Fast Fabrication Nanopores on a PMMA Membrane by a Local High Electric Field Controlled Breakdown.

The sensitivity and accuracy of nanopore sensors are severely hindered by the high noise associated with solid-state nanopores. To mitigate this issue, the deposition of organic polymer materials onto silicon nitride (SiNx) membranes has been effective in obtaining low-noise measurements. Nonetheless, the fabrication of nanopores sub-10 nm on thin polymer membranes remains a significant challenge. This work proposes a method for fabricating nanopores on polymethyl methacrylate (PMMA) membrane by the local high electrical field controlled breakdown, exploring the impact of voltage and current on the breakdown of PMMA membranes and discussing the mechanism underlying the breakdown voltage and current during the formation of nanopores. By improving the electric field application method, transient high electric fields that are one-seven times higher than the breakdown electric field can be utilized to fabricate nanopores. A comparative analysis was performed on the current noise levels of nanopores in PMMA-SiNx composite membranes and SiNx nanopores with a 5 nm diameter. The results demonstrated that the fast fabrication of nanopores on PMMA-SiNx membranes exhibited reduced current noise compared to SiNx nanopores. This finding provides evidence supporting the feasibility of utilizing this technology for efficiently fabricating low-noise nanopores on polymer composite membranes.

The Property of a Key Amino Acid Determines the Function of Farnesyl Pyrophosphate Synthase in Sporobolomyces pararoseus NGR.

Farnesyl pyrophosphate synthase (FPPS) catalyzes the synthesis of C15 farnesyl diphosphate (FPP) from C5 dimethylallyl diphosphate (DMAPP) and two or three C5 isopentenyl diphosphates (IPPs). FPP is an important precursor for the synthesis of isoprenoids and is involved in multiple metabolic pathways. Here, farnesyl pyrophosphate synthase from Sporobolomyces pararoseus NGR (SpFPPS) was isolated and expressed by the prokaryotic expression system. The SpFPPS full-length genomic DNA and cDNA are 1566 bp and 1053 bp, respectively. This gene encodes a 350-amino acid protein with a predicted molecular mass of 40.33 kDa and a molecular weight of 58.03 kDa (40.33 kDa + 17.7 kDa), as detected by SDS-PAGE. The function of SpFPPS was identified by induction, purification, protein concentration and in vitro enzymatic activity experiments. Structural analysis showed that Y90 was essential for chain termination and changing the substrate scope. Site-directed mutation of Y90 to the smaller side-chain amino acids alanine (A) and lysine (K) showed in vitro that wt-SpFPPS catalyzed the condensation of the substrate DMAPP or geranyl diphosphate (GPP) with IPP at apparent saturation to synthesize FPP as the sole product and that the mutant protein SpFPPS-Y90A synthesized FPP and C20 geranylgeranyl diphosphate (GGPP), while SpFPPS-Y90K hydrolyzed the substrate GGPP. Our results showed that FPPS in S. pararoseus encodes the SpFPPS protein and that the amino acid substitution at Y90 changed the distribution of SpFPPS-catalyzed products. This provides a baseline for potentially regulating SpFPPS downstream products and improving the carotenoid biosynthesis pathway.

Haglund resection versus Haglund non-resection for calcific insertional Achilles tendinopathy with Haglund deformity: A retrospective study.

