant differences were found in electrophysiological parameters at the baseline between the two groups. At the end of the 8-week follow-up, however, the EGPA group was associated with a longer QT interval, corrected QT (QTc) interval and ventricular ERP, larger dispersion of QT, QTc, and ERP, and higher inducibility of tachyarrhythmia and VFT when compared to the MI group. In addition, the density of TH and NGF in the peri-infarcted zone was also significantly increased in the EGPA group in comparison to the MI group. CONCLUSIONS: After the 8-week follow-up, EGPA increased the ventricular arrhythmia inducibility in the canine post-MI model, likely by increasing ventricular electrophysiological instability and promoting ventricular sympathetic remodeling.

Circulating Iron Levels Interaction with Central Obesity on the Risk of Nonalcoholic Fatty Liver Disease: A Case-Control Study in Southeast China.

OBJECTIVES: We aimed to evaluate the associations between body iron stores and the risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese population and explore whether this effect may be modified by other factors. METHODS: A 1: 1 frequency-matched case-control study was conducted, including 482 NAFLD cases and 490 gender- and age-matched controls. Serum levels of ferritin, hepcidin, and C-reactive protein were measured. RESULTS: Multivariate logistic regression analysis showed that hepcidin was not associated with NAFLD risk; however, elevated serum ferritin was significantly associated with increased risk of NAFLD (adjusted OR 1.619, 95% CI 1.158-2.267), and hepcidin:ferritin ratio was significantly associated with decreased risk of NAFLD -(OR-adjusted 0.702, 95% CI 0.501-0.984). When stratified by gender, a significant association was found between elevated serum ferritin and hepcidin:ferritin ratio and NAFLD only for women (ORadjusted 2.131, 95% CI 1.151-3.944 and ORadjusted 0.414, 95% CI 0.219-0.781, respectively). A significant multiplicative interaction between central obesity and elevated serum hepcidin was observed (p < 0.05). CONCLUSIONS: Elevated serum ferritin and hepcidin:ferritin ratio are associated with NAFLD in a Chinese population. Although serum hepcidin is not associated with NAFLD, it may augment the risk effect of central obesity on NAFLD.

Malignant Arrhythmia with Variants of Desmocollin-2 and Desmoplakin Genes.

Malignant arrhythmia is a fast cardiac arrhythmia that can lead to a hemodynamic abnormality within a short time, most of which is ventricular tachycardia or ventricular fibrillation (VF), which should be managed in time. Both organic and nonorganic cardiac diseases have the potential to cause malignant arrhythmia. We report a noteworthy case of malignant arrhythmia in a teenager during exercise. Transthoracic echocardiography, cardiac magnetic resonance (CMR), electrophysiological study, magnetic resonance imaging of the brain, electroencephalography, chest X-ray, and blood tests were all normal. Twelve-lead electrocardiography showed incomplete right bundle branch block (IRBBB). Two heterozygous missense variants of the desmocollin-2 gene (DSC2, c.G2446A/p.V816M) and desmoplakin gene (DSP, c.G3620A/p.R1207K) were detected in the peripheral blood of this teenager and his father by genetic testing, which encoded a desmosomal protein that was related to arrhythmogenic right ventricular cardiomyopathy (ARVC). In these two rare variants, DSC2 V816M has been reported but uncertain significance, whereas DSP R1207K is never reported. Therefore, the two site variants in DSC2 and DSP genes are likely to become a new research focus for diagnosis and treatment of ARVC in the future. Meanwhile, this report emphasizes that, in addition to a standard set of laboratory tests and examinations, genetic testing may be useful for analyzing the causes of malignant arrhythmia.

