Shijie Mu

Bacterial contamination remains a critical safety concern in platelet transfusion, and there is an urgent demand for decontamination technologies that eliminate contaminating bacteria without damaging platelet viability and physiological function. Herein, Fe₃O₄-QCS-PEI-Cu-apt microparticles with enlarged magnetic cores were rationally fabricated to improve aptamer immobilization, aiming at targeted bacterial elimination via near-infrared (NIR) irradiation while maintaining platelet function. Fluorescence assays confirmed their specific targeting capability toward Staphylococcus aureus (S. aureus) without binding to platelets. Magnetic separation experiments demonstrated that the aptamer-functionalized microparticles could efficiently capture and remove 91.35% of S. aureus from platelets. NIR irradiation of the Fe₃O₄-QCS-PEI-Cu core induced marked bactericidal activity against S. aureus in suspension, as determined by plate counting and LIVE/DEAD staining. This antibacterial ability originated from the intrinsic photo-responsive property of the composite rather than from aptamer-mediated recognition, and could be easily extended to bacteria captured by aptamer-functionalized particles. Comprehensive biocompatibility evaluations, including morphological observation, hematological parameter analysis, CD62P expression detection, and thromboelastography (TEG) were performed. And the results demonstrated that there were no significant changes in platelet morphology, count, activation state, or overall hemostatic function, apart from an increase in the α angle. This platform achieves efficient targeted NIR-triggered antibacterial efficacy while maintaining excellent platelet compatibility, offering a promising strategy to enhance the safety of platelet transfusion.

Background: Platelets play a crucial role in regulating coagulation. However, balancing the supply and clinical demands of platelet concentrates is a tough challenge. It is urgent to explore a novel platelet substitute with biosafety and efficacy in traumatic hemorrhage. Methods: The platelet-like PLGA-PSP nanoparticles were synthesized by covalently coupling the linear platelet-specific peptides including CBP, VBP and FMP to the active carboxyl functional group of PLGA-PEG nanoparticles. The biosafety of the platelet-like PLGA-PSP nanoparticles was assessed. Subsequently, in vitro experiments were conducted to verify the effects of PLGA-PSP nanoparticles on platelet adhesion, aggregation and activation. Furthermore, the hemostatic efficacy of PLGA-PSP nanoparticles was confirmed in the tail vein, liver and femoral artery hemorrhage of normal and thrombocytopenic mice. Results: We successfully designed and synthesized the non-toxic PLGA-PSP nanoparticles with specific hemostatic ability that significantly induced platelet adhesion and aggregation without triggering unexpected platelet activation. Moreover, the application of PLGA-PSP nanoparticles was demonstrated to effectively reduce the bleeding time and blood loss in the tail vein, liver and femoral artery of both normal and thrombocytopenic mice. Conclusion: The novel platelet-like PLGA-PSP nanoparticles present a promising therapeutic option for the rapid hemostasis of traumatic hemorrhage based on the biosafety and efficacy.

Bacterial infection is one of the leading causes of human death globally and is considered to be an urgent public health challenge. It is important to accurately and rapidly detect and kill pathogenic microorganisms. Therefore, a multifunctional platform for sensitive detection and efficient elimination of pathogenic bacteria should be developed to reduce the threat of bacteria. In this study, an integrated strategy based on Fe₃O₄-quaternary ammonium chitosan-polyetherimide-Cu-aptamer (Fe₃O₄-QCS-PEI-Cu-aptamer) and ladder-branch hybridization chain reaction (HCR) was proposed for the detection and inactivation of Staphylococcus aureus (S. aureus). The aptamer-complementary chain (aptamer-CP) conjugated to the surface of Fe₃O₄-QCS-PEI-Cu induces CP release in the presence of S. aureus, further initiating the ladder-branch HCR reaction and achieving signal amplification. Under optimal conditions, the developed sensor demonstrated a limit of detection (LOD) of 3 CFU/mL for S. aureus and exhibited high selectivity against several other pathogenic bacteria. Moreover, the Fe₃O₄-QCS-PEI-Cu-aptasensor showed potent antibacterial properties under near infrared (NIR) irradiation, achieving an antimicrobial efficiency of 99.946%. This strategy synergistically combined the high-sensitivity molecular detection with the antibacterial activity of novel nanomaterials activated by near infrared light, providing a new insight into the prevention of bacterial infections. Graphical Abstract

