Artificial intelligence-driven microbiome data analysis for estimation of postmortem interval and crime location.

Microbial communities, demonstrating dynamic changes in cadavers and the surroundings, provide invaluable insights for forensic investigations. Conventional methodologies for microbiome sequencing data analysis face obstacles due to subjectivity and inefficiency. Artificial Intelligence (AI) presents an efficient and accurate tool, with the ability to autonomously process and analyze high-throughput data, and assimilate multi-omics data, encompassing metagenomics, transcriptomics, and proteomics. This facilitates accurate and efficient estimation of the postmortem interval (PMI), detection of crime location, and elucidation of microbial functionalities. This review presents an overview of microorganisms from cadavers and crime scenes, emphasizes the importance of microbiome, and summarizes the application of AI in high-throughput microbiome data processing in forensic microbiology.

Autophagy inhibition and reactive oxygen species elimination by acetyl-CoA acetyltransferase 1 through fused in sarcoma protein to promote prostate cancer.

BACKGROUND: Prostate cancer is a major health issue affecting the male population worldwide, and its etiology remains relatively unknown. As presented on the Gene Expression Profiling Interactive Analysis database, acetyl-CoA acetyltransferase 1 (ACAT1) acts as a prostate cancer-promoting factor. ACAT1 expression in prostate cancer tissues is considerably higher than that in normal tissues, leading to a poor prognosis in patients with prostate cancer. Here, we aimed to study the role of the ACAT1-fused in sarcoma (FUS) complex in prostate cancer and identify new targets for the diagnosis and treatment of the disease. METHODS: We conducted immunohistochemical analysis of 57 clinical samples and in vitro and in vivo experiments using a mouse model and plasmid constructs to determine the expression of ACAT1 in prostate cancer. RESULTS: The relationship between the expression of ACAT1 and the Gleason score was significant. The expression of ACAT1 was higher in tissues with a Gleason score of > 7 than in tissues with a Gleason score of ≤7 (P = 0.0011). In addition, we revealed that ACAT1 can interact with the FUS protein. CONCLUSIONS: In prostate cancer, ACAT1 promotes the expression of P62 and Nrf2 through FUS and affects reactive oxygen species scavenging. These effects are due to the inhibition of autophagy by ACAT1. That is, ACAT1 promotes prostate cancer by inhibiting autophagy and eliminating active oxygen species. The expression of ACAT1 is related to prostate cancer. Studying the underlying mechanism may provide a new perspective on the treatment of prostate cancer.

PLEKHH2 binds ß-arrestin1 through its FERM domain, activates FAK/PI3K/AKT phosphorylation, and promotes the malignant phenotype of non-small cell lung cancer.

PLEKHH2 is an important FERM domain containing-protein. However, the role of PLEKHH2 in human solid tumors has not been reported yet. We report that PLEKHH2 showed enhanced cytoplasmic expression in non-small cell lung cancer (NSCLC). Its overexpression was positively correlated with high TNM stage, low differentiation, lymphatic node metastasis, and poor prognosis. In A549 and H1299 cells, high expression of PLEKHH2 significantly promoted cell proliferation, migration, invasion, and increased the expression of proliferation- and invasion-related proteins. It also enhanced the phosphorylation of FAK and promoted the activity of the PI3K/AKT pathway. Immunofluorescence and co-immunoprecipitation analyses were performed to elucidate the molecular mechanism underlying PLEKHH2-mediated regulation of proliferation and invasion in lung cancer cells. Upon transfection of full length PLEKHH2 or its FERM domain, we observed enhanced binding of PLEKHH2 to ß-arrestin1, whereas FAK- ß-arrestin1 binding was diminished and this led to an increase in FAK phosphorylation. PLEKHH2-mutant plasmids without the FERM domain could not effectively promote its binding to ß-arrestin1, activation of FAK phosphorylation, PI3K/AKT activation, or the malignant phenotype. Our findings suggested that PLEKHH2 is an important oncogene in NSCLC. PLEKHH2 binding to ß-arrestin1 through the FERM domain competitively inhibits ß-arrestin1 binding to FAK, which causes the dissociation of FAK from the FAK-ß-arrestin1 complex. Furthermore, the dissociation of FAK promotes its autophosphorylation, activates the PI3K/AKT signaling pathway, and subsequently promotes lung cancer cell proliferation, migration, and invasion. These results provide evidence for the potential use of PLEKHH2 inhibition as an anticancer therapy.

