Long noncoding RNA UCA1 promotes the chondrogenic differentiation of human bone marrow mesenchymal stem cells via regulating PARP1 ubiquitination.

Bone marrow mesenchymal stem cells (BMSCs) possess the potential to differentiate into cartilage cells. Long noncoding RNA (lncRNAs) urothelial carcinoma associated 1 (UCA1) has been confirmed to improve the chondrogenic differentiation of marrow mesenchymal stem cells (MSCs). Herein, we further investigated the effects and underlying mechanisms of these processes. The expression of UCA1 was positively associated with chondrogenic differentiation and the knockdown of UCA1 has been shown to attenuate the expression of chondrogenic markers. RNA pull-down assay and RNA immunoprecipitation showed that UCA1 could directly bind to PARP1 protein. UCA1 could improve PARP1 protein via facilitating USP9X-mediated PARP1 deubiquitination. Then these processes stimulated the NF-κB signaling pathway. In addition, PARP1 was declined in UCA1 knockdown cells, and silencing of PARP1 could diminish the increasing effects of UCA1 on the chondrogenic differentiation from MSCs and signaling pathway activation. Collectively, these outcomes suggest that UCA1 could act as a mediator of PARP1 protein ubiquitination and develop the chondrogenic differentiation of MSCs.

An innovative approach to assess spinal canal expansion following French-door cervical laminoplasty by intraoperative ultrasonography.

OBJECTIVE: To investigate the feasibility and effectiveness of applying intraoperative ultrasound (IOUS) to evaluate spinal canal expansion in patients undergoing French-door cervical laminoplasty (FDCL). MATERIALS AND METHODS: Twenty-five patients who underwent FDCL for multilevel degenerative cervical myelopathy were prospectively recruited. Formulae describing the relationship between laminoplasty opening angle (LOA) and laminoplasty opening size, the increase in sagittal canal diameter and the spinal canal area were deduced with trigonometric functions. The LOA was measured with IOUS imaging during surgery, and other spinal canal parameters were assessed. Actual spinal canal enlargement was verified on postoperative CT images. Linear correlation analysis and Bland‒Altman analysis were used to evaluate correlation and agreement between the intraoperative and postoperative measurements. RESULTS: The LOA at C5 measured with IOUS was 27.54 ± 3.12°, and it was 27.23 ± 3.02° on postoperative CT imaging. Linear correlation analysis revealed a significant correlation between IOUS and postoperative CT measurements (r = 0.88; p < 0.01). Bland-Altman plots showed good agreement between these two methods, with a mean difference of 0.30°. For other spinal canal expansion parameter measurements, correlation analysis showed a moderate to a high degree of correlation (p < 0.01), and Bland-Altman analysis indicated good agreement. CONCLUSION: In conclusion, during the French-door cervical laminoplasty procedure, application of IOUS can accurately evaluate spinal canal expansion. This innovative method may be helpful in improving surgical accuracy by enabling the operator to measure and determine canal enlargement during surgery, leading to ideal clinical outcomes and fewer postoperative complications. CLINICAL RELEVANCE STATEMENT: The use of intraoperative ultrasonography to assess spinal canal expansion following French-door cervical laminoplasty may improve outcomes for patients undergoing this procedure by providing more accurate measurements of spinal canal expansion. KEY POINTS: • Spinal canal expansion after French-door cervical laminoplasty substantially influences operative prognosis; insufficient or excessive lamina opening may result in unexpected outcomes. • Prediction of spinal canal expansion during surgery was previously impracticable, but based on this study, intraoperative ultrasonography offers an innovative approach and strongly agrees with postoperative CT measurement. • Since this is the first research to offer real-time canal expansion guidance for cervical laminoplasty, it may improve the accuracy of the operation and produce ideal clinical outcomes with fewer postoperative complications.

Predictive value of intraoperative contrast-enhanced ultrasound in functional recovery of non-traumatic cervical spinal cord injury.