Autoimmune diseases (ADs) arise from an abnormal immune response of the body against substances and tissues normally present in the body. More than a hundred of ADs have been described in the literature so far. Although their etiology remains largely unclear, various types of ADs tend to share more associated genes with other types of ADs than with non-AD types. Here we present GAAD, a gene and AD association database. In GAAD, we collected 44,762 associations between 49 ADs and 4249 genes from public databases and MEDLINE documents. We manually verified the associations to ensure the quality and credibility. We reconstructed and recapitulated the relationships among ADs using their shared genes, which further validated the quality of our data. We also provided a list of significantly co-occurring gene pairs among ADs; with embedded tools, users can query gene co-occurrences and construct customized co-occurrence network with genes of interest. To make GAAD more straightforward to experimental biologists and medical scientists, we extracted additional information describing the associations through text mining, including the putative diagnostic value of the associations, type and position of gene polymorphisms, expression changes of implicated genes, as well as the phenotypical consequences, and grouped the associations accordingly. GAAD is freely available at http://gaad.medgenius.info.

Background: Malignant gliomas are the most common primary brain tumors. Various genetic factors play important roles in the development and prognosis of glioma. The present study focuses on the impact of MPHOSPH6, TNIP1 and several other genes (ACYP2, NAF1, TERC, TERT, OBFC1, ZNF208 and RTEL1) on telomere length and how this affects the prognosis of glioma.Methods: Forty‐three polymorphisms in nine genes from 605 glioma patients were selected. The association between genotype and survival outcome was analyzed using the Kaplan–Meier method, Cox regression analysis and the log‐rank test.Results: The 1‐year overall survival (OS) rates of patients younger than 40 years of age was higher compared to those in patients older than 40 years of age. The 1‐year OS rate of patients who underwent total resection was higher than that of patients whose gliomas were not completely resected. The 1‐year OS rates of patients undergoing chemotherapy and of patients who did not undergo chemotherapy were 39.90% and 26.80%, respectively. Univariate analyses showed that ACYP2 rs12615793 and TERT rs2853676 loci affected progression‐free survival in glioma patients; both ZNF208 rs8105767 and ACYP2 rs843720 affected the OS of patients with low‐grade gliomas. Multivariate analyses suggested that MPHOSPH6 rs1056629 and rs1056654, and TERT rs2853676 loci were associated with good prognoses of patients with glioma or high‐grade gliomas, whereas ZNF208 rs8105767 was associated with good prognosis of patients with low‐grade glioma.Conclusions: Age, surgical resection and chemotherapy influenced the survival rates of glioma patients. TERT, MPHOSPH6, ACYP2 and ZNF208 genes were found to affect glioma prognosis.

Several genome-wide association studies of primary biliary cirrhosis (PBC) in European and Japanese origins have shown significant association of dozens of genetic loci contributive to the susceptibility of PBC. Most of the loci were related to immune response pathway. In this study, we tested whether the lipid metabolic gene HELZ2 was associated with the pathogenesis of PBC. In 586 PBC cases (358 in case 1 group and 201 in case 2 group) and 726 healthy controls of Chinese Han, six nonsynonymous SNPs were genotyped by MassArray iPLEX. The same control were used for the two groups of PBC cases. Allele frequencies were calculated by χ2 test based on 2 × 2 contingency tables. All data were analyzed using the PLINK tool set. The odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated, and p values (corrected for multiple testing by Bonferroni adjustment) less than 0.05 were considered statistically significant. The A allele of rs79267778 was significantly associated with PBC (ORcombined = 4.204 [1.670–10.582], p combined = 1.87E−04). It changed the amino acid at position 1904 (NM_001037335) from Threonine (ACG) to Methionine (ATG). This site was highly conserved in mammals and predicted to be POSSIBLY DAMAGING with a score of 0.469 by PolyPhen-2. It’s further predicted that T1904 M could INCREASE the protein stability with a confidence at 25.18 % under the condition of pH 7.0 and 37 °C. The result was the first time to show evidence of the lipid metabolic gene HELZ2 related to autoimmune disease, at least in PBC of Chinese Han.