Biocontrol of rusted root rot in Panax ginseng by a combination of extracts from Bacillus amyloliquefaciens YY8 crude protein and Enterobacteriaceae YY115 ethyl acetate.

BACKGROUND: Rusted root rot is one of the most common root diseases in Panax ginseng, and Cylindrocarpon destructans is one of the main pathogenic fungus. The objective of this study was to screen and explore the extracts of biocontrol bacteria isolated from ginseng rhizosphere soil against Cylindrocarpon destructans. RESULTS: Bacterial strains Bacillus amyloliquefaciens YY8 and Enterobacteriacea YY115 were isolated and found to exhibit in vitro antifungal activity against C. destructans. A combination of crude protein extract from B. amyloliquefaciens YY8 and ethyl acetate extract from Enterobacteriacea YY115 in a 6:4 ratio exhibited the strongest antifungal activity against C. destructans. Measurements of electrical conductivity, protein content, and nucleic acid content in suspension cultures of C. destructans treated with a mixture extracts indicated that the extracts disrupted the cell membranes of rusted root rot mycelia, resulting in the leakage of electrolytes, proteins, and nucleic acids from the cells, and ultimately inhibiting the growth of C. destructans. The combined extracts suppressed the infection of ginseng roots discs by C. destructans effectively. CONCLUSION: The extracts obtained from the two bacterial strains effectively inhibited C. destructans in P. ginseng. It can provide scientific basis for the development of new biological control pesticides, reduce the use of chemical pesticides, and promote the sustainable development of agriculture.

Melatonin ameliorates osteoarthritis rat cartilage injury by inhibiting matrix metalloproteinases and JAK2/STAT3 signaling pathway.

OBJECTIVE: To observe the effect of melatonin intervention on rat knee osteoarthritis (KOA) model and explore its mechanism. METHODS: A total of 81 Sprague-Dawley (SD) rats were employed. Haematoxylin and eosin (H&E) staining and safranin o-solid green staining were used to observe the changes of pathology in KOA, and inflammation factors in serum were detected by enzyme-linked immunosorbent assay (ELISA), type II collagen (Col-II) was detected by immunohistochemistry, chondrocyte apoptosis was detected by TdT-mediated dUTP nick-end labeling (TUNEL). The expression of matrix metalloproteinases (MMPs) and JAK2/STAT3 signaling were detected by western blot. RESULTS: Melatonin treatment ameliorated the histomorphology of knee joint in rats compared to the model group. The contents of TNF-α, IL-6, and IL-1ß in serum were decreased after melatonin treatment. In addition, compared to the model group, the positive expression of Col-II increased, the chondrocyte apoptosis decreased after melatonin treatment. Interestingly, the expression levels of MMP3, MMP9, MMP13, p-JAK2 and p-STAT3 decreased (p < 0.05). Importantly, melatonin combined with AG490 is significantly ameliorates histomorphology of knee joint, reduced cartilage loss compared with melatonin treatment alone. CONCLUSIONS: Melatonin treatment can effectively diminish the cartilage injury. Its mechanism may be related to protect the articular cartilage by reducing the release of inflammatory factors, inhibit the expression of MMPs and JAK2/STAT3 signaling.

Breakage risk of different sacroiliac screws in unilateral sacral fractures a finite element analysis.

OBJECTIVE: To compare the breakage risk of lengthened sacroiliac screws and ordinary sacroiliac screws to treat unilateral vertical sacral fractures and provide a reference for clinical application. METHODS: A finite element model of Tile C pelvic ring injury (unilateral type Denis II fracture of the sacrum) was produced. The sacral fractures were fixed with a lengthened sacroiliac screw and ordinary sacroiliac screw in 6 types of models. The maximal von Mises stresses and stress distributions of the two kinds of screws when standing on both feet were measured and compared. RESULTS: The maximal von Mises stress of the lengthened screw was less than that of the ordinary screw. Compared with ordinary screw, the stress distribution in the lengthened screw was more homogeneous. CONCLUSIONS: The breakage risk of screws fixed in double segments is lower than that of screws fixed in single segments, the breakage risk of lengthened screws is lower than that of ordinary screws, and the breakage risk of screws fixed in S2 segments is lower than that of screws fixed in S1 segments.