OBJECTIVES: To evaluate the ability of intraoperative CEUS to predict neurological recovery in patients with degenerative cervical myelopathy (DCM). METHODS: Twenty-six patients with DCM who underwent laminoplasty and intraoperative ultrasound (IOUS) were included in this prospective study. The modified Japanese Orthopaedic Association (mJOA) scores and MRI were assessed before surgery and 12 months postoperatively. The anteroposterior diameter (APD), maximum spinal cord compression (MSCC), and area of signal changes in the cord at the compressed and normal levels were measured and compared using MRI and IOUS. Conventional blood flow and CEUS indices (time to peak, ascending slope, peak intensity (PI), and area under the curve (AUC)) at different levels during IOUS were calculated and analysed. Correlations between all indicators and the neurological recovery rate were evaluated. RESULTS: All patients underwent IOUS and intraoperative CEUS, and the total recovery rate was 50.7 ± 33.3%. APD and MSCC improved significantly (p < 0.01). The recovery rate of the hyperechoic lesion group was significantly worse than that of the isoechoic group (p = 0.016). 22 patients were analysed by contrast analysis software. PI was higher in the compressed zone than in the normal zone (24.58 ± 3.19 versus 22.43 ± 2.39, p = 0.019). ΔPI compress-normal and ΔAUC compress-normal of the hyperechoic lesion group were significantly higher than those of the isoechoic group (median 2.19 versus 0.55, p = 0.017; 135.7 versus 21.54, p = 0.014, respectively), and both indices were moderately negatively correlated with the recovery rate (r = - 0.463, p = 0.030; r = - 0.466, p = 0.029). CONCLUSIONS: Signal changes and microvascular perfusion evaluated using CEUS during surgery are valuable predictors of cervical myelopathy prognosis. CLINICAL RELEVANCE STATEMENT: In the spinal cord compression area of degenerative cervical myelopathy, especially in the hyperechoic lesions, intraoperative CEUS showed more significant contrast agent perfusion than in the normal area, and the degree was negatively correlated with the neurological prognosis. KEY POINTS: • Recovery rates in patients with hyperechoic findings were lower than those of patients without lesions detected during intraoperative ultrasound. • The peak intensity of CEUS was higher in compressed zones than in the normal parts of the spinal cord. • Quantitative CEUS comparisons of the peak intensity and area under the curve at the compressed and normal levels of the spinal cord revealed differences that were inversely correlated to the recovery rate.

Distinct Photochemistry of Odd-Carbon PAHs from the Even-Carbon Ones During the Photoaging and Analysis of Soot.

Polycyclic aromatic hydrocarbons (PAHs) are the primary organic carbons in soot. In addition to PAHs with even carbon numbers (PAHeven), substantial odd-carbon PAHs (PAHodd) have been widely observed in soot and ambient particles. Analyzing and understanding the photoaging of these compounds are essential for assessing their environmental effects. Here, using laser desorption ionization mass spectrometry (LDI-MS), we reveal the substantially different photoreactivity of PAHodd from PAHeven in the aging process and their MS detection through their distinct behaviors in the presence and absence of elemental carbon (EC) in soot. During direct photooxidation of organic carbon (OC) alone, the PAHeven are oxidized more rapidly than the PAHodd. However, the degradation of PAHodd becomes preponderant over PAHeven in the presence of EC during photoaging of the whole soot. All of these observations are proposed to originate from the more rapid hydrogen abstraction reaction from PAHodd in the EC-photosensitized reaction, owing to its unique structure of a single sp3-hybridized carbon site. Our findings reveal the photoreactivity and reaction mechanism of PAHodd for the first time, providing a comprehensive understanding of the oxidation of PAHs at a molecular level during soot aging and highlight the enhanced effect of EC on PAHodd ionization in LDI-MS analysis.

Effect of a magnetic field on droplet freezing and frost formation on cold surfaces.

The effect of a magnetic field on condensed droplet freezing and frost formation was investigated using visualized experimental devices in this study. The size, shape, freezing time of droplets, and frost shape on the magnetic field considerably differ from those on the nonmagnetic surface. Moreover, the magnetic field could suppress droplet freezing and frost formation. The magnetic field suppression effect on droplet freezing and frost formation was analyzed according to the polarity characteristics of water molecules.

Preliminarily exploring the intraoperative ultrasonography characteristics of patients with degenerative cervical myelopathy.