BACKGROUND: Calcific insertional Achilles tendinopathy(CIAT) with Haglund deformity is a type of recalcitrant tendinopathy. The necessity of concomitant removal of Haglund deformity during CIAT treatment is controversial. The present study aimed to evaluate the functional outcomes between Haglund resection and Haglund non-resection in the treatment of CIAT with Haglund deformity. METHODS: A retrospective study included 29 patients who were underwent Achilles tendon debridement, bursal excision, and subsequent tendon reattachment.for CIAT with Haglund deformity. All patients were divided into 2 groups according to Haglund resection (resection group, n = 16) and Haglund non-resection (non-resection group, n = 13) using the parallel line method on lateral calcaneal X ray after surgery. Patients were evaluated in terms of the American Orthopedic Foot and Ankle Society (AOFAS), Visual Analog Scale (VAS) and Victorian Institute of Sports Assessment-Achilles (VISA-A) scores and the mean time of activities of daily living (ADL). Anatomy changes included the Fowler-Philip angle, calcaneal pitch angle and Achilles tendon force arm were measured with radiography preoperatively and postoperatively. RESULTS: Both groups exhibited a significant increase in AOFAS, VAS and VISA-A scores after surgery. There were no significant differences between the resection group and the non-resection group for the AOFAS (92.38 ± 5.7 vs. 93.15 ± 12.17; P = 0.82), VAS (0.5 ± 0.52 vs. 0.61 ± 0.87; P = 0.66) and VISA-A questionnaire (82.56 ± 13.46 vs. 74.92 ± 16.4; P = 0.18) at the latest follow-up. The mean time of ADL in the non-resection group was significantly faster compared to that of the resection group (8.15 ± 2.51 weeks vs. 11.31 ± 4.06 weeks, P = 0.02). The Fowler-Philip angle of the resection group decreased from 55.55° ± 12.34° preoperatively to 44.52° ± 10.24° at the latest follow-up (P = 0.001). The Fowler-Philip angle of the non-resection group decreased from 54.38° ± 8.41° preoperatively to 46.52° ± 8.02° at the latest follow-up (P = 0.016). The calcaneal pitch angle of the resection group increased from 22.76° ± 5.37° preoperatively to 25.98° ± 6. 4° at the latest follow-up (P = 0.018). The Achilles tendon force arm of the resection group decreased from 178.50 mm ± 5.37 mm preoperatively to 173.90 mm ± 8.07 mm at the latest follow-up (P = 0.018). CONCLUSION: Resection or non-resection of the posterosuperior calcaneal tuberosity for CIAT with Haglund deformity would both provide satisfactory functional outcomes. Haglund non-resection may expedite patients' return to their daily activities, suggesting a Haglund deformity resection may be unnecessary in the surgical treatment for CIAT with Haglund deformity.

Exploring the Impact of Coconut Peat and Vermiculite on the Rhizosphere Microbiome of Pre-Basic Seed Potatoes under Soilless Cultivation Conditions.

Soilless cultivation of potatoes often utilizes organic coconut peat and inorganic vermiculite as growing substrates. The unique microbial communities and physicochemical characteristics inherent to each substrate significantly influence the microecological environment crucial for potato growth and breeding. This study analyzed environmental factors within each substrate and employed Illumina sequencing alongside bioinformatics tools to examine microbial community structures, their correlation with environmental factors, core microbial functions, and the dynamics of microbial networks across various samples. These included pure coconut peat (CP1) and pure vermiculite (V1), substrates mixed with organic fertilizer for three days (CP2 and V2), and three combinations cultivated with potatoes for 50 days (CP3, V3, and CV3-a 1:1 mix of coconut peat and vermiculite with organic fertilizer). Vermiculite naturally hosts a more diverse microbial community. After mixing with fertilizer and composting for 3 days, and 50 days of potato cultivation, fungal diversity decreased in both substrates. Coconut peat maintains higher bacterial diversity and richness compared to vermiculite, harboring more beneficial bacteria and fungi, resulting in a more complex microbial network. However, vermiculite shows lower bacterial diversity and richness, with an accumulation of pathogenic microorganisms. Among the 11 environmental factors tested, water-soluble nitrogen (WSN), total nitrogen (TN), available potassium (AK), total organic carbon (TOC) and air-filled porosity (AFP) were significantly associated with microbial succession in the substrate.The nutritional type composition and interaction patterns of indigenous microorganisms differ between vermiculite and coconut peat. Adding abundant nutrients significantly affects the stability and interaction of the entire microbial community, even post-potato cultivation. When using vermiculite for soilless cultivation, precise control and adjustment of nutrient addition quantity and frequency are essential.

The combination of DNA nanostructures and materials for highly sensitive electrochemical detection.

