Lilrb4 ameliorates ileal injury in rats with hemorrhagic shock and suppresses the activation of NF-κB signaling pathway.

Hemorrhagic shock (HS) leads to intestinal damage and subsequent multiple organ dysfunction syndrome. Intestinal barrier dysfunction is the main cause of multiple organ failure associated with HS. Leukocyte immunoglobulin-like receptor B4 (Lilrb4) belongs to the Ig superfamily and is a vital natural immunomodulatory receptor. The purpose of this study was to identify the role and molecular mechanism of Lilrb4 in HS-induced ileal injury. In this work, HS was established by femoral artery cannula and 90 min of HS (blood pressure, 35-40 mmHg), followed by resuscitation. RNA sequencing analysis showed that Lilrb4 was highly expressed in the ileum of HS rats. As observed, HS rats exhibited severe ileal injury, characterized by enlarged subepithelial space, edema, exfoliation and extensive loss of villi. Whereas, lentivirus system-mediated Lilrb4 overexpression considerably mitigated these alterations. HS led to increased release of markers associated with intestinal injury, which was effectively reversed by Lilrb4 overexpression. In addition, after resuscitation, Lilrb4 overexpression inhibited HS-triggered inflammatory response, as evidenced by decreased levels of proinflammatory cytokines. Lilrb4 also inhibited the activation of NF-κB signal induced by HS. Notably, Lilrb4 modulated the balance of regulatory T (Treg)-T helper 17 (Th17) cells in the mesenteric lymph node (MLN), which may also contribute to its protective role in HS progression. In aggregate, these findings confirmed that Lilrb4 overexpression protected against ileal injury caused by HS, indicating that Lilrb4 may be a potential candidate for the treatment of HS.

Single-cell sequencing reveals the immune landscape of breast cancer patients with brain metastasis.

BACKGROUND: Breast cancer has the highest incidence rate of cancer worldwide, and brain metastases (BrM) are among the most malignant cases. While some patients have benefited from immune checkpoint inhibitors (ICIs), the complex anatomical structure of the brain and the heterogeneity of metastatic tumors have made it difficult to characterize the tumor immune microenvironment (TME) of metastatic tumors. METHODS: To address this, we used single-cell RNA sequencing (scRNA-seq) to analyze immune cells in the cerebrospinal fluid (CSF) of BrM patients with breast cancer, thereby providing a comprehensive view of the immune microenvironment landscape of BrM. RESULTS: Based on canonical marker genes, we identified nine cell types, and further identified their subtypes through differential expression gene (DEG) analysis. We compared the changes in cells and functions in the immune microenvironment of patients with different prognoses. Our analysis revealed a series of genes that promote tumor immune function (CCR5, LYZ, IGKC, MS4A1, etc.) and inhibit tumor immune function (SCGB2A2, CD24, etc.). CONCLUSIONS: The scRNA-seq in CSF provides a noninvasive method to describe the TME of breast cancer patients and guide immunotherapy.

From Immunogen to COVID-19 vaccines: Prospects for the post-pandemic era.

The COVID-19 pandemic has affected millions of people and posed an unprecedented burden on healthcare systems and economies worldwide since the outbreak of the COVID-19. A considerable number of nations have investigated COVID-19 and proposed a series of prevention and treatment strategies thus far. The pandemic prevention strategies implemented in China have suggested that the spread of COVID-19 can be effectively reduced by restricting large-scale gathering, developing community-scale nucleic acid testing, and conducting epidemiological investigations, whereas sporadic cases have always been identified in numerous places. Currently, there is still no decisive therapy for COVID-19 or related complications. The development of COVID-19 vaccines has raised the hope for mitigating this pandemic based on the intercross immunity induced by COVID-19. Thus far, several types of COVID-19 vaccines have been developed and released to into financial markets. From the perspective of vaccine use in globe, COVID-19 vaccines are beneficial to mitigate the pandemic, whereas the relative adverse events have been reported progressively. This is a review about the development, challenges and prospects of COVID-19 vaccines, and it can provide more insights into all aspects of the vaccines.

Self-assembled micelle derived from pterostilbene ameliorate acute inflammatory bowel disease.

PEGylated pterostilbene micelle (PTENPs) with higher bioavailability, biocompatibility, and water solubility were prepared. Then we detected the therapeutic effects in the treatment of inflammatory bowel disease (IBD), together with its potential mechanisms. The anti-oxidant effects and anti-inflammatory effects of PTENPs were determined under in vitro and in vivo conditions. Besides, the cellular toxicity of the PTENPs was determined in vitro, and biocompatibility testing was performed on a colitis mice model to determine its safety. The self-assembled PTENPs showed potency in treating IBD, which was featured by effectively anti-oxidant capacity, inhibition of cellular damages, and an anti-inflammatory role. In addition, PTENPs could inhibit the activation of TLR4, thereby inhibiting the NF-κB and MAPK signaling pathways. Meanwhile, it could protect colonic tissues from oxidative damage, which promoted the remission of colonic inflammation with low toxicity. Compared with free PTE, PTENPs could effectively ameliorate acute IBD with low toxicity, which may be related to the inactivation of TLR4, and inhibition of NF-κB and MAPK signaling pathways.

