Exercise ameliorates muscular excessive mitochondrial fission, insulin resistance and inflammation in diabetic rats via irisin/AMPK activation.

This study aimed to investigate the effects of exercise on excessive mitochondrial fission, insulin resistance, and inflammation in the muscles of diabetic rats. The role of the irisin/AMPK pathway in regulating exercise effects was also determined. Thirty-two 8-week-old male Wistar rats were randomly divided into four groups (n = 8 per group): one control group (Con) and three experimental groups. Type 2 diabetes mellitus (T2DM) was induced in the experimental groups via a high-fat diet followed by a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 30 mg/kg body weight. After T2DM induction, groups were assigned as sedentary (DM), subjected to 8 weeks of treadmill exercise training (Ex), or exercise training combined with 8-week cycloRGDyk treatment (ExRg). Upon completion of the last training session, all rats were euthanized and samples of fasting blood and soleus muscle were collected for analysis using ELISA, immunofluorescence, RT-qPCR, and Western blotting. Statistical differences between groups were analyzed using one-way ANOVA, and differences between two groups were assessed using t-tests. Our findings demonstrate that exercise training markedly ameliorated hyperglycaemia, hyperlipidaemia, and insulin resistance in diabetic rats (p < 0.05). It also mitigated the disarranged morphology and inflammation of skeletal muscle associated with T2DM (p < 0.05). Crucially, exercise training suppressed muscular excessive mitochondrial fission in the soleus muscle of diabetic rats (p < 0.05), and enhanced irisin and p-AMPK levels significantly (p < 0.05). However, exercise-induced irisin and p-AMPK expression were inhibited by cycloRGDyk treatment (p < 0.05). Furthermore, the administration of CycloRGDyk blocked the effects of exercise training in reducing excessive mitochondrial fission and inflammation in the soleus muscle of diabetic rats, as well as the positive effects of exercise training on improving hyperlipidemia and insulin sensitivity in diabetic rats (p < 0.05). These results indicate that regular exercise training effectively ameliorates insulin resistance and glucolipid metabolic dysfunction, and reduces inflammation in skeletal muscle. These benefits are partially mediated by reductions in mitochondrial fission through the irisin/AMPK signalling pathway.

A Novel Cervical Sagittal Classification for Asymptomatic Population Based on Cluster Analysis.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To propose a novel cervical sagittal classification for asymptomatic people so as to deepen the understanding of cervical sagittal alignment. SUMMARY OF BACKGROUND DATA: Cervical spine sagittal morphology varies in people. There is a lack of widely-accepted cervical sagittal classification method. METHODS: In all, 183 asymptomatic subjects were included. A series of global and segmental cervical sagittal parameters were measured. Subjects with cervical lordosis (CL)<0 degrees were incorporated directly into the kyphosis (K) group. For subjects with CL ≥0 degrees, a two-step cluster analysis was used to arrive at the optimal number of clusters. The results of the expressions for the subtypes were derived by graphing. The 60 randomly selected lateral cervical spine films were evaluated by 4 spine surgeons at 4-week intervals using our classification method, the Toyama classification method and the Donk classification method. The 3 classification methods' reliability was expressed by the intra-group correlation coefficient (ICC), and convenience was expressed by the measuring time. Finally, the distribution of 4 subtypes was depicted, and sagittal parameters were compared among subtypes. RESULTS: Four subtypes of the cervical spine were suggested: Large lordosis (LL): CL≥-1.5×T1 slope (TS)+70°; Small lordosis (SL): -1.5×TS+50°≤CL<-1.5×TS+70°; Straight (S): 0°≤CL<-1.5×TS+50°; and K: CL<0°. The measuring time for our classification method was significantly less than the Toyama classification method (P<0.001). Our classification method showed high inter-observer reliability (ICC=0.856) and high to excellent intra-observer reliability (ICC between 0.851 and 0.913). SL was the most common type (37.7%). Men had more LL type and women had more S type and K type. The proportion of S and K increased with age. Cervical sagittal parameters were significantly different among the subtypes except for C4 vertebral body (VB) angle (P=0.546), C2-C7 SVA (P=0.628) and NT (P=0.816). CONCLUSIONS: We proposed a novel cervical sagittal classification for an asymptomatic population, which proved to be simple to implement with satisfactory reliability.

