Engineering Innervated Musculoskeletal Tissues for Regenerative Orthopedics and Disease Modeling.

Musculoskeletal (MSK) disorders significantly burden patients and society, resulting in high healthcare costs and productivity loss. These disorders are the leading cause of physical disability, and their prevalence is expected to increase as sedentary lifestyles become common and the global population of the elderly increases. Proper innervation is critical to maintaining MSK function, and nerve damage or dysfunction underlies various MSK disorders, underscoring the potential of restoring nerve function in MSK disorder treatment. However, most MSK tissue engineering strategies have overlooked the significance of innervation. This review first expounds upon innervation in the MSK system and its importance in maintaining MSK homeostasis and functions. This will be followed by strategies for engineering MSK tissues that induce post-implantation in situ innervation or are pre-innervated. Subsequently, research progress in modeling MSK disorders using innervated MSK organoids and organs-on-chips (OoCs) is analyzed. Finally, the future development of engineering innervated MSK tissues to treat MSK disorders and recapitulate disease mechanisms is discussed. This review provides valuable insights into the underlying principles, engineering methods, and applications of innervated MSK tissues, paving the way for the development of targeted, efficacious therapies for various MSK conditions.

Telemedicine network latency management system in 5G telesurgery: a feasibility and effectiveness study.

BACKGROUND: Network latency is the most important factor affecting the performance of telemedicine. The aim of the study is to assess the feasibility and efficacy of a novel network latency management system in 5G telesurgery. METHODS: We conducted 20 telesurgery simulation trials (hitching rings to columns) and 15 remote adrenalectomy procedures in the 5G network environment. Telemedicine Network Latency Management System and the traditional "Ping command" method (gold standard) were used to monitor network latency during preoperative simulated telesurgery and formal telesurgery. We observed the working status of the Telemedicine Network Latency Management System and calculated the difference between the network latency data and packet loss rate detected by the two methods. In addition, due to the lower latency of the 5G network, we tested the alert function of the system using the 4G network with relatively high network latency. RESULTS: The Telemedicine Network Latency Management System showed no instability during telesurgery simulation trials and formal telesurgery. After 20 telesurgery simulation trials and 15 remote adrenalectomy procedures, the p-value for the difference between the network latency data monitored by the Telemedicine Network Latency Management System and the "Ping command" method was greater than 0.05 in each case. Meanwhile, the surgeons reported that the Telemedicine Network Latency Management System had a friendly interface and was easy to operate. Besides, when the network latency exceeded a set threshold, a rapid alarm sounded in the system. CONCLUSION: The Telemedicine Network Latency Management System was simple and easy to operate, and it was feasible and effective to use it to monitor network latency in telesurgery. The system had an intuitive and concise interface, and its alarm function increased the safety of telesurgery. The system's own multidimensional working ability and information storage capacity will be more suitable for telemedicine work.

Sub-satisfactory stenting recanalization of severe vascular stenosis of the posterior circulation can significantly improve cerebral hemodynamic perfusion.

PURPOSE: To investigate the effect of sub-satisfactory stenting recanalization of severe vascular stenosis of the posterior circulation on cerebral hemodynamic perfusion. MATERIALS AND METHODS: Patients with severe vascular stenosis of the posterior circulation who had undergone three-dimensional cerebral angiography before and after stenting were retrospectively enrolled. Computational fluid dynamic (CFD) analysis of hemodynamic parameters at the stenosis, perforating branch, and normal arterial segments proximal and distal to the stenosis were performed. RESULTS: Sixty-two patients with basilar artery stenosis aged 60.9 ±â€¯9.6 years were enrolled, and stent angioplasty resulted in the reduction of stenosis degree from 85.3 ±â€¯7.2% before to 18.6 ±â€¯6.4% after stenting. After stenting, at the proximal normal artery, the total pressures had significantly (P < 0.05) decreased, whereas all the other parameters (WSS, cell Reynolds number, velocity, vorticity, turbulence intensity, turbulence kinetic energy and dissipation rate) had significantly (P < 0.05) increased. At the stenosis, all hemodynamic parameters had significantly decreased. At the stenosis perforating branch, the WSS, cell Reynolds number, velocity, and vorticity were all significantly decreased, and the total pressure, turbulence intensity, kinetic energy, and dissipation rate were all significantly increased. At the distal normal artery, the total flow pressure (perfusion pressure) and velocity were both significantly (P < 0.05) increased, and the total pressure, WSS, cell Reynolds number, vorticity, turbulence intensity, kinetic energy, and dissipation rate were all significantly (P < 0.05) decreased. The hemodynamic parameters after stenting were closer to those after virtual stenosis repair at all measurements. CONCLUSION: Sub-satisfactory recanalization has significantly restored the stenosis and improved the hemodynamic parameters near the stenosis and at the root of the perforating branch, thus significantly improving the cerebral perfusion, similar to the changes of hemodynamic status and cerebral perfusion after virtual removal of the vascular stenosis. This may indicate the good effect of sub-satisfactory stenting recanalization of the vascular stenosis at the posterior circulation.