Human placental mesenchymal stem cell derived exosomes exhibit anti-inflammatory effects via TLR4-mediated NF-κB/MAPK and PI3K signaling pathways.

Exosomes are a type of nanoparticles in 40-200 nm extracellular vesicles secreted from living cells, containing a plurality of biologically active substances, which can be used as carriers of intercellular delivery signals. Among them, mesenchymal stem cell (MSC)-derived exosomes have been reported to play important roles in injury repair, alleviating inflammation; thus, MSC-derived exosomes have become hot spot in noncellular therapies. The role of human placental MSC-derived exosomes (hplMSC-Exos) in inflammation and their potential mechanisms are unclear. Therefore, we investigated the anti-inflammatory effects of hplMSC-Exos in lipopolysaccharide (LPS)-induced RAW264.7 cells and their intrinsic mechanisms. Our data demonstrated that hplMSCs-Exos can adjust inflammation by regulating TLR4-mediated NF-κB/MAPK and PI3K signaling pathways, indicating that hplMSCs-Exos can act as a new strategy for inflammatory treatment.

Bovine Serum Albumin-Cross-Linked Polyaniline Nanowires for Ultralow Fouling and Highly Sensitive Electrochemical Protein Quantification in Human Serum Samples.

Biofouling represents a serious challenge for the assaying of disease markers with various biosensors in complex biological samples due to the accompanied nonspecific protein adsorption. Herein, a highly sensitive and antifouling biosensing interface was constructed based on a cost-effective inert protein bovine serum albumin (BSA) cross-linked with polyaniline nanowires (PANI-NWs). Compared with the physically adsorbed BSA that was commonly used to block nonspecific adsorption or binding of proteins, the cross-linked BSA exhibited a significantly enhanced antifouling capability. The BSA/PANI-NW-modified electrode interface possessed excellent antifouling capability and electrochemical activity owing to the presence of the cross-linked BSA and the conducting polymer polyaniline. With further immobilization of the peptide aptamer for immunoglobulin G (IgG) recognition onto the BSA/PANI-NW interface, an electrochemical biosensor with excellent selectivity and sensitivity was prepared. The IgG biosensor possessed a linear range from 1.0 ng mL-1 to 10 µg mL-1 and a low detection limit of 0.27 ng mL-1, and it was capable of assaying IgG in complex human serum samples with acceptable accuracy when compared with the assay results obtained using commercial enzyme-linked immunosorbent assay kits. It is expected that the unique BSA-cross-linked conducting polymers can be used for the construction of various electrochemical sensors and biosensors that can be applied in complex biological media.

A Review of Multi-Compartment Infectious Disease Models.

Multi-compartment models have been playing a central role in modelling infectious disease dynamics since the early 20th century. They are a class of mathematical models widely used for describing the mechanism of an evolving epidemic. Integrated with certain sampling schemes, such mechanistic models can be applied to analyse public health surveillance data, such as assessing the effectiveness of preventive measures (e.g. social distancing and quarantine) and forecasting disease spread patterns. This review begins with a nationwide macromechanistic model and related statistical analyses, including model specification, estimation, inference and prediction. Then, it presents a community-level micromodel that enables high-resolution analyses of regional surveillance data to provide current and future risk information useful for local government and residents to make decisions on reopenings of local business and personal travels. r software and scripts are provided whenever appropriate to illustrate the numerical detail of algorithms and calculations. The coronavirus disease 2019 pandemic surveillance data from the state of Michigan are used for the illustration throughout this paper.

Designed antifouling peptides planted in conducting polymers through controlled partial doping for electrochemical detection of biomarkers in human serum.

An antifouling electrochemical biosensing platform was constructed based on conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) planted with designed peptides. The designed peptides containing doping and antifouling sequences were anchored to an electrode surface, followed by the electrochemical polymerization of PEDOT. The negatively charged doping sequence of the peptide was gradually doped into the PEDOT during the polymerization process, and by controlling the polymerization time, it was able to exactly dope the whole doping sequence into the PEDOT film, leaving the antifouling sequence of the peptide stretched out of the PEDOT surface. Therefore, an excellent conducting and antifouling platform was constructed just like planting a peptide tree in the PEDOT soil. With antibodies immobilized on the peptide, an antifouling electrochemical biosensor for the detection of a typical biomarker CA15-3 was developed. Owing to the unique properties of the conducting polymer PEDOT and the antifouling peptide, the electrochemical biosensor exhibited high sensitivity and long-term stability, and it was capable of detecting CA15-3 in serum of breast cancer patients without suffering from biofouling. The strategy of planting designed antifouling peptides in conducting polymers offered an effective way to develop electrochemical sensors for practical biomarkers assaying in complex biological samples.

