As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

Xenotransplantation is one of the effective ways to overcome the shortage of donor organs. However, the molecular incompatibility between xenotransplantation donors and recipients can cause rejection, which greatly limits the clinical application of xenotransplantation. In recent years, researchers have deeply explored the mechanism of xenotransplantation rejection through xenotransplantation models of pig-to-monkey and pig-to-brain death recipients, and found that the innate immune system plays an important role in rejection. Macrophages, as phagocytes in the innate immune system, not only damage xenografts through phagocytosis but also interact with other immune cells to influence the immune microenvironment of xenotransplantation. However, due to the heterogeneity of macrophages, their phenotypes and functions in xenotransplantation rejection remain unclear. Therefore, it is necessary to further explore the role of macrophages in xenotransplantation rejection. This article reviews the latest research progress of macrophages in xenotransplantation rejection, aiming to explore the mechanisms of macrophages in xenotransplantation rejection and provide references for future research.

CD47 is a transmembrane protein widely expressed on cell surface, which is considered as a key molecule for immune escape. With an increasing number of related studies, the role of CD47 and its ligands in immunomodulatory effects has been gradually understood. Recent studies have investigated the role of CD47 in ischemia-reperfusion injury of allogenetic kidney transplantation, rejection and xenotransplantation. Nevertheless, the specific role and the key mechanism remain elusive. In this article, the structure and function of CD47, common CD47 ligands, the relationship between CD47 and kidney transplantation, and the application of CD47 in kidney transplantation were reviewed, the latest research progress of CD47 in kidney transplantation was summarized, and the limitations of current research and subsequent research direction were analyzed, aiming to provide reference for subsequent application of CD47 in allogeneic and kidney xenotransplantation.

Circular RNA(circRNA)represents a unique class of closed-loop structured non-coding RNAs involved in various biological processes such as cell proliferation,differentiation,and apopto-sis.They play a significant role in the development of numerous diseases,and also serve as poten-tial biomarkers and therapeutic targets.To explore the impact of circRNA on viral replication,this study performed an omics measurement and analysis of circRNA differential expression in MC38 cells infected with HY12 enterovirus.It was found that,following HY12 virus infection,the ex-pressionlevels of 570 circRNAs were upregulated,while 381 circRNAs were downregulated.A-mong the upregulated circRNAs,the significantly upregulated circRNA mmu_circ_0001083 was selected for further investigation into its association with HY12 infection and its impact on viral replication.The results indicated that after HY12 virus infection,the expression of host circRNA mmu_circ_0001083 significantly increased,and its expression level was dependent on the virus dos-age and time.Compared to normal MC38 cells infected with the HY12 virus,cells with knocked down expression of circRNA mmu_circ_0001083 showed reduced expression of the 2C protein and significantly lower viral titers.Conversely,after HY12 virus infection in MC38 cells with overexpressed circRNA mmu_circ_0001083,there was an increase in the expression of the 2C pro-tein and a significant rise in viral titers.These results suggest that the upregulation of host cir-cRNA mmu_circ_0001083 is significantly positively correlated with the replication of HY12 virus,meaning mmu_circ_0001083 plays a positive regulatory role in the replication of HY12.This find-ing lays a foundation for future in-depth studies on the regulatory mechanisms of circRNA on viral replication.

The NMGCF-19 strain is an E.coli strain isolated and identified in our laboratory from lambs manifesting severe diarrhea and meningitis.Previous analysis of the genome sequence of NMGCF-19 strain showed that the outer membrane protein A(ompA)gene was a potential viru-lent gene.In order to determine whether the ompA gene is associated with the pathogenicity of NMGCF-19 strain and the underlying mechanism,the NMGCF-19 strain with ompA knockout(NMGCF-19△ompA)was generated in this study using CRISPR/Cas9 technology and used to de-termine the role of ompA gene in mediating the encephalitis by NMGCF-19 infection and the un-derlying mechanism using the mouse model system.The results showed that the neuronal cell nec-rosis in the hippocampus in mice infected by NMGCF-19△ompA was significantly reduced and was not focal compared with that of mice infected with the wild-type NMGCF-19 strain.The number of bacteria in brain of mice infected by NMGCF-19 △ompA was significantly reduced in comparison to that of mice infected by NMGCF-19.Simultaneously,the mRNA and protein expression levels of the tight junction proteins ZO-1 and Occludin were both increased in mice infected by NMGCF-19 △ompA strain compared with the mice infected by NMGCF-19 strain.These results suggest that the ompA gene is a virulent gene and plays an important role in the invasion of the blood-brain barrier by NMGCF-19 strain in mice.

