Research progress and potential application of microRNA and other non-coding RNAs in forensic medicine.

At present, epigenetic markers have been extensively studied in various fields and have a high value in forensic medicine due to their unique mode of inheritance, which does not involve DNA sequence alterations. As an epigenetic phenomenon that plays an important role in gene expression, non-coding RNAs (ncRNAs) act as key factors mediating gene silencing, participating in cell division, and regulating immune response and other important biological processes. With the development of molecular biology, genetics, bioinformatics, and next-generation sequencing (NGS) technology, ncRNAs such as microRNA (miRNA), circular RNA (circRNA), long non-coding RNA (lncRNA), and P-element induced wimpy testis (PIWI)-interacting RNA (piRNA) are increasingly been shown to have potential in the practice of forensic medicine. NcRNAs, mainly miRNA, may provide new strategies and methods for the identification of tissues and body fluids, cause-of-death analysis, time-related estimation, age estimation, and the identification of monozygotic twins. In this review, we describe the research progress and application status of ncRNAs, mainly miRNA, and other ncRNAs such as circRNA, lncRNA, and piRNA, in forensic practice, including the identification of tissues and body fluids, cause-of-death analysis, time-related estimation, age estimation, and the identification of monozygotic twins. The close links between ncRNAs and forensic medicine are presented, and their research values and application prospects in forensic medicine are also discussed.

Boosting the Cycle Performance of Iron Trifluoride Based Solid State Batteries at Elevated Temperatures by Engineering the Cathode Solid Electrolyte Interface.

Iron trifluoride (FeF3) is attracting tremendous interest due to its lower cost and the possibility to enable higher energy density in lithium-ion batteries. However, its cycle performance deteriorates rapidly in less than 50 cycles at elevated temperatures due to cracking of the unstable cathode solid electrolyte interface (CEI) followed by active materials dissolution in liquid electrolyte. Herein, by engineering the salt composition, the Fe3O4-type CEI with the doping of boron (B) atoms in a polymer electrolyte at 60 °C is successfully stabilized. The cycle life of the well-designed FeF3-based composite cathode exceeds an unprecedented 1000 cycles and utilizes up to 70% of its theoretical capacities. Advanced electron microscopy combined with density functional theory (DFT) calculations reveal that the B in lithium salt migrates into the cathode and promotes the formation of an elastic and mechanic robust boron-contained CEI (BOR-CEI) during cycling, by which the durability of the CEI to frequent cyclic large volume changes is significantly enhanced. To this end, the notorious active materials dissolution is largely prohibited, resulting in a superior cycle life. The results suggest that engineering the CEI such as tuning its composition is a viable approach to achieving FeF3 cathode-based batteries with enhanced performance.

A Tibetan group from Ngawa Tibetan and Qiang Autonomous Prefecture, southwest China, is rich in genetic polymorphisms at 36 autosomal STR loci and shares a complex genetic structure with other Chinese populations.

The Tibetan people are ancient and populous, constituting the seventh-largest of the fifty-five ethnic minority groups in China. The Ngawa Tibetan and Qiang Autonomous Prefecture (NTQAP), situated on the border of northwest and southwest China, has its distinct group relationships. Short tandem repeat (STR) is extremely polymorphic and extensively used in the application of forensic medicine and population genetics. However, it is not clear the genetic information including linkage disequilibrium (LD) by 36 autosomal STR (A-STR) markers in the Tibetan group from NTQAP. The Tibetan population from NTQAP of southwest China was examined for 36 A-STR loci in the research. Every marker across the 36 A-STR loci was consistent with Hardy-Weinberg equilibrium (HWE). The results of the calculation revealed that the total discrimination power (TDP) is 1-2.2552 × 10-42 and the cumulative probability of exclusion (CPE) is 1-1.3031 × 10-16. Subsequently, a total of 345 alleles with allelic frequencies ranging from 0.00382 to 0.55343 were identified, and the allelic numbers varied from 5 in both the TH01 and TPOX markers to 28 in the SE33 locus. The Ngawa Tibetan population, along with other Chinese populations, exhibited influences from historical factors and regional distribution, as indicated by the results of population genetics analysis. We thus first explored the genetic characteristics and correlated forensic parameters of the 36 A-STR markers in NTQAP to fill the gap in the Tibetan population. It was discovered that these 36 autosomal STR markers supplemented forensic STR databases and offered extremely valuable polymorphisms for Chinese forensic applications, such as parentage testing and personal identification. Moreover, the study would contribute additional information regarding the substructure and diversity in the Chinese population.

Genetic Polymorphism Analysis of 24 Y-STRs in a Han Chinese Population in Luzhou, Southwest China.

