BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

BACKGROUND:Autologous bone,allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic,but the rate of non-healing is still high.The key is to ignore the importance of periosteum in the bone healing process.In the early stage of the project,the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site,which promoted bone regeneration to a certain extent.However,the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells,resulting in the risk of inactivation or diffusion of delivered biological factors.Therefore,it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.OBJECTIVE:To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.METHODS:By combining L-polylactic acid-based microsol electrospinning,type Ⅰ collagen self-assembly and gel stem cell transplantation technology,a bionic periosteum(M@C-B)was constructed,in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects.The physicochemical properties of the periosteum were characterized by scanning electron microscopy,transmission electron microscopy,and Fourier transform infrared spectroscopy.A co-culture system was established between the bionic periosteum and macrophages,bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities.Finally,the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model.RESULTS AND CONCLUSION:(1)Transmission electron microscopy results showed that the micro-sol electrospinning(MS)formed a distinct core-shell structure.Scanning electron microscopy indicated that after the assembly of the collagen-l artificial periosteum(M@C)on the surface of the vascular endothelial growth factor-loaded micro-sol,a distinct"spider web-like"fibrous structure was deposited.Infrared spectroscopy further confirmed the successful self-assembly of collagen-l.Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group,maintaining internal vascular endothelial growth factor activity and sustained release.(2)Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum:MS,purely aligned poly(L-lactic acid)(PLLA)surface self-assembled collagen-l artificial periosteum(PLLA@C),and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-l-bone marrow mesenchymal stem cells artificial periosteum(M@C-B).Among them,the M@C-B group had the highest number of live cells and the fastest proliferation rate.(3)Alkaline phosphatase staining,alizarin red staining,and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells.Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups(MS and M@C-B)had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes,with the M@C-B group being the most prominent.(4)Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype.(5)In vivo studies further confirmed that the M@C-B group showed superior bone mineral density,trabecular thickness,relative bone volume,and trabecular spacing compared to other groups.(6)These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum,through the rapid regulation of the bone defect immune microenvironment by the collagen-l-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase,synergistically promotes bone healing.

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that Yersinia pestis LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and β-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.

Objectives:To compare the efficacy of unilateral biportal endoscopy(UBE)versus percutaneous endoscopy(PE)for treating cervical spondylotic radiculopathy(CSR)using meta-analysis.Methods:A compre-hensive search was conducted in PubMed,Embase,Cochrane Library,Web of Science,China National Knowl-edge Infrastructure(CNKI),Wanfang Database,and China Biomedical Literature Database for studies published since their inceptions up to June 2025 that reported clinical outcomes and complications of UBE and PE in the treatment of CSR.The Cochrane Risk of Bias tool was used to assess randomized controlled trials,while the Newcastle-Ottawa scale(NOS)was applied to evaluate retrospective studies.Outcome indicators were ex-tracted including visual analogue scale(VAS)scores for neck and upper limb pain,neck disability index(NDI),operative time,intraoperative blood loss,length of hospital stay,incision size,preoperative and postoperative serum creatine kinase(CK)and C-reactive protein(CRP)levels,and postoperative complications.Meta-analysis was performed using Review Manager 5.4 software.Results:A total of 10 literatures were included,all of which were retrospective studies,and six studies were 8 points of NOS scores,three studies were 7 points,and one study was 6 point,indicating moderate to high quality.The total sample comprised 782 patients(UBE:n=388;PE:n=394).Meta-analysis revealed no significant difference in operative time between groups[MD=-6.67,95％CI(-17.47,4.13),P=0.23].Intraoperative blood loss was significantly lower in the PE group[MD=10.86,95％CI(0.64,21.07),P=0.04].No significant difference was observed in postoperative length of hospital stay[MD=0.49,95％CI(-0.00,0.99),P=0.05].Incision size was significantly smaller in the PE group[MD=7.13,95％CI(1.76,12.50),P=0.009].There were no significant intergroup differences in postoperative CK[MD=1.25,95％CI(-5.08,7.75),P=0.70]or CRP levels[MD=-0.03,95％CI(-0.08,0.02),P=0.23].There was no significant difference in neck pain VAS scores at various timepoints between the two groups[MD=-0.07,95％CI(-0.17,0.04),P=0.20].However,the UBE group was significantly lower in upper limb pain VAS scores at 3 months postoperatively[MD=-0.14,95％CI(-0.26,-0.01),P=0.03].No significant differences were found in NDI scores across follow-up periods[MD=-0.24,95％CI(-0.50,0.02),P=0.07]or in complication rates[OR=1.02,95％CI(0.51,2.03),P=0.95].Conclusions:Both UBE and PE operations are effective and safe in the treatment of CSR.The PE technique is associated with less intraoperative blood loss and smaller incisions,while UBE provides superior improvement in upper limb pain at the 3-month follow-up.