Due to the wide range of electrochemical devices available, DNA nanostructures and material-based technologies have been greatly broadened. They have been actively used to create a variety of beautiful nanostructures owing to their unmatched programmability. Currently, a variety of electrochemical devices have been used for rapid sensing of biomolecules and other diagnostic applications. Here, we provide a brief overview of recent advances in DNA-based biomolecular assays. Biosensing platform such as electrochemical biosensor, nanopore biosensor, and field-effect transistor biosensors (FET), which are equipped with aptamer, DNA walker, DNAzyme, DNA origami, and nanomaterials, has been developed for amplification detection. Under the optimal conditions, the proposed biosensor has good amplification detection performance. Further, we discussed the challenges of detection strategies in clinical applications and offered the prospect of this field.

A novel and efficient murine model for investigating tendon-to-bone healing.

BACKGROUND: Tendon-to-bone healing is a critical challenge in sports medicine, with its cellular and molecular mechanisms yet to be explored. An efficient murine model could significantly advance our understanding of this process. However, most existing murine animal models face limitations, including a propensity for bleeding, restricted operational space, and a steep learning curve. Thus, the need for a novel and efficient murine animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing is becoming increasingly evident. METHODS: In our study, forty-four 9-week-old male C57/BL6 mice underwent transection and reattachment of the Achilles tendon insertion to investigate tendon-to-bone healing. At 2 and 4 weeks postoperatively, mice were killed for histological, Micro-CT, biomechanical, and real-time polymerase chain reaction tests. RESULTS: Histological staining revealed that the original tissue structure was disrupted and replaced by a fibrovascular scar. Although glycosaminoglycan deposition was present in the cartilage area, the native structure had been destroyed. Biomechanical tests showed that the failure force constituted approximately 44.2% and 77.5% of that in intact tissues, and the ultimate tensile strength increased from 2 to 4 weeks postoperatively. Micro-CT imaging demonstrated a gradual healing process in the bone tunnel from 2 to 4 weeks postoperatively. The expression levels of ACAN, SOX9, Collagen I, and MMPs were detected, with all genes being overexpressed compared to the control group and maintaining high levels at 2 and 4 weeks postoperatively. CONCLUSIONS: Our results demonstrate that the healing process in our model is aligned with the natural healing process, suggesting the potential for creating a new, efficient, and reproducible mouse animal model to investigate the cellular and molecular mechanisms of tendon-to-bone healing.

A new perspective in the prevention and treatment of antitumor therapy-related cardiotoxicity: Intestinal microecology.

The continuous development of antitumor therapy has significantly reduced the mortality of patients with malignancies. However, the antitumor-related cardiotoxicity has become the leading cause of long-term mortality in patients with malignancies. Besides, the pathogenesis of antitumor-related cardiotoxicity is still unclear, and practical means of prevention and treatment are lacking in clinical practice. Therefore, the major challenge is how to combat the cardiotoxicity of antitumor therapy effectively. More and more studies have shown that antitumor therapy kills tumor cells while causing damage to sensitive tissues such as the intestinal mucosa, leading to the increased permeability of the intestine and the dysbiosis of intestinal microecology. In addition, the dysbiosis of intestinal microecology contributes to the development and progression of cardiovascular diseases through multiple pathways. Thus, the dysbiosis of intestinal microecology may be a potential mechanism and target for antitumor-related cardiotoxicity. We summarized the characteristics of intestinal microecology disorders induced by antitumor therapy and the association between intestinal microecological dysbiosis and CVD. And on this basis, we hypothesized the potential mechanisms of intestinal microecology mediating the occurrence of antitumor-related cardiotoxicity. Then we reviewed the previous studies targeting intestinal microecology against antitumor-associated cardiotoxicity, aiming to provide a reference for future studies on the occurrence and prevention of antitumor-related cardiotoxicity by intestinal microecology.

Gut microbiota influence frailty syndrome in older adults: mechanisms and therapeutic strategies.