Han is the largest of China's 56 ethnic groups and the most populous ethnic group in the world. The Luzhou region is located in southwest China, at the junction of three provinces. The unique historical factors contribute to the genetic polymorphism information. Short tandem repeats (STRs) are highly polymorphic, but the polymorphism of the Y chromosomal STRs (Y-STRs) loci in the Luzhou region is still unclear. It is of great significance to provide Y-STRs genetic data for the Han population from the Luzhou areas of southwest China. A total of 910 unrelated male individuals of the Han population from the Luzhou area were recruited, and 24 Y-STRs were analyzed. The population structure and phylogenetic relationships were compared with those of another 11 related Han populations. A total of 893 different haplotypes were achieved from 910 samples, of which 877 (98.21%) haplotypes were unique. Haplotype diversity and discrimination were 0.999956 and 0.981319, respectively. The lowest genetic diversity of DYS437 is 0.4321, and the highest genetic diversity of DYS385a/b is 0.9642. Pair-to-pair genetic distance and relative probability values indicate that Luzhou Han people are close to Sichuan Han people, Guangdong Han people, and Hunan Han people, which is consistent with geographical distribution, historical influence, and economic development. The 24 Y-STR markers of the southwest Luzhou Han population were highly polymorphic, which provided us with genetic polymorphism information and enriched the population genetic database. Therefore, it is of great value to our forensic applications and population genetics research.

The influence of permeability and heterogeneity on chemical flooding efficiency and remaining oil distribution-based on NMR displacement imaging.

To investigate the impact of permeability and heterogeneity on oil displacement efficiency and remaining oil distribution of chemical flooding, three groups of high and ultrahigh permeability core samples from an ultrahigh water-cut oilfield in western China were selected as the research objects in this study. High-pressure mercury injection, scanning electron microscopy, wettability test, and other methods were used to characterize the reservoir properties of core samples. Six groups of experiments were performed using the nuclear magnetic resonance (NMR) displacement imaging technology to simulate the oilfield development process considering the economic benefits. The displacement stage with the best oil displacement effect in the process of waterflooding, chemical flooding and then waterflooding was defined, and the control effect of permeability and heterogeneity on the improvement of oil displacement efficiency by polymer-surfactant binary flooding was discussed. The distribution position of remaining oil in different displacement stages was quantitatively and visually displayed, and its control factors were revealed. The research shows that during the simulation process of first waterflooding followed by chemical flooding and then waterflooding in the oilfield, the T2 spectrum signal amplitude increases the most in the two stages, one is from saturated oil flooding to 50% water cut and the other one is from 95% water cut to the end of 1 PV polymer flooding. The oil displacement efficiency increases the most, and the oil is primarily discharged from pore throats larger than 90 ms (or with pore throat radius of 8.37 µm). Compared with heterogeneity, permeability plays a more obvious controlling role in improving the oil displacement efficiency of polymer-surfactant binary flooding. The influence of fingering phenomenon on the distribution of remaining oil is most obvious in the second waterflooding, and the distribution of remaining oil with polymer slug is more obviously affected by the fingering phenomenon than that with polymer-surfactant slug. The study results provide theoretical guidance for tapping the remaining oil potential of old oilfields with high to ultrahigh permeabilities.

Genetic Polymorphism and Population Genetic Structure Analysis of 21 Autosomal STR Loci for a Han-Chinese Population from Luzhou of Southwest China.

The Han nationality is an ancient and populous people, and different places in China may have their distinct group relationships. Luzhou area, as a crossroads of several provinces in Southwest China, lacks autosomal short tandem repeat (STR) research and population genetics research. In this study, 21 autosomal STR loci were evaluated in 1959 Han-Chinese individuals from Luzhou area. There was no substantial linkage disequilibrium (LD) among the 21 autosomal STR markers, and all markers were in Hardy-Weinberg equilibrium (HWE). The total discrimination power (TDP) and cumulative probability of exclusion (CPE) of the 21 autosomal STR loci were calculated to be 1-9.8505 × 10-16 and 1-1.9406 × 10-9, respectively. There were 333 alleles for 21 STRs with allelic frequencies ranging from 0.00026 to 0.51302, and the number of alleles ranged from 7 in locus TPOX to 29 in locus Penta E. According to the results of population comparison and population differentiation, historical influences, geographical distribution, cultural integration, and economic development may have an impact on the Luzhou Han population and other Chinese populations. These 21 STR loci were found to enrich autosomal STR information in forensic databases and provide highly informative polymorphisms for our forensic practice in China, including personal identification and parentage testing.

