A Novel Cargo Delivery System-AnCar-ExoLaIMTS Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-ExoLaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-ExoLaIMTS show obvious differences. The AnCar-ExoLaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-ExoLaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-ExoLaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.

A brain-tumor neural circuit controls breast cancer progression in mice.

Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the underlying neural mechanism remains unclear. Here, we used neuroscience and cancer tools to investigate how the brain contributes to tumor progression via nerve-tumor crosstalk in a mouse model of breast cancer. We show that tumor-bearing mice exhibited significant anxiety-like behaviors and that corticotropin-releasing hormone (CRH) neurons in the central medial amygdala (CeM) were activated. Moreover, we detected newly formed sympathetic nerves in tumors, which established a polysynaptic connection to the brain. Pharmacogenetic or optogenetic inhibition of CeMCRH neurons and the CeMCRH→lateral paragigantocellular nucleus (LPGi) circuit significantly alleviated anxiety-like behaviors and slowed tumor growth. Conversely, artificial activation of CeMCRH neurons and the CeMCRH→LPGi circuit increased anxiety and tumor growth. Importantly, we found alprazolam, an antianxiety drug, to be a promising agent for slowing tumor progression. Furthermore, we show that manipulation of the CeMCRH→LPGi circuit directly regulated the activity of the intratumoral sympathetic nerves and peripheral nerve-derived norepinephrine, which affected tumor progression by modulating antitumor immunity. Together, these findings reveal a brain-tumor neural circuit that contributes to breast cancer progression and provide therapeutic insights for breast cancer.

The clinical symptoms and neurocognitive impairment of first-episode deficit and nondeficit subtype of schizophrenia / 中华行为医学与脑科学杂志

Objective:To ulteriorly explore the differences of psychotic symptoms and neurocognitive between patients with first-episode deficit subtype of schizophrenia (FDS) and patients with first-episode nondeficit subtype of schizophrenia (FNDS).Methods:From January 2021 to September 2021, a total of 88 first-episode treatment-naive schizophrenia were recruited from the Mental Health Center of West China Hospital and divided into FDS group( n=44) and FNDS group( n=44) according to the schedule for the deficit syndrome (SDS), and 44 healthy subjects were included as healthy control group (HC group, n=44). Positive and negative syndrome scale (PANSS) was used to assess psychotic symptoms of patients and Wechsler adult intelligence scale, trail making test and logic memory test were used to evaluate intelligence quotient and neurocognitive function of all subjects.SPSS 22.0 was used for statistical analysis, and independent samples t-test and one-way analysis of variance (ANOVA) were used to compare variables that met normal distribution, while the Mann-Whitney U test and Kruskal-Wallis H test were used to compare variables that did not meet normal distribution. Results:(1) There were significant differences in psychotic symptoms between the FDS group and the FNDS group.Compared with the FNDS group, the FDS group had higher total score of PANSS ((95.95±16.82) vs (88.39±16.29)), negative symptoms ((27.57±7.52) vs (16.57±5.76)) and anergastic reaction ((13.43±3.82) vs (7.00(5.00, 9.00)), and lower positive symptoms scores ((21.95±6.88) vs (25.41±6.07)), activation ((8.00(5.00, 9.00) vs (9.27±3.47)), depression ((5.50(4.00, 9.00) vs (8.00(6.00, 12.00)) and supplementary item ((13.60±4.17) vs (17.30±5.39))(all P<0.05). (2) There were differences in neurocognitive functions between FDS group and FNDS group, and which in FDS and FNDS group were worse than that in HC group.Spatial memory (block design test: (23.70±11.05) vs (31.72±11.49)) and information processing speed (digit symbol test: (38.38±15.85) vs (47.97±14.99)) of FDS group were significantly lower than those of FNDS group(both P<0.05). Intelligence quotient, information processing speed and spatial memory of FDS group and FNDS group were lower than those of HC group(all P<0.05). Conclusion:FDS patients has more severe negative symptoms and anergastic reaction, and exit worse information processing speed and spatial memory dysfunction than FNDS patients.This unique pattern of impairment suggests that information processing speed and spatial memory may be important classification indicators for differentiating the deficit subtype of schizophrenia in the early stage.

[Distribution and Potential Ecological Risk Assessment of Heavy Metals in Sediments of Lake Qinghai].