Biomechanical comparison of three minimally invasive fixations for unilateral pubic rami fractures.

BACKGROUND: To compare the mechanical characteristics of a percutaneous superior pubic intramedullary screw, percutaneous bridging plate and percutaneous screw-rod system of the anterior ring for the treatment of unilateral vertical pubic fractures to provide a reference for clinical application. METHODS: A finite element model of pelvic anterior ring injury (unilateral vertical pubic fracture) was produced. The fractures were fixed with a percutaneous superior pubic intramedullary screw, percutaneous bridging plate and percutaneous screw-rod system of the anterior ring and their combinations in 5 types of models. The fracture stabilities under vertical, bilateral and anterior-posterior load were quantified and compared based on the displacement of the hip joints' midpoint as quantificational index of fracture stability. RESULTS: In the condition of bilateral and anterior-posterior load, the vertical, bilateral and anterior-posterior displacements of the hip joints' midpoint of different models were significantly different respectively. In general, the displacements of the 5 pelvic anterior ring fixations were ranked from maximum to minimum as follows: bridging plate, pelvic anterior screw-rod system, combination of bridging plate and pelvic anterior screw-rod system, superior pubic intramedullary screw and combination of superior pubic intramedullary screw and pelvic anterior screw-rod system. CONCLUSION: For the fixation in unilateral pubic fractures of pelvic ring injury, the percutaneous superior pubic intramedullary screw is optimal, the percutaneous pelvic anterior screw-rod system is the second choice, and percutaneous bridging plate ranks the third. The percutaneous pelvic anterior screw-rod system can significantly increase fixation stability of the percutaneous superior pubic intramedullary screw and the percutaneous bridging plate.

[Mathematical analysis of the influences of femoral and tibial bone cuts on the dynamic alignment in total knee arthroplasty].

OBJECTIVE: To investigate the influences of the distal femoral cut, the anterior and posterior femoral cuts, the proximal tibial cut on the dynamic alignment of the lower extremity in total knee arthroplasty. METHODS: Based on the three-dimensional geometric model, imitating the flexion movement of the knee without axial rotation after total knee arthroplasty, the influence of each of the three bone cuts on the dynamic alignment was analyzed with the assumption of standard bone cuts of the other two and equality of the medial and lateral soft tissue balancing. The dynamic alignment was defined as the angle between the mechanical axis of the tibia and the sagittal plane of the body when the knee was in any angle of flexion. With two of the three major bone cuts standard, the track of the tibial movement was established when the other one bone cut deviated from the ideal section of angle A. Based on the principle of geometry, the mathematical formula were established to present the influences of three bone cuts on the dynamic alignment of the lower extremity. RESULTS: All of the three kinds of bone cuts in total knee arthroplasty influenced the dynamic alignment of the lower extremity not just in one static position, but during the whole range of motion. At the θ angle of knee flexion, the alignment of the lower extremity was arcsin(cosθsinA) when the varus/valgus femoral component alignment was A; the alignment of the lower extremity was arcsin(sinθsinA) when the rotational femoral component alignment was A; the alignment of the lower extremity was A when the varus/valgus tibial component alignment was A. CONCLUSION: The influences of the distal femoral cut, the anterior and posterior femoral cuts, the proximal tibial cut on the dynamic alignment of the lower extremity in total knee arthroplasty are dynamically changed during the flexion movement of the knee.

Femoral rotation influences dynamic alignment of the lower extremity in total knee arthroplasty.

PURPOSE: Besides the long-leg standing X-ray film focusing on static standing mechanical alignment of the lower extremity, dynamic alignment from full extension to 90° flexion after total knee arthroplasty (TKA) is rarely mentioned. Computer-assisted surgical technology enables surgeons to measure and assess knee behaviour during surgery. This study was designed to analyse the influences of femoral rotation on dynamic alignment of the lower extremity in TKA. METHODS: Seventy-six consecutive patients with end-stage knee osteoarthritis were enrolled. External rotation osteotomy of the distal femur during TKA was completed according to the pre-operative external rotation angle (ERA), intra-operative transepicondylar axis (TEA) and anteroposterior (AP) line. Passive dynamic alignment of the lower extremity during knee flexion was recorded. The variation trend of hip-knee-ankle (HKA) alignment and the influences of femoral external rotation osteotomy were analysed. RESULTS: Postoperative deviation of HKA alignment from 0° to 90° flexion was associated with the rotational alignment of the femoral component (r = -0.769, p < 0.001). Variation trend of HKA alignment during knee flexion tended to be varus, valgus and neutral according to the selected angle of external rotation osteotomy of the distal femur. CONCLUSION: External rotation osteotomy of the distal femur played a crucial role in determining dynamic HKA alignment in TKA.