Objective Examine and analyze the current situation of the construction of national regional medical centers for children in China,in order to provide reference for promoting the high-quality development of national regional medical centers for children and other categories.Methods Refer to literature and official websites of relevant national departments and hospitals to obtain the required data and establish an analysis database for children's national regional medical centers.Using PEST analysis method,conduct research from four perspectives:politics,economy,society,and technology.Results The development trend of national regional medical centers for children is good,with a favorable policy environment,increasing demand for children's medical and health services,and high social expectations.However,there are issues such as targeted support policies that need to be improved,varying levels of economic security,regional cultural conflicts,and differences in technological resource levels.Conclusion It is suggested to improve the targeted policy support system,establish a sound compensation mechanism,actively integrate into the overall development of regional society,and integrate the advantages of various technological resources.

There is a large gap between production and demand of plant oil in China, which leads to the heavy reliance on imports. Diacylglycerol acyltransferase (DGAT) and phospholipid: diacylglycerol acyltransferase (PDAT) are two key enzymes responsible for the synthesis of triacylglycerol, thereby affecting the yield and quality of plant oil. This paper comprehensively reviews the research progress in DGAT and PDAT in terms of their biological functions in plant oil synthesis, the molecular mechanisms of regulating plant lipid metabolism, growth, and development under stress, and their roles in driving oil synthesis under the background of synthetic biology. Furthermore, future research and application of DGAT and PDAT are prospected. This review aims to provide a basis for deeply understanding the molecular mechanism of plant oil synthesis and improving the quality and productivity of oil crops by the utilization of DGAT and PDAT genes.
Diacylglycerol O-Acyltransferase/physiology* ; Plant Oils/metabolism* ; Acyltransferases/metabolism* ; Lipid Metabolism/genetics* ; Gene Expression Regulation, Plant ; Triglycerides/biosynthesis*

Objectives:To compare the efficacy of unilateral biportal endoscopy(UBE)versus percutaneous endoscopy(PE)for treating cervical spondylotic radiculopathy(CSR)using meta-analysis.Methods:A compre-hensive search was conducted in PubMed,Embase,Cochrane Library,Web of Science,China National Knowl-edge Infrastructure(CNKI),Wanfang Database,and China Biomedical Literature Database for studies published since their inceptions up to June 2025 that reported clinical outcomes and complications of UBE and PE in the treatment of CSR.The Cochrane Risk of Bias tool was used to assess randomized controlled trials,while the Newcastle-Ottawa scale(NOS)was applied to evaluate retrospective studies.Outcome indicators were ex-tracted including visual analogue scale(VAS)scores for neck and upper limb pain,neck disability index(NDI),operative time,intraoperative blood loss,length of hospital stay,incision size,preoperative and postoperative serum creatine kinase(CK)and C-reactive protein(CRP)levels,and postoperative complications.Meta-analysis was performed using Review Manager 5.4 software.Results:A total of 10 literatures were included,all of which were retrospective studies,and six studies were 8 points of NOS scores,three studies were 7 points,and one study was 6 point,indicating moderate to high quality.The total sample comprised 782 patients(UBE:n=388;PE:n=394).Meta-analysis revealed no significant difference in operative time between groups[MD=-6.67,95％CI(-17.47,4.13),P=0.23].Intraoperative blood loss was significantly lower in the PE group[MD=10.86,95％CI(0.64,21.07),P=0.04].No significant difference was observed in postoperative length of hospital stay[MD=0.49,95％CI(-0.00,0.99),P=0.05].Incision size was significantly smaller in the PE group[MD=7.13,95％CI(1.76,12.50),P=0.009].There were no significant intergroup differences in postoperative CK[MD=1.25,95％CI(-5.08,7.75),P=0.70]or CRP levels[MD=-0.03,95％CI(-0.08,0.02),P=0.23].There was no significant difference in neck pain VAS scores at various timepoints between the two groups[MD=-0.07,95％CI(-0.17,0.04),P=0.20].However,the UBE group was significantly lower in upper limb pain VAS scores at 3 months postoperatively[MD=-0.14,95％CI(-0.26,-0.01),P=0.03].No significant differences were found in NDI scores across follow-up periods[MD=-0.24,95％CI(-0.50,0.02),P=0.07]or in complication rates[OR=1.02,95％CI(0.51,2.03),P=0.95].Conclusions:Both UBE and PE operations are effective and safe in the treatment of CSR.The PE technique is associated with less intraoperative blood loss and smaller incisions,while UBE provides superior improvement in upper limb pain at the 3-month follow-up.

Objective Examine and analyze the current situation of the construction of national regional medical centers for children in China,in order to provide reference for promoting the high-quality development of national regional medical centers for children and other categories.Methods Refer to literature and official websites of relevant national departments and hospitals to obtain the required data and establish an analysis database for children's national regional medical centers.Using PEST analysis method,conduct research from four perspectives:politics,economy,society,and technology.Results The development trend of national regional medical centers for children is good,with a favorable policy environment,increasing demand for children's medical and health services,and high social expectations.However,there are issues such as targeted support policies that need to be improved,varying levels of economic security,regional cultural conflicts,and differences in technological resource levels.Conclusion It is suggested to improve the targeted policy support system,establish a sound compensation mechanism,actively integrate into the overall development of regional society,and integrate the advantages of various technological resources.