Unified Cross-Structural Motion Retargeting for Humanoid Characters.

Motion retargeting for animation characters has potential applications in fields such as animation production and virtual reality. However, current methods either assume that the source and target characters have the same skeletal structure, or require designing and training specific model architectures for each structure. In this paper, we aim to address the challenge of motion retargeting across previously unseen skeletal structures with a unified dynamic graph network. The proposed approach utilizes a dynamic graph transformation module to dynamically transfer latent motion features to different structures. We also take into consideration for intricate hand movements and model both torso and hand joints as graphs in a unified manner for whole-body motion retargeting. Our model allows the use of motion data from different structures to train a unified model and learns cross-structural motion retargeting in an unsupervised manner with unpaired data. Experimental results demonstrate the superiority of the proposed method in terms of data efficiency and performance on both seen and unseen structures.

A novel visible-light-driven Z-scheme C3N5/BiVO4 heterostructure with enhanced photocatalytic degradation performance.

As a visible-light response semiconductor materials, bismuth vanadate (BiVO4) is extensively applied in photodegradation organic dye field. In this study, we synthesized C3N5 nanosheets and coupled with decahedral BiVO4 to construct a Z-scheme C3N5/BiVO4 heterostructure with close interface contact. By introducing C3N5 into BiVO4, the built Z-scheme transfer pathway provides silky channel for charge carrier migration between different moieties and enables photoexcited electrons and holes accumulated on the surface of BiVO4 and C3N5. The accelerated separation of charge carriers ensures C3N5/BiVO4 heterostructures with a powerful oxidation capacity compared with pure BiVO4. Due to the synergistic effect in Z-scheme heterostructure, the C3N5/BiVO4 demonstrated an improved photodegradation ability of rhodamine B (RhB) and methylene blue (MB) that of bare BiVO4.

miR-557 inhibits hepatocellular carcinoma progression through Wnt/ß-catenin signaling pathway by targeting RAB10.

Accumulating evidence suggests that aberrant miRNAs participate in carcinogenesis and progression of hepatocellular carcinoma (HCC). Abnormal miR-557 expression is reported to interfere with the progression of several human cancers. However, the potential roles of miR-557 in HCC remain largely unknown. In the current study, we found that miR-557 was down-regulated in HCC tissues and cell lines, and was closely related to recurrence and metastasis of HCC. Notably, overexpression of miR-557 inhibited proliferation, migration, invasion, epithelial-to-mesenchymal transition (EMT) progression, blocked cells in G0/G1 phase of MHCC-97H cells in vitro, and suppressed tumor growth in vivo. However, loss of miR-557 facilitated these parameters in Huh7 cells both in vitro and in vivo. Moreover, RAB10 was identified as a direct downstream target of miR-557 through its 3'-UTR. Furthermore, RAB10 re-expression or knockdown partially abolished the effects of miR-557 on proliferation, migration, invasion, and EMT progression of HCC cells. Mechanistically, overexpression of miR-557 suppressed Wnt/ß-catenin signaling by inhibiting GSK-3ß phosphorylation, increasing ß-catenin phosphorylation, and decreasing ß-catenin transport to the nucleus, while knockdown of miR-557 activated Wnt/ß-catenin signaling. Moreover, the TOP/FOP-Flash reporter assays showed that miR-557 overexpression or knockdown significantly suppressed or activated Wnt signaling activity, respectively. Additionally, low expression of miR-557 and high expression of RAB10 in HCC tissues was closely associated with tumor size, degree of differentiation, TNM stage and poor prognosis in HCC patients. Taken together, these results demonstrate that miR-557 blocks the progression of HCC via the Wnt/ß-catenin pathway by targeting RAB10.

Anatomical Brushite-Coated Mg-Nd-Zn-Zr Alloy Cage Promotes Cervical Fusion: One-Year Results in Goats.