Lake Qinghai is the largest closed saltwater lake in China. In recent years, because of the rapid development of industry, agriculture, and tourism, the lake has been increasingly affected by human activities, which has attracted the attention of many scholars. In order to understand the distribution of heavy metals in the surface sediments of Lake Qinghai, the contents of Zn, Cu, Pb, Co, Ni, As, Cd, and Cr were investigated, the metal fractions were extracted, and the sources, as well as potential ecological risks, were analyzed. The results showed that:① the ω(As) (13.21 mg·kg-1) and ω(Cd) (0.21 mg·kg-1) in the surface sediments of Lake Qinghai were 1.13 and 1.53 times higher than the environmental background values, respectively, and the other heavy metal contents were all lower than the environmental background values. There were similar spatial distribution characteristics of analyzed metals except for As, with higher values measured in the northwestern area of the lake and the 151 Terminal. ② Except for Cd, the analyzed heavy metals mainly existed in the form of the residual state; by contrast, Cd mainly existed in the form of the bioavailable state, which has high potential toxicity to aquatic organisms. ③ Combined with the results of the correlation and principal component analysis, the metals including Zn, Cu, Pb, Co, Ni, Cd, and Cr were thought to mainly come from the natural environment, whereas the source of As was related to human activities, such as agricultural production. ④ According to potential risk analyses, the average of the metal potential ecological risk factors was 76.57, which indicated a slight ecological hazard level. However, it should be noted that the potential ecological hazard level and release risk of Cd at each site were higher than those of the other metals, especially in the regions nearing the estuary of Heima River, Lake Gahai, and the sand island, which showed higher levels of enrichment and potential release risk. Therefore, further attention should be paid to the potential impacts of Cd in sediments of these regions on the water environment and ecosystem.

Aberration of Serum and Tissue N-Glycans in Mouse ß1,4-GalT1 Y286L Mutant Variants.

ß1,4-GalT1 is a type II membrane glycosyltransferase. It catalyzes the production of lactose in the lactating mammary gland and is supposedly also involved in the galactosylation of terminal GlcNAc of complex-type N-glycans. In-vitro studies of the bovine ß4Gal-T1 homolog showed that replacing a single residue of tyrosine with leucine at position 289 alters the donor substrate specificity from UDP-Gal to UDP-N-acetyl-galactosamine (UDP-GalNAc). The effect of this peculiar change in ß1,4GalT1 specificity was investigated in-vivo, by generating biallelic Tyr286Leu ß1,4GalT1 mice using CRISPR/Cas9 and crossbreeding. Mice bearing this mutation showed no appreciable defects when compared to wild-type mice, with the exception of biallelic female B4GALT1 mutant mice, which were unable to produce milk. The detailed comparison of wild-type and mutant mice derived from liver, kidney, spleen, and intestinal tissues showed only small differences in their N-glycan pattern. Comparable N-glycosylation was also observed in HEK 293 wild-type and knock-out B4GALT1 cells. Remarkably and in contrast to the other analyzed tissue samples, sialylation and galactosylation of serum N-glycans of biallelic Tyr286Leu GalT1 mice almost disappeared completely. These results suggest that ß1,4GalT1 plays a special role in the synthesis of serum N-glycans. The herein described Tyr286Leu ß1,4GalT1 mutant mouse model may, therefore, prove useful in the investigation of the mechanism which regulates tissue-dependent galactosylation.

RGD-hirudin-based low molecular weight peptide prevents blood coagulation via subcutaneous injection.

Thromboembolic disease is a common cardio-cerebral vascular disease that threatens human life and health. Thrombin not only affects the exogenous coagulation pathway, but also the endogenous pathway. Thus, it becomes one of the most important targets of anticoagulant drugs. RGD-hirudin is an anticoagulant drug targeting thrombin, but it can only be administered intravenously. We designed a low molecular weight peptide based on RGD-hirudin that could prevent blood clots. We first used NMR to identify the key amino acid residues of RGD-hirudin that interacted with thrombin. Then, we designed a novel direct thrombin inhibitor peptide (DTIP) based on the structure and function of RGD-hirudin using homology modeling. Molecular docking showed that the targeting and binding of DTIP with thrombin were similar to those of RGD-hirudin, suggesting DTIP interacted directly with thrombin. The active amino acids of DTIP were identified by alanine scanning, and mutants were successfully constructed. In blood clotting time tests in vitro, we found that aPTT, PT, and TT in the rat plasma added with DTIP were greatly prolonged than in that added with the mutants. Subcutaneous injection of DTIP in rats also could significantly prolong the clotting time. Thrombelastography analysis revealed that DTIP significantly delayed blood coagulation. Bio-layer interferometry study showed that there were no significant differences between DTIP and the mutants in thrombin affinity constants, suggesting that it might bind to other sites of thrombin rather than to its active center. Our results demonstrate that DTIP with low molecular weight can prevent thrombosis via subcutaneous injection.