Susceptibility Loci in SLC15A1, UGT1A3, and CWC27 Genes Associated with Bladder Cancer in the Northeast Chinese Population.

Bladder cancer (BCa) is an increasingly severe clinical and public health issue. Therefore, we aim to investigate BCa susceptibility loci in the Chinese population. In this study, 487 BCa patients and 563 controls were recruited from the First Affiliated Hospital of China Medical University from July 2015 to September 2020. A total of ten single-nucleotide polymorphisms (SNPs) in solute carrier family 15 member 1 (SLC15A1), CWC27 spliceosome associated cyclophilin (CWC27), or UDP glucuronosyltransferase family 1 member A3 (UGT1A3) genes were genotyped. The associations between the candidate SNPs and BCa were analyzed using genotype and haplotype analysis. The results demonstrated that Rs4646227 of SLC15A1 has a significant association with BCa. The patients with CG (OR =2.513, p < 0.05) and GG (OR =2.859, p < 0.05) genotypes had an increasing risk of BCa compared with the CC genotype. For the CWC27 gene, genotypic frequency analysis revealed that the GT or TT genotype of rs2042329 and the CT or TT genotype of rs1870437 were more frequent in BCa patients than those in the control group, indicating that these genotypes were associated with a higher risk of BCa (all p < 0.05). Haplotypes of SLC15A1, UGT1A3, and CWC27 genes found that the C-C-C haplotype of SLC15A1 was associated with a lower risk of BCa while the C-G-C haplotype was associated with a higher risk. For the UGT1A3 gene, a moderate protective effect was observed with the most frequent T-T-C haplotype, and for the CWC27 gene, most of the haplotypes showed no association with BCa, except the G-G-C-T haplotype (order of SNPs: rs2042329-rs7735338-rs1870437-rs2278351, OR =0.81, p =0.038). In sum, this study indicated that rs2042329 and rs1870437 in the CWC27 gene and rs4646227 in the SLC15A1 gene are independent indicators for BCa risk in Chinese people. Further large-scale studies are required to validate these findings. Also, this study provided the theoretical basis for developing new therapeutic drug targeting of BCa.

Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm.

Identifying biomarkers for abdominal aortic aneurysms (AAA) is key to understanding their pathogenesis, developing novel targeted therapeutics, and possibly improving patients outcomes and risk of rupture. Here, we identified AAA biomarkers from public databases using single-cell RNA-sequencing, weighted co-expression network (WGCNA), and differential expression analyses. Additionally, we used the multiple machine learning methods to identify biomarkers that differentiated large AAA from small AAA. Biomarkers were validated using GEO datasets. CIBERSORT was used to assess immune cell infiltration into AAA tissues and investigate the relationship between biomarkers and infiltrating immune cells. Therefore, 288 differentially expressed genes (DEGs) were screened for AAA and normal samples. The identified DEGs were mostly related to inflammatory responses, lipids, and atherosclerosis. For the large and small AAA samples, 17 DEGs, mostly related to necroptosis, were screened. As biomarkers for AAA, G0/G1 switch 2 (G0S2) (Area under the curve [AUC] = 0.861, 0.875, and 0.911, in GSE57691, GSE47472, and GSE7284, respectively) and for large AAA, heparinase (HPSE) (AUC = 0.669 and 0.754, in GSE57691 and GSE98278, respectively) were identified and further verified by qRT-PCR. Immune cell infiltration analysis revealed that the AAA process may be mediated by T follicular helper (Tfh) cells and the large AAA process may also be mediated by Tfh cells, M1, and M2 macrophages. Additionally, G0S2 expression was associated with neutrophils, activated and resting mast cells, M0 and M1 macrophages, regulatory T cells (Tregs), resting dendritic cells, and resting CD4 memory T cells. Moreover, HPSE expression was associated with M0 and M1 macrophages, activated and resting mast cells, Tregs, and resting CD4 memory T cells. Additional, G0S2 may be an effective diagnostic biomarker for AAA, whereas HPSE may be used to confer risk of rupture in large AAAs. Immune cells play a role in the onset and progression of AAA, which may improve its diagnosis and treatment.

