Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease

The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and therapy.The induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease therapies.The current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem cells.The benefits of induced pluripotent stem cell-based research are highlighted.Various dopaminergic neuron differentiation protocols from induced pluripotent stem cells are compared.The emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are evaluated.Finally,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.

A FLEXIBLE OBJECTIVE-CONSTRAINT APPROACH AND A NEW ALGORITHM FOR CONSTRUCTING THE PARETO FRONT OF MULTIOBJECTIVE OPTIMIZATION PROBLEMS

In this article, a novel scalarization technique, called the improved objective-constraint approach, is introduced to find efficient solutions of a given multiobjective programming problem. The presented scalarized problem extends the objective-constraint problem. It is demonstrated that how adding variables to the scalarized problem, can lead to find conditions for (weakly, properly) Pareto optimal solutions. Applying the obtained necessary and sufficient conditions, two algorithms for generating the Pareto front approximation of bi-objective and three-objective programming problems are designed. These algorithms are easy to implement and can achieve an even approximation of (weakly, properly) Pareto optimal solutions. These algorithms can be generalized for optimization problems with more than three criterion functions, too. The effectiveness and capability of the algorithms are demonstrated in test problems.

法舒地尔缓解β-淀粉样蛋白1-42诱导的SH-SY5Y细胞凋亡

背景:法舒地尔对阿尔茨海默病小鼠脑内的线粒体动力学有调节作用,并且可以抑制神经炎症,但能否调节线粒体自噬和NLRP3炎症小体进而减轻β-淀粉样蛋白毒性尚不清楚。目的:探究法舒地尔对β-淀粉样蛋白1-42诱导的人源神经母细胞瘤细胞株SH-SY5Y凋亡和线粒体自噬以及NLRP3炎症小体的调节作用。方法:将SH-SY5Y细胞接种于孔板内,细胞贴壁后分3组干预:对照组不加入任何药物,模型组加入20μmol/L β-淀粉样蛋白1-42,法舒地尔组同时加入20μmol/L β-淀粉样蛋白1-42与15 mg/L法舒地尔,干预24 h后,采用MTT法检测细胞活性,TUNEL染色检测细胞凋亡,qRT-PCR和Western blot检测凋亡相关蛋白表达,免疫荧光染色和Western blot检测线粒体自噬相关蛋白表达,免疫荧光染色和Western blot检测NLRP3炎症小体相关蛋白表达。结果与结论:(1)与对照组比较,模型组细胞活性降低、凋亡率升高(P<0.05);与模型组比较,法舒地尔组细胞活性升高、凋亡率降低(P<0.05);(2)qRT-PCR和Western blot检测结果显示,与对照组比较,模型组细胞Bax mRNA与蛋白表达升高(P<0.05),Bcl-2 mRNA与蛋白表达降低(P<0.05);与模型组比较,法舒地尔组细胞Bax mRNA与蛋白表达降低(P<0.05),Bcl-2 mRNA与蛋白表达升高(P<0.05);(3)免疫荧光染色和Western blot检测结果显示,与对照组相比,模型组细胞PINK1、帕金森病蛋白和LC3蛋白表达降低(P<0.05),p62蛋白表达升高(P<0.05);与模型组相比,法舒地尔组细胞PINK1、帕金森病蛋白和LC3蛋白表达升高(P<0.05),p62蛋白表达降低(P<0.05);(4)免疫荧光染色和Western blot检测结果显示,与对照组相比,模型组细胞NLRP3、ASC、Caspase-1和白细胞介素1β蛋白表达升高(P<0.05);与模型组相比,法舒地尔组细胞NLRP3、ASC、Caspase-1和白细胞介素1β蛋白表达降低(P<0.05);(5)结果表明,法舒地尔可以减轻β-淀粉样蛋白1-42诱导的SH-SY5Y细胞凋亡,其机制可能与激活线粒体自噬且抑制NLRP3炎症小体激活有关。

Laparoscopic left hemihepatectomy guided by indocyanine green fluorescence: A cranial-dorsal approach

BACKGROUND Advancements in