NK4 inhibits the proliferation and induces apoptosis of human rheumatoid arthritis synovial cells.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by proliferation and insufficient apoptosis of synovial cells. NK4 is a hepatocyte growth factor antagonist and is implicated in cell proliferation, viability, and apoptosis of many tumour cells. This study aimed to investigate the role of NK4 in the regulation of human RA synovial cell proliferation and apoptosis. Fibroblast-like synoviocytes (FLSs) isolated from RA patients and MH7A synovial cells were subjected to MTT, flow cytometry, and Western blot analysis. We found that NK4 suppressed cell proliferation through cell cycle arrest at the G0/G1 phase and induced apoptosis in RA synovial cells. Furthermore, NK4 altered the expression of cell cycle and apoptosis-related proteins such as cyclin D1, cyclin B1, PCNA, p21, p53, Bcl-2, Bax, cleaved caspase-9, and cleaved caspase-3. Additionally, NK4 reduced the phosphorylation level of NF-κB p65 and upregulated the expression of sirt1, but did not change the levels of p38 and p-p38 in RA-FLS and MH7A cells. In conclusion, NK4 inhibits the proliferation and induces apoptosis of human RA synovial cells. NK4 is a promising therapeutic target for RA. We demonstrated that NK4 inhibited cell proliferation by inducing apoptosis and arresting cell cycle in RA-FLS and MH7A cells. The apoptotic effects of NK4 may be mediated in part by decreasing Bcl-2 protein level, increasing Bax and caspase 3 protein levels, and inhibiting NF-κB signalling in RA-FLS and MH7A cells. These findings reveal potential mechanism underlying the role of NK4 in RA synovial cells and suggest that NK4 is a promising agent for RA treatment.

Rs12976445 Polymorphism Is Associated with Post-Ablation Recurrence of Atrial Fibrillation by Modulating the Expression of MicroRNA-125a and Interleukin-6R.

BACKGROUND This study aimed to identify the relationship between miR-125a polymorphism rs12976445 and the post-ablation recurrence of atrial fibrillation (AF), as well as to explore the underlying mechanism of miR-125a in AF recurrence. MATERIAL AND METHODS Microarray analysis was performed to search for miRNAs potentially involved in the regulation of AF recurrence, while real-time PCR (polymerase chain reaction) and Western blot analyses were carried out to study the expression of miR-125a (microRNA-125a), IL-6R (interleukin-6 receptor), and IL-16 (interleukin-16) in different experimental groups, so as to understand the regulatory relationships among miR-125a, IL-6R, and IL-16. Subsequently, a logistic regression analysis was utilized to investigate the survival status of recurrent AF in subjects harboring different genotypes of rs12976445. RESULTS The subjects in the GG and GC/CC groups of miR-125a polymorphism rs12976445 showed no obvious difference regarding all demographic characteristics that were collected in this study. In addition, 19 miRNAs were identified as potentially involved in the regulation of AF recurrence. Among these miRNAs, 6 were upregulated and 13 were downregulated in the group with early recurrence. According to real-time PCR results, the expression of miR-125a was dramatically upregulated in LRAF (late recurrence of atrial fibrillation) as well as in subjects harboring the GG genotype. On the contrary, the level of IL-6R mRNA was dramatically downregulated in LRAF and subjects harboring the GG genotype. Furthermore, IL-6R was confirmed as a candidate target of miR-125a by a luciferase reporter assay. CONCLUSIONS MicroRNA-125a polymorphism rs12976445 plays a role in AF recurrence via the regulation of IL-6R.

Sex hormones play roles in determining musk composition during the early stages of musk secretion by musk deer (Moschus berezovskii).