Comparison of the risk of breakage of two kinds of sacroiliac screws in the treatment of bilateral sacral fractures.

PURPOSE: This study aimed at comparing the risk of breakage of lengthened sacroiliac screw and ordinary sacroiliac screw for the treatment of bilateral vertical sacral fractures to provide reference for clinical application. METHODS: A finite element model of type C pelvic ring injury (bilateral type Denis II fracture of sacrum) was produced. The bilateral sacral fractures were fixed with lengthened sacroiliac screw and ordinary sacroiliac screw in seven types of models, respectively. The maximal Von Mises stresses and stress distribution of the two kinds of screws in the case of standing on both feet were measured and compared. RESULTS: (1) Whether in lengthened sacroiliac screw or ordinary sacroiliac screw, the maximal Von Mises stress of screw fixation only in S1 segment is the largest, and the maximal Von Mises stress of screw fixation only in S2 segment is minor, and the maximal Von Mises stress of screw fixation in S1 and S2 segments, respectively, is the least. (2) When S1 and S2 were both fixed with ordinary screws, the maximal Von Mises stress of screw in S1 segment is larger than that of S2. When S1 and S2 were both fixed with lengthened screws, the maximal Von Mises stress of screw in S1 segment is similar to that of S2. (3) The maximal Von Mises stresses of bilateral symmetrical screws are similar. (4) When only S1 was fixed, the maximal Von Mises stress of lengthened screw is less than that of ordinary screw. When only S2 was fixed, the maximal Von Mises stress of lengthened screw is larger than that of ordinary screw. When S1 and S2 were both fixed, the maximal Von Mises stress of lengthened screw is slightly less than that of ordinary screw. (5) Whether in lengthened screw or ordinary screw, the stress concentrations all exhibited at the regions of screws corresponding to the sacral fracture regions and the part between sacral bilateral fracture lines. Compared with ordinary screw, the stress distribution in lengthened screw is more homogeneous. Whether in lengthened screw or ordinary screw, the stress distribution of only one sacral segment fixation is more concentrated than that of two sacral segments' fixation. When S1 and S2 were both fixed, the stress distribution of upper screw is more concentrated and that of lower screw is more homogeneous. CONCLUSION: In a finite elements simulated type C pelvic ring disruption (bilateral type Denis II sacral fracture), the breakage risk of screws fixed in double-segment bilaterally symmetrically is low, and the breakage risk of screws fixed in S2 segment is lower than that of S1 segment. The bilaterally symmetrical screw fixation in double-segment is strongly recommended to reduce the breakage risk of screws. In addition, the breakage risk of lengthened screws is lower than that of ordinary screws except when screws are fixed in only S2 segment, which merits attention.

Diabetes mellitus increases the incidence of deep vein thrombosis after total knee arthroplasty.

INTRODUCTION: Many patients undergoing total knee arthroplasty (TKA) have diabetes mellitus, which may increase the risk of deep vein thrombosis (DVT) after TKA. We therefore assessed whether diabetes mellitus increased the incidence of DVT within 14 days after TKA. MATERIALS AND METHODS: The incidence of DVT within 14 days of surgery was compared in diabetic and non-diabetic patients undergoing TKA in our hospital between June 2011 and February 2013. The relationships between diabetes mellitus and DVT were analyzed. RESULTS: Of the 358 enrolled patients, 70 (19.6%) had diabetes and 288 (80.4%) did not. DVT occurred within 14 days in 198 patients, 52 of 70 (74.3%) in the diabetes group and 146 of 288 (50.7%) in the non-diabetes group (p = 0.012). DVT of the contralateral leg was observed in 16 and 50 patients, respectively (p = 0.452). Logistic regression analysis showed that the risk of DVT was 2.71-fold higher in patients with than without diabetes mellitus (95% CI 1.183-6.212, p = 0.018). There were no significant differences in age, gender, hypertension, BMI, duration of surgery, intra-operative blood loss, and duration of tourniquet between the two groups. CONCLUSIONS: The incidence of DVT 14 days after TKA was significantly higher in patients with than without diabetes.