In this study, an anatomical brushite-coated Mg-Nd-Zn-Zr alloy cage was fabricated for cervical fusion in goats. The purpose of this study was to investigate the cervical fusion effect and degradation characteristics of this cage in goats. The Mg-Nd-Zn-Zr alloy cage was fabricated based on anatomical studies, and brushite coating was prepared. Forty-five goats were divided into three groups, 15 in each group, and subjected to C2/3 anterior cervical decompression and fusion with tricortical bone graft, Mg-Nd-Zn-Zr alloy cage, or brushite-coated Mg-Nd-Zn-Zr alloy cage, respectively. Cervical radiographs and computed tomography (CT) were performed 3, 6, and 12 months postoperatively. Blood was collected for biocompatibility analysis and Mg2+ concentration tests. The cervical spine specimens were obtained at 3, 6, and 12 months postoperatively for biomechanical, micro-CT, scanning electron microscopy coupled with energy dispersive spectroscopy, laser ablation-inductively coupled plasma-time-of-flight mass spectrometry, and histological analysis. The liver and kidney tissues were obtained for hematoxylin and eosin staining 12 months after surgery for biosafety analysis. Imaging and histological analysis showed a gradual improvement in interbody fusion over time; the fusion effect of the brushite-coated Mg-Nd-Zn-Zr alloy cage was comparable to that of the tricortical bone graft, and both were superior to that of the Mg-Nd-Zn-Zr alloy cage. Biomechanical testing showed that the brushite-coated Mg-Nd-Zn-Zr alloy cage achieved better stability than the tricortical bone graft at 12 months postoperatively. Micro-CT showed that the brushite coating significantly decreases the corrosion rate of the Mg-Nd-Zn-Zr alloy cage. In vivo degradation analysis showed higher Ca and P deposition in the degradation products of the brushite-coated Mg-Nd-Zn-Zr alloy cage, and no hyperconcentration of Mg was detected. Biocompatibility analysis showed that both cages were safe for cervical fusion surgery in goats. To conclude, the anatomical brushite-coated Mg-Nd-Zn-Zr alloy cage can promote cervical fusion in goats, and the brushite-coated Mg-Nd-Zn-Zr alloy is a potential material for developing absorbable fusion cages.

Electrospun Composite PLLA-PPSB Nanofiber Nerve Conduits for Peripheral Nerve Defects Repair and Regeneration.

Peripheral nerve injury (PNI) is a common clinical problem and regenerating peripheral nerve defects remain a significant challenge. Poly(polyol sebacate) (PPS) polymers are developed as promising materials for biomedical applications due to their biodegradability, biocompatibility, elastomeric properties, and ease of production. However, the application of PPS-based biomaterials in nerve tissue engineering, especially in PNI repair, is limited. In this study, PPS-based composite nanofibers poly(l-lactic acid)-poly(polycaprolactone triol-co-sebacic acid-co-N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid sodium salt) (PLLA-PPSB) are aimed to construct through electrospinning and assess their in vitro biocompatibility with Schwann cells (SCs) and in vivo repair capabilities for peripheral nerve defects. For the first time, the biocompatibility and bioactivity of PPS-based nanomaterial are examined at the molecular, cellular, and animal levels for PNI repair. Electrospun PLLA-PPSB nanofibers display favorable physicochemical properties and biocompatibility, providing an effective interface for the proliferation, glial expression, and adhesion of SCs in vitro. In vivo experiments using a 10-mm rat sciatic nerve defect model show that PLLA-PPSB nanofiber nerve conduits enhance myelin formation, axonal regeneration, angiogenesis, and functional recovery. Transcriptome analysis and biological validation indicate that PLLA-PPSB nanofibers may promote SC proliferation by activating the PI3K/Akt signaling pathway. This suggests the promising potential of PLLA-PPSB nanomaterial for PNI repair.

C4 constant vertebra: a novel benchmark of physiological cervical sagittal alignment.