BACKGROUND: How to quickly read and interpret intraoperative ultrasound (IOUS) images of patients with degenerative cervical myelopathy (DCM) to obtain meaningful information? Few studies have systematically explored this topic. PURPOSE: To systematically and comprehensively explore the IOUS characteristics of patients with DCM. MATERIALS AND METHODS: This single-center study retrospectively included patients with DCM who underwent French-door laminoplasty (FDL) with IOUS guidance from October 2019 to March 2022. One-way ANOVA and Pearson's /Spearman's correlation analysis were used to analyze the correlations between the cross-sectional area of the spinal cord (SC) and individual characteristics; the relationships between the morphology, echogenicity, pulsation, decompression statuses, compression types of SC, location of the spinal cord central echo complex (SCCEC) and the disease severity (the preoperative Japanese Orthopedic Association score, preJOA score); the difference of the spinal cord pulsation amplitude(SCPA) and the SCCEC forward movement rate (FMR) between the compressed areas(CAs) and the non-compressed areas (NCAs). RESULTS: A total of 38 patients were successfully enrolled (30 males and 8 females), and the mean age was 57.05 ± 10.29 (27-75) years. The cross-sectional area of the SC was negatively correlated with age (r = - 0.441, p = 0.006). The preJOA score was significantly lower in the heterogeneous group than in the homogeneous group (P < 0.05, p = 0.005). The hyperechoic area (HEA) was negatively while the SCCEC FMR was positively correlated with the preJOA score (r = - 0.334, p = 0.020; r = 0.286, p = 0.041). The SCCEC FMR and SCPA in CAs were significantly greater than those in NCAs (p < 0.05, p = 0.007; P < 0.001, P = 0.000). CONCLUSION: The cross-sectional area of the SC decreases with age in adults. More changes in intramedullary echogenicity and less moving forward of the SCCEC often indicate poor SC status, and the SCCEC FMR and SCPA are more pronounced in CAs.

Quantitative evaluation of the impact of indoor relative humidity on deposition of aerosols generated during tooth grinding in a real-world clinical setting.

OBJECTIVES: Exposure to aerosol particles generated from tooth grinding has a negative impact on the health of dental personnel. The aim of this study was to quantitatively analyze the impact of indoor relative humidity (IRH) on the deposition of these suspended particles in a well-controlled dental environment. MATERIALS AND METHODS: In this study, a humidity control system was employed to effectively regulate and maintain indoor relative humidity (IRH). A novel computer-assisted numerical control system was developed to pre-treat the molar specimens, and accurately simulate clinical tooth grinding procedures. Each procedure was performed in triplicate, with an online real-time particle counter (ORPC; TR-8301, TongrenCo.) measuring aerosol production. All testing devices were controlled remotely. The data obtained were statistically analyzed using descriptive statistics and non-parametric tests (Kruskal-Wallis/ Dunn's post hoc test with Bonferroni correction, p < 0.05). RESULTS: The findings showed that with increasing IRH, the maximum peak concentration of aerosol particles decreased by 397% from 6.51 × 107 particles/m3 at 30% to 1.64 × 107 particles/m3 at 80%. The Kruskal-Wallis test results indicated a statistically significant effect of IRH on the aerosol increment (p < 0.05). CONCLUSIONS: Increasing the IRH level can effectively promote the deposition of aerosol particles, with a return to baseline within 15 min after reaching 60% or above. CLINICAL RELEVANCE: Our study suggested that maintaining IRH above 70% during the cleaning process, allowing natural recovery to ambient humidity levels within 15 min after cleaning, and taking basic precautions, may lead to an adequate reduction in the possible health risks of aerosol contamination.

Study of aerosol dispersion and control in dental practice.