Musk is a secreted external hormone or information compound that is stored in musk scent glands of the males of species within the family Moschidae, such as Moschus berezovskii. The secretion of musk changes periodically during the courtship and reproduction periods, with the early stage of secretion occurring from May to July, and the maturation stage occurring from August to April of the following year. In this study, we analyzed the dynamic changes in musk components from June to April of the following year. The result showed that musk morphological character, water content, total ion chromatographic pattern, and composition undergo seasonal change. Luminescence immunoassay and radioimmunoassay analyses were performed to determine corresponding fecal hormone levels. The results showed that testosterone, estrogen, and cortisol levels in feces change on a seasonal basis, and are significantly higher in June than in other months (p < 0.01). Correlation analysis showed that the contents of four examined musk components (muscone, cyclopentadecanone, cholesterol, and cholestenol) from June to August were significantly highly negatively correlated with fecal testosterone and estradiol levels (p < 0.01). In contrast, the correlation coefficients were low or not significant from August to April of the following year. These results indicate that testosterone and estradiol may play a major role in determining musk composition during the early stage of musk secretion but not during the course of musk maturation, which suggests that musk secretion may be promoted by increases in sex hormones in June.

Unveiling the Impact of ApoF Deficiency on Liver and Lipid Metabolism: Insights from Transcriptome-Wide m6A Methylome Analysis in Mice.

Lipid metabolism participates in various physiological processes and has been shown to be connected to the development and progression of multiple diseases, especially metabolic hepatopathy. Apolipoproteins (Apos) act as vectors that combine with lipids, such as cholesterol and triglycerides (TGs). Despite being involved in lipid transportation and metabolism, the critical role of Apos in the maintenance of lipid metabolism has still not been fully revealed. This study sought to clarify variations related to m6A methylome in ApoF gene knockout mice with disordered lipid metabolism based on the bioinformatics method of transcriptome-wide m6A methylome epitranscriptomics. High-throughput methylated RNA immunoprecipitation sequencing (MeRIP-seq) was conducted in both wild-type (WT) and ApoF knockout (KO) mice. As a result, the liver histopathology presented vacuolization and steatosis, and the serum biochemical assays reported abnormal lipid content in KO mice. The m6A-modified mRNAs were conformed consensus sequenced in eukaryotes, and the distribution was enriched within the coding sequences and 3' non-coding regions. In KO mice, the functional annotation terms of the differentially expressed genes (DEGs) included cholesterol, steroid and lipid metabolism, and lipid storage. In the differentially m6A-methylated mRNAs, the functional annotation terms included cholesterol, TG, and long-chain fatty acid metabolic processes; lipid transport; and liver development. The overlapping DEGs and differential m6A-modified mRNAs were also enriched in terms of lipid metabolism disorder. In conclusion, transcriptome-wide MeRIP sequencing in ApoF KO mice demonstrated the role of this crucial apolipoprotein in liver health and lipid metabolism.

Universal materials model of deep-learning density functional theory Hamiltonian.

Realizing large materials models has emerged as a critical endeavor for materials research in the new era of artificial intelligence, but how to achieve this fantastic and challenging objective remains elusive. Here, we propose a feasible pathway to address this paramount pursuit by developing universal materials models of deep-learning density functional theory Hamiltonian (DeepH), enabling computational modeling of the complicated structure-property relationship of materials in general. By constructing a large materials database and substantially improving the DeepH method, we obtain a universal materials model of DeepH capable of handling diverse elemental compositions and material structures, achieving remarkable accuracy in predicting material properties. We further showcase a promising application of fine-tuning universal materials models for enhancing specific materials models. This work not only demonstrates the concept of DeepH's universal materials model but also lays the groundwork for developing large materials models, opening up significant opportunities for advancing artificial intelligence-driven materials discovery.

Licochalcone A alleviates ferroptosis in doxorubicin-induced cardiotoxicity via the PI3K/AKT/MDM2/p53 pathway.