BACKGROUND: Cervical sagittal alignment is essential, and there is considerable debate as to what constitutes physiological sagittal alignment. The purpose of this study was to identify constant parameters for characterizing cervical sagittal alignment under physiological conditions. METHODS: A cross-sectional study was conducted in which asymptomatic subjects were recruited to undergo lateral cervical spine radiographs. Each subject was classified according to three authoritative cervical sagittal morphology classifications, followed by the evaluation of variations in radiological parameters across morphotypes. Moreover, the correlations among cervical sagittal parameters, age, and cervicothoracic junction parameters were also investigated. RESULTS: A total of 183 asymptomatic Chinese subjects were enrolled with a mean age of 48.4 years. Subjects with various cervical sagittal morphologies had comparable C4 endplate slope angles under all three different typing systems. Among patients of different ages, C2-C4 endplate slope angles remained constant. Regarding the cervicothoracic junction parameters, T1 slope and thoracic inlet angle affected cervical sagittal parameters, including cervical lordosis and C2-7 sagittal vertical axis, and were correlated with the endplate slope angles of C5 and below and did not affect the endplate slope angles of C4 and above. In general, the slope of the C4 inferior endplate ranges between 13° and 15° under different physiological conditions. CONCLUSIONS: In the asymptomatic population, the C4 vertebral body maintains a constant slope angle under physiological conditions. The novel concept of C4 as a constant vertebra would provide a vital benchmark for diagnosing pathological sagittal alignment abnormalities and planning the surgical reconstruction of cervical lordosis.

Exercise ameliorating myocardial injury in type 2 diabetic rats by inhibiting excessive mitochondrial fission involving increased irisin expression and AMP-activated protein kinase phosphorylation.

PURPOSE: Though exercise generates beneficial effects on diabetes-associated cardiac damage, the underlying mechanism is largely unclear. Therefore, we prescribed a program of 8-week treadmill training for type 2 diabetes mellitus (T2DM) rats and determined the role of irisin signaling, via interacting with AMP-activated protein kinase (AMPK), in mediating the effects of exercise on myocardial injuries and mitochondrial fission. METHODS: Forty 8-week-old male Wistar rats were randomly divided into groups of control (Con), diabetes mellitus (DM), diabetes plus exercise (Ex), and diabetes plus exercise and Cyclo RGDyk (ExRg). Ex and ExRg rats received 8 weeks of treadmill running, and the rats in the ExRg group additionally were treated with a twice weekly injection of Cyclo RGDyk, an irisin receptor-αV/ß5 antagonist. At the end of the experiment, murine blood samples and heart tissues were collected and analyzed with methods of ELISA, Western blot, real-time quantitative polymerase chain reaction, as well as immunofluorescence staining. RESULTS: Exercise effectively mitigated T2DM-related hyperglycemia, hyperinsulinemia, lipid dysmetabolism, and inflammation, which could be diminished by Cyclo RGDyk treatment. Additionally, exercise alleviated T2DM-induced myocardial injury and excessive mitochondrial fission, whereas the beneficial effects were blocked by the administration of Cyclo RGDyk. T2DM significantly decreased serum irisin concentrations and fibronectin type III domain-containing protein 5 (FNDC5)/irisin gene and protein expression levels in the rat heart, whereas exercise could rescue T2DM-reduced FNDC5/irisin expression. Blocking irisin receptor signaling diminished the exercise-alleviated mitochondrial fission protein expression and elevated AMPK phosphorylation. CONCLUSION: Exercise is effective in mitigating diabetes-related insulin resistance, metabolic dysfunction, and inflammation. Irisin signaling engages in exercise-associated beneficial effects on myocardial injury and excessive mitochondrial fission in diabetes rats involving elevated AMPK phosphorylation.

Comparison of short-term efficacy analysis of medium-rectal cancer surgery with robotic natural orifice specimen extraction and robotic transabdominal specimen extraction.

BACKGROUND: With the development of minimally invasive technology, the trauma caused by surgery get smaller, At the same time, the specimen extraction surgery through the natural orifice is more favored by experts domestically and abroad, robotic surgery has further promoted the development of specimen extraction surgery through the natural orifice. The aim of current study is to compare the short-term outcomes of robotic-assisted natural orifice specimen extraction (NOSES ) and transabdominal specimen extraction(TRSE ) in median rectal cancer surgery. METHODS: From January 2020 to January 2023, 87 patients who underwent the NOSES or TRSE at the First Affiliated Hospital of Nanchang University were included in the study, 4 patients were excluded due to liver metastasis. Of these, 50 patients were in the TRSE and 33 patients in the NOSES. Short-term efficacy was compared in the two groups. RESULTS: The NOSES group had less operation time (P < 0.001), faster recovery of gastrointestinal function (P < 0.001), shorter abdominal incisions (P < 0.001), lower pain scores(P < 0.001). lower Inflammatory indicators of the white blood cell count and C-reactive protein content at 1, 3, and 5 days after surgery (P < 0.001, P = 0.037). There were 9 complications in the NOSES group and 11 complications in the TRSE group(P = 0.583). However, there were no wound complications in the NOSES group. The number of postoperative hospital stays seems to be same in the two groups. And there was no significant difference in postoperative anus function (P = 0.591). CONCLUSIONS: This study shows that NOSES and TRSE can achieve similar radical treatment effects, NOSES is a feasible and safe way to take specimens for rectal cancer surgery in accordance with the indication for NOSES.

