Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

Objective To explore the role of zinc finger protein 36 (ZFP36) in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and preosteoblasts. Methods ZFP36 expression was observed in primary mouse BMSCs and mouse preosteoblasts (MC3T3-E1 cells) during induced osteogenic differentiation. Zfp36-deficient cell models were constructed in the two cells using RNA interference technique and the changes in differentiation capacities of the transfected cells into osteoblasts were observed. Transcriptome sequencing was used to investigate the potential mechanisms of ZFP36 for regulating osteoblast differentiation of the two cells. U0126, a ERK/MAPK signal suppressor, was used to verify the regulatory mechanism of Zfp36 in osteogenic differentiation of Zfp36-deficient cells. Results During the 14-day induction of osteogenic differentiation, both mouse BMSCs and MC3T3-E1 cells exhibited increased expression of ZFP36, and its mRNA expression reached the peak level on Day 7 (P<0.0001). The Zfp36-deficient cell models showed reduced intensity of alkaline phosphatase (ALP) staining and alizarin red staining with significantly lowered expressions of the osteogenic marker genes including Alpl, Sp7, Bglap and Ibsp (P<0.01). Transcriptome sequencing verified the reduction of bone mineralization-related gene expressions in Zfp36-deficient cells and indicated the involvement of ERK signaling in the potential regulatory mechanism of Zfp36. Immunoblotting showed that pERK protein expression increased significantly in Zfp36-deficient cells compared with the control cells. In Zfp36-deficient MC3T3-E1 cells, inhibition of activated ERK/MAPK signaling with U0126 resulted in obviously enhanced ALP staining and significantly increased expressions of osteoblast differentiation markers Runx2 and Bglap (P<0.05). Conclusions ZFP36 is involved in the regulation of osteoblast differentiation of mouse BMSCs and preosteoblasts, and ZFP36 deficiency causes inhibition of osteoblast differentiation of the cells by activating the ERK/MAPK signaling pathway.

The elucidation of resources pertaining to the Chimonanthus praecox varieties and the establishment of a fingerprint serve as crucial underpinnings for advancing scientific inquiry and industrial progress in relation to C. praecox. Employing the SSR molecular marker technology, an exploration of the genetic diversity of 175 C. praecox varieties (lines) in the Yanling region was conducted, and an analysis of the genetic diversity among these varieties was carried out using the UPDM clustering method in NTSYSpc 2.1 software. We analyzed the genetic structure of 175 germplasm using Structure v2.3.3 software based on a Bayesian model. General linear model (GLM) association was utilized to analyze traits and markers. The genetic diversity analysis revealed a mean number of alleles (Na) of 6.857, a mean expected heterozygosity (He) of 0.496 3, a mean observed heterozygosity (Ho) of 0.503 7, a mean genetic diversity index of Nei՚s of 0.494 9, and a mean Shannon information index of 0.995 8. These results suggest that the C. praecox population in Yanling exhibits a rich genetic diversity. Additionally, the population structure and the UPDM clustering were examined. In the GLM model, a total of fifteen marker loci exhibited significant (P < 0.05) association with eight phenotypic traits, with the explained phenotypic variation ranging from 14.90% to 36.03%. The construction of fingerprints for C. praecox varieties (lines) was accomplished by utilizing eleven primer pairs with the highest polymorphic information content, resulting in the analysis of 175 SSR markers. The present study offers a thorough examination of the genetic diversity and SSR molecular markers of C. praecox in Yanling, and establishes a fundamental germplasm repository of C. praecox, thereby furnishing theoretical underpinnings for the selection and cultivation of novel and superior C. praecox varieties, varietal identification, and resource preservation and exploitation.
Bayes Theorem ; Biomarkers ; Phenotype ; Cluster Analysis ; Genetic Variation

Purpose/Significance To explore the feasibility of applying blockchain technology to the current healthcare system of hos-pitals,and to achieve the purpose of protecting patients'privacy to the greatest extent possible at a lower cost.Method/Process 505 questionnaires are randomly distributed and collected from people of different age groups in Beijing,Tianjin,Shanghai and Shenzhen who have a certain degree of understanding of blockchain technology,and the results are analyzed.Result/Conclusion Different age groups are highly concerned about personal privacy and privacy protection,and are willing to accept blockchain as an emerging technology.There is a greater demand and acceptance for the application of blockchain technology in the primary health care systems.