Intra-tumoral angiogenesis correlates with immune features and prognosis in glioma.

Gliomas are the most common malignant tumor in the brain. As with other tumors, the progression of glioma depends on intra-tumoral angiogenesis. However, the effect of angiogenesis on gliomas is still not fully understood. In this study, we developed an angiogenesis pathway score using Gene Set Variation Analysis (GSAV) in R to assess the status of intra-glioma angiogenesis in The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA mRNAseq_325, CGGA mRNA-array), and GSE16011 datasets. We found that the angiogenesis pathway score not only accurately predicted the prognosis of glioma patients, but also accurately distinguished the malignant phenotype and immune characteristics of gliomas. In addition, as an independent prognostic factor, the score could predict glioma sensitivity to radiotherapy and chemotherapy. In summary, we used the angiogenesis pathway score to reveal the relationship between glioma angiogenesis and the malignant phenotype, immune characteristics, and prognosis of glioma.

Rivaroxaban ameliorates angiotensin II-induced cardiac remodeling by attenuating TXNIP/Trx2 interaction in KKAy mice.

As an anticoagulant, Rivaroxaban has recently been reported to be protective in cardiac injury. Based on those previous research results, we detected the roles of Rivaroxaban in Angiotensin II (AngII)-induced cardiac remodeling with KKAy mice and unraveled the underlying mechanisms. Rivaroxaban inhibited cardiac fibrosis and hypertrophy in AngII-infused KKAy mice. In addition, it also inhibited mitochondrial dysfunction. Noteworthily, Rivaroxaban altered the expression of many genes associated with mitochondrial function. Rivaroxaban inhibited the expression of thioredoxin binding protein (TXNIP) as well as the activation of apoptosis stimulating kinase 1 (ASK1). In H9c2 cells treated with AngII and high glucose, Rivaroxaban inhibited TXNIP/thioredoxin2 (Trx2) interaction. Moreover, TXNIP knockout abolished AngII-induced cardiac fibrosis and hypertrophy. Thus, Rivaroxaban ameliorates AngII-induced cardiac remodeling via the suppression of TXNIP signaling in KKAy mice, providing novel mechanism underlying the protective roles of Rivaroxaban against cardiac damage.

[Anatomical study on reverse flap of dorso-ulnar aspect of mid-hand and its clinical application].

OBJECTIVE: To provide anatomical bases for dorso-ulnar aspect of mid-hand reverse flap. METHODS: After red latex was infused into the arteries of 40 sides of adult cadava upper limbs, the origin, course, branches, distribution and distal anastomosis on the dorsal carpal branch of ulnar arteries were observed. And the mid-hand flap transfer was used to repair two cases of soft tissue defect (ranged 4.5-5.0 cm x 2.0-3.5 cm on ring and little fingers). RESULTS: The dorsal carpal branch begins with ulnar artery (3.9 +/- 1.2) cm above the pisiform with diameter of (1.3 +/- 0.2) mm, and branches off into ascending and descending branches. The descending one is the continuing of dorsal branch, it crosses the ulnar edge of the fifth metecarpal bone and anastomizes with the digital artery of little finger or hypothenar branch of deep palmar (accounted for 70%). While the other ascending branch with the former two branches formed anastomosis accounts for 30%. The two cases got healed in one-stage. The function of fingers recovered after 3-4 month follow-up. CONCLUSION: The reverse flap of dorso-ulnar aspect of mid-hand is available to repair the soft tissue defect on dorsum of hand with neighbor finger.