Regulating Relative Nitrogen Locations of Diazine Functionalized Covalent Organic Frameworks for Overall H2 O2 Photosynthesis.

Nitrogen-heterocycle-based covalent organic frameworks (COFs) are considered promising candidates for the overall photosynthesis of hydrogen peroxide (H2 O2 ). However, the effects of the relative nitrogen locations remain obscured and photocatalytic performances of COFs need to be further improved. Herein, a collection of COFs functionalized by various diazines including pyridazine, pyrimidine, and pyrazine have been judiciously designed and synthesized for photogeneration of H2 O2 without sacrificial agents. Compared with pyrimidine and pyrazine, pyridazine embedded in TpDz tends to stabilize endoperoxide intermediate species, leading toward the more efficient direct 2e- oxygen reduction reaction (ORR) pathway. Benefiting from the effective electron-hole separation, low charge transfer resistance, and high-efficiency ORR pathway, an excellent production rate of 7327 µmol g-1 h-1 and a solar-to-chemical conversion (SCC) value of 0.62 % has been achieved by TpDz, which ranks one of the best COF-based photocatalysts. This work might shed fresh light on the rational design of functional COFs targeting photocatalysts in H2 O2 production.

Exercise for prevention of falls and fall-related injuries in neurodegenerative diseases and aging-related risk conditions: a meta-analysis.

Introduction: Neurodegenerative diseases often cause motor and cognitive deterioration that leads to postural instability and motor impairment, while aging-associated frailty frequently results in reduced muscle mass, balance, and mobility. These conditions increase the risk of falls and injuries in these populations. This study aimed to determine the effects of exercise on falls and consequent injuries among individuals with neurodegenerative diseases and frail aging people. Methods: Electronic database searches were conducted in PubMed, Cochrane Library, SportDiscus, and Web of Science up to 1 January 2023. Randomized controlled trials that reported the effects of exercise on falls and fall-related injuries in neurodegenerative disease and frail aging people were eligible for inclusion. The intervention effects for falls, fractures, and injuries were evaluated by calculating the rate ratio (RaR) or risk ratio (RR) with 95% confidence interval (CI). Results: Sixty-four studies with 13,241 participants met the inclusion criteria. Exercise is effective in reducing falls for frail aging people (RaR, 0.75; 95% CI, 0.68-0.82) and participants with ND (0.53, 0.43-0.65) [dementia (0.64, 0.51-0.82), Parkinson's disease (0.49, 0.39-0.69), and stroke survivors (0.40, 0.27-0.57)]. Exercise also reduced fall-related injuries in ND patients (RR, 0.66; 95% CI, 0.48-0.90) and decreased fractures (0.63, 0.41-0.95) and fall-related injuries (0.89, 0.84-0.95) among frail aging people. For fall prevention, balance and combined exercise protocols are both effective, and either short-, moderate-, or long-term intervention duration is beneficial. More importantly, exercise only induced a very low injury rate per participant year (0.007%; 95% CI, 0-0.016) and show relatively good compliance with exercise (74.8; 95% CI, 69.7%-79.9%). Discussion: Exercise is effective in reducing neurodegenerative disease- and aging-associated falls and consequent injuries, suggesting that exercise is an effective and feasible strategy for the prevention of falls.

Comparison of robotic-assisted and laparoscopic-assisted natural orifice specimen extraction surgery in short-terms outcomes of middle rectal cancer.