OBJECTIVES: In this study, we investigated the dispersion patterns of aerosols and droplets in dental clinics and developed a suction device to evaluate its effectiveness in reducing aerosols during dental procedures. MATERIALS AND METHODS: Firstly, the continuous images of oral aerosols and droplets were photographed with a high-speed camera, and the trajectories of these particles were recognized and processed by Image J to determine key parameters affecting particle dispersion: diffusion velocity, distance, and angle. Secondly, based on the parameter data, the flow field of aerosol particles around the oral cavity was simulated using computational fluid dynamics (CFD), and the flow field under adsorption conditions was simulated to demonstrate the aerodynamic characteristics and capture efficiencies of the single-channel and three-channel adsorption ports at different pressures. Finally, according to the simulated data, a three-channel suction device was developed, and the capture efficiency of the device was tested by the fluorescein tracer method. RESULTS: The dispersion experimental data showed that aerosol particles' maximum diffusion velocity, distance, and angle were 6.2 m/s, 0.55 m, and 130°, respectively. The simulated aerosol flow-field distribution was consistent with the aerosol dispersion patterns. The adsorption simulation results showed that the outlet flow rate of single-channel adsorption was 184.5 L/s at - 350 Pa, and the aerosol capture efficiency could reach 79.4%. At - 350 Pa and - 150 Pa, the outlet flow rate of three-channel adsorption was 228.9 L/s, and the capture efficiency was 99.23%. The adsorption experimental data showed that the capture efficiency of three-channel suction device was 97.71%. CONCLUSIONS: A three-channel suction device was designed by simulations and experiments, which can capture most aerosols in the dental clinic and prevent them from spreading. CLINICAL RELEVANCE: Using three-channel suction devices during oral treatment effectively reduces the spread of oral aerosols, which is essential to prevent the spread of epidemics and ensure the health and safety of patients and dental staff.

Tumor-microenvironment responsive nano-carrier system for therapy of prostate cancer.

Poor selectivity, low bioavailability and serious systemic side-effects have limited the application of traditional chemotherapy method for treatment of prostate cancer. Stimuli-responsive drug delivery systems for chemotherapy are mainly based on the unique characteristics of tumor microenvironment. In this study, the GSH-sensitive poly-TTG-SS@DTX NPs (DTX-loaded poly-Tetraethylene glycol nanoparticles) were designed and synthesized, which were characterized with nanosized diameter (92.8 ± 2.5 nm) and negatively charged surface charge (-24.7 ± 5.56 mV). Experiments in vitro showed that poly-TTG-SS@DTX NPs had good compatibility to healthy cells and strong anti-tumor effect because of rapid and sustained drug release of DTX from poly-TTG-SS@DTX NPs under the tumor-microenvironment condition. The cellular activity remained greater than 90% when the concentration of poly-TTG-SS NPs reached as high as 100 µg/mL treated on healthy cells. The killing effect of DTX loading NPs group on C4-2 cells was stronger than that of free anti-tumor drug and free DTX combined with the blank nano-carrier (25.21% vs 19.93% vs 20.96%). In conclusion, poly-TTG-SS@DTX NPs may provide a new therapeutic strategy for the chemotherapy of prostate cancer.

Salinity elevates Cd bioaccumulation of sea rice cultured under co-exposure of cadmium and salt.

Salt-tolerant rice (sea rice) is a key cultivar for increasing rice yields in salinity soil. The co-existence of salinity and cadmium (Cd) toxicities in the plant-soil system has become a great challenge for sustainable agriculture, especially in some estuaries and coastal areas. However, little information is available on the Cd accumulating features of sea rice under the co-stress of Cd and salinity. In this work, a hydroponic experiment with combined Cd (0, 0.2, 0.8 mg/L Cd2+) and saline (0, 0.6%, and 1.2% NaCl, W/V) levels and a pot experiment were set to evaluate the Cd toxic risks of sea rice. The hydroponic results showed that more Cd accumulated in sea rice than that in the reported high-Cd-accumulating rice, Chang Xianggu. It indicated an interesting synergistic effect between Cd and Na levels in sea rice, and the Cd level rose significantly with a concomitant increase in Na level in both shoot (r = 0.54, p < 0.01) and root (r = 0.66, p < 0.01) of sea rice. Lower MDA content was found in sea rice, implying that the salt addition probably triggered the defensive ability against oxidative stress. The pot experiment indicated that the coexistent Cd and salinity stress further inhibited the rice growth and rice yield, and the Cd concentration in rice grain was below 0.2 mg/kg. Collectively, this work provides a general understanding of the co-stress of Cd and salinity on the growth and Cd accumulation of sea rice. Additional work is required to precisely identify the phytoremediation potential of sea rice in Cd-polluted saline soil.

Potential of intraoperative ultrasonographic assessment of the spinal cord central echo complex in predicting postoperative neurological recovery of degenerative cervical myelopathy.