Correction to: The Association Between Phosphorylated Neurofilament Heavy Chain (pNF-H) and Small Fiber Neuropathy (SFN) in Patients with Impaired Glucose Tolerance.

In the original article, there was some error in Table 2. The correct table is given below.

The Association Between Phosphorylated Neurofilament Heavy Chain (pNF-H) and Small Fiber Neuropathy (SFN) in Patients with Impaired Glucose Tolerance.

INTRODUCTION: Small fiber neuropathy (SFN)-the early stage of diabetic peripheral neuropathy (DPN)-progresses gradually and is difficult to diagnose using neurophysiological tests. To facilitate the early diagnosis of SFN, biomarkers for SFN must be identified. The purpose of this study was to investigate the characteristics of SFN in prediabetic patients and the relationship between pNF-H and SFN. METHODS: 44 IGT patients (inpatients and outpatients) were selected at random. 33 healthy subjects served as controls. Data on clinical characteristics and laboratory parameters were collected. Quantitative sensory testing (QST), electromyography (EMG), and Sudoscan were performed, and pNF-H was measured by ELISA. RESULTS: 24 of the 44 patients with impaired glucose tolerance (IGT) were diagnosed with SFN according to the modified Toronto Diabetic Neuropathy Expert Group consensus criteria. The thermal sensory thresholds of the IGT-SFN group were significantly different from those of the CTRL group (p < 0.05), except for the heat pain threshold. The sensory nerve action potential (SNAP) of the sural nerve was 12.39 in the IGT-SFN group, which was significantly lower than those in the other groups. No significant difference in nerve conduction velocity (NCV) was observed among the three groups. The electrochemical skin conductance (ESC) in the IGT-SFN group was 69.78 ± 14.03uS, which was significantly lower than that in the CTRL group. The pNF-H in the IGT-SFN group was 170.6 (140.0, 223.6) pg/ml, which was significantly higher than those in the CTRL and IGT-non-SFN groups (76.55 and 64.7 pg/ml, respectively). Multivariate regression analysis demonstrated that pNF-H and 2h plasma glucose were independently correlated with SFN; the ORs (95% CI) were 1.429 (1.315, 1.924) and 2.375 (1.157, 4.837), respectively. CONCLUSIONS: Serum pNF-H may be associated with SFN in IGT patients, and serum pNF-H could therefore serve as a sensitive biomarker for the detection of SFN.

Diverse regulatory manners of human telomerase reverse transcriptase.

Human telomerase reverse transcriptase (hTERT) is the core subunit of human telomerase and plays important roles in human cancers. Aberrant expression of hTERT is closely associated with tumorigenesis, cancer cell stemness maintaining, cell proliferation, apoptosis inhibition, senescence evasion and metastasis. The molecular basis of hTERT regulation is highly complicated and consists of various layers. A deep and full-scale comprehension of the regulatory mechanisms of hTERT is pivotal in understanding the pathogenesis and searching for therapeutic approaches. In this review, we summarize the recent advances regarding the diverse regulatory mechanisms of hTERT, including the transcriptional (promoter mutation, promoter region methylation and histone acetylation), post-transcriptional (mRNA alternative splicing and non-coding RNAs) and post-translational levels (phosphorylation and ubiquitination), which may provide novel perspectives for further translational diagnosis or therapeutic strategies targeting hTERT.

Advancements in Single-cell Sequencing and the Prospect of Its Forensic Application / 法医学杂志

Single-cell sequencing is a technique that analyzes DNA and RNA sequences on the cellular level with next generation sequencing. The ultra high resolution of single-cell sequencing provides new perspectives and opens new frontiers for our understanding of many areas of life sciences, including forensic genome. This paper summarizes the recent advancements in single-cell sequencing and the prospect of its forensic application.

Prolyl isomerase Pin1: a promoter of cancer and a target for therapy.

