Research progress in clinical trials of stem cell therapy for stroke and neurodegenerative diseases.

The incidence of stroke and neurodegenerative diseases is gradually increasing in modern society, but there is still no treatment that is effective enough. Stem cells are cells that can reproduce (self-renew) and differentiate into the body, which have shown significance in basic research, while doctors have also taken them into clinical trials to determine their efficacy and safety. Existing clinical trials mainly include middle-aged and elderly patients with stroke or Parkinson's disease (mostly 40-80 years old), mainly involving injection of mesenchymal stem cells and bone marrow mesenchymal stem cells through the veins and the putamen, with a dosage of mostly 106-108 cells. The neural and motor functions of the patients were restored after stem cell therapy, and the safety was found to be good during the follow-up period of 3 months to 5 years. Here, we review all clinical trials and the latest advances in stroke, Alzheimer's disease, and Parkinson's disease, with the hope that stem cell therapy will be used in the clinic in the future to achieve effective treatment rates and benefit patients.

Discovery of imidazo[1,2-b]pyridazine macrocyclic derivatives as novel ALK inhibitors capable of combating multiple resistant mutants.

Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (TKI) often loses effectiveness against non-small cell lung malignancies (NSCLCs) with ALK gene rearrangements (ALK+). 19 novel imidazo[1,2-b]pyridazine macrocyclic derivatives were designed, synthesized, and tested for their biological activities in an effort to develop ALK inhibitors that would overcome second-generation ALK-TKIs, particularly the G1202R mutation and the lorlatinib-resistant L1196M/G1202R double mutations. Of all the target substances, O-10 had the most effective enzymatic inhibitory activity, with IC50 values for ALKWT, ALKG1202R, and ALKL1196M/G1202R of 2.6, 6.4, and 23 nM, respectively. O-10, on the other hand, reduced the growth of ALK-positive Karpas299, BaF3-EML4-ALKG1202R, and BaF3-EML4-ALKL1196M/G1202R cells with IC50 values of 38, 52, and 64 nM, respectively. This was equally effective to the reference drug Repotrectinib (IC50 = 40, 164, and 208 nM). The kinase selectivity profile, liver microsome stability test and in vivo pharmacokinetic properties in SD rats of compound O-10 were further evaluated. O-10 was regarded as an effective ALK inhibitor for the treatment of mutations overall.

The effects of ultrasonic vibration on riveting quality.

Ultrasonic vibration can reduce the forming force, decrease the friction in the metal forming process and improve the surface quality of the workpiece effectively. The effects of ultrasonic vibration on riveting quality were systematically studied by numerical simulation and experimental methods. The riveting force, interference, riveting head and microstructure of rivet under different vibration conditions were analyzed, in order to study the influence of the ultrasonic vibration on the riveting process. The study results show that the ultrasonic vibration can reduce the riveting force and decrease the friction. Thus, the flow of rivet material was promoted and the interference and interferometric uniformity were enlarged. Riveting quality was improved, and the improvement effect increased with the increase of amplitude. Compared with the conventional riveting, the relative interference was increased by 27.32% and the shear strength was increased by 17.16%, when the amplitude is 5.77 µm.

Making Every Step Count: Minute-by-Minute Characterization of Step Counts Augments Remote Activity Monitoring in People With Multiple Sclerosis.

Background: Ambulatory disability is common in people with multiple sclerosis (MS). Remote monitoring using average daily step count (STEPS) can assess physical activity (activity) and disability in MS. STEPS correlates with conventional metrics such as the expanded disability status scale (Expanded Disability Status Scale; EDSS), Timed-25 Foot walk (T25FW) and timed up and go (TUG). However, while STEPS as a summative measure characterizes the number of steps taken over a day, it does not reflect variability and intensity of activity. Objectives: Novel analytical methods were developed to describe how individuals spends time in various activity levels (e.g., continuous low versus short bouts of high) and the proportion of time spent at each activity level. Methods: 94 people with MS spanning the range of ambulatory impairment (unaffected to requiring bilateral assistance) were recruited into FITriMS study and asked to wear a Fitbit continuously for 1-year. Parametric distributions were fit to minute-by-minute step data. Adjusted R2 values for regressions between distributional fit parameters and STEPS with EDSS, TUG, T25FW and the patient-reported 12-item MS Walking scale (MSWS-12) were calculated over the first 4-weeks, adjusting for sex, age and disease duration. Results: Distributional fits determined that the best statistically-valid model across all subjects was a 3-compartment Gaussian Mixture Model (GMM) that characterizes the step behavior within 3 levels of activity: high, moderate and low. The correlation of GMM parameters for baseline step count measures with clinical assessments was improved when compared with STEPS (adjusted R2 values GMM vs. STEPS: TUG: 0.536 vs. 0.419, T25FW: 0.489 vs. 0.402, MSWS-12: 0.383 vs. 0.378, EDSS: 0.557 vs. 0.465). The GMM correlated more strongly (Kruskal-Wallis: p = 0.0001) than STEPS and gave further information not included in STEPS. Conclusions: Individuals' step distributions follow a 3-compartment GMM that better correlates with clinic-based performance measures compared with STEPS. These data support the existence of high-moderate-low levels of activity. GMM provides an interpretable framework to better understand the association between different levels of activity and clinical metrics and allows further analysis of walking behavior that takes step distribution and proportion of time at three levels of intensity into account.

Multi-wavelength coherent random laser in bio-microfibers.