BACKGROUND AND PURPOSE: The spinal cord central echo complex (SCCEC) is a special ultrasonography-based intramedullary structure, but its clinical significance in degenerative cervical myelopathy (DCM) is undefined. This study aimed to explore the potential of the SCCEC in predicting postoperative neurological recovery in DCM. METHODS: Thirty-two DCM patients who underwent intraoperative ultrasonography-guided French-door laminoplasty were prospectively enrolled. The modified Japanese Orthopaedic Association (mJOA) score was evaluated preoperatively and 12 months postoperatively. SCCEC width (SCCEC-W), and anteroposterior diameter (APD) and transverse diameter (TD) of the spinal cord were measured on transverse ultrasonographic images, while the tissue widths from anterior and posterior borders of the spinal cord to the SCCEC were measured on sagittal ultrasonographic images. The APD of the spinal cord and occupying rate of the spinal canal were measured on preoperative magnetic resonance imaging (MRI). RESULTS: All patients achieved improvements in mJOA scores, with an average recovery rate (RR) of 68.69 ± 20.22%. Spearman correlation analysis revealed that SCCEC-W, and ratios between the SCCEC-W and APD/TD based on ultrasonography, correlated moderately with mJOA score RR, with coefficients of -0.527, -0.605 and -0.514, respectively. The ratio between SCCEC-W and ultrasonographic TD correlated moderately with preoperative APD of the spinal cord. The MRI measurements and ultrasonography-based tissue widths showed no significant correlation with mJOA score RR. CONCLUSIONS: The SCCEC may have predictive potential as an intraoperative indicator of neurological recovery in treating DCM. SCCEC-W may be related to spinal cord compression in DCM.

Comparison of the outcome of different bone grafts combined with modified core decompression for the treatment of ARCO II stage femoral head necrosis.

PURPOSE: Treatment of ONFH at an early stage is a challenging issue. The modified minimally invasive core decompression combined with bone graft implantation remains controversial. This study aimed to compare the early-middle outcomes of four groups with different bone grafts. METHODS: A total of 182 patients (192 hips) with ONFH at the ARCO II stage were randomly divided into four groups. The free fibular graft group (FFG), free vascularized fibular graft group (FVFG), autologous iliac bone group (ABG), and ß-tricalcium bioceramics phosphate graft (ß-TCPG) group. Each group was treated with the modified minimally invasive core decompression and bone graft implantation. The operation time and blood loss were recorded by the same observer. The clinical outcome was evaluated by the Harris Hip Score and VAS score (before, 14 days after surgery, and at the last follow-up). The radiographic progression of ONFH was evaluated at least 36 months of follow-up. RESULTS: All cases were successful without any complications after the operation. The patients were followed up for 42 to 48 (44.62 ± 1.81) months. There were statistically significant differences among the four groups in operation time (F value = 1520.67; P < 0.01) and blood loss (F value = 5366.81; P < 0.01). The Harris Hip Score in each group was improved significantly from pre-operation to last follow-up (all P < 0.01). At the last follow-up, the difference in the Harris Hip Score in each group was not statistically significant (F value = 0.54; P = 0.984). The VAS scores in each group were decreased significantly from the pre-operation to14 days after surgery (all P < 0.01). At 14 days after surgery, the difference in the VAS score in each group was not statistically significant (F value = 0.64; P = 0.59). At the last follow-up, three hips collapsed on the femoral head in the FFG group, two in the FVFG group, two in the ABG group, and three in the ß-TCPG group. CONCLUSION: The four different bone graft implantation showed satisfactory early-middle outcomes. As compared to other bone grafts, the ß-TCP bioceramics graft has the advantages of shorter operation time and lesser blood loss. It may be a choice as a bone graft for the treatment of ONFH at an early stage.

Overexpression of Rictor in the injured spinal cord promotes functional recovery in a rat model of spinal cord injury.