Licochalcone A (Lico A), a flavonoid found in licorice, possesses multiple pharmacological activities in modulating oxidative stress, glycemia, inflammation, and lipid metabolism. This study aimed to explore the potential mechanism of Lico A in mitigating ferroptosis associated with doxorubicin-induced cardiotoxicity (DIC). Initially, network pharmacology analysis was applied to identify the active components present in licorice and their targeted genes associated with DIC. Subsequently, to assess the role of Lico A in a DIC mouse model, electrocardiograms, myocardial injury markers, and myocardial histopathological changes were measured. Additionally, cell viability, reactive oxygen species (ROS), ferrous iron, glutathione/glutathione disulfide (GSH/GSSG), and malondialdehyde (MDA) were measured in the cell model as hallmarks of ferroptosis. Finally, the PI3K/AKT/MDM2/p53 signaling pathway and ferroptosis-related proteins were measured in vitro and in vivo. Bioinformatics results revealed that 8 major compounds of licorice, including Lico A, primarily regulated targets such as p53 and the PI3K/AKT signaling pathways in DIC. In the mouse model of DIC, Lico A significantly ameliorated serum biomarkers, histopathology, and electrocardiogram abnormalities. Pretreatment with Lico A enhanced the viability of H9C2 cells treated with doxorubicin. Furthermore, Lico A administration resulted in decreased levels of ROS, ferrous iron, and MDA and increased levels of GSH/GSSG. At the protein level, Lico A increased the phosphorylation of PI3K/AKT/MDM2, reduced p53 accumulation, and induced the upregulation of SLC7A11 and GPX4 expression. However, selective inhibition of PI3K/AKT and plasmid-based overexpression of p53 significantly abolished the anti-ferroptosis functions of Lico A. In conclusion, Lico A attenuates DIC by suppressing p53-mediated ferroptosis through activating PI3K/AKT/MDM2 signaling.

Competing risk analysis of cardiovascular mortality in multiple myeloma survivors.

Background: The survival of multiple myeloma (MM) patients has significantly improved, and several factors increase the risk of cardiovascular death (CVD) mortality in MM. This study aims to determine the prognostic significance of factors associated with long-term CVD risk in MM survivors. Methods: The data of MM survivors whose survival time was longer than 36 months were retrieved from the Surveillance, Epidemiology, and End Result (SEER) database between 2000 and 2015. Cox proportional hazards regressions and competing risk survival analyses were utilized to assess the CVD-associated risk factors. Propensity score matching (PSM) was further conducted to ensure the comparability of cardiovascular risk factors. The nomogram was based on these epidemiological factors to estimate individualized CVD probabilities for MM survivors, and its performance was assessed by Harrell's concordance index (C-index) and calibration curve. Results: A total of 32,528 survivors with MM were enrolled, and 2,061 (6.34%) suffered from CVD. In Cox proportional hazards regressions and competing risk survival analyses, age, period of diagnosis, sex, race, married status, income, chemotherapy, and radiotherapy were the independent risk factors for CVD. After PSM, there was a significant difference in cumulative incidence curves, using a competing-risks method, between the following matched groups: male vs. female group, white vs. non-white group, married vs. unmarried group, income <$75,000 vs. income ≥$75,000 group, chemotherapy vs. non-chemotherapy group, and radiotherapy vs. non-radiotherapy group. The nomogram predicted CVD probabilities with a training C-index of 0.700 and a validation C-index of 0.726. Calibration curves validated that the nomograms could accurately predict the CVD probabilities both in the training and validation group. Conclusions: Among MM survivors, the mortality risk of cardiovascular diseases differs with age, sex, period at diagnosis, race/ethnicity, marital status, chemotherapy, and radiotherapy. Our nomograms, based on epidemiological variables, may be used to predict 5-, 10-, and 15-year cardiovascular disease outcomes of MM survivors.

Analysis on Changes and Influencing Factors of the Intestinal Microbiota of Alpine Musk Deer between the Place of Origin and Migration.