Frailty syndrome denotes a decreased capacity of the body to maintain the homeostasis and stress of the internal environment, which simultaneously increases the risk of adverse health outcomes in older adults, including disability, hospitalization, falls, and death. To promote healthy aging, we should find strategies to cope with frailty. However, the pathogenesis of frailty syndrome is not yet clear. Recent studies have shown that the diversity, composition, and metabolites of gut microbiota significantly changed in older adults with frailty. In addition, several frailty symptoms were alleviated by adjusting gut microbiota with prebiotics, probiotics, and symbiosis. Therefore, we attempt to explore the pathogenesis of frailty syndrome in older people from gut microbiota and summarize the existing interventions for frailty syndrome targeting gut microbiota, with the aim of providing timely and necessary interventions and assistance for older adults with frailty.

Nanopore Single-molecule Analysis of Biomarkers: Providing Possible Clues to Disease Diagnosis.

Biomarker detection has attracted increasing interest in recent years due to the minimally or non-invasive sampling process. Single entity analysis of biomarkers is expected to provide real-time and accurate biological information for early disease diagnosis and prognosis, which is critical to the effective disease treatment and is also important in personalized medicine. As an innovative single entity analysis method, nanopore sensing is a pioneering single-molecule detection technique that is widely used in analytical bioanalytical fields. In this review, we overview the recent progress of nanopore biomarker detection as new approaches to disease diagnosis. In highlighted studies, nanopore was focusing on detecting biomarkers of different categories of communicable and noncommunicable diseases, such as pandemic Covid-19, AIDS, cancers, neurologic diseases, etc. Various sensitive and selective nanopore detecting strategies for different types of biomarkers are summarized. In addition, the challenges, opportunities, and direction for future development of nanopore-based biomarker sensors are also discussed.

An aptamer-assisted nanopore strategy with a salt gradient for direct protein sensing.

Nanopore sensing is at the forefront of the technological revolution of the protein research field and has been widely used in molecular diagnosis and molecular dynamics, as well as for various sequencing applications. However, direct protein sensing with biological nanopores is still challenging owing to the large molecular size. Here, we propose an aptamer-assisted nanopore strategy for direct protein sensing and demonstrate its proof-of-concept utilities by experiments with SARS-Cov-2 nucleocapsid protein (NP), the most abundantly expressed viral protein, that is widely used in clinical diagnosis for COVID-19. NP binds with an oligonucleotide-tailed aptamer to form a protein-DNA complex which induces a discriminative two-level pattern of current blockades. We reveal the potential molecular interaction mechanism for the characteristic blockades and identify the salt gradient condition as the dominant factor of the phenomenon. Furthermore, we achieve a high sensitivity of 10 pM for NP detection within one hour and make a preliminary exploration on clinical diagnosis. This work promises a new platform for rapid and label-free protein detection.

Regulation of cell differentiation to promote pullulan synthesis in Aureobasidium pullulans NG.

Pullulan is a polymer produced by Aureobasidium spp. The yield of pullulan production can be impacted by the cellular differentiation of Aureobasidium spp., which changes with alterations in the growth environment. To improve pullulan yield, identifying key factors that regulate cellular differentiation is crucial. In this study, the main form of pullulan synthesis in Aureobasidium pullulans NG was through swollen cells (SC). The results showed that citric acid (CA) can regulate the cellular differentiation of Aureobasidium pullulans NG by accumulating higher levels of CA in the cells to maintain growth in SC form and increase pullulan production. The addition of 1.0% CA to Aureobasidium pullulans NG for 96 h resulted in a significant increase in pullulan production, producing 18.32 g/l compared to the control group which produced 10.23 g/l. Our findings suggest that controlling cellular differentiation using CA is a promising approach for enhancing pullulan production in Aureobasidium pullulans. KEY POINTS: • The regulation of cell differentiation in Aureobasidium pullulans NG is demonstrated to be influenced by citric acid. • Intracellular citric acid levels in Aureobasidium pullulans NG have been shown to support the growth of swollen cells. • Citric acid has been found to increase pullulan production in Aureobasidium pullulans NG.