Rictor is an essential component that directly activates the mammalian target of rapamycin (mTOR) activity, which contributes to the intrinsic axon growth capacity of adult sensory neurons after injury. However, whether its action also applies to regeneration after spinal cord injury (SCI) remains unknown. In this study, rats were given spinal cord contusion at the T9-10 level to establish the SCI model and were subsequently treated with intraspinal cord injection of a Rictor overexpression lentiviral vector to locally upregulate the Rictor expression in the injured spinal cord. Thereafter, we investigated the therapeutic effects of Rictor overexpression in the injured spinal cords of SCI rats. Rictor overexpression not only significantly attenuated the acute inflammatory response and cell death after SCI but also markedly increased the shift in macrophages around the lesion from the M1 to M2 phenotype compared to those of the control lentiviral vector injection-treated group. Furthermore, Rictor overexpression dramatically increased neurogenesis in the lesion epicenter, subsequently promoting the tissue repair and functional recovery in SCI rats. Interestingly, the mechanism underlying the beneficial effects of Rictor overexpression on SCI may be associated with the Rictor overexpression playing a role in the anti-inflammatory response and driving macrophage polarization toward the M2 phenotype, which benefits resident neuronal and oligodendrocyte survival. Our findings demonstrate that Rictor is an effective target that affects the generation of molecules that inhibit spinal cord regeneration. In conclusion, localized Rictor overexpression represents a promising potential strategy for the repair of SCI.

Inadequate spinal cord expansion in intraoperative ultrasound after decompression may predict neurological recovery of degenerative cervical myelopathy.

OBJECTIVE: To compare the neurological recovery between patients with adequate and inadequate immediate spinal cord expansion after sufficient decompression in degenerative cervical myelopathy (DCM). METHODS: Twenty-seven patients subjected to French-door laminoplasty underwent the guidance of intraoperative ultrasound (IOUS) and were prospectively included. The modified Japanese Orthopedic Association (mJOA) score was evaluated before surgery and at 12 months postoperatively. The maximum spinal cord compression (MSCC) after sufficient decompression was calculated on the IOUS image; patients were divided into adequate (MSCC ≥ 0.95) and inadequate (MSCC < 0.95) expansion groups according to the MSCC. The mJOA score, spinal cord hyperechogenicity, age at surgery, symptom duration, occupational rate of the spinal canal, and the minimum anteroposterior diameter of the spinal cord between the two groups were compared. RESULTS: Initially, 2 cases showed residual compression on IOUS; after further decompression, all patients acquired sufficient decompression. All patients achieved improvements in mJOA scores with an average recovery rate of 68.6 ± 20.3%. The recovery rate of the mJOA score of the inadequate expansion group was significantly inferior to that of the adequate expansion group (59.2 ± 21.7% versus 76.2 ± 16.2%, p = 0.028). The spinal cord hyperechogenicity was more common in the inadequate expansion group, while the spinal cord anteroposterior diameter of the inadequate expansion group was significantly smaller than that of the adequate expansion group. CONCLUSIONS: The application of IOUS in French-door laminoplasty could help to confirm sufficient decompression for the treatment of DCM. Inadequate spinal cord expansion after sufficient decompression had the high possibility of predicting less satisfactory neurological recovery of DCM. KEY POINTS: • The intraoperative ultrasound revealed that not all degenerative cervical myelopathy patients acquired adequate spinal cord expansion after sufficient decompression. • Patients who failed to acquire adequate spinal cord expansion commonly combined with spinal cord hyperechogenicity and trended to achieve less satisfactory neurological recovery after surgical decompression. • Inadequate spinal cord expansion after sufficient decompression had the high possibility of predicting less satisfactory neurological recovery of patients with degenerative cervical myelopathy.

Modeling and prediction of the transmission dynamics of COVID-19 based on the SINDy-LM method.

The transmission dynamics of COVID-19 is investigated in this study. A SINDy-LM modeling method that can effectively balance model complexity and prediction accuracy is proposed based on data-driven technique. First, the Sparse Identification of Nonlinear Dynamical systems (SINDy) method is used to discover and describe the nonlinear functional relationship between the dynamic terms in the model in accordance with the observation data of the COVID-19 epidemic. Moreover, the Levenberg-Marquardt (LM) algorithm is utilized to optimize the obtained model for improving the accuracy of the SINDy algorithm. Second, the obtained model, which is consistent with the logistic model in mathematical form with small errors and high robustness, is leveraged to review the epidemic situation in China. Otherwise, the evolution of the epidemic in Australia and Egypt is predicted, which demonstrates that this method has universality for constructing the global COVID-19 model. The proposed model is also compared with the extreme learning machine (ELM), which shows that the prediction accuracy of the SINDy-LM method outperforms that of the ELM method and the generated model has higher sparsity.