In China, the population of wild musk deer, belonging to the family Moschidae, has drastically decreased in recent years owing to human activities and environmental changes. During the 1990s, artificial breeding of Alpine musk deer was conducted in Xinglong Mountain, Gansu Province, China, and their ex situ conservation was explored for over a decade. Ex situ protection is beneficial for expanding the population of animals and maintaining their genetic diversity; however, it can also induce metabolic diseases and parasitic infections and reduce reproductive capacity. The gut microbiota of animals has a considerable impact on host energy metabolism and immune regulation, thereby playing a crucial role in the overall health and reproductive success of the host. In this study, by comparing the differences in the intestinal microbiome of the musk deer according to their place of origin and migration, the changes in their gut microbiota and the influencing factors were explored to provide a theoretical basis for monitoring the health status of the musk deer. We used 16S rRNA high-throughput sequencing technology to analyze the structure and diversity of the gut microbiota of Alpine musk deer in Gansu (G, place of origin) and Sichuan (S, place of migration). The results showed that the dominant bacteria and genera in the intestinal microbiome of captive musk deer were similar in the places of origin and migration, but significant differences were observed in their relative abundance (p < 0.05). Regarding Firmicutes and Actinobacteria, which are related to plant cellulose digestion, the relative abundance in group G was higher than that in group S; regarding Proteobacteria and Verrucomicrobia, which are related to fat and starch intake, the relative abundance in group S was higher than that in group G; the relative abundance of Bacillus and Clostridium sensu stricto, which are related to fiber digestibility, was higher in group G than in group S; the relative abundance of conditional pathogens Acinetobacter and Escherichia-Shigella was higher in group S than in group G. The results of α and ß diversity analysis also showed significant differences between the two groups (p < 0.05). The ACE and Shannon indices of musk deer in group G were considerably higher than those in group S, and the Simpson index of musk deer in group S was greater than that in group G, indicating that the abundance and diversity of intestinal microbiome were higher in musk deer of Gansu than those of Sichuan. Comparison of the changes in the intestinal microbiome of the musk deer according to the place of origin and migration showed that the plant cellulose content in the food of the musk deer, the fat content in the concentrated feed, and changes in the feeding environment have an impact on the intestinal microbiome. Effective monitoring of the health and immunity of the musk deer is crucial for ensuring their overall health, which in turn will aid in formulating a scientific and reasonable management plan for their conservation.

Diagnostic value of triglyceride-glucose index and related parameters in metabolism-associated fatty liver disease in a Chinese population: a cross-sectional study.

OBJECTIVE: Our study aimed to explore the diagnostic value of triglyceride-glucose (TyG) and its related parameters in metabolism-associated fatty liver disease (MAFLD). DESIGN: A cross-sectional study of residents who attended medical checkups at the First Hospital of Nanping City, Fujian Medical University, between 2015 and 2017. SETTING: One participation centre. PARTICIPANTS: 2605 subjects met the inclusion-exclusion criteria and were grouped according to whether they had MAFLD. RESULTS: The TyG index and its associated parameters are positively associated with the risk of developing MAFLD (p<0.001). Restriction cube spline analysis showed a significant dose-response relationship between the TyG index and MAFLD. The risk of developing MAFLD increases significantly with a higher TyG index. After adjusting for confounders, this relationship remains (OR: 4.89, 95% CI 3.98 to 6.00). The areas under the receiver operating characteristic curves of the TyG index for MAFLD detection were 0.793 (0.774 to 0.812). The areas under the curve (AUC) of TyG-related parameters were improved, among which TyG-waist circumference (TyG-WC) showed the largest AUC for MAFLD detection (0.873, 95% CI 0.860 to 0.887). In addition, the best cut-off value of the TyG-WC was 716.743, with a sensitivity and specificity of 88.7% and 71.4%, respectively. CONCLUSION: The TyG index effectively identifies MAFLD, and the TyG-related parameters improved the identification and diagnosis of MAFLD, suggesting that TyG-related parameters, especially TyG-WC, may be a useful marker for diagnosing MAFLD.

Specific mating behavior of Malayan pangolin (Manis javanica) in captivity.

