Multi-omics integration strategy in the post-mortem interval of forensic science.

Estimates of post-mortem interval (PMI), which often serve as pivotal evidence in forensic contexts, are fundamentally based on assessments of variability among diverse molecular markers (including proteins and metabolites), their correlations, and their temporal changes in post-mortem organisms. Nevertheless, the present approach to estimating the PMI is not comprehensive and exhibits poor performance. We developed an innovative approach that integrates multi-omics and artificial intelligence, using multimolecular, multimarker, and multidimensional information to accurately describe the intricate biological processes that occur after death, ultimately enabling inference of the PMI.

Single-cell RNA-sequencing analysis reveals enhanced non-canonical neurotrophic factor signaling in the subacute phase of traumatic brain injury.

Background: Traumatic brain injury (TBI) is a leading cause of long-term disability in young adults and induces complex neuropathological processes. Cellular autonomous and intercellular changes during the subacute phase contribute substantially to the neuropathology of TBI. However, the underlying mechanisms remain elusive.

Forensic identification of sudden cardiac death: a new approach combining metabolomics and machine learning.

The determination of sudden cardiac death (SCD) is one of the difficult tasks in the forensic practice, especially in the absence of specific morphological changes in the autopsies and histological investigations. In this study, we combined the metabolic characteristics from corpse specimens of cardiac blood and cardiac muscle to predict SCD. Firstly, ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS)-based untargeted metabolomics was applied to obtain the metabolomic profiles of the specimens, and 18 and 16 differential metabolites were identified in the cardiac blood and cardiac muscle from the corpses of those who died of SCD, respectively.

Chinese Medicinal Herb-Derived Carbon Dots for Common Diseases: Efficacies and Potential Mechanisms.

The management of hemorrhagic diseases and other commonly refractory diseases (including gout, inflammatory diseases, cancer, pain of various forms and causes) are very challenging in clinical practice. Charcoal medicine is a frequently used complementary and alternative drug therapy for hemorrhagic diseases. However, studies (other than those assessing effects on hemostasis) on charcoal-processed medicines are limited.

Synergistic Effect of Granular Seed Substrates and Soluble Additives in Structural Control of Prismatic CaCO Thin Films.

In biomineralization and bioinspired mineralization, substrates and additives function synergistically in providing structural control of the mineralized layers including their orientation, polymorph, morphology, hierarchical architecture, etc. Herein, a novel type of granular aragonitic CaCO-poly(acrylic acid) substrate guides the mineralization of prismatic CaCO thin films of distinct morphology and polymorph in the presence of different additives including organic compounds and polymers. For instance, weakly charged amino acids lead to columnar aragonite overlayers, while their charged counterparts and organic acids/bases inhibit the overgrowth.

Seeded Mineralization Leads to Hierarchical CaCO Thin Coatings on Fibers for Oil/Water Separation Applications.

Like their biogenic counterparts, synthetic minerals with hierarchical architectures should exhibit multiple structural functions, which nicely bridge the boundaries between engineering and functional materials. Nevertheless, design of bioinspired mineralization approaches to thin coatings with distinct micro/nanotextures remains challenging in the realm of materials chemistry. Herein, a general morphosynthetic method based on seeded mineralization was extended to achieve prismatic-type thin CaCO coatings on fibrous substrates for oil/water separation applications.

Total morphosynthesis of biomimetic prismatic-type CaCO thin films.

Biomimetic mineralization can lead to advanced crystalline composites with common chemicals under ambient conditions. An exceptional example is biomimetic nacre with its superior fracture toughness. The synthesis of the prismatic layer with stiffness and wear resistance nonetheless remains an elusive goal.

Proteasome inhibition in vivo promotes survival in a lethal murine model of severe acute respiratory syndrome.

Ubiquitination is a critical regulator of the host immune response to viral infection, and many viruses, including coronaviruses, encode proteins that target the ubiquitination system. To explore the link between coronavirus infection and the ubiquitin system, we asked whether protein degradation by the 26S proteasome plays a role in severe coronavirus infections using a murine model of SARS-like pneumonitis induced by murine hepatitis virus strain 1 (MHV-1). In vitro, the pretreatment of peritoneal macrophages with inhibitors of the proteasome (pyrrolidine dithiocarbamate [PDTC], MG132, and PS-341) markedly inhibited MHV-1 replication at an early step in its replication cycle, as evidenced by inhibition of viral RNA production.

Targeted deletion of fgl2 leads to impaired regulatory T cell activity and development of autoimmune glomerulonephritis.

Mice with targeted deletion of fibrinogen-like protein 2 (fgl2) spontaneously developed autoimmune glomerulonephritis with increasing age, as did wild-type recipients reconstituted with fgl2-/- bone marrow. These data implicate FGL2 as an important immunoregulatory molecule and led us to identify the underlying mechanisms. Deficiency of FGL2, produced by CD4+CD25+ regulatory T cells (Treg), resulted in increased T cell proliferation to lectins and alloantigens, Th 1 polarization, and increased numbers of Ab-producing B cells following immunization with T-independent Ags.

LPS-induced occult loss in mice requires FGL2.

Problem: FGL2 prothrombinase is required for spontaneous abortion (resorptions) in the CBA x DBA/2 model, and for abortions in C57Bl/6 (B6) mice triggered by Salmonella enteritidis lipopolysaccharide (LPS). Unlike abortions, occult losses in B6 mice, which begin before gestation day 9.5 in mice, do not require the tumor necrosis factor-alpha receptor type 1, and may be triggered by either Salmonella enteritidis or Escherichia coli LPS.

Targeted deletion of Fgl-2/fibroleukin in the donor modulates immunologic response and acute vascular rejection in cardiac xenografts.

Background: Xenografts ultimately fail as a result of acute vascular rejection (AVR), a process characterized by intravascular thrombosis, fibrin deposition, and endothelial cell activation.

Methods And Results: We studied whether targeted deletion of Fgl-2, an inducible endothelial cell procoagulant, (Fgl-2-/-) in the donor prevents AVR in a mouse-to-rat cardiac xenotransplantation model. By 3 days after transplant, Fgl-2+/+ grafts developed typical features of AVR associated with increased levels of donor Fgl-2 mRNA.

[Detection of cDNA end sequence of porcine fibrinogen like protein2 and it's structure analysis].

The purpose of this study is to detect the end sequence of porcine FGL2 gene cDNA and make a preliminary analysis of it's structure. Porcine DNA library was screened by a cDNA probe labeled with radioactive isotope alpha-32P dCTP. Rapid amplification of cDNA end (RACE): Retroverse transcription product of total RNA extracted from normal porcine tissue was used as the template, gene specific primers were designed and advantage 2 polymerase mix was used in PCR, of which using porcine genomic DNA as the template:forward primer was designed according to the acquired consensus region of human and pig FGL2 3' sequences while reverse primer was designed from human FGL2 3' end downstream sequence; TA cloning.

[The study of cis-element HNF4 in the regulation of mfg12 prothrombinase/fibroleukin gene expression in response to nucleocapsid protein of MHV-3].

Objective: To identify the transcription factor(s) that is essential for activation of mfgl2 prothrombinase/fibroleukin gene in response to nucleocapsid protein of murine hepatitis virus type 3 (MHV-3).

Methods: Western blotting was performed to investigate whether HNF4 is expressed in macrophages of Ba1b/c mice where mfgl2 is expressed. Confocus microscope immunofluorescence was performed to show whether N protein of MHV enters into the nucleus of infected cells, which is a critical step for the N protein to facilitate its transactivation property.