Pin1 is the only known peptidyl-prolyl cis-trans isomerase (PPIase) that specifically recognizes and isomerizes the phosphorylated Serine/Threonine-Proline (pSer/Thr-Pro) motif. The Pin1-mediated structural transformation posttranslationally regulates the biofunctions of multiple proteins. Pin1 is involved in many cellular processes, the aberrance of which lead to both degenerative and neoplastic diseases. Pin1 is highly expressed in the majority of cancers and its deficiency significantly suppresses cancer progression. According to the ground-breaking summaries by Hanahan D and Weinberg RA, the hallmarks of cancer comprise ten biological capabilities. Multiple researches illuminated that Pin1 contributes to these aberrant behaviors of cancer via promoting various cancer-driving pathways. This review summarized the detailed mechanisms of Pin1 in different cancer capabilities and certain Pin1-targeted small-molecule compounds that exhibit anticancer activities, expecting to facilitate anticancer therapies by targeting Pin1.

Development of a massively parallel sequencing assay for investigating sequence polymorphisms of 15 short tandem repeats in a Chinese Northern Han population.

Massively parallel sequencing (MPS) has been used in forensic genetics in recent years owing to several advantages, e.g. MPS can provide precise descriptions of the repeat allele structure and variation in the repeat-flanking regions, increasing the discriminating power among loci and individuals. However, it cannot be fully utilized unless sufficient population data are available for all loci. Thus, there is a pressing need to perform population studies providing a basis for the introduction of MPS into forensic practice. Here, we constructed a multiplex PCR system with fusion primers for one-directional PCR for MPS of 15 commonly used forensic autosomal STRs and amelogenin. Samples from 554 unrelated Chinese Northern Han individuals were typed using this MPS assay. In total, 313 alleles obtained by MPS for all 15 STRs were observed, and the corresponding allele frequencies ranged between 0.0009 and 0.5162. Of all 15 loci, the number of alleles identified for 12 loci increased compared to capillary electrophoresis approaches, and for the following six loci more than double the number of alleles was found: D2S1338, D5S818, D21S11, D13S317, vWA, and D3S1358. Forensic parameters were calculated based on length and sequence-based alleles. D21S11 showed the highest heterozygosity (0.8791), discrimination power (0.9865), and paternity exclusion probability in trios (0.7529). The cumulative match probability for MPS was approximately 2.3157 × 10-20 .

A 472-SNP panel for pairwise kinship testing of second-degree relatives.

Kinship testing based on genetic markers, as forensic short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs), has valuable practical applications. Paternity and first-degree relationship can be accurately identified by current commonly-used forensic STRs and reported SNP markers. However, second-degree and more distant relationships remain challenging. Although ∼105-106 SNPs can be used to estimate relatedness of higher degrees, genome-wide genotyping and analysis may be impractical for forensic use. With rapid growth of human genome data sets, it is worthwhile to explore additional markers, especially SNPs, for kinship analysis. Here, we reported an autosomal SNP panel consisted of 342 SNP selected from >84 million SNPs and 131 SNPs from previous systems. We genotyped these SNPs in 136 Chinese individuals by multiplex amplicon Massively Parallel Sequencing, and performed pairwise gender-independent kinship testing. The specificity and sensitivity of these SNPs to distinguish second-degree relatives and the unrelated was 99.9% and 100%, respectively, compared with 53.7% and 99.9% of 19 commonly-used forensic STRs. Moreover, the specificity increased to 100% by the combined use of these STRs and SNPs. The 472-SNP panel could also greatly facilitate the discrimination among different relationships. We estimated that the power of ∼6.45 SNPs were equivalent to one forensic STR in the scenario of 2nd-degree relative pedigree. Altogether, we proposed a panel of 472 SNP markers for kinship analysis, which could be important supplementary of current forensic STRs to solve the problem of second-degree relative testing.

Therapeutic Effect Evaluation of Neuromuscular Electrical Stimulation With or Without Strengthening Exercise on Spastic Cerebral Palsy.