Safety and efficacy of enterprise stenting for symptomatic atherosclerotic severe posterior circulation stenosis.

PURPOSE: To investigate the safety and efficacy of Enterprise stent angioplasty and risk factors for the prognoses in treating symptomatic severe posterior circulation atherosclerotic stenosis (SSPCAS). MATERIALS AND METHODS: Patients with SSPCAS who were treated with the Enterprise stent angioplasty were retrospectively enrolled. The clinical data, peri-procedural complications, postoperative residual stenosis, in-stent restenosis and recurrent stroke at follow-up were analyzed. RESULTS: 262 patients with 275 stenotic lesions treated with the Enterprise stent angioplasty were enrolled. The stenosis degree was reduced from 86.3 ± 6.2% before to 19.3 ± 5.4% after stenting. Complications occurred in 14 (5.3%) patients. Clinical follow-up was performed in 245 (93.51%) patients for 16.5 ± 7.3 months. During 1 year follow-up, 7 patients (2.9%) had recurrent symptoms, including 4 patients with stenting in the intracranial vertebral artery and 3 in the basilar artery. Imaging follow-up was conducted in 223 (85.11%) patients. In-stent restenosis was present in 35 patients (15.7%), with the restenosis rate of 26.4% (n = 23) in the intracranial vertebral artery, which was significantly (P < 0.001) greater than in the basilar artery (8.8%). Six patients (17.1%) with in-stent restenosis were symptomatic. The stenotic length was the only significant (P = 0.026 and 0.024, respectively) independent risk factor for 1 year stroke or death events and in-stent restenosis. CONCLUSION: The Enterprise stent can be safely and efficaciously applied in the treatment of symptomatic severe posterior circulation atherosclerotic stenosis, with a relatively low rate of in-stent restenosis and recurrent stroke within 1 year. The stenotic length was the only significant independent risk factor for 1 year stroke or death events and in-stent restenosis.

Schiff base synergized with protonation of PEI to achieve smart antibacteria of nanocellulose packaging films.

Microbial growth and reproduction can cause food spoilage. Developing the controlled release packaging films for food is an ideal solution. In this study, polyethyleneimine (PEI) was grafted to cellulose nanofibers (CNF) films by Schiff base, and when the CNF/PEI films were stimulated by pH, PEI released from the CNF/PEI films due to Schiff base hydrolysis, improving the antibacterial efficiency of PEI. Stimulated by acid with pH of 4, the PEI cumulative release rate of the CNF/PEI800 and the CNF/PEI2000 films reached to 92.90 % and 87.28 %, respectively. At the same time, the amino groups of PEI protonated by obtaining H+, the charge density increased, and PEI molecular chains extended, enhancing the antibacterial activity of films. The Zeta potential value on the surface of the CNF/PEI film increased with the decrease of pH value. Schiff base synergized with protonation of PEI to achieve smart antibacteria of CNF packaging films. The antibacterial rates of the film against L. monocytogenes and E. coli were 94.7 % and 90.6 % at pH 4, but 29.5 % and 23.6 % at pH 8, respectively. The developed films also had good barrier properties of oxygen, visible light and mechanical properties, and had an attractive application prospect in food preservation to control release of antibacterial agent.

Endovascular recanalization of symptomatic non-acute occlusion of the vertebrobasilar artery.