Impact of BSG/CD147 gene expression on diagnostic, prognostic and therapeutic strategies towards malignant cancers and possible susceptibility to SARS-CoV-2.

BACKGROUND: BSG (CD147) is a member of the immunoglobulin superfamily that shows roles for potential prognostics and therapeutics for metastatic cancers and SARS-CoV-2 invasion for COVID-19. The susceptibility of malignant cancers to SARS-CoV-2 as well as the correlations between disease outcome and BSG expression in tumor tissues have not been studied in depth. METHODS: In this study, we explored the BSG expression profile, survival correlation, DNA methylation, mutation, diagnostics, prognostics, and tumor-infiltrating lymphocytes (TILs) from different types of cancer tissues with corresponding healthy tissues. In vitro studies for cordycepin (CD), N6-(2-hydroxyethyl) adenosine (HEA), N6, N6-dimethyladenosine (m62A) and 5'-uridylic acid (UMP) on BSG expression were also conducted. RESULTS: We revealed that BSG is conserved among different species, and significantly upregulated in seven tumor types, including ACC, ESCA, KICH, LIHC, PAAD, SKCM and THYM, compared with matched normal tissues, highlighting the susceptibility of these cancer patients to SARS-CoV-2 invasion, COVID-19 severity and progression of malignant cancers. High expression in BSG was significantly correlated with a short OS in LGG, LIHC and OV patients, but a long OS in KIRP patients. Methylation statuses in the BSG promoter were significantly higher in BRCA, HNSC, KIRC, KIRP, LUSC, PAAD, and PRAD tumor tissues, but lower in READ. Four CpGs in the BSG genome were identified as potential DNA methylation biomarkers which could be used to predict malignant cancers from normal individuals. Furthermore, a total of 65 mutation types were found, in which SARC showed the highest mutation frequency (7.84%) and THYM the lowest (0.2%). Surprisingly, both for disease-free and progression-free survival in pan-cancers were significantly reduced after BSG mutations. Additionally, a correlation between BSG expression and immune lymphocytes of CD56bright natural killer cell, CD56dim natural killer cell and monocytes, MHC molecules of HLA-A, HLA-B, HLA-C and TAPBP, immunoinhibitor of PVR, PVRL2, and immunostimulators of TNFRSF14, TNFRSF18, TNFRSF25, and TNFSF9, was revealed in most cancer types. Moreover, BSG expression was downregulated by CD, HEA, m62A or UMP in cancer cell lines, suggesting therapeutic potentials for interfering entry of SARS-CoV-2. CONCLUSIONS: Altogether, our study highlights the values of targeting BSG for diagnostic, prognostic and therapeutic strategies to fight malignant cancers and COVID-19. Small molecules CD, HEA, m62A and UMP imply therapeutic potentials in interfering with entry of SARS-CoV-2 and progression of malignant cancers.

CircPCNX Promotes PDGF-BB-Induced Proliferation and Migration of Human Aortic Vascular Smooth Muscle Cells Through Regulating miR-1278/DNMT1 Axis.

BACKGROUND: Human aortic vascular smooth muscle cells (HA-VSMCs) play vital roles in the pathogenesis of vascular diseases. Circular RNAs (circRNAs) have been reported to regulate the biological functions of HA-VSMCs. In this study, the functions of circRNA pecanex homolog (circPCNX) in platelet-derived growth factor-BB (PDGF-BB)-induced HA-VSMCs were investigated. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the expression of circPCNX, DNA methyltransferase 1 (DNMT1), and microRNA-1278 (miR-1278). 5'-Ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry analysis, wound healing assay, and transwell assay were used to examine cell proliferation, cell cycle, and migration. Western blot assay was utilized to measure protein levels. RNA immunoprecipitation (RIP) assay, RNA pull down assay, and dual-luciferase reporter assay were adopted to analyze the relationships among circPCNX, miR-1278, and DNMT1. RESULTS: CircPCNX was upregulated in PDGF-BB-treated HA-VSMCs in a dose- or time-dependent manner. CircPCNX knockdown alleviated PDGF-BB-induced cell proliferation, cell cycle progression, and migration in HA-VSMCs. CircPCNX knockdown could reverse PDGF-BB-induced HA-VSMC progression by regulating DNMT1. Moreover, circPCNX was identified to regulate DNMT1 expression by sponging miR-1278. Inhibition of miR-1278 reversed circPCNX knockdown-mediated effects on cell proliferation and migration in PDGF-BB-induced HA-VSMCs. MiR-1278 overexpression suppressed PDGF-BB-stimulated HA-VSMC proliferation and migration by targeting DNMT1. CONCLUSION: CircPCNX promoted PDGF-BB-induced HA-VSMC proliferation and migration by elevating DNMT1 expression through sponging miR-1278.