Silencing Celsr2 inhibits the proliferation and migration of Schwann cells through suppressing the Wnt/ß-catenin signaling pathway.

After a peripheral nerve injury, the remaining Schwann cells undergo proliferation and adopt a migratory phenotype to prepare for the regeneration of nerves. Celsr2 has been reported to play an important role in the development and maintenance of the function of the nervous system. However, the role and mechanism of Celsr2 during peripheral nerve regeneration remain unknown. Here, we showed that after sciatic nerve injury, Celsr2 mRNA and protein were significantly increased in nerve tissues. In addition, silencing Celsr2 decreased the ki67-positve portion and the migration distance of Schwann cells in vivo. In vitro, the results of MTT and EdU staining, transwell and wound healing assays indicated that Celsr2 siRNA-transfected primary Schwann cells showed significant decrease in proliferation and migration compared to that seen in negative control (NC)-transfected cells. Furthermore, we found that Wnt/ß-catenin luciferase activity was reduced, as were the expression of ß-catenin in the nucleus and the mRNA levels of its downstream genes Cyclin D1 and MMP-7 in Celsr2 siRNA-transfected primary Schwann cells. Further investigations showed that silencing Celsr2 inhibited the phosphorylation of GSK3ß. Moreover, specific activators of the Wnt/ß-catenin pathway, LiCl or mutant ß-catenin (S33Y), partially reversed the inhibitory effect of Celsr2 siRNA. Taken together, our data indicated that silencing Celsr2 inhibited Schwann cells migration and proliferation through the suppressing Wnt/ß-catenin pathway, providing a potential target for peripheral nerve regeneration.

Short-term predictive potential of quantitative assessment of spinal cord impairment in patients undergoing French-door Laminoplasty for degenerative cervical myelopathy: preliminary results of an exploratory study exploiting intraoperative ultrasound data.

BACKGROUND: To study the correlation of neurological function in degenerative cervical myelopathy (DCM) patients with quantitative assessment of spinal cord compression and impairment by intraoperative ultrasound imaging (IOUSI). METHODS: Twenty-three patients who underwent French-Door laminoplasty for multilevel DCM were followed for 6 months. Modified Japanese Orthopaedic Association (mJOA) score and cervical MRI were assessed before surgery and at postoperative 6 months. IOUS, used to guide decompression, were recorded. The anteroposterior diameter (APD) and the gray values of the IOUSI hyperechogenicity of the midsagittal IOUSI at the narrowest level and at the lesion-free level, and the APD and traverse diameter at the traverse maximum compression level of IOUSI were measured. Maximum spinal cord compression (MSCC), compression rate (CR), and IOUSI gray value ratio (Rgray) were calculated. The appearance of preoperative T2W MRI increased signal intensity (ISI), and the signal change rate (SCR) on postoperative T2W MRI of 9 patients were also measured and calculated, and compared with that of IOUSI hyperechogenicity. RESULTS: Average mJOA score increased significantly from 11.57 ± 2.67 before surgery to 15.39 ± 1.50 at 6 months after surgery, with an average recovery rate (RR) of 71.11 ± 22.81%. The difference between the appearance of preoperative T2W MRI ISI and IOUSI hyperechogenicity was not significant. Spearman correlation analysis found that the IOUSI Rgray were negatively correlated with the RR of mJOA score with a coefficient of - 0.77, and the IOUSI Rgray was not correlated with the postoperative MRI SCR. CONCLUSIONS: In DCM patients, the gray values of IOUSI can be measured accurately. The IOUSI Rgray correlated with postoperative neurological recovery significantly.

Short-term hypoxia upregulated Mas receptor expression to repress the AT1 R signaling pathway and attenuate Ang II-induced cardiomyocyte apoptosis.