Purpose: The study aimed to investigate the safety, effect, and risk factors of endovascular recanalization of symptomatic non-acute occlusion of the vertebrobasilar artery (SNOVA). Materials and methods: Patients with SNOVA were retrospectively enrolled and treated with endovascular recanalization. The clinical data, endovascular treatment, peri-procedural complications, and follow-up outcomes were analyzed. Results: A total of 88 patients were enrolled, with an interval to recanalization of 2-89 days (median 23) and an mRS of 2-5 (median 3 and IQR 1). Occlusion was in the intracranial vertebral artery in 68 (77.27%) patients and basilar artery in 20 (22.73%), with an occlusion length of 4.5-43.7 mm (mean 18.3 ± 8.8). Endovascular recanalization was successful in 81 (92.0%) patients. Post-dilatation was performed in 23 (28.4%) patients. After stenting, the residual stenosis was 10%-40% (mean 20.2% ± 7.6%). Peri-procedural complications occurred in 17 (19.3%) patients, with a mortality rate of 5.7%. In total, 79 (95.18%) patients underwent follow-up 5-29 (mean 16.9 ± 5.5) months later, with an mRS score of 0-6 (median 1 and IQR 1) at follow-up, being significantly (p < 0.0001) better than that at discharge. Stroke occurred in 9 patients (11.4%) in 1 year. In-stent restenosis occurred in 19 (25.33%) patients. Significant (p < 0.05) independent risk factors were blunt occlusion for successful recanalization, duration to recanalization and blunt occlusion for peri-procedural complications, and post-dilatation for both in-stent restenosis and 1-year stroke or death events. Conclusion: Endovascular recanalization of symptomatic non-acute occlusion of the vertebrobasilar artery is feasible even for a long occlusion segment, with a high recanalization rate, a low complication rate, and a good prognosis. Blunt occlusion and duration from the onset to recanalization may affect successful recanalization and peri-procedural complications while post-dilatation may affect in-stent restenosis and prognosis.

MRI arterial spin labeling in evaluating hemorrhagic transformation following endovascular recanalization of subacute ischemic stroke.

Objective: To investigate the value of the MRI arterial spin labeling (ASL) in evaluating the blood-brain barrier permeability of anterior circulation ischemic lesions in subacute ischemic stroke (SIS) and the risk of hemorrhage transformation (HT) after endovascular recanalization. Materials and methods: Patients with anterior circulation SIS treated with endovascular recanalization were prospectively enrolled. The imaging presentations in the MRI ASL sequences, dynamic contrast-enhanced (DCE) sequence, and Xper CT were studied. The relative cerebral blood flow (rCBF), volume transfer constant (Ktrans), and the weighted Kappa coefficient (rKtrans) were analyzed. Results: Among 27 eligible patients, HT occurred in 7 patients (25.92%). Patients with HT had significantly higher rCBF value (1.56 ± 0.16 vs. 1.16 ± 0.16), Ktrans, (0.08 ± 0.03 min vs. 0.03 ± 0.01 min) and rKtrans (3.02 ± 0.89 vs. 1.89 ± 0.56). The ASL imaging sequence had a high consistency with the DCE sequence and Xper CT with a high weighted Kappa coefficient of 0.91 for the DCE sequence and 0.70 for the Xper CT imaging. The DCE sequence was also highly consistent with the Xper CT in imaging classification with a high weighted Kappa coefficient of 0.78. The rCBF value in the 21 patients with the subcortical and basal ganglia infarction was significantly lower than that in the other 6 patients with the cortical infarction (1.222 ± 0.221 vs. 1.413 ± 0.259, t = 1.795, P = 0.004). Conclusion: The MRI ASL sequence has an important role in evaluating the blood-brain barrier permeability and the risk of hemorrhagic transformation of anterior circulation SIS following endovascular recanalization.

One-stop stroke management platform reduces workflow times in patients receiving mechanical thrombectomy.