A recombinant enzyme-mediated nucleic acid amplification(RAA)technology combined with colloidal gold test strips was developed for the rapid detection of bovine enterovirus(BEV).Using the highly conserved BEV 5'UTR as the target sequence,the primers were designed and screened.Downstream primer labeled with biotin at the 5'end and the probe labeled with 6-FAM at the 5'end were used to establish the RT-RAA method.The test strips were assembled by using mouse-derived anti-6-FAM monoclonal antibody as the gold standard antibody,with a streptavidin encapsulated in the detection line and sheep anti-mouse IgG encapsulated in the quality control line.A RT-RAA-LFD method was established by combing RAA technique with the prepared later-al flow device test strips for the detection of bovine enterovirus nucleic acids.The specificity,sensi-tivity,repeatability,and clinical application of the method are also evaluated.The results showed that the optimal primer concentration of this method was 5 μmol/L,and the amplification of BEV nucleic acids was accomplished by reacting at 35 ℃ for 8 min with the lowest detection limit of 101 copies/μL.No cross-reactivity with bovine viral diarrhea virus,bovine parvovirus,and foot-and-mouth disease virus was observed.The efficacy for the prepared test strips was at least for 90 d kept at 4 ℃.Detection of 74 clinical samples yielded a similar result compared with RT-PCR method.The above results demonstrated that the BEV RT-RAA-LFD method established in this study has high sensitivity,specificity,and more convenient to use,which is suitable for clinical de-tection on-site and provides a new technical tool for the diagnosis and epidemiological investigation of BEV infection.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*

Prenatal care services are an important part of my country's public health services, and play an important role in enhancing the pregnancy and childbirth experience of urban migrant women and improving their pregnancy and childbirth outcomes. The accessibility of prenatal care services is an important indicator for evaluating the equalization of basic public services. This paper outlines the concept and measurement dimensions of the accessibility of prenatal care services. This paper also analyzes the factors affecting the accessibility of prenatal care services for urban migrant women in my country from the perspectives of service providers, demanders, and both parties, and proposes strategies to improve the accessibility of prenatal care services for urban migrant women.