Hypertension-stimulated cardiac hypertrophy and apoptosis play critical roles in the progression of heart failure. Our previous study suggested that hypertensive angiotensin II (Ang II) enhanced insulin-like growth factor receptor II (IGF-IIR) expression and cardiomyocyte apoptosis, which are involved JNK activation, sirtuin1 (SIRT1) degradation, and heat-shock transcription factor 1 (HSF1) acetylation. Moreover, previous studies have implied that short-term hypoxia (STH) might exert cardioprotective effects. However, the effects of STH on Ang II-induced cardiomyocyte apoptosis remain unknown. In this study, we found that STH reduced myocardial apoptosis caused by Ang II via upregulation of the Mas receptor (MasR) to inhibit the AT1 R signaling pathway. STH activates MasR to counteract the Ang II pro-apoptotic signaling cascade by inhibiting IGF-IIR expression via downregulation of JNK activation and reduction of SIRT1 degradation. Hence, HSF could remain deacetylated, and repress IGF-IIR expression. These effects decrease the activation of downstream pro-apoptotic and hypertrophic cascades and protect cardiomyocytes from Ang II-induced injury. In addition, we also found that silencing MasR expression enhanced Ang II-induced cardiac hypertrophy and the apoptosis signaling pathway. These findings suggest a critical role for MasR in cardiomyocyte survival. Altogether, our findings indicate that STH protects cardiomyocytes from Ang II-stimulated apoptosis. The protective effects of STH are associated with the upregulation of MasR to inhibit AT1 R signaling. STH could be a potential therapeutic strategy for cardiac diseases in hypertensive patients.

Simultaneous determination of 35 ultra-trace level organophosphorus pesticide residues in Sanjie Zhentong capsules of traditional Chinese medicine using ultra high performance liquid chromatography with tandem mass spectrometry.

The aim of this study was to develop an analytical method for the simultaneous determination of ultra-trace levels of 35 organophosphorus pesticide residues in Sanjie Zhentong capsules, a traditional Chinese medicine prescription. A method based on multiclass and multiresidue sample preparation was developed. First, samples were hydrated with water at 4°C. A ratio of 1:3 sample/water was used for each of the sample amounts. Then, different extraction solvents were screened. This step was followed by a dispersive solid-phase extraction clean-up procedure using both primary secondary amine and polyamide. A comprehensive sensitive multiresidue liquid chromatography tandem mass spectrometry method was investigated and validated. Good linearity was achieved in the range of 10-500 µg/kg for each analyte. The average recovery ranged from 70 to 120%, except for methamidophos, fonophos, diazinon, and chlorpyriphos-ethyl, the recoveries of which ranged from 60-70% at the lower concentration level. The precision values were lower than 10% for all the compounds in three concentration levels. The limits of detection and limits of quantification values were 0.01-2.1 and 0.05-3.4 µg/kg, respectively. The matrix effects were determined, and most of the compounds showed signal suppression. Finally, this optimized procedure was applied for the analysis of real samples.

[Simultaneous determination of six triterpenoid acids from Guizhi Fuling capsules by UPLC-MS/MS].

To establish a UPLC-MS/MS method for simultaneous determination of six triterpenoid constituents (pachymic acid, dehydropachymic acid, dehydrotumulosic acid, polyporenic acid C, dehydroeburicoic acid and dehydrotra metenolic acid) in Guizhi Fuling capsules (GFC). Chromatographic analysis was conducted on Agilent Porosheell 120 SB-C18 column (4.6 mm×150 mm, 2.7 µm), with 0.1% formic acid aqueous solution-methanol as the mobile phase for gradient elution at a flow rate of 0.4 mL•min-1. The column temperature was 30 ℃ and the sample size was 5 µL. The samples were analyzed by tandem mass spectrometer with negative electrospray ionization (ESI) source, and monitored under a multiple reaction monitoring (MRM) mode, with the quantitative ion pairs m/z 527.8→465.5 (pachymic acid), m/z 525.6→465.6 (dehydropachymic acid), m/z 483.4→337.3 (dehydrotumulosic acid), m/z 481.5→419.5 (polyporenic acid C), m/z 467.4→337.1 (dehydroeburicoic acid), m/z 453.4→337.0 (dehydrotra metenolic acid). Six triterpenoid acids showed good linear relationships within the investigated concentration ranges (r> 0.996 8), with RSDs of precision less than 6.2%, and all RSDs of repeatability less than 5.9%. The average recovery rate was 97.90%, 100.2%, 99.60%, 101.7%, 102.6% and 103.0% respectively. The method was rapid, accurate, repeatable and could be used as a method for quantitative determination of triterpenoid acids in Chinese medicine prescriptions, providing a reference method for the quality control of Guizhi Fuling capsules and providing a reference for the content determination for Chinese medicine prescriptions containing Poria cocos.