Background and purpose: Clinical outcome in patients who received thrombectomy treatment is time-dependent. The purpose of this study was to evaluate the efficacy of the one-stop stroke management (OSSM) platform in reducing in-hospital workflow times in patients receiving thrombectomy compared with the traditional model. Methods: The data of patients who received thrombectomy treatment through the OSSM platform and traditional protocol transshipment pathway were retrospectively analyzed and compared. The treatment-related time interval and the clinical outcome of the two groups were also assessed and compared. The primary efficacy endpoint was the time from door to groin puncture (DPT). Results: There were 196 patients in the OSSM group and 210 patients in the control group, in which they were treated by the traditional approach. The mean DPT was significantly shorter in the OSSM group than in the control group (76 vs. 122 min; P < 0.001). The percentages of good clinical outcomes at the 90-day time point of the two groups were comparable (P = 0.110). A total of 121 patients in the OSSM group and 124 patients in the control group arrived at the hospital within 360 min from symptom onset. The mean DPT and time from symptom onset to recanalization (ORT) were significantly shorter in the OSSM group than in the control group. Finally, a higher rate of good functional outcomes was achieved in the OSSM group than in the control group (53.71 vs. 40.32%; P = 0.036). Conclusion: Compared to the traditional transfer model, the OSSM transfer model significantly reduced the in-hospital delay in patients with acute stroke receiving thrombectomy treatment. This novel model significantly improved the clinical outcomes of patients presenting within the first 6 h after symptom onset.

ZnO nanoparticles stabilized oregano essential oil Pickering emulsion for functional cellulose nanofibrils packaging films with antimicrobial and antioxidant activity.

The growth and reproduction of microorganisms can cause food spoilage in the process of food transportation and storage. Active packaging is a good way to inhibit food spoilage and prolong the shelf lives of foods. In this study, O/W Pickering emulsion with ZnO nanoparticles as solid particles and oregano essential oil as the oil phase was prepared and used to functionalize cellulose nanofibrils (CNFs) film, and excellent antimicrobial and antioxidant activity was obtained. When the concentration of ZnO nanoparticles was 1.5 wt% and the mass fraction of the oil phase was 20%, the Pickering emulsion with a particle size of 26.85 µm exhibited strong standing stability. The Pickering emulsion was blended with the film-forming matrix CNFs to prepare active packaging films by casting. The Pickering emulsion evenly dispersed in the film to form microcapsules which encapsulated oregano essential oil entirely. The antimicrobial activity against Listeria monocytogenes was 89.61%, the DPPH radical scavenging rate was 58.52%, while the barrier properties of the developed films against oxygen, water vapor and visible light were improved. The active CNFs film prepared by Pickering emulsion could inhibit the growth of microorganism and prolong the shelf lives of foods.

A Combined Measurement Method for Large-Size Aerospace Components.

Automated and high-accuracy three-dimensional (3D) shape measurement is required in quality control of large-size components for the aerospace industry. To eliminate the contradiction between global measurement and local precision measurement control in 3D digitalization for the key local features of the large-size components, a combined measurement method is proposed, including a 3D scanner, a laser tracker, and an industrial robot used as an orienting device, to achieve high-accuracy measurement. As for improving the overall measurement accuracy, an accurate calibration method based on coordinate optimization of common points (COCP) and coordinate optimization of global control points (COGP) is proposed to determine the coordinate systems. Firstly, a coordinate optimization method of common points (COCP) is recommended. Then, a coordinate optimization method of global control points (COGP) based on the angular constraint is proposed for minimizing the measurement errors and improving the measurement accuracy of the position and orientation of the 3D scanner. Finally, a combined measurement system is established, and validation experiments are carried out in laboratory within a distance of 4 m. The calibration experiment results demonstrate that the max and mean errors of the coordinate transformation have been reduced from 0.037 and 0.022 mm to 0.021 and 0.0122 mm. Additionally, the measurement experiment results also show that the combined measurement system features high accuracy.

Monodisperse silica nanoparticle suspension for developing latent blood fingermarks.