The endothelial glycocalyx(EG)is a polyglycoprotein complex present on the internal vascular surface,and its impairment is associated with the progression of multiple diseases,including atherosclerosis,stroke,sepsis,diabetes,kidney disease,hypertension,and lung edema.Therefore,glycocalyx health can be used as a biomarker to evaluate vascular health.Aging leads to dysfunctional changes in the glycocalyx;for example,its thickness decreases,and the genes of enzymes involved in its synthesis and digestion are dysregulated.As a natural barrier to the vascular system,age-related glycocalyx disruption is associated with vascular dysfunction,including impairment of vascular contraction and dilation,enhancement of permeability,dysregulation of inflammatory and immune reactions,and imbalance of anticoagulation and thrombin.From the perspective of'structure determines function'studies on the changing regularity of the thickness,components,microstructure,and mechanical properties of EG with aging and its relationship with vascular dysfunction are of great significance for the prevention,diagnosis,and treatment of atherosclerosis and other age-related cardiovascular diseases.

Objective:To analyze the association between zygomatic change and bone setback or resection and propose a quantitative guidance for L-shaped reduction malarplasty by linear regression analysis based on computed tomographic (CT) scan images.Methods:A retrospective observational study was conducted on patients who underwent L-shaped reduction malarplasty with mortice and tenon joint at the zygomatic arch in Department of Orthognathic and Temporomandibular Joint Surgery, West China Hospital of Stomatology, Sichuan University from January 2017 to September 2022. Bone setback and resection were performed in cases required a classical L-shaped osteoectomy with oblique bone resection (Group Ⅰ). Bone setback was performed in cases required a modified L-shaped osteotomy without bone resection (Group Ⅱ). Wound healing and the occurrence of complications were followed up after operation. The amount of bone setback and resection were calculated by using preoperative and postoperative CT scan images. The unilateral width changes of the anterior, middle, and posterior zygomatic regions(ΔZBP-MFP, ΔZMP-MFP, ΔZAP-MFP, respectively) as well as zygomatic protrusion change(Δzygomatic protrusion) were also evaluated. SPSS 20.0 software was used for statistical analysis. The measurement data was expressed as Mean±SD. Zygomatic width and protrusion change of the two groups was compared by independent t-test. Comparison of complication rates between the two groups was performed using the χ2 test. Correlation analysis using Pearson correlation coefficients was performed between bone resection or setback and zygomatic width or protrusion change. Linear regression analysis was also performed. Results:A total of 80 patients were enrolled. Group Ⅰ consisted of 40 patients [6 males and 34 females; aged (25.2±3.8) years, ranging from 19 to 33 years] who underwent a classical L-shaped osteotomy with both bone setback and resection, while Group Ⅱ consisted of 40 patients [10 males and 30 females; aged (26.0±3.0) years, ranging from 20 to 35 years] who underwent a modified L-shaped osteotomy with bone setback but without bone resection. All patients healed uneventfully during the follow-up period[(12.5±3.3) months, ranging from 5 to 20 months]. There was no significant difference in the incidence of complications such as infection, transient paresthesia, severe swelling and hematoma between the two groups ( P>0.05). No severe complications, such as facial asymmetry, sagging cheek, bone nonunion, were observed. All patients significantly improved facial contours. There was a statistically significant difference (all P<0.01) in ΔZBP-MFP [ (2.52±0.76) mm vs. (1.85±0.40) mm], ΔZMP-MFP [ (3.30±0.54) mm vs. (2.94±0.51) mm] and Δzygomatic protrusion [ (4.42±1.20) mm vs. (3.59±0.84) mm] between Group Ⅰ and Group Ⅱ. No statistical difference was found in ΔZAP-MFP ( P>0.05). Significant correlation was observed between the bone setback or resection and the changes of anterior, middle zygomatic width as well as protrusion in both the two groups ( r=0.60-0.92, all P<0.01), and the linear regression equation was established. The correlation between bone setback or resection and the posterior zygomatic width change was not significant ( P>0.05). Conclusion:There are linear correlations between the unilateral anterior, middle zygomatic width change, zygomatic protrusion change and the unilateral bone setback or resection. The linear regression equations can be used as a quantitative guidance for preoperative surgical planning.