Driving force of deteriorated cellular environment in heart failure: Metabolic remodeling.

Heart Failure (HF) has been one of the leading causes of death worldwide. Though its latent mechanism and therapeutic manipulation are updated and developed ceaselessly, there remain great gaps in the cognition of heart failure. High morbidity and readmission rates among HF patients are waiting to be addressed. Recent studies have found that myocardial energy metabolism was closely related to heart failure, in which substrate utilization, as well as intermediate metabolism disorders, insulin resistance, oxidative stress, and mitochondrial dysfunction, might underlie systolic dysfunction and progression of HF. This article centers on the changes and counteraction of cardiac energy metabolism in the failing heart. Therefore, targeting impaired energy provision is of great potential in the treatment of HF. And shifting the objective from traditional neurohormones to improving the cellular environment is expected to further optimize the management of HF.

Finding New Targets for the Treatment of Heart Failure: Endoplasmic Reticulum Stress and Autophagy.

Heart failure is a progressive disease with an annual mortality rate of about 10% and is the end-stage stage of various heart diseases, which places a huge socioeconomic burden on the healthcare system. The development of heart failure has received increasing attention as a potential way to improve the treatment of this disease. Many studies have shown that endoplasmic reticulum stress and autophagy play an important role in the occurrence and development of heart failure. With the in-depth study of endoplasmic reticulum stress and autophagy, both are considered promising targets for pharmacological interventions to treat heart failure, but the mechanism of heart failure between the two is not clear. This review will highlight the effects of endoplasmic reticulum stress, autophagy, and their interactions in the development and development of heart failure, thereby helping to provide direction for the future development of targeted therapies for patients with heart failure. CLINICAL RELEVANCE: This study explored the new targets for the treatment of heart failure: endoplasmic reticulum stress and autophagy. Targeted drug therapy for endoplasmic reticulum stress and autophagy is expected to provide a new intervention target for the treatment of heart failure.

Analysis of starch dissolved in ionic liquid by glass nanopore at single molecular level.

In this paper, the glass nanopore technology was proposed to detect a single molecule of starch dissolved in ionic liquid [1-butyl-3-methylimidazolium chloride (BmimCl)]. Firstly, the influence of BmimCl on nanopore detection is discussed. It is found that a certain amount of strong polar ionic liquids will disturb the charge distribution in nanopores and increase the detection noise. Then, by analysis of the characteristic current signal of the conical nanopore, the motion behaviour of starch near the entrance of the nanopore was studied and analysis the dominant ion of starch in the BmimCl dissolution process. Finally, based on nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy simply discussed the mechanism of amylose and amylopectin dissolved in BmimCl. These results confirm that branched chain structure would affect the dissolution of polysaccharides in ionic liquids and the contribution of anions to the dissolution of polysaccharides are dominant. It is further proved that the current signal can be used to judge the charge and structure information of the analyte, and the dissolution mechanism can be assist analyzed at the single molecule level.

Up-regulation of CREB-1 regulates tendon adhesion in the injury tendon healing through the CREB-1/TGF-ß3 signaling pathway.