Traditional fingermark developing methods are unsuitable for developing and extracting latent blood fingermarks on dark surfaces at crime scene because of their ineffectiveness or tedious operation procedures. In the present work, an effective and simple method was developed to serve this purpose using a suspension of monodisperse silica nanoparticles (MSNs). A suspension of 0.1 g/mL of MSNs was prepared by dispersing MSNs ultrasonically into an ethanol solution containing 1.0% Tween 80 and then uniformly sprayed onto the latent blood fingermarks on black plastic bags. Approximately 20 s later, ethanol was sprayed to clean the superfluous developing liquid. After the ethanol had evaporated, the latent fingermarks became visible as a result of the photonic crystal effect produced by the MSNs that had adsorbed to the fingermark ridges. The developed fingermarks were then photographed using a digital camera under a white or monospectral light source, revealing fine ridges and clear fingermark details. This novel, simple and effective method uses the photonic crystal effect of MSNs to develop latent blood fingermarks without the need for surface functionalization and conjugation to dye or fluorescently label molecules. The method can detect latent blood fingermarks that have been retained on a black plastic bag surface for at least 30 d. Given the simplicity and effectiveness of the developed method, MSNs may be a useful alternative material for use in developing latent fingermarks. Further research on the topic is warranted.

Astrocyte-derived exosomes transfer miR-190b to inhibit oxygen and glucose deprivation-induced autophagy and neuronal apoptosis.

Our previous work has verified that astrocytes (AS)-derived exosomes (AS-Exo) inhibited autophagy and ameliorated neuronal damage in experimental ischemic stroke. However, the mechanism of AS-Exo regulation of autophagy remains unclear. The aim of this study was to investigate the regulatory mechanism of AS-Exo on neuronal autophagy. The mouse hippocampal neuronal cell line HT-22 was cultured in oxygen and glucose deprivation (OGD) condition to mimic ischemic injury. The primary astrocytes were used to isolate exosomes. Exosome labeling and uptake by HT-22 cells were observed by confocal laser microscopy. miR-190b expression was determined by qRT-PCR. HT-22 cell vitality and apoptosis were determined by CCK-8 assay and TUNEL staining, respectively. Levels of TNF-α, IL-6 and IL-1ß were analyzed by ELISA. Protein levels of apoptosis-related cleaved caspase-3, Bax, Bcl-2 and autophagy-related Beclin-1, LC3-I/II, Atg7, P62 were determined by western blot. A dual-luciferase reporter assay was performed to confirm the direct interaction between miR-190b and Atg7. miR-190b expression in AS-Exo was found to be significantly higher than that in AS. AS-Exo-mediated transfer of miR-190b attenuated OGD-induced neuronal apoptosis via suppressing autophagy. Moreover, Atg7 was identified as a target of miR-190b. AS-Exo-mediated transfer of miR-190b regulated autophagy by targeting Atg7. Collectively, our data indicated that AS-Exo transferred miR-190b to inhibit OGD-induced autophagy and neuronal apoptosis.

Nonlinear optical properties of InP/ZnS core-shell quantum dots.

The nonlinear optical properties of an InP/ZnS core-shell quantum dot toluene solution were investigated using a Z-scan and transient absorption technique with femtosecond pulses and nanosecond pulses at 532 nm wavelengths, respectively. The research results showed that InP/ZnS core-shell quantum dots exhibited saturated absorption under the excitation of femtosecond pulses, and the switch from saturated absorption to reverse saturated absorption was observed under the excitation of nanosecond pulses. The mechanism of the switch was attributed to excited-state absorption. Moreover, the nonlinear refraction was shown as self-focusing and self-defocusing under the excitation of femtosecond and nanosecond pulses, respectively, which were attributed to the Kerr effect of electrons and the thermal effect of InP/ZnS quantum dots, respectively. The investigations show that InP/ZnS core-shell quantum dots are good materials, and have many potential applications in optical and electrical fields.

Astrocyte-derived exosomes suppress autophagy and ameliorate neuronal damage in experimental ischemic stroke.