BACKGROUND: Surgery is becoming less invasive as technology advances. Natural orifice specimen extraction surgery (NOSES) ushered in a new era of minimally invasive techniques. At the same time, NOSES is gaining popularity in the world. With their distinct advantages, surgical robots have advanced the development of NOSES. The aim of current study was to compare the short-term outcomes between robotic-assisted NOSES and laparoscopic-assisted NOSES for the treatment of middle rectal cancer. METHODS: Patients with middle rectal cancer who underwent robotic-assisted or laparoscopic-assisted NOSES at the First Affiliated Hospital of Nanchang University between January 2020 and June 2022 had their clinicopathological data collected retrospectively. 46 patients were enrolled in the study: 23 in the robotic group and 23 in the laparoscopic group. Short-term outcomes and postoperative anal function in the two groups were compared. RESULTS: There was no significant difference in the clinicopathological data between the two groups. The robotic group had less intraoperative blood loss (p = 0.04), less postoperative abdominal drainage (p = 0.02), lower postoperative white blood cell counts (p = 0.024) and C-reactive protein levels (p = 0.017), and shorter catheter removal time when compared to the laparoscopic group (p = 0.003). Furthermore, there were no significant difference in mean operative time (159 ± 31 min vs 172 ± 41 min) between the robotic and laparoscopic groups (p = 0.235), but time to naked the rectum (86.4 ± 20.9 min vs. 103.8 ± 31.5 min p = 0.033) and time of digestive tract reconstruction (15.6 ± 3.88 min vs. 22.1 ± 2.81 min p < 0.01) in the robotic group were significantly shorter than laparoscopic group. The robotic group had lower postoperative Wexner scores than the laparoscopic group. CONCLUSIONS: This research reveals that combining a robotic surgical system and NOSES results in superior outcomes, with short-term outcomes preferable to laparoscopic-assisted NOSES.

Brushite-coated Mg-Nd-Zn-Zr alloy promotes the osteogenesis of vertebral laminae through IGF2/PI3K/AKT signaling pathway.

Biodegradable magnesium (Mg) alloys have been extensively investigated in orthopedic implants due to their suitable mechanical strength and high biocompatibility. However, no studies have reported whether Mg alloys can be used to repair lamina defects, and the biological mechanisms regulating osteogenesis are not fully understood. The present study developed a lamina reconstruction device using our patented biodegradable Mg-Nd-Zn-Zr alloy (JDBM), and brushite (CaHPO4·2H2O, Dicalcium phosphate dihydrate, DCPD) coating was developed on the implant. Through in vitro and in vivo experiments, we evaluated the degradation behavior and biocompatibility of DCPD-JDBM. In addition, we explored the potential molecular mechanisms by which it regulates osteogenesis. In vitro, ion release and cytotoxicity tests revealed that DCPD-JDBM had better corrosion resistance and biocompatibility. We found that DCPD-JDBM extracts could promote MC3T3-E1 osteogenic differentiation via the IGF2/PI3K/AKT pathway. The lamina reconstruction device was implanted on a rat lumbar lamina defect model. Radiographic and histological analysis showed that DCPD-JDBM accelerated the repair of rat lamina defects and exhibited lower degradation rate compared to uncoated JDBM. Immunohistochemical and qRT-PCR results showed that DCPD-JDBM promoted osteogenesis in rat laminae via IGF2/PI3K/AKT pathway. This study shows that DCPD-JDBM is a promising biodegradable Mg-based material with great potential for clinical applications.

Transvaginal versus transabdominal specimen extraction surgery for right colon cancer: A propensity matching study.