Impact of TMPRSS2 Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2.

As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the TMPRSS2 gene in pan-cancers as well as in COVID-19-infected lung tissues. The results indicate that TMPRSS2 expression was highest in prostate cancer. A high expression of TMPRSS2 was significantly associated with a short overall survival in breast invasive carcinoma (BRCA), sarcoma (SARC), and uveal melanoma (UVM), while a low expression of TMPRSS2 was significantly associated with a short overall survival in lung adenocarcinoma (LUAD), demonstrating TMPRSS2 roles in cancer patient susceptibility and severity. Additionally, TMPRSS2 expression in COVID-19-infected lung tissues was significantly reduced compared to healthy lung tissues, indicating that a low TMPRSS2 expression may result in COVID-19 severity and death. Importantly, TMPRSS2 mutation frequency was significantly higher in prostate adenocarcinoma (PRAD), and the mutant TMPRSS2 pan-cancer group was significantly associated with long overall, progression-free, disease-specific, and disease-free survival rates compared to the wild-type (WT) TMPRSS2 pan-cancer group, demonstrating loss of functional roles due to mutation. Cancer cell lines were treated with small molecules, including cordycepin (CD), adenosine (AD), thymoquinone (TQ), and TQFL12, to mediate TMPRSS2 expression. Notably, CD, AD, TQ, and TQFL12 inhibited TMPRSS2 expression in cancer cell lines, including the PC3 prostate cancer cell line, implying a therapeutic role for preventing COVID-19 in cancer patients. Together, these findings are the first to demonstrate that small molecules, such as CD, AD, TQ, and TQFL12, inhibit TMPRSS2 expression, providing novel therapeutic strategies for preventing COVID-19 and cancers.

Hsa_circ_0030042 Ameliorates Oxidized Low-Density Lipoprotein-Induced Endothelial Cell Injury via the MiR-616-3p/RFX7 Axis.

Atherosclerosis (AS) is a common etiology of cardiovascular disease. As an emerging functional biomarker, circular RNAs (circRNAs) are involved in various diseases, including cardiovascular disease. However, the mechanism of action of circ_0030042 in AS has not been reported.Human umbilical vein endothelial cells (HUVECs) stimulated by ox-LDL served as a cellular model of AS. Gene expression was detected using quantitative real-time polymerase chain reaction. The influence of circ_0030042 on cell viability, proliferation, and apoptosis was verified using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, and flow cytometry assays. An enzyme-linked immunosorbent assay was performed to measure the contents of tumor necrosis factor-α, interleukin (IL) -6, and IL-1ß. Western blot assay was utilized to determine the protein levels of Bax, Bcl-2, PCNA, and regulatory factor X 7 (RFX7). The interrelationship between miR-616-3p and circ_0030042 or RFX7 was validated using dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays.The expression of circ_0030042 was downregulated in ox-LDL-induced HUVECs. It was found that overexpression of circ_0030042 facilitated cell proliferation, repressed apoptosis, and reduced the level of inflammatory factors in HUVECs. Circ_0030042 and miR-616-3p had a targeting relationship, and the miR-616-3p mimic eliminated the effects of overexpressed circ_0030042 on ox-LDL-induced HUVECs. RFX7 was a downstream gene of miR-616-3p and was lowly expressed in ox-LDL-induced HUVECs. The miR-616-3p inhibitor stimulated cell proliferation, arrested apoptosis, and caused a decline in the levels of inflammatory factors, whereas knockdown of RFX7 abolished the effects.Circ_0030042 weakened ox-LDL-induced HUVEC injury by regulating the miR-616-3p/RFX7 pathway, thereby influencing AS progression. Circ_0030042 is likely to be a potential biomarker for the future treatment of patients with AS.

HSPA6 and its role in cancers and other diseases.

Heat Shock Protein Family A (Hsp70) Member 6 (HSPA6) (Online Mendelian Inheritance in Man: 140555) belongs to the HSP70 family and is a partially conserved inducible protein in mammals. The HSPA6 gene locates on the human chromosome 1q23.3 and encodes a protein containing two important structural domains: The N-terminal nucleotide-binding domain and the C-terminal substrate-binding domain. Currently, studies have found that HSPA6 not only plays a role in the tumorigenesis and tumor progresses but also causes non-tumor-related diseases. Furthermore, HSPA6 exhibits to inhibit tumorigenesis and tumor progression in some types of cancers but promotes in others. Even though HSPA6 research has increased, its exact roles and mechanisms are still unclear. This article reviews the structure, expression, function, research progress, possible mechanism, and perspective of HSPA6 in cancers and other diseases, highlighting its potential role as a targeted therapeutic and prognostic marker.