Pangolin is a mysterious animal in the Family Pholidota, Mammalia. Malayan pangolin (Manis javanica) is one of eight existing species and is listed in Manis. With the number of wild pangolins (Manis spp.) rapidly decreasing, captive breeding has become an important way to protect them from extinction. The research on mating behavior of pangolins is an important content to understand its reproductive characteristics and develop breeding management. From 2016 to 2022, a total of 360 mating events were observed in six males and 24 females through closed circuit television (CCTV) surveillance. The results show that males do not engage in complex courtship behavior before mating. In addition, we found that male pangolins adopted a ventrolateral mating position. Once males selected the side (left/right) of the female pangolin from which to approach to mate, they usually remained on the same side for subsequent mating, suggesting that male pangolins may have a preference in mating position. Finally, all mating events were observed at 1.72 ± 1.47 (n = 83, Mean ± SD) days after cohabitation and adjustment time before mating (from the male touching the female to intromission) took 4.98 ± 3.86 mins (n = 323). During mating, males hugged females and remained still for 47.37 ± 10.08 seconds (n = 323), which is the ejaculation and post-ejaculation quiescent time. Remarkably, we observed for the first time two peak mating times, 19:00 to 22:00 and 1:00 to 3:00, suggesting that they may have a preference for mating times. This study provides new insight into the mating behavior of M. javanica and contributes to the development of scientific conservation measures to improve the reproductive capacity of M. javanica.

Weaning period and growth patterns of captive Sunda pangolin (Manis javanica) cubs.

This study tracked and recorded the weight changes of 13 captive Sunda pangolin cubs from lactation to maturity to explored the appropriate weaning time and reveal the rules of its weight growth. SPSS 25.0 was used to build a cubic equation model to fit the body weight change rules of 4 individuals who nonvoluntarily ingested artificial feed (NIAF) at 127 days after birth and 5 individuals who voluntarily ingested artificial feed (VIAF) at 86-108 days after birth. The body weight of NIAF cubs aged 0-120 days and VIAF cubs aged 0-150 days were estimated according to the fitting model. An independent sample T-test was performed on the mean body weight of the two groups during the late lactation period. The results showed that at 105 days after birth, the body weight of the VIAF group was significantly higher than that of the NIAF group (P = 0.049), and the body weight of the VIAF group was extremely significantly higher than that of the NIAF group at 114 days (P = 0.008); The peak cumulative body weight of the NIAF cubs during lactation appeared around 130 days of age (n = 3); The mortality rate was 66.7% (n = 3) after about 150 days if the feed was continuously consumed nonvoluntarily. It was concluded that the milk secretion period of the mother is about 0-5 months after giving birth; the weaning period of the cubs should be 4-5 months after birth. If the cubs don't follow the mother to eat artificial feed for 3 months after birth, it can start be induced with artificial diet which adds termites, and the time point cannot be later than 130 days, otherwise it is not conducive to the survival of the cubs; When sexually mature, the body length and body weight of female cubs account for about 84% and 60% of the adult, respectively; the body maturity and body weight of female cubs tend to be stable about 15.3 months and 16.4 months, respectively. Finally, a special needle-shaped nipples and nursing patterns of female Sunda pangolins were also recorded in this study. These findings play an important role in guiding the nursing of captive Sunda pangolin cubs and other pangolin cubs. It is expected to improve the survival rate of the cubs by exploring the appropriate weaning time and the rules of weight growth. By scientifically planning the reproductive cycle of the female Sunda pangolins, our goal is to expand the population size and eventually release to the wild, meanwhile improving knowledge of this critically endangered species.

[Effect of xuezhlkang capsule in intervening different Chinese medical syndrome patterns of non-alcoholic fatty liver disease complicated with carotid atherosclerosis].