[Efficacies of percutaneous multiple needle puncturing for releasing hip adductor muscle during total hip arthroplasty].

OBJECTIVE: To summarize our experiences of applying percutaneous multiple needle puncturing technique for releasing adductor muscle during total hip arthroplasty (THA) for ischemic necrosis of femoral head and provide rationales for clinical practice. METHODS: From January 2008 to December 2012, 36 adult patients with ischemic necrosis of femoral head (36 hips) and 36 adult patients with femoral neck fracture (36 hips) were recruited. The group of ischemic necrosis of femoral head was designated as experiment group in which there were 29 males and 7 females with an average age of 67.9 (60-78) years. According to the Ficat system, there were type III (n = 24) and type IV (n = 12) . The affected leg shortening of this group prior to surgery was over 2 cm. The group of femoral neck fracture was selected as control group in which there were 16 males and 20 females with an average age of 70.1 (60-82) years. According to the Garden system, there were type III (n = 16) and type IV (n = 20). All cases underwent THA with Press-fit prosthesis. After fixing prosthetic components, leg length discrepancy was corrected. And percutaneous multiple needle puncturing was applied for releasing adductor muscle in experiment group. The follow-up period was 2 years. The safety and efficiency were evaluated by HHS (Harris Hip Score) and the range of motion (ROM) of hip extorsion and abduction. RESULTS: There was no occurrence of such early complications as palsy of obturator nerve, hematoma in adductor muscle area or serious deep vein embolism.No serious complications of deep infection, femoral head dislocation, recurrent adductor muscle contracture, prosthesis loosening, subsidence, excursion or penetration occurred up until the final follow-up. The range of hip motion of extorsion and abduction: (1) in experimental group, the postoperative ROM (abduction:44.9 ± 0.8, extorsion:45.1 ± 0.9) was significantly larger than that of preoperative (abduction: 30.0 ± 4.6, extorsion:31.5 ± 4.6) ; (2) the postoperative ROM of experimental group had no significant changes until the final follow-up (abduction: 44.7 ± 0.9, extorsion:45.25 ± 0.81); (3) at the last time of follow-up, no significant inter-group difference existed in ROM (abduction:44.86 ± 0.68, extorsion:45.6 ± 0.8). HHS: (1) in experimental group, HHS increased significantly from 39.64 ± 3.93 preoperatively to 82.8 ± 3.6 at 3 months postoperatively; (2) in two groups, HHS of 2 years postoperation (experimental group: 88.6 ± 4.1, control group: 89.1 ± 4.0) was significantly larger than that of 3 months postoperation (experimental group: 82.8 ± 3.6, control group:83.1 ± 3.1); (3) at the time of 3 months and 2 years postoperation, no significant inter-group difference existed in HHS. CONCLUSION: The technique percutaneous multiple needle puncturing for releasing adductor muscle during THA for ischemic necrosis of femoral head is both safe and efficacious. And it solves the problems of soft tissue balancing mini-invasiveness.

Human Mesenchymal Stem Cells Improve Angiogenesis and Bone Formation in Severed Finger Rats through SIRT1/Nrf2 Signaling.