The aims of this study were to investigate the effect of neuromuscular electrical stimulation (NMES) combined with strengthening exercise on movement in children with spastic cerebral palsy (CP). One hundred children with spastic CP were randomly divided into a treatment group (NMES and strengthening exercise, n = 50) and a control group (only NMES, n = 50). We compared the Comprehensive Spasticity Scale (CSS) score, Gross Motor Function Measure (GMFM) score, and walking speed before treatment and 6 weeks and 3 months after treatment between the 2 groups. There was no difference in CSS score between the treatment and control groups before the therapy (12.0 ± 3.4 vs 12.3 ± 3.6), which decreased much more in the treatment group after 6 weeks (7.6 ± 3.0 vs 9.5 ± 2.8) and 3 months (7.4 ± 2.4 vs 9.4 ± 2.6) with significant differences ( P < .05). No difference in GMFM score was observed between the treatment and control groups before the therapy (44.5 ± 13.2 vs 44.0 ± 12.6), which increased much more in the treatment group after 6 weeks (70.6 ± 15.2 vs 56.7 ± 14.3) and 3 months (71.0 ± 16.4 vs 58.0 ± 15.6) with significant differences ( P < .05). The walking speed improved over time, which was the same before the treatment (0.43 ± 0.13 m/s vs 0.45 ± 0.14 m/s), and was significantly greater in the treatment group than that in the control group (6 weeks: 0.69 ± 0.15 m/s vs 0.56 ± 0.12 m/s, P < .05; 3 months: 0.72 ± 0.17 m/s vs 0.57 ± 0.18 m/s, P < .05). NMES combined with strengthening exercise was more effective than NMES alone in the recovery of spastic CP.

Preparation of poorly soluble drug curcumin nanocrystalline self-stabilized Pickering emulsion / 中草药

Objective: To prepare curcumin nanocrystalline (Cur-NC) self-stabilized Pickering emulsion (Cur-NCSPE). Methods: Cur-NCSPE was prepared by high pressure homogenization. The influences of homogenization pressure on Cur-NC size and drug content on Cur-NCSPE formation were studied. The morphology and structure of emulsion droplets were observed by optical microscope and scanning electron microscope. Furthermore, the stability and in vitro release properties of Cur-NCSPE were evaluated. Results: The particle size of Cur-NC was slightly changed when homogeneous pressure was greater than 100 MPa. With the increase of Cur, the amount of Cur-NC on the surface of oil droplets increases, and the particle size decreases. When the amount of drug added can completely cover the surface of oil droplets, increasing the amount of drug had little effect on the particle size. Cur-NCSPE was more stable than Cur-NC and Cur, and the in vitro release rate of Cur-NCSPE was significantly higher than that of Cur-NC and Cur coarse power. Conclusion: The Cur-NCSPE is prepared successfully, which is expected to provide a novel oral administration technology platform for the poorly soluble drugs.

Magnolol pretreatment attenuates heat stress-induced IEC-6 cell injury.

OBJECTIVE: Heat stress (HS) is an important environmental stressor that adversely influences livestock during the summer. The aim of this study was to investigate whether magnolol protects against HS-induced intestinal epithelial cell injury. MATERIALS AND METHODS: An intestinal epithelial cell line (IEC-6) was subjected to HS at 42 °C, with and without magnolol pretreatment. Cell injury was detected by monitoring lactate dehydrogenase (LDH) release. MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay was used to assess cell proliferation and viability, including identifying effective concentrations of magnolol. Flow cytometry confirmed G1-phase cell-cycle arrest and its alleviation by magnolol. Active DNA synthesis was measured by incorporation of nucleic acid 5-ethynyl-2'-deoxyuridine (EdU). G1-phase cell-cycle-related gene expression was assessed by real-time reverse transcription polymerase chain reaction (RT-PCR) and levels of G1-phase-related proteins by Western blotting. RESULTS: HS induced IEC-6 cell injury and decreased cell viability, as demonstrated by data from LDH and MTS assays, respectively. Based on a number of criteria, IEC-6 cells subjected to HS were arrested in the G1 phase of the cell cycle. Magnolol pretreatment decreased HS-induced cell injury through relief of this cell-cycle arrest. CONCLUSIONS: Magnolol pretreatment attenuates HS-induced injury in IEC-6 cells. Magnolol is potentially promising as a protective strategy for HS in livestock.

Whole genome nucleosome sequencing identifies novel types of forensic markers in degraded DNA samples.

In the case of mass disasters, missing persons and forensic caseworks, highly degraded biological samples are often encountered. It can be a challenge to analyze and interpret the DNA profiles from these samples. Here we provide a new strategy to solve the problem by taking advantage of the intrinsic structural properties of DNA. We have assessed the in vivo positions of more than 35 million putative nucleosome cores in human leukocytes using high-throughput whole genome sequencing, and identified 2,462 single nucleotide variations (SNVs), 128 insertion-deletion polymorphisms (indels). After comparing the sequence reads with 44 STR loci commonly used in forensics, five STRs (TH01, TPOX, D18S51, DYS391, and D10S1248)were matched. We compared these "nucleosome protected STRs" (NPSTRs) with five other non-NPSTRs using mini-STR primer design, real-time PCR, and capillary gel electrophoresis on artificially degraded DNA. Moreover, genotyping performance of the five NPSTRs and five non-NPSTRs was also tested with real casework samples. All results show that loci located in nucleosomes are more likely to be successfully genotyped in degraded samples. In conclusion, after further strict validation, these markers could be incorporated into future forensic and paleontology identification kits, resulting in higher discriminatory power for certain degraded sample types.