Catalytic fast pyrolysis of polyethylene terephthalate plastic for the selective production of terephthalonitrile under ammonia atmosphere.

Terephthalonitrile (TPN) was directly produced from polyethylene terephthalate (PET) plastic via catalytic fast pyrolysis with ammonia. The optimal condition for producing TPN was over 1 g γ-Al2O3-2 wt% catalyst at 500 °C under carrier gas (50% NH3 and 50% N2) with yield of nitriles and TPN of 58.1 and 52.3 C%, respectively. The selectivity of TPN in the nitriles was around 90%. Meanwhile, a bit of aromatics, benzonitrile, acetonitrile were also produced as by-products with the total yields of less than 3 C%. The catalyst deactivated slightly after 5 cycles. Possible reaction routes were proposed and it was found that terephthalic acid, benzoic acid, related esters and amides were the major intermediates from PET to nitriles. Acetonitrile could be produced from acetaldehyde and its corresponding imines. In addition, 32.1 C% TPN with high purity (>95%) was obtained via freezing recrystallization. Catalytic pyrolysis with ammonia process was a promising technology for converting waste PET plastics to TPN. This study provided a new method for producing N-containing chemicals from polyester plastics.

Prognostic analysis of gastric mucosal dysplasia after endoscopic resection: A single-center retrospective study.

PURPOSE: To analyze the prognostic factors of gastric mucosal dysplasia after endoscopic resection. METHODS: 362 patients with gastric mucosal dysplasia diagnosed by endoscopic biopsy and undergoing endoscopic resection from March 2012 to March 2016 were enrolled. Follow-up was longer than 30 months. Basic characteristics of enrolled patients were recorded, including age, gender, surgical procedures, lesion location, pathological type, lesion size, Helicobacter pylori (HP) infection, operation time and wound area. The relationship between the above factors and postoperative residual lesions and recurrence after endoscopic resection of gastric mucosal dysplasia was analyzed. RESULTS: Included were 200 males and 162 females, aged 28-78 years, (mean 59.3±11.5). Operation time and wound area were not correlated with postoperative recurrence of gastric mucosal dysplasia resected by endoscopic mucosal resection (EMR) (p>0.05). Operation time in patients undergoing endoscopic submucosal dissection (ESD) was longer compared with those of controls (p=0.032). Additionally, wound area was smaller in patients with postoperative residual disease (p=0.003) and postoperative recurrence (p=0.048) after ESD compared with controls. Intestinal metaplasia was a common risk factor for postoperative residual disease and postoperative recurrence of gastric mucosal dysplasia. Lesion location and complete resection were independent risk factors for postoperative recurrence of gastric mucosal dysplasia. Also, pathological findings and HP infection were independent risk factors for recurrence of gastric mucosal dysplasia after endoscopic resection. CONCLUSIONS: In patients undergoing ESD of gastric mucosal dysplasia, prolonged operation time may increase the possibility of postoperative residual disease. Complete resection may reduce the possibility for recurrence. Intestinal metaplasia may serve as a common independent risk factor for postoperative residual disease and recurrence of gastric mucosal dysplasia after endoscopic resection.

Meta-analysis of MMP2 -1306T allele as a protective factor in digestive cancer.

BACKGROUND AND AIMS: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity on matrix proteins and abolishes a Sp-1 binding site and consequently decreases its activity. Many studies have been carried out on the association between MMP2 -1306C/T polymorphism and digestive cancer risk, but results were somewhat controversial and underpowered. METHODS: To examine the risk of digestive cancer associated with -1306C/T polymorphism of MMP2, we performed a meta-analysis of ten case-control studies. Eligible studies were identified by searching the electronic literature using Pubmed and Embase. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. RESULTS: Overall, we found that -1306T allele can decrease digestive cancer risk in three different genotype models (T-allele vs. C-allele, OR=0.73, 95% CI: 0.54-0.98, p=0.034; TC vs. CC, OR=0.64, 95% CI: 0.53-0.78, p <0.001; TT+TC vs. CC, OR=0.68, 95% CI: 0.53-0.86, p=0.002). Similarly, in the stratified analysis by cancer type, ethnicity and source of control, significantly decreased cancer risk was indicated. Moreover, in the subgroup of smokers, -1306T allele may protect people against digestive cancer risk (TT+TC vs. CC, OR=0.71, 95% CI: 0.51-0.98, p=0.037). CONCLUSIONS: Our meta-analysis showed evidence that MMP2 -1306T allele may be a protective factor for digestive cancer risk as well as a low-penetrance susceptibility digestive cancer biomarker.