Background: The transvaginal route for specimen extraction is considered ideal for colorectal surgery, but its safety is still questioned. There has been little research on transvaginal natural orifice specimen extraction surgery (NOSES) in the right hemicolectomy. As a result, we conducted a study comparing transvaginal NOSES to traditional transabdominal specimen extraction surgery. Patients and methods: Data on female patients who underwent radical right hemicolectomy at the First Affiliated Hospital of Nanchang University between January 2015 and December 2020 were collected retrospectively. A total of 847 patients were compliant, with 51 undergoing the transvaginal specimen extraction surgery (NOSES) group and 796 undergoing the transabdominal specimen extraction surgery (TISES) group. A propensity score matching method (1:2) was used to balance the clinicopathological characteristics of the two groups. Results: Finally, 138 patients were enrolled in our study, with 46 in the NOSES group and 92 in the TISES group. Compared to the TISES group, the NOSES group had less intraoperative blood loss (p = 0.036), shorter time to first flatus (p < 0.001), shorter time to first liquid diet (p < 0.001), lower postoperative white blood cell counts (p = 0.026), lower C-reactive protein levels (p = 0.027), and lower visual analog scale (VAS) scores (p < 0.001). Regarding the quality of life after surgery, the NOSES group had better role function (p < 0.01), emotional function (p < 0.001), and improved symptoms of postoperative pain (p < 0.001) and diarrhea (p = 0.024). The scar satisfaction was significantly higher in the NOSES group than in the TISES group. Overall survival and disease-free survival in two groups were similar. Conclusion: The short-term results of transvaginal NOSES were superior to conventional transabdominal specimen extraction surgery. At the same time, transvaginal NOSES could improve the abdominal wall appearance and quality of life. The long-term survival was similar in the two surgical approaches. Therefore, transvaginal NOSES is worthy of our implementation and promotion.

Technical Notes for Establishing a Cervical Fusion Model in Goats Based on Distinctive Anatomy.

Goat is an adequate experimental model for cervical spine testing. However, studies on the anatomy of the cervical spine in goats are limited, and there is no uniform standard for establishing a single-segment anterior cervical discectomy and fusion (ACDF) model in goats. To address this issue, we investigated the cervical spine anatomy of goats and provided a technical basis for establishing a single-segment ACDF model in goats. We measured the imaging anatomical parameters using Mimics Medical 20.0 software. We then performed histological analysis of the cervical spine segment 2-3 (C2-3) segment of six goat cervical spine specimens. Based on the measurements and histological analysis, the fusion cage was designed to be wedge-shaped, the length of the plate was 25 mm, and the length of the screw was 15 mm. Based on the anatomical characteristics of goats, we believed that the C2-3 segment of goats was most suitable for a single-segment ACDF model in goats, and the decompression should be performed medial to the pterygoid joint on both sides, the thickness of the removed endplate was ∼0.6 mm, the cage implanted in the anterior two-thirds of the intervertebral space could maximize the contact area of the cage-endplate interface, and the location of the midline spur could position the implantation of the internal fixtures. Radiological examination at 12 weeks postoperatively suggested that the internal fixtures were in place and new bone formation was visible. These results demonstrated that these technical notes based on anatomical features were practical and could minimize damage to animals.

TLR4 aggravates microglial pyroptosis by promoting DDX3X-mediated NLRP3 inflammasome activation via JAK2/STAT1 pathway after spinal cord injury.

BACKGROUND: Toll-like receptor 4 (TLR4) participates in the initiation of neuroinflammation in various neurological diseases, including central nervous system injuries. NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated microglial pyroptosis is crucial for the inflammatory response during secondary spinal cord injury (SCI). However, the underlying mechanism by which TLR4 regulates NLRP3 inflammasome activation and microglial pyroptosis after SCI remains uncertain. METHODS: We established an in vivo mouse model of SCI using TLR4-knockout (TLR4-KO) and wild-type (WT) mice. The levels of pyroptosis, tissue damage and neurological function recovery were evaluated in the three groups (Sham, SCI, SCI-TLR4-KO). To identify differentially expressed proteins, tandem mass tag (TMT)-based proteomics was conducted using spinal cord tissue between TLR4-KO and WT mice after SCI. For our in vitro model, mouse microglial BV2 cells were exposed to lipopolysaccharides (1 µg/ml, 8 h) and adenosine triphosphate (ATP) (5 mM, 2 h) to induce pyroptosis. A series of molecular biological experiments, including Western blot (WB), real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), immunofluorescence (IF), immunohistochemical (IHC), chromatin immunoprecipitation (ChIP), Dual-Luciferase Reporter assay (DLA) and co-immunoprecipitation (Co-IP), were performed to explore the specific mechanism of microglial pyroptosis in vivo and in vitro. RESULTS: Our results indicated that TLR4 promoted the expression of dead-box helicase 3 X-linked (DDX3X), which mediated NLRP3 inflammasome activation and microglial pyroptosis after SCI. Further analysis revealed that TLR4 upregulated the DDX3X/NLRP3 axis by activating the JAK2/STAT1 signalling pathway, and importantly, STAT1 was identified as a transcription factor promoting DDX3X expression. In addition, we found that biglycan was increased after SCI and interacted with TLR4 to jointly regulate microglial pyroptosis through the JAK2/STAT1/DDX3X/NLRP3 axis after SCI. CONCLUSION: Our study preliminarily identified a novel mechanism by which TLR4 regulates NLRP3 inflammasome-mediated microglial pyroptosis in response to SCI-providing a novel and promising therapeutic target for SCI.