AIM: To explore the mechanism of the healing of tendon tissue and anti-adhesion, and to discuss the role of the transforming growth factor-ß3 (TGF-ß3)/cAMP response element binding protein-1 (CREB-1) signaling pathway in the healing process of tendons. METHOD: All mice were divided into four groups of 1, 2, 4, and 8 weeks respectively. Each time group was divided into four treatment groups: the amplification group, the inhibition group, the negative group, and the control group. When the tendon injury model was established, the CREB-1 virus was injected into the tendon injury parts. A series of methods such as gait behaviourism, anatomy, histological examination, immunohistochemical examination and collagen staining were employed to assess the tendon healing and the protein expression of TGF-ß3, CREB-1, Smad3/7 and type I/III collagen (COL-I/III). CREB-1 virus was sent to tendon stem cells to assess the protein expression of TGF-ß1, TGF-ß3, CREB-1, COL-I/III by methods such as immunohistochemistry and Western blot. RESULTS: The amplification group showed better gait behaviourism than the inhibition group in the healing process. The amplification group also had less adhesion than the negative group. Hematoxylin-eosin (HE) staining of tendon tissue sections showed that the number of fibroblasts in the amplification group was less than the inhibition group, and the immunohistochemical results indicated that the expression of TGF-ß3, CREB-1, and Smad7 at each time point was higher than the inhibition group. The expression of COL-I/III and Smad3 in the amplification group was lower than the inhibition group at all time points. The collagen staining indicated that the ratio of type I/III collagen in the amplification group was higher than the negative group at 2,4,8 week. The CREB-1 amplification virus could promote the protein expression of TGF-ß3, CREB-1 and inhibit the protein expression of TGF-ß1 and COL-I/III in the tendon stem cells. CONCLUSION: In the process of tendon injury healing, CREB-1 could promote the secretion of TGF-ß3, so as to promote the tendon healing and have the effect of anti-adhesion in tendons. It might provide new intervention targets for anti-adhesion treatment of tendon injuries.

Nanopore discrimination and sensitive plasma detection of multiple natriuretic peptides: The representative biomarker of human heart failure.

Natriuretic peptides can relieve cardiovascular stress and closely related to heart failure. Besides, these peptides also have preferable interactions of binding to cellular protein receptors, and subsequently mediate various physiology actions. Hence, detection of these circulating biomarkers could be evaluated as a predictor ("Gold standard") for rapid, early diagnosis and risk stratification in heart failure. Herein, we proposed a measurement to discriminate multiple natriuretic peptides via the peptide-protein nanopore interaction. The nanopore single-molecular kinetics revealed that the strength of peptide-protein interactions was in the order of ANP > CNP > BNP, which was demonstrated by the simulated peptide structures using SWISS-MODEL. More importantly, the peptide-protein interaction analyzing also allowed us to measure the peptide linear analogs and structure damage in peptide by single-chemical bond breakup. Finally, we presented an ultra-sensitive detection of plasma natriuretic peptide using asymmetric electrolyte assay, obtaining a detection limit of ∼770 fM for BNP. At approximately, it is 1597 times lower than that of using symmetric assay (∼1.23 nM), 8 times lower than normal human level (∼6 pM), and 13 times lower than the diagnostic values (∼10.09 pM) complied in the guideline of European Society of Cardiology. That said, the designed nanopore sensor is benefit for natriuretic peptides measurement at single molecule level and demonstrates its potential for heart failure diagnosis.

Double-bundle reconstruction of the anterior talofibular ligament by partial peroneal brevis tendon.

BACKGROUND: Anatomic anterior talofibular ligament (ATFL) reconstruction with autologous single-bundle tendon has been widely used in the treatment of ATFL injury. However, there are few clinical reports of using the peroneus brevis tendon (PBT) for double-bundle ATFL reconstruction. The aim of this study was to investigate the clinical effect of double-bundle ATFL reconstruction with PBT. METHODS: This was a retrospective review of all patients diagnosed with ATFL injury presenting from August 2019 to December 2021. Fifty-three patients were selected after screening based on the inclusion and exclusion criteria. The following data were compared before and after surgery: Visual Analogue Scale (VAS) score, American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson Ankle Functional Score (KAFS), the pain interference (PI) and physical function (PF) scores of the Patient-Reported Outcomes Measurement Information System (PROMIS), the diameter and width of PBT in ultrasound and muscle strength. RESULTS: All functional scores (VAS, PI/PF, AO-FAS, KAFS) and muscle strength were significantly improved at the last follow-up (P < 0.05). The diameter and width of the PBT on ultrasound postoperation were smaller than those preoperatively. CONCLUSION: Double-bundle ATFL reconstruction with the partial PBT technique is a feasible, anatomic reconstruction technique for chronic lateral instability of the ankle, which meets the anatomical characteristics of the double bundle of the ligament, and the absence of partial PBT does not affect the peroneal muscle strength. LEVEL OF EVIDENCE: Level IV, retrospective case series.