The Correlation Between Immune Invasion and SARS-COV-2 Entry Protein ADAM17 in Cancer Patients by Bioinformatic Analysis.

SARS-Cov-2 caused the COVID-19 pandemic worldwide. ADAM17 functions as a disintegrin and transmembrane metalloproteinase domain protein involved in the regulation of SARS-CoV-2 receptor ACE2. However, its impact on cancer patients infected with COVID-19 and its correlation with immune cell infiltration is unclear. This study compared ADAM17 expression between normal and tumor tissues based on GEPIA. The correlations between ADAM17 expression and immune cell infiltration and immunomodulators were investigated. Besides, treated drugs for targeting ADAM17 were searched in the TISDB database. We found that ADAM17 was highly conserved in many species and was mainly expressed in lung, brain, female tissues, bone marrow and lymphoid tissues. It was also highly expressed in respiratory epithelial cells of rhinitis and bronchus. ADAM17 expression in tumors was higher than that in several paired normal tissues and was negatively correlated with the prognosis of patients with malignant tumors. Interestingly, ADAM17 expression significantly correlated with immunomodulators and immune cell infiltration in normal and tumor tissues. Moreover, eight small molecules targeting ADAM17 only demonstrate therapeutic significance. These findings imply important implications for ADAM17 in cancer patients infected with COVID-19 and provide new clues for development strategy of anti-COVID-19.

Genetic polymorphism of 19 autosomal STR loci in the Yi ethnic minority of Liangshan Yi autonomous prefecture from Sichuan province in China.

The Yi is one of fifty-six ethnic populations and one of the most ancient ethnic groups in China. The Liangshan Yi Autonomous Prefecture (LYAP) in Sichuan Province has the single largest Yi community in China. To establish a Yi population database in the LYAP of Sichuan in China, a Goldeneye™ DNA Identification System 20A Kit with 19 autosomal STRs (short tandem repeats) was used. As a result, the total discrimination power (TDP) and the cumulative probability of exclusion (CPE) for these STRs in 1016 unrelated individuals were 0.999999999999999999999897 and 0.9999999597, respectively. Totals of 273 alleles for 19 STRs and 8-22 alleles for each locus were found. The allelic frequencies ranged from 0.0005 to 0.5084. The forensic parameter averages of these STRs were as follows: observed heterozygosity (Hobs) of 78.44%, expected heterozygosity (Hexp) of 79.89%, discrimination power (DP) of 92.66%, and probability of exclusion (PE) of 57.68%. Penta E presented the highest levels of Hobs and DP, whereas TPOX showed the lowest Hobs and DP values. Nei's standard genetic distance matrix among 31 populations found that the nearest genetic distance to the Yi population was the Sichuan Han (0.0056). Altogether, we first reported the forensic parameters and allele frequencies of 19 autosomal STRs of the Yi group in Liangshan. These 19 STR makers could provide highly informative polymorphisms for individual identification, paternity testing and genetic population analyses.

Critical role of SIRT1 upregulation on the protective effect of lncRNA ANRIL against hypoxia/reoxygenation injury in H9c2 cardiomyocytes.

Dysregulation of long non­coding RNA (IncRNA) antisense non­coding RNA in the INK4 locus (ANRIL) is associated with the risk of myocardial infarction (MI). Therefore, the present study aimed to determine the mechanisms underlying this association, which is currently poorly understood, to the best of our knowledge. The current study used an in vitro myocardial ischemia and reperfusion (MI/R) model, in which H9c2 cardiomyocytes were exposed to hypoxia/reoxygenation (H/R), which demonstrated that ANRIL expression was downregulated and that ANRIL positively regulated sirtuin 1 (SIRT1) expression following H/R injury. Subsequently, it was demonstrated that ANRIL upregulated SIRT1 expression by sponging microRNA­181a (miR­181a). In addition, ANRIL overexpression reduced lactate dehydrogenase release and apoptosis of H9c2 cardiomyocytes exposed to H/R, indicating that ANRIL prevented H/R­induced cardiomyocyte injury. Moreover, both miR­181a overexpression and SIRT1 knockdown significantly decreased the protective effects of ANRIL on H/R­induced cardiomyocyte injury, thus demonstrating that SIRT1 upregulation via sponging miR­181a is a critical mechanism that mediates the function of ANRIL. These results provided a novel mechanistic insight into the role of ANRIL in H/R­injured cardiomyocytes and suggested that the ANRIL/miR­181a/SIRT1 axis may be a therapeutic target for reducing MI/R injury.