Injectable pH-responsive adhesive hydrogels for bone tissue engineering inspired by the underwater attachment strategy of marine mussels.

A major challenge in tissue engineering is the development of alternatives to traditional bone autografts and allografts that can regenerate critical-sized bone defects. Here we present the design of injectable pH-responsive double-crosslinked adhesive hydrogels inspired by the molecular mechanism and environmental post-processing of marine mussel adhesive. Nine adhesive hydrogel formulations were developed through the conjugation of crosslinkable catechol functional groups (DOPA) and the synthetic oligomer oligo[poly(ethylene glycol) fumarate] (OPF), varying the DOPA content (w/w%) and molecular weight (MW) of the OPF backbone to produce formulations with a range of swelling ratios, porosities, and crosslink densities. DOPA incorporation altered the surface chemistry, mechanical properties, and surface topography of hydrogels, resulting in an increase in material stiffness, slower degradation, and enhanced pre-osteoblast cell attachment and proliferation. When injected within simulated bone defects, DOPA-mediated interfacial adhesive interactions also prevented the displacement of scaffolds, an effect that was maintained even after swelling within physiological conditions. Taken together, OPF-DOPA hydrogels represent a promising new material to enhanced tissue integration and the prevention of the post-implantation migration of scaffolds that can occur due to biomechanical loading in vivo.

Research Progress of Highly Efficient Noble Metal Catalysts for the Oxidation of 5-Hydroxymethylfurfural.

5-hydroxymethylfurfural (HMF) is considered to be one of the most pivotal multifunctional biomass platform chemicals. This Review discusses recent advances in catalytic oxidation of HMF towards high-value products. The reaction mechanism of different noble metals and the path of HMF oxidation to high-value products have been deeply investigated in the noble metal catalytic system. The reaction mechanisms of different noble metals and HMF conversion paths were compared in detail. Moreover, the factors affecting the performance of different noble metal catalysts were summarized. Finally, effective strategies were put forward to improve the catalytic performance of noble metal catalysts. The purpose is to provide a valuable reference for the academic research on the preparation of oxidation products from biomass-based HMF and the industrial application of noble metal catalysts.

Size-dependent osteogenesis of black phosphorus in nanocomposite hydrogel scaffolds.

A promising new strategy emerged in bone tissue engineering is to incorporate black phosphorus (BP) into polymer scaffolds, fabricating nanocomposite hydrogel platforms with biocompatibility, degradation controllability, and osteogenic capacity. BP quantum dot is a new concept and stands out recently among the BP family due to its tiny structure and a series of excellent characteristics. In this study, BP was processed into nanosheets of three different sizes via different exfoliation strategies and then incorporated into cross-linkable oligo[poly(ethylene glycol) fumarate] (OPF) to produce nanocomposite hydrogels for bone regeneration. The three different BP nanosheets were designated as BP-L, BP-M, and BP-S, with a corresponding diameter of 242.3 ± 90.0, 107.1 ± 47.9, and 18.8 ± 4.6 nm. The degradation kinetics and osteogenic capacity of MC3T3 pre-osteoblasts in vitro were both dependent on the BP size. BP exhibited a controllable degradation rate, which increased with the decrease of the size of the nanosheets, coupled with the release of phosphate in vitro. The osteogenic capacity of the hydrogels was promoted with the addition of all BP nanosheets, compared with OPF hydrogel alone. The smallest BP quantum dots was shown to be optimal in enhancing MC3T3 cell behaviors, including spreading, distribution, proliferation, and differentiation on the OPF hydrogels. These results reinforced that the supplementation of BP quantum dots into OPF nanocomposite hydrogel scaffolds could potentially find application in the restoration of bone defects.