Objective:To explore the preparation and preliminary research on the characteristics of modified nano-bioglass hydrogel.Methods:(1) The nano-bioglass suspension was prepared by adding 67 mL nano-silica suspension into 400 mL saturated calcium hydroxide solution, and its suspension stability was observed. (2) The hydrogel with final mass fraction of 10% gelatin and 1% sodium alginate was prepared and set as control group. On the basis of the hydrogel in control group, the nano-bioglass suspension prepared in experiment (1) was added to prepare the hydrogel with the final mass fraction of 0.5% bioglass, 10% gelatin, and 1% sodium alginate, and the hydrogel was set as the experimental group. The gelling time at 4 and 25 ℃and the dissolution time at 37 ℃ of hydrogel in 2 groups were recorded, and the gelation at 4 and 25 ℃and dissolution condition at 37 ℃of the hydrogel in 2 groups were observed. The hydrogel in 2 groups were collected and cross-linked with 25 g/L calcium chloride solution after cold bath at 4 ℃, and the compression modulus was measured by Young′s modulus tester. In addition, the hydrogel in 2 groups were collected and cross-linked as before, and freeze-drying hydrogel was made at -20 ℃. The relative volumes were measured and the porosity of hydrogel in 2 groups was calculated. The number of sample in the experiment was 3. (3) Fibroblasts (Fbs) were isolated and cultured from 12 C57BL/6J mice of 24 hours old and the morphology was observed by inverted microscope, and the third passage of Fbs were cultured for the following experiment. Fbs were collected to make single cell suspension with the cell concentration of 1×10 5/mL. The single cell suspension was divided into experimental group and control group according the random number table (the same grouping method below), which were added with hydrogel in experimental group and control group prepared in experiment (2), respectively. At culture hour 12, 24, and 48, cells of 3 wells in each group were collected to detect the survival rate by cell counting kit 8 method. (4) The third passage Fbs were collected to prepare the single cell suspension with the cell concentration of (3.0~4.5)×10 7/mL, which was divided into experimental group and control group, with 1 tube in each group. The single cell suspension in 2 groups were added with green fluorescent probe DIO for staining and then added with 9 mL hydrogel in experimental group and control group prepared in experiment (2), respectively. The mixed solution of Fbs and hydrogel in 2 groups was cross-linked as before to make cell-loaded hydrogel. On culture day 3, the survival of cells in the hydrogel was observed by laser confocal microscope. The cell-loaded hydrogel was prepared as before and without added with green fluorescent probe DIO. On culture day 7, the adhesion and extension of cells in the hydrogel were observed by scanning electron microscope. (5) Twelve 6-week-old female BALB/c-nu nude mice were collected and divided into experimental group and control group, with 6 mice in each group. A round full-thickness skin defect wound with diameter of 1 cm was made on the back of each mouse. Immediately after injury, one cell-loaded hydrogel block in the experimental group and the control group prepared in experiment (4) was placed in the wound of each mouse in the experimental group and the control group, respectively. On post injury day (PID) 7 and 14, 3 nude mice in each group were sacrificed to collect the wound and wound margin tissue, which was stained with hematoxylin-eosin to observe the wound healing. Data were statistically analyzed with independent sample t test. Results:(1) The nano-bioglass particles could be uniformly dispersed in water and had good suspension stability. (2) The hydrogels of the 2 groups were molten at 37 ℃, and no precipitation of particle was observed. The dissolving time of the hydrogel in the experimental group and the control group at 37 ℃ was 5 and 10 min, respectively. The gelation time of the hydrogel in the experimental group and the control group at 25 ℃ was 30 and 180 min, respectively, and the gelation time of the 2 groups at 4 ℃ was 5 and 10 min, respectively. The compression modulus of hydrogel in the experimental group was (53±6) kPa, which was significantly higher than (23±6) kPa in the control group ( t=6.364, P<0.01). The porosity of the hydrogel in the experimental group was (86.1±2.1)%, which was similar to (88.2±4.4)% in the control group ( t=1.210, P>0.05). (3) The cells were in long fusiform, and the proportion of nuclei was high, which was accorded with the morphological characteristics of Fbs. At culture hour 12, 24, and 48, the survival rate of cells in the experimental group was (84±4)%, (89±4)%, and (130±10)%, which was similar to (89±5)%, (90±4)%, and (130±11)% in the control group, respectively ( t=1. 534, 0.611, 0.148, P>0.05). (4) On culture day 3, the cells in the two groups had complete morphology in the hydrogel, no nuclear lysis or disappearance were observed, the cytoplasm remained intact, and the fluorescence intensity of the cells in the experimental group was significantly stronger than that in the control group. On culture day 7, the cells in the experimental group and the control group adhered and stretched in the hydrogel, and the number of cells in the experimental group adhered to the hydrogel was significantly more than that in the control group. On PID 7, the wound area of the nude mice in the control group and the experimental group were reduced, the reduction area of mice in the experimental group was more obvious, and a large amount of inflammatory cells were seen in and around the wound in the 2 groups. On PID 14, the wound area of the nude mice in the control group was larger than that of the experimental group, and the number of inflammatory cells in and around the wound was significantly more than that in the experimental group. Conclusions:Nano-bioglass hydrogel possesses good physical, chemical, and biological properties, cell loading potential, and the ability to promote wound healing, which means it has a good potential in clinical application.

Objective: To explore the correlation between serum high density lipoprotein (HDL) levels and cognitive function in patients with bipolar disorder. Methods: A total of 99 patients with bipolar disorder were enrolled from the inpatient of Suzhou Guangji Hospital.Serum HDL levels were measured by enzymatic colourimetry.Cognitive function was assessed by the repeatable battery for the assessment of neuropsychological status (RBANS). The relationship between serum high density lipoprotein and cognitive function was analyzed by correlation analysis and stepwise multiple regression analysis. Results: Serum HDL levels ((1.39±0.55)mmol/L)were positively correlated with the RBANS total score (68.92±12.48)(r=0.238, P=0.034) and language score(80.59±15.97) (r=0.239, P=0.033) in patients with bipolar disorder.Stepwise multiple regression analysis showed that serum HDL level was the influencing factor of total score of RBANS(β=4.791, t=2.151, P=0.035)and speech function(β=7.363, t=2.247, P=0.027). Conclusion Serum HDL levels can influence cognitive function, especially speech function in patients with bipolar disorder.