The aim of this study was to investigate the role of astrocyte-derived exosomes (AS-Exo) on neuronal damage in ischemic stroke. We isolated astrocytes from 3- to 4-day-old C57BL/6 mice and astrocytes were identified by GFAP immunostaining. Exosomes were obtained from astrocyte supernatant by overspeed centrifugation. For investigating the effect of AS-Exo on the apoptosis of neurons after oxygen and glucose deprivation (OGD), the exosome labeling and uptake by neurons were observed by confocal laser microscopy, then HT-22 cell vitality and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assay and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in OGD-induced HT-22 was analyzed by Enzyme-linked immunosorbent assay (ELISA). Apoptosis-related protein in HT-22 was analyzed by Western blot. For investigating the effect of AS-Exo on the OGD neurons autophagy, expression of Beclin-1, LC3-I, LC3-II and P62 in OGD-induced HT-22 was analyzed by Western blot. For animal experiments, C57BL/6 mice (6-8 weeks old) models of middle cerebral artery occlusion were used to create permanent focal ischemia. AS-Exo were injected intravenously through the tail vein into ischemic mice at a concentration of 80 µg per 2 ml after 60 min of the ligation operation The results showed that AS-Exo enhanced neurons viability; inhibited OGD-induced apoptosis, inhibited OGD-induced expressions of caspase-3 and Bax and levels of TNF-α, IL-6 and IL-1ß in HT-22 cells. Further findings showed AS-Exo inhibited OGD-induced neurons apoptosis via regulating autophagy. AS-Exo ameliorated neuronal damage through regulating autophagy in vivo. Our data indicate that AS-Exo suppress autophagy and ameliorate neuronal damage in experimental ischemic stroke.

Enhanced antitumor effects of radiotherapy combined local nimustine delivery rendezvousing with oral temozolomide chemotherapy in glioblastoma patients.

BACKGROUND: Glioblastoma (GBM) is one of the worst cancers with bad prognosis despite systemic chemotherapy and radiotherapy after surgery. METHODS: In this study, 71 patients with GBM were enrolled and randomly assigned to two groups: Receiving radiotherapy with concomitant and adjuvant temozolomide (TMZ) (TMZ, standard therapy) after surgery, or receiving radiotherapy with concomitant and adjuvant local delivery of nimustine (ACNU) rendezvousing with oral TMZ (rendezvous therapy). In the follow-up of all patients and the progression-free survival (PFS), overall survival (OS), Karnofsky performance score (KPS) and toxicities were recorded. RESULTS: For the whole cohort, the median OS was 18.0 months, and the median PFS was 7.8 months. A significantly longer OS was observed in patients received rendezvous therapy than those who receiving standard therapy (18.5 months vs. 16.0 months; P = 0.014), as well as PFS (8.8 months vs. 7.0 months; P = 0.008). The KPS ≥70 rates were 81.8%, 40.9%, 20.5% in 1, 2, and 3 years for the rendezvous therapy group, significantly superior to standard therapy group. The most common toxicities were tolerable gastrointestinal reaction, liver dysfunction, and hematological toxicities, which were relieved with symptomatic treatment. Grade 3 or 4 toxicity was documented in 8 (18.3%) patients in rendezvous therapy group, while it was observed in 6 (22.2%) patients in standard therapy group during whole treatment process. CONCLUSIONS: Compared to standard therapy, the antitumor effects of rendezvous therapy were more effective in GBM patients without increasing the toxicities.

Comparison of autologous bone marrow mononuclear cells transplantation and mobilization by granulocyte colony-stimulating factor in experimental spinal injury.

BACKGROUND: Recent studies have shown that autologous adult stem cells may be a protocol of treatment for spinal cord injury (SCI) in humans. The purpose of this study was to compare the effect of an injection of autologous bone marrow mononuclear cells (BMMCs) and bone-marrow cell mobilization induced by granulocyte colony stimulating factor (G-CSF) in rats with SCI. METHODS: Adult rats were assigned into three groups: control group (SCI only), SCI + BMMCs, and SCI + G - CSF. Neurological scores and electrophysiological testing were done in all rats before SCI, and at 1, 7, 14, 28, 56 days post-SCI. Simultaneously, immunohistochemical labeling and TUNEL assay were performed at the given time. RESULTS: From 1 week post-SCI onward, animals treated with BMMCs or G-CSF had higher BBB scores than control group. Motor and somatosensory evoked potentials (MEPs and SEPs, respectively) of the treated group were significantly better than those in control group at 2 weeks. After sacrifice, compared with the control, animals treated with BMMCs and G-CSF significantly increased expressions of Brdu, NSE, GFAP, Factor VIII, BDNF, and reduced expression of apoptosis cells around the lesion site. Our results indicate that administration of BMMCs and G-CSF in a SCI model achieves similarly positive effect on functional and histologic recovery. CONCLUSIONS: The use of G-CSF may be a viable alternative to BMMCs for autograft in patients with SCI.