Objective:To evaluate the stability of the zygomatic complex in reduction malarplasty (RM) with different fixation method.Methods:The clinical data of patients with zygomatic arch protrusion at the Department of Orthognathic and Temporomandibular Joint Surgery, West China Hospital of Stomatology, Sichuan University from January 2018 to January 2021 were analyzed retrospectively. All patients underwent L-shaped osteotomy reduction malarplasty which were divided into zygomatic body fixation (ZBF) and zygomatic arch fixation (ZAF) according to fixation technique. As for ZBF, there were 4 different groups including two bicortical screws (2LS), an L-shaped plate with one bicortical screw (LPLS), an L-shaped plate with short-wing on the zygoma (LPwZ) and an L-shaped plate with short-wing on the maxilla (LPwM). As for ZAF, there were 3 different groups including mortice-tenon (MT), 3-hole plate (3HP) and short screw (SS). CT imaging data of two postoperative periods (1 week later; 6 months later) were collected. ITK-SNAP and 3D Slicer software were applied to evaluate the difference in the displacement distance of relevant landmarks of the zygomatic complex, so as to compare the postoperative stability of RM under different fixation methods. Statistical analyses were performed using IBM SPSS Statistics, version 25.0, and Kruskal-Wallis method was used to compare the difference of relevant landmarks displacement distance between ZBF group and ZAF group. P<0.05 was considered statistically significant. Results:60 patients (120 zygomatic arches) who were composed of 21 men and 39 women, aged (27.1±4.9) years were included. There were 30 samples in each group of ZBF and 40 samples in each group of ZAF. Compared with the single L-shaped plate (LPwZ, LPwM) group, the displacement distance of zygomatic complex in 2LS and LPLS groups was shorter ( P<0.05). The three fixation method of zygomatic arch (MT, 3HP, SS) had similar effects on the displacement of zygomatic complex ( P>0.05). Conclusion:After RM, the "two-bridge" fixation method (2LS and LPLS) provides better stability than the single L-shaped plate. The stability of all ZAF is similar when combined with 2LS or LPLS.

Objective:To analyze the association between zygomatic change and bone setback or resection and propose a quantitative guidance for L-shaped reduction malarplasty by linear regression analysis based on computed tomographic (CT) scan images.Methods:A retrospective observational study was conducted on patients who underwent L-shaped reduction malarplasty with mortice and tenon joint at the zygomatic arch in Department of Orthognathic and Temporomandibular Joint Surgery, West China Hospital of Stomatology, Sichuan University from January 2017 to September 2022. Bone setback and resection were performed in cases required a classical L-shaped osteoectomy with oblique bone resection (Group Ⅰ). Bone setback was performed in cases required a modified L-shaped osteotomy without bone resection (Group Ⅱ). Wound healing and the occurrence of complications were followed up after operation. The amount of bone setback and resection were calculated by using preoperative and postoperative CT scan images. The unilateral width changes of the anterior, middle, and posterior zygomatic regions(ΔZBP-MFP, ΔZMP-MFP, ΔZAP-MFP, respectively) as well as zygomatic protrusion change(Δzygomatic protrusion) were also evaluated. SPSS 20.0 software was used for statistical analysis. The measurement data was expressed as Mean±SD. Zygomatic width and protrusion change of the two groups was compared by independent t-test. Comparison of complication rates between the two groups was performed using the χ2 test. Correlation analysis using Pearson correlation coefficients was performed between bone resection or setback and zygomatic width or protrusion change. Linear regression analysis was also performed. Results:A total of 80 patients were enrolled. Group Ⅰ consisted of 40 patients [6 males and 34 females; aged (25.2±3.8) years, ranging from 19 to 33 years] who underwent a classical L-shaped osteotomy with both bone setback and resection, while Group Ⅱ consisted of 40 patients [10 males and 30 females; aged (26.0±3.0) years, ranging from 20 to 35 years] who underwent a modified L-shaped osteotomy with bone setback but without bone resection. All patients healed uneventfully during the follow-up period[(12.5±3.3) months, ranging from 5 to 20 months]. There was no significant difference in the incidence of complications such as infection, transient paresthesia, severe swelling and hematoma between the two groups ( P>0.05). No severe complications, such as facial asymmetry, sagging cheek, bone nonunion, were observed. All patients significantly improved facial contours. There was a statistically significant difference (all P<0.01) in ΔZBP-MFP [ (2.52±0.76) mm vs. (1.85±0.40) mm], ΔZMP-MFP [ (3.30±0.54) mm vs. (2.94±0.51) mm] and Δzygomatic protrusion [ (4.42±1.20) mm vs. (3.59±0.84) mm] between Group Ⅰ and Group Ⅱ. No statistical difference was found in ΔZAP-MFP ( P>0.05). Significant correlation was observed between the bone setback or resection and the changes of anterior, middle zygomatic width as well as protrusion in both the two groups ( r=0.60-0.92, all P<0.01), and the linear regression equation was established. The correlation between bone setback or resection and the posterior zygomatic width change was not significant ( P>0.05). Conclusion:There are linear correlations between the unilateral anterior, middle zygomatic width change, zygomatic protrusion change and the unilateral bone setback or resection. The linear regression equations can be used as a quantitative guidance for preoperative surgical planning.