In this paper, pure silk protein was extracted from Bombyx mori silks and fabricated into a new kind of disordered bio-microfiber structure using electrospinning technology. Coherent random lasing emission with low threshold was achieved in the silk fibroin fibers. The random lasing emission wavelength can be tuned in the range of 33 nm by controlling the pump location with different scattering strengths. Therefore, the bio-microfiber random lasers can be a wide spectral light source when the system is doped with a gain or energy transfer medium with a large fluorescence emission band. Application of the random lasers of the bio-microfibers as a low-coherence light source in speckle-free imaging had also been studied.

Ultrasensitive all-fiber inline Fabry-Perot strain sensors for aerodynamic measurements in hypersonic flows.

This work proposes an ultrasensitive, temperature-insensitive, all-fiber inline Fabry-Perot (FP) strain sensor for aerodynamic coefficients measurements of a hypervelocity ballistic correlation model 2 in a Φ1 hypersonic wind tunnel. The FP sensors fabricated using 157 nm laser micromachining system are structurally simple, small-sized, and high-temperature resistance. 16 FP sensors are installed on a six-force balance, which is mounted inside the model, to sense the aerodynamic forces and moments of the model, and then the model's aerodynamic coefficients are calculated based on aerodynamic theory according to the test data. A new temperature-compensated method is proposed to improve measurement accuracy of aerodynamic coefficients via eliminating temperature-induced measurement errors. Experimental results show, at high temperatures, the FP sensors based on the balance (FP balance) exhibits a high-repeatability precision of the aerodynamic coefficients measurement of less than 1%, and match well with the results of the traditional method using foil-resistive strain sensors. This enhanced-sensitivity FP sensor is currently the most promising alternative to foil-resistive strain sensors for aerodynamic tests among kinds of fiber-optic strain sensors to the best of our knowledge. The FP balance satisfies the requirements of practical application of aerodynamic characteristic tests, and opens up another test system of the field.

Constitutive model of 6063 aluminum alloy under the ultrasonic vibration upsetting based on Johnson-Cook model.

Establishing an accurate constitutive relation in ultrasonic vibration assisted metal forming, can provides a reliable theoretical basis for analyzing the mechanism of the ultrasonic vibration on materials. A constitutive model of 6063 aluminum alloy under the ultrasonic vibration upsetting at room temperature was constructed based on Johnson-Cook Model and experimental results. The influence of amplitude and frequency on the yield strength, hardening coefficient and exponent were analyzed quantitatively. Results showed that the yield strength was reduced due to the softening effect induced by the ultrasonic vibration. The maximum decreasing amount was 68.8% when imposing the maximum ultrasonic energy in this study. The hardening coefficient and exponent increased by 10.9% and 16.6% in maximum, respectively. However, the ultrasonic vibration has little impact on the strain rate hardening. The modified Johnson-Cook constitutive model under the ultrasonic vibration upsetting was established and was in good agreement with the experimental results.

Highly Integrated All-Fiber FP/FBG Sensor for Accurate Measurement of Strain under High Temperature.

Accurate measurement of strain is one of the most important issues for high temperature environments. We present a highly integrated all-fiber sensor to achieve precise measurements of strain/high-pressure, which consists of a fiber Bragg grating (FBG) inscribed by an 800 nm femtosecond laser cascaded with a micro extrinsic Fabry⁻Perot (FP) cavity fabricated by the 157 nm laser micromachining technique. FBG is sensitive to temperature, but insensitive to strain/pressure, whereas the FP is sensitive to strain/pressure, but has a small dependence on temperature. Therefore, such a cascaded sensor could be used for dual-parameter measurement and can work well at high temperatures. Experimental results indicate that this device exhibits a good strain characteristic at high temperatures and excellent high-pressure performance at room temperature. Due to its highly sensitive wavelength response, the proposed sensor will have remarkable potential applications in dual parameter sensing in harsh environments.

A nanocrystalline-amorphous mixed layer obtained by ultrasonic shot peening on pure titanium at room temperature.

A nanocrystalline-amorphous (NC-A) mixed layer was obtained by ultrasonic shot peening (USP) on pure titanium at room temperature and observed by X-ray diffraction pattern (XRD), scanning electron microscope (SEM) and high-resolution transmission electron microscope (HRTEM). The results showed that the amorphization percentage in the NC-A mixed layer increased continuously with the increase of the peening duration, shot diameter and sonotrode amplitude or the decrease of the peening distance. The maximum amorphization percentage achieved in this study was 44.09%. Moreover, with the amorphization percentage in the NC-A mixed layer increasing, the surface hardness increased constantly. Base on the experimental results, the amorphization mechanism during USP treatment was also analyzed.

Effects of ultrasonic vibration on the compression of pure titanium.

The technology of ultrasonic vibration assisted plastic forming possesses a great many merits, such as reducing the deformation resistance and friction, as well as improving the surface quality of parts. In this study, the ultrasonic vibration assisted compression tests were carried out on pure titanium in order to improve its formability. The results indicating that the ultrasonic vibration had no effort on elastic deformation, and the temperature of material only increased by 6 °C after compression with applying the ultrasonic vibration. Therefore the influence of temperature increase on reduction of flow stress could be ignored. After excluding interface friction and temperature effects, ultrasonic vibration can still decline the flow stress, the mechanism of deformation includes ultrasonic softening, stress superposition and strain hardening. In the intermittent vibration tests, the material shows the residual softening effect after stopping vibration. By observing the microstructure of material with SEM, it shows that the ultrasonic vibration can promote the generation of deformation twins, causing the grain refinement and the reduction of the twins, which is the major factor of affecting the residual softening effect.