OBJECTIVE: To observe the intervening effects of Xuezhikang Capsule (XZK) on levels of blood lipid and other related indices in patients with different Chinese medical syndrome patterns of non-alcoholic fatty liver disease complicated carotid atherosclerosis (NAFLD-CAS), and to seek out the most appropriate pattern to indicate XZK for making guidance of its utilization. METHODS: Chinese medical syndrome in 74 patients of NAFLD-CAS were classified into 4 patterns, 34 of Pi-deficiency phlegm-dampness pattern (A), 24 of dampness-heat accumulation pattern (B), 12 of phlegm-stasis intertwined pattern (C), and 4 of Gan-Shen yin-deficiency pattern (D). Excepting those of pattern D were excluded due to too small samples, all patients were treated with XZK for 3 months. Blood levels of blood lipids, including triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), as well as high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor alpha (TNF-alpha) were detected and compared before and after treatment. RESULTS: The effective rate of XZK on patients of the three patterns, in A-C order, was 97.06%, 91.67%, 91.67%, respectively, with the optimal overall efficacy showed on pattern A. All the indices detected significantly decreased after treatment in all three patterns (P < 0.01), among them, excepting the difference of TG level between groups showed no significance (P > 0.05), the decrements of others were more significant in pattern A than in other two patterns (P < 0.05 or P < 0.01). CONCLUSION: XZK could reduce the levels of blood lipids, hs-CRP and TNF-alpha in NAFLD-CAS patients, and the Pi-deficiency phlegm-dampness syndrome pattern was the optimal indication of XZK treatment.

[Effect of atorvastatin on advanced glycation end products induced monocyte chemoattractant protein-1 expression in cultured human endothelial cells].

OBJECTIVE: To investigate the effects of atorvastatin on advanced glycation end products (AGE) induced monocyte chemoattractant protein-1 (MCP-1) expression in human umbilical vein endothelial cells (HUVECs) and whether this effect could be linked to peroxisome proliferator-activated receptor-γ (PPAR-γ) and nuclear factor-κB (NF-κB). METHODS: Grouping: (1) Blank control group; (2) BSA group; (3) AGE group: cells were incubated with different concentrations of AGE (10(-4), 10(-3), 10(-2) and 10(-1) g/L) for 24 hours; (4) AGE + Atorvastatin group: cells were incubated with different concentrations of atorvastatin (0.1, 1, 10 µmol/L) for 1 hour, then incubated with AGE (10(-1) g/L) for 24 hours; (5) PPAR-γ agonist (15 d-PGJ2) group: cells were incubated with 15 d-PGJ2 (10 µmol/L) for 1 hour, then incubated with AGE (10(-1) g/L) for 24 hours; (6) PPAR-γ inhibitor (GW9662) group: cells were incubated with GW9662 (5000 nmol/L) for 1 hour, then incubated with atorvastatin (1 µmol/L) and AGE (10(-1) g/L) for 24 hours. Collagenase was used to isolate the endothelial cell from human umbilical vein; RT-PCR was performed to examine the mRNA expression of MCP-1 and PPAR-γ; Western blot was performed to detect NF-κB p65 protein. RESULTS: (1) The expression of MCP-1 mRNA was increased in proportion with increasing concentrations of AGEs which could be blocked by atorvastatin in a dose-dependent manner. (2) AGE (10(-1) g/L) significantly downregulated the expression of PPAR-γ mRNA (0.22 ± 0.08 vs. 0.69 ± 0.09, P < 0.01) while upregulated the expression of phospho-NF-κB p65 protein (0.78 ± 0.06 vs. 0.31 ± 0.01, P < 0.01) and nonphospho-NF-κB p65 protein (1.61 ± 0.16 vs. 0.59 ± 0.14, P < 0.01) compared with the control group which could be significantly attenuated by atorvastatin. (3) PPAR-γ agonist decreased the expression of phospho-NF-κB p65 protein (0.21 ± 0.01 vs. 0.78 ± 0.06, P < 0.01), nonphospho-NF-κB p65 protein (0.67 ± 0.14 vs. 1.61 ± 0.16, P < 0.01) and MCP-1 mRNA (0.17 ± 0.02 vs. 0.93 ± 0.12, P < 0.01) compared with AGE (10(-1) g/L) group. (4) PPAR-γ inhibitor antagonized the effect of atorvastatin on the expression of phospho-NF-κB p65 protein, nonphospho-NF-κB p65 protein and MCP-1 mRNA stimulated by AGE in HUVECs (P < 0.01). CONCLUSION: The anti-inflammatory properties of atorvastatin in AGE stimulated HUVECs may partly be attributed to the effect on upregulation of PPAR-γ and downregulation of NF-κB signaling pathway.