Objective:To evaluate the stability of the zygomatic complex in reduction malarplasty (RM) with different fixation method.Methods:The clinical data of patients with zygomatic arch protrusion at the Department of Orthognathic and Temporomandibular Joint Surgery, West China Hospital of Stomatology, Sichuan University from January 2018 to January 2021 were analyzed retrospectively. All patients underwent L-shaped osteotomy reduction malarplasty which were divided into zygomatic body fixation (ZBF) and zygomatic arch fixation (ZAF) according to fixation technique. As for ZBF, there were 4 different groups including two bicortical screws (2LS), an L-shaped plate with one bicortical screw (LPLS), an L-shaped plate with short-wing on the zygoma (LPwZ) and an L-shaped plate with short-wing on the maxilla (LPwM). As for ZAF, there were 3 different groups including mortice-tenon (MT), 3-hole plate (3HP) and short screw (SS). CT imaging data of two postoperative periods (1 week later; 6 months later) were collected. ITK-SNAP and 3D Slicer software were applied to evaluate the difference in the displacement distance of relevant landmarks of the zygomatic complex, so as to compare the postoperative stability of RM under different fixation methods. Statistical analyses were performed using IBM SPSS Statistics, version 25.0, and Kruskal-Wallis method was used to compare the difference of relevant landmarks displacement distance between ZBF group and ZAF group. P<0.05 was considered statistically significant. Results:60 patients (120 zygomatic arches) who were composed of 21 men and 39 women, aged (27.1±4.9) years were included. There were 30 samples in each group of ZBF and 40 samples in each group of ZAF. Compared with the single L-shaped plate (LPwZ, LPwM) group, the displacement distance of zygomatic complex in 2LS and LPLS groups was shorter ( P<0.05). The three fixation method of zygomatic arch (MT, 3HP, SS) had similar effects on the displacement of zygomatic complex ( P>0.05). Conclusion:After RM, the "two-bridge" fixation method (2LS and LPLS) provides better stability than the single L-shaped plate. The stability of all ZAF is similar when combined with 2LS or LPLS.

Objective To analyze thoracolumbar vertebral fractures(A3)treated by multiple manipulations using the finite element method and to explore the feasibility and advantages of the composite surgical method for treating thoracolumbar vertebral fractures(A3).Methods For three-dimensional reconstruction of thoracolumbar vertebral fractures(A3),the model was loaded with simulated hyperextension posture restoration,simple press restoration,press restoration under hyperextension posture,and composite manipulation.Subsequentially,the stress distribution of the model and displacement of the fractured vertebral body were observed.Results The equivalent stress under composite manipulation was 111.88 MPa,which was greater than that under other manipulations,and the stress under composite manipulation was more concentrated in the anterior and middle columns of the vertebral body.The peak stress under composite manipulation was 122.53 MPa,which was greater than that under other manipulations,and the stress was centrally distributed in fracture region of the fractured vertebral body.The fracture displacement under composite manipulation was 3.94 mm,which was greater than that under other manipulations,and the displacement distribution decreased from the posterior column to the anterior mid-column.The anterior longitudinal and intertransverse interligamentous ligaments of the fractured vertebral body experienced the greatest stress under composite manipulation,and the joint capsule ligaments experienced the greatest stress under hyperextension postural restoration,simple press restoration,and press restoration under the hyperextension posture.Conclusions Compound manipulation for treating thoracolumbar vertebral fractures(A3)has obvious advantages over other manipulative restorations and is a reasonable program for the current treatment of thoracolumbar vertebral fractures(A3).