N-Acetyl-L-cysteine facilitates tendon repair and promotes the tenogenic differentiation of tendon stem/progenitor cells by enhancing the integrin α5/ß1/PI3K/AKT signaling.

BACKGROUND: Tendon injury is associated with oxidative stress, leading to reactive oxygen species (ROS) production and inflammation. N-acetyl-L-cysteine (NAC) is a potent antioxidant. However, how NAC affects the biological functions of tendon stem/progenitor cells (TSPCs) and tendon repair has not been clarified.  METHOD: The impacts of NAC on the viability, ROS production, and differentiation of TSPCs were determined with the cell counting kit-8, fluorescence staining, Western blotting, and immunofluorescence. The effect of NAC on gene transcription in TSPCs was analyzed by transcriptomes and bioinformatics and validated by Western blotting. The potential therapeutic effect of NAC on tendon repair was tested in a rat model of Achilles tendon injury. RESULTS: Compared with the untreated control, treatment with 500 µM NAC greatly promoted the proliferation of TSPCs and significantly mitigated hydrogen peroxide-induced ROS production and cytotoxicity in vitro. NAC treatment significantly increased the relative protein expression of collagen type 1 alpha 1 (COL1A1), tenascin C (TNC), scleraxis (SCX), and tenomodulin (TNMD) in TPSCs. Bioinformatics analyses revealed that NAC modulated transcriptomes, particularly in the integrin-related phosphoinositide 3-kinase (PI3K)/AKT signaling, and Western blotting revealed that NAC enhanced integrin α5ß1 expression and PI3K/AKT activation in TSPCs. Finally, NAC treatment mitigated the tendon injury, but enhanced the protein expression of SCX, TNC, TNMD, and COLIA1 in the injured tissue regions of the rats. CONCLUSION: NAC treatment promoted the survival and differentiation of TSPCs to facilitate tendon repair after tendon injury in rats. Thus, NAC may be valuable for the treatment of tendon injury.

Comparison of cortical versus cancellous bone fixation in tendon-to-bone healing with a rat trans-calcaneal suture model for Achilles tendon sleeve avulsion.

BACKGROUND: Trans-calcaneal suture technique is an economical and effective method for repairing Achilles tendon sleeve avulsion. Whether cancellous bone fixation upon this technique could accelerate tendon-to-bone healing is unknown. The purpose of this study is to compare the effect of cortical versus cancellous bone fixation on tendon-bone healing with a novel rat trans-calcaneal suture model. METHODS: Trans-calcaneal suture treatment was carried out on the right hindlimb in male Sprague-Dawley rats (N = 80). They were randomly divided into the cortical group (Achilles fixed to the calcaneal cortical bone, n = 40) and the cancellous group (Achilles fixed to the calcaneal cancellous bone, n = 40). Gait analysis and immunohistochemistry were performed 1, 4, 7, and 14 days after the operation. Gross observation, biomechanical analysis, micro-CT, and histological analysis were performed 4 and 8 weeks after surgery. Independent-samples t tests were used for comparison between groups. RESULTS: At 1, 4, and 7 days, the swing time of the affected limb in the cancellous group decreased, while the duty cycle, the maximum contact area, the print area, and the mean intensity increased significantly. The cross-sectional area of the tendon-bone junction in the cancellous group was smaller, and the failure load and stiffness were higher 4 weeks after the operation. The cancellous group showed more proportion of new bone and a relatively well-organized and dense connective tissue interface with better fibrocartilage-like tissue at 4 weeks after the operation. The ratio of ED2 + macrophages in the cancellous group was significantly higher than in the cortical group on 1, 4, 7, and 14 days. There were no significant differences in gait at 2 weeks, in appearance, biomechanics, new bone formation, and histology at 8 weeks after surgery between the two groups. CONCLUSION: In the new rat trans-calcaneal suture model, cancellous fixation can accelerate tendon-to-bone healing in the early stage, which perhaps is related to the abundant bone marrow tissue in the cancellous bone that modulates the inflammatory processes.