BACKGROUND: This study employed a severed finger rat model to analyze the effects of human mesenchymal stem cells (MSCs) on angiogenesis, inflammatory response, apoptosis, and oxidative stress, to evaluate the possible mechanism of the repair effect of MSCs on severed finger (SF) rats. METHODS: Sixty Sprague-Dawley (SD) rats were categorized into five groups (n = 12). The pathological changes of severed finger tissues were investigated by Hematoxylin and eosin (H&E) staining on day 14 after the rats were sacrificed. The levels of inflammatory factors and oxidative stress factors were detected by ELISA. Terminal Deoxynucleotidyl Transferase (TdT) dUTP Nick End Labeling (TUNEL) was employed to assess the apoptosis of chondrocytes in severed finger tissues. The expression of osteocalcin (OCN), osteopontin (OPN), Collagen I (Col-1), and CD31 were detected by immunohistochemistry or immunofluorescence assay, respectively. The expression levels of related proteins were determined by western blot. RESULT: Our study presented evidence that MSCs treatment improved pathological changes of skin and bone tissue, diminished the inflammatory response, prevented oxidative stress injury, suppressed chondrocyte apoptosis, and promoted angiogenesis, and bone formation compared to the model group. In addition, EX527 treatment attenuated the effect of MSCs, SRT1720 and ML385 co-treatment also attenuated the effect of MSCs. Importantly, the MSCs treatment increased the expression of Sirtuin 1(SIRT1)/Nuclear factor erythroid2-related factor 2(Nrf2) relate proteins. CONCLUSION: Our study indicated that the mechanism of the effect of MSCs on a severed finger was related to the SIRT1/ Nrf2 signaling pathway.

Bipolar hip arthroplasty using conjoined tendon preserving posterior lateral approach in treatment of displaced femoral neck fractures.

BACKGROUND: Hip fractures account for 23.8% of all fractures in patients over the age of 75 years. More than half of these patients are older than 80 years. Bipolar hemiarthroplasty (BHA) was established as an effective management option for these patients. Various approaches can be used for the BHA procedure. However, there is a high risk of postoperative dislocation. The conjoined tendon-preserving posterior (CPP) lateral approach was introduced to reduce postoperative dislocation rates. AIM: To evaluate the effectiveness and safety of the CPP lateral approach for BHA in elderly patients. METHODS: We retrospectively analyzed medical data from 80 patients with displaced femoral neck fractures who underwent BHA. The patients were followed up for at least 1 year. Among the 80 patients, 57 (71.3%) were female. The time to operation averaged 2.3 d (range: 1-5 d). The mean age was 80.5 years (range: 67-90 years), and the mean body mass index was 24.9 kg/m2 (range: 17-36 kg/m2). According to the Garden classification, 42.5% of patients were type Ⅲ and 57.5% of patients were type Ⅳ. Uncemented bipolar hip prostheses were used for all patients. Torn conjoined tendons, dislocations, and adverse complications during and after surgery were recorded. RESULTS: The mean postoperative follow-up time was 15.3 months (range: 12-18 months). The average surgery time was 52 min (range: 40-70 min) with an average blood loss of 120 mL (range: 80-320 mL). The transfusion rate was 10% (8 of 80 patients). The gemellus inferior was torn in 4 patients (5%), while it was difficult to identify in 2 patients (2.5%) during surgery. The posterior capsule was punctured by the fractured femoral neck in 3 patients, but the conjoined tendon and the piriformis tendon remained intact. No patients had stem varus greater than 3 degrees or femoral fracture. There were no patients with stem subsidence more than 5 mm at the last follow-up. No postoperative dislocations were observed throughout the follow-up period. No significance was found between preoperative and postoperative mean Health Service System scores (87.30 ± 2.98 vs 86.10 ± 6.10, t = 1.89, P = 0.063). CONCLUSION: The CPP lateral approach can effectively reduce the incidence of postoperative dislocation without increasing perioperative complications. For surgeons familiar with the posterior lateral approach, there is no need for additional surgical instruments, and it does not increase surgical difficulty.

Knockdown of DAPK1 inhibits IL-1ß-induced inflammation and cartilage degradation in human chondrocytes by modulating the PEDF-mediated NF-κB and NLRP3 inflammasome pathway.

Osteoarthritis (OA) is a common joint disease that is characterized by inflammation and cartilage degradation. Death-associated protein kinase 1 (DAPK1) is a multi-domain serine/threonine kinase and has been reported to be involved in the progression of OA. However, its role and mechanism in OA remain unclear. Here, we found the expression of DAPK1 in OA cartilage tissues was higher than that in normal cartilage tissues. The expression of DAPK1 in chondrocytes was up-regulated by IL-1ß. Knockdown of DAPK1 promoted cell viability and anti-apoptotic protein expression, while it inhibited the apoptosis rate and pro-apoptotic protein expressions in IL-1ß-induced chondrocytes. In addition, DAPK1 inhibition reduced the levels of inflammatory cytokines and expressions of matrix metalloproteinases (MMPs), and increased the expressions of collagen II and aggrecan. The data of mechanistic investigation indicated that the expression of pigment epithelium-derived factor (PEDF) was positively regulated by DAPK1. Overexpression of PEDF attenuated the effects of DAPK1 knockdown on IL-1ß-induced cell viability, apoptosis, inflammation, and cartilage degradation. Furthermore, PEDF overexpression restored the activity of the NF-κB pathway and NLRP3 inflammasome after DAPK1 knockdown. Collectively, down-regulation of DAPK1 inhibited IL-1ß-induced inflammation and cartilage degradation via the PEDF-mediated NF-κB and NLRP3 inflammasome pathways.