Characterization of the promoter region of the bovine long-chain acyl-CoA synthetase 1 gene: Roles of E2F1, Sp1, KLF15, and E2F4.

The nutritional value and eating qualities of beef are enhanced when the unsaturated fatty acid content of fat is increased. Long-chain acyl-CoA synthetase 1 (ACSL1) plays key roles in fatty acid transport and degradation, as well as lipid synthesis. It has been identified as a plausible functional and positional candidate gene for manipulations of fatty acid composition in bovine skeletal muscle. In the present study, we determined that bovine ACSL1 was highly expressed in subcutaneous adipose tissue and longissimus thoracis. To elucidate the molecular mechanisms involved in bovine ACSL1 regulation, we cloned and characterized the promoter region of ACSL1. Applying 5'-rapid amplification of cDNA end analysis (RACE), we identified multiple transcriptional start sites (TSSs) in its promoter region. Using a series of 5' deletion promoter plasmids in luciferase reporter assays, we found that the proximal minimal promoter of ACSL1 was located within the region -325/-141 relative to the TSS and it was also located in the predicted CpG island. Mutational analysis and electrophoretic mobility shift assays demonstrated that E2F1, Sp1, KLF15 and E2F4 binding to the promoter region drives ACSL1 transcription. Together these interactions integrate and frame a key functional role for ACSL1 in mediating the lipid composition of beef.

[Molecular networks and mechanisms of epithelial-mesenchymal transition regulated by miRNAs in the malignant melanoma cell line].

Melanoma is a malignant cutaneous cancer of high metastasis and lethal rates. Epithelial-mesenchymal transition (EMT) plays an important role in the embryonic developmental process that is often activated during tumorigenesis and metastasis. In this study, we integrated of mRNA and miRNA transcriptome sequencing data of melanocyte and melanoma cell lines to identify genes involved in the process of tumor EMT in the first place, and uncovered 11 miRNAs including miR-130a-3p, miR-130b-3p, miR-125a-5p, miR-30a-3p, miR-195-5p, miR-345-5p, miR-509-3-5p, miR-374a-5p, miR-509-5p, miR-148a-3p and miR-330-3p, negatively related with EMT genes using the Mirsystem software. Bioinformatics analysis with target genes of these miRNAs revealed two networks closely related with cellular development and cell-to-cell interactions, as well as multiple signaling pathways participating in EMT. Validation of the 11 miRNAs with molecular biology experiments demonstrated that four miRNAs regulated oncogenes in melanomas, including miR-195-5p, miR-130a-3p, miR-509-5p, and miR-509-3-5p. Our study integrates two kinds of omics data to screen for EMT-related miRNAs, providing a new research idea in the precision genomics of cancer research.

[Genetic variability and phylogenetic analysis of 39 short tandem repeat loci in Beijing Han population].

In this study, we studied the genetic polymorphisms of short tandem repeat (STR) loci from 13 CODIS and 26 non-CODIS system in Beijing Han population for the first time, and established a database of 39 STR loci whose forensic parameters were further evaluated. Our results demonstrated no significant deviation from the Hardy-Weinberg equilibrium of 39 STR loci and no pairwise linkage disequilibrium between them. The power of discriminations, expected heterozygosity, polymorphic information content, and power of exclusion of 39 STR loci ranged from 0.7740-0.9818, 0.6000-0.9350, 0.5317-0.9047 and 0.2909-0.8673. The cumulated discrimination power and cumulative probability of exclusion were 0.999999999999999999999999999999999999999964971 and 0.999999999973878, respectively. Moreover, the genetic distance was calculated based on allele frequency and phylogenetic tree was built using STR loci data from Beijing Han and other 11 Chinese ethnic groups.This study provides important basic data for Chinese forensic DNA database and population genetics database, and has important significance in carrying out forensic individual identification, paternity testing, and population genetic study.