Exploration of the molecular targets and mechanisms of suxiao xintong dropping pills for myocardial infarction by network pharmacology method.

BACKGROUND: Suxiao Xintong dropping pills (SXXTDP), a traditional Chinese medicine, is widely applied for treating myocardial infarction (MI). However, its therapy mechanisms are still unclear. Therefore, this research is designed to explore the molecular mechanisms of SXXTDP in treating MI. METHODS: The active ingredients of SXXTDP and their corresponding genes of the active ingredients were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. MI-related genes were identified via analyzing the expression profiling data (accession number: GSE97320). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to study the shared genes of drug and disease. Through protein-protein interaction (PPI) network and the Cytoscape plugin cytoHubba, the hub genes were screened out. The compounds and hub targets binding were simulated through molecular docking method. RESULTS: We obtained 21 active compounds and 253 corresponding target genes from TCMSP database. 1833 MI-related genes were identified according to P<0.05 and |log2FC| ≥ 0.5. 27 overlapping genes between drug and disease were acquired. GO analysis indicated that overlapping genes were mainly enriched in MAP kinase activity and antioxidant activity. KEGG analysis indicated that overlapping genes were mainly enriched in IL-17 signaling pathway and TNF signaling pathway. We obtained 10 hub genes via cytoHubba plugin. Six of the 10 hub genes, including PTGS2, MAPK14, MMP9, MAPK1, NFKBIA, and CASP8, were acted on molecular docking verification with their corresponding compounds of SXXTDP. CONCLUSION: SXXTDP may exert cardioprotection effect through regulating multiple targets and multiple pathways in MI.

Temporal and spatial dynamics of gastrointestinal parasite infection in Père David's deer.

BACKGROUND: The Père David's deer (Elaphurus davidianus) population was established from only a small number of individuals. Their genetic diversity is therefore relatively low and transmissible (parasitic) diseases affecting them merit further attention. Parasitic infections can affect the health, survival, and population development of the host. However, few reports have been published on the gastrointestinal parasites of Père David's deer. The aims of this study were: (1) to identify the intestinal parasites groups in Père David's deer; (2) to determine their prevalence and burden and clarify the effects of different seasons and regions on various indicators of Père David's deer intestinal parasites; (3) to evaluate the effects of the Père David's deer reproductive period on these parasites; (4) to reveal the regularity of the parasites in space and time. METHODS: In total, 1,345 Père David's deer faecal samples from four regions during four seasons were tested using the flotation (saturated sodium nitrate solution) to identify parasites of different genus or group, and the McMaster technique to count the number of eggs or oocysts. RESULTS: Four groups of gastrointestinal parasites were found, of which strongyles were dominant; their prevalence and burden were significantly higher than other groups. Significant temporal and spatial effects on gastrointestinal parasitic infection were found. Parasite diversity, prevalence, parasite burden, and aggregation were the highest in summer. Among the four regions, parasite diversity, prevalence, and burden were the highest in the Dongting Lake area. In addition, parasite diversity and burden during the reproductive period of Père David's deer was significantly higher than during the post-reproductive period. CONCLUSIONS: The summer season and the reproductive period of Père David's deer had great potential for parasite transmission, and there is a high risk of parasite outbreaks in the Dongting Lake area.