Curcumin-Encapsulated Co-ZIF-8 for Ulcerative Colitis Therapy: ROS Scavenging and Macrophage Modulation Effects.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by the disruption of the intestinal epithelial barrier. This study described the synthesis and characterization of CCM-Co-ZIF-8, a novel composite material with enzyme-like activities similar to catalase, peroxidase, and superoxide dismutase. CCM-Co-ZIF-8 demonstrated the ability to scavenge reactive oxygen species that play a critical role in UC pathogenesis. In vitro studies using lipopolysaccharide-induced RAW264.7 cells showed that CCM-Co-ZIF-8 exhibited anti-inflammatory activity by promoting the transition of macrophages from an M1 to an M2 phenotype. In vivo experiments using a mouse model of UC demonstrated that CCM-Co-ZIF-8 suppressed the expression of proinflammatory cytokines. These findings suggested that CCM-Co-ZIF-8 might hold promise as a therapeutic strategy for the treatment of UC.

Diabetes mellitus and the incidence of deep vein thrombosis after total knee arthroplasty: a retrospective study.

We explored if there was an increased risk of DVT in patients with diabetes mellitus undergoing total knee arthroplasty within 14days followup. We reviewed 245 patients undergoing total knee arthroplasty in our hospital between 2003 and 2011. The incidence of DVT within 14days after operations was compared between diabetic patients and non-diabetic patients. There were 37 patients with DVT in the diabetes group and 88 in the non-diabetes group within 14days followup (p=0.002). The risk of DVT in patients with diabetes mellitus was 2.76 times the risk in patients without diabetes mellitus using logistic regression modeling (OR=2.76, p=0.003). Although it is still controversial, patients with diabetes had a higher incidence rate of DVT after total knee arthroplasty in our study.

Current and Novel Therapeutics for Articular Cartilage Repair and Regeneration.

Articular cartilage repair is a sophisticated process that has is being recently investigated. There are several different approaches that are currently reported to promote cartilage repair, like cell-based therapies, biologics, and physical therapy. Cell-based therapies involve the using stem cells or chondrocytes, which make up cartilage, to promote the growth of new cartilage. Biologics, like growth factors, are also being applied to enhance cartilage repair. Physical therapy, like exercise and weight-bearing activities, can also be used to promote cartilage repair by inducing new cartilage growth and improving joint function. Additionally, surgical options like osteochondral autograft, autologous chondrocyte implantation, microfracture, and others are also reported for cartilage regeneration. In the current literature review, we aim to provide an up-to-date discussion about these approaches and discuss the current research status.

Role of vascular endothelial growth factor B in nonalcoholic fatty liver disease and its potential value.

Nonalcoholic fatty liver disease (NAFLD) refers to fatty liver disease caused by liver injury factors other than alcohol. The disease is characterized by diffuse fat infiltration, including simple steatosis (no inflammatory fat deposition), nonalcoholic fatty hepatitis, liver fibrosis, and so on, which may cause liver cirrhosis, liver failure, and even liver cancer in the later stage of disease progression. At present, the pathogenesis of NAFLD is still being studied. The "two-hit" theory, represented by lipid metabolism disorder and inflammatory reactions, is gradually enriched by the "multiple-hit" theory, which includes multiple factors, such as insulin resistance and adipocyte dysfunction. In recent years, vascular endothelial growth factor B (VEGFB) has been reported to have the potential to regulate lipid metabolism and is expected to become a novel target for ameliorating metabolic diseases, such as obesity and type 2 diabetes. This review summarizes the regulatory role of VEGFB in the onset and development of NAFLD and illustrates its underlying molecular mechanism. In conclusion, the signaling pathway mediated by VEGFB in the liver may provide an innovative approach to the diagnosis and treatment of NAFLD.

Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion.

BACKGROUND: Impaired glucose tolerance (IGT) is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes. When IGT occurs, insulin sensitivity decreases, causing a reduction in insulin secretion and an increase in glucagon secretion. Recently, vascular endothelial growth factor B (VEGFB) has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity. Therefore, we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion, thus contributing to the prevention and cure of prediabetes. AIM: To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT. METHODS: We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression. Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay, and the protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) was determined using western blot. Further, mRNA expression of forkhead box protein O1, phosphoenolpyruvate carboxykinase, and glucose-6 phosphatase was detected via quantitative polymerase chain reaction, and the correlation between the expression of proteins was analyzed via bioinformatics. RESULTS: In mice with IGT and VEGFB knockout, glucagon secretion increased, and the protein expression of PI3K/AKT decreased dramatically. Further, in mice with VEGFB overexpression, glucagon levels declined, with the activation of the PI3K/AKT signaling pathway. CONCLUSION: VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

Superlarge living hyaline cartilage graft contributed by the scale-changed porous 3D culture system for joint defect repair.

It is known that an excellent hyaline cartilage phenotype, an internal microstructure with safe crosslinking and available size flexibility are the key factors of cartilage grafts that allow for clinical application. Living hyaline cartilage grafts (LhCGs) constructed by phase-transfer hydrogel (PTCC) systems were reported to have a hyaline phenotype and bionic microstructure. By employing chondrocytes to secrete matrix in the hydrogel and then removing the material to obtain material-free tissuein vitro, LhCG technology exhibited superior performance in cartilage repair. However, PTCC systems could only produce small-sized LhCGs because of medium delivery limitations, which hinders the clinical application of LhCGs. In this study, we prepared three different noncrosslinked gelatin microspheres with diameters from 200 µm to 500 µm, which replaced the original pore-forming agent. The new PTCC system with the mixed and gradient porous structure was used for the preparation of superlarge LhCGs with a continuous structure and hyaline phenotype. Compared to the original technique, the porous gradient structure promoted nutrient delivery and cartilage matrix secretion. The small size of the microporous structure promoted the rapid formation of matrix junctions. The experimental group with a mixed gradient increased cartilage matrix secretion significantly by more than 50% compared to the that of the control. The LhCG final area reached 7 cm2without obvious matrix stratification in the mixed gradient group. The design of the scale-changed porous PTCC system will make LhCGs more promising for clinical application.

An Efficient Voltammetric Sensor Based on Graphene Oxide-Decorated Binary Transition Metal Oxides Bi2O3/MnO2 for Trace Determination of Lead Ions.

Herein we present a facile synthesis of the graphene oxide-decorated binary transition metal oxides of Bi2O3 and MnO2 nanocomposites (Bi2O3/MnO2/GO) and their applications in the voltammetric detection of lead ions (Pb2+) in water samples. The surface morphologies, crystal structures, electroactive surface area, and charge transferred resistance of the Bi2O3/MnO2/GO nanocomposites were investigated through the scanning electron microscopy (SEM), power X-ray diffraction (XRD), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) techniques, respectively. The Bi2O3/MnO2/GO nanocomposites were further decorated onto the surface of a glassy carbon electrode (GCE), and Pb2+ was quantitatively analyzed by using square-wave anodic stripping voltammetry (SWASV). We explored the effect of the analytical parameters, including deposition potential, deposition time, and solution pH, on the stripping peak current of Pb2+. The Bi2O3/MnO2/GO nanocomposites enlarged the electroactive surface area and reduced the charge transferred resistance by significant amounts. Moreover, the synergistic enhancement effect of MnO2, Bi2O3 and GO endowed Bi2O3/MnO2/GO/GCE with extraordinary electrocatalytic activity toward Pb2+ stripping. Under optimal conditions, the Bi2O3/MnO2/GO/GCE showed a broad linear detection range (0.01-10 µM) toward Pb2+ detection, with a low limit of detection (LOD, 2.0 nM). The proposed Bi2O3/MnO2/GO/GCE electrode achieved an accurate detection of Pb2+ in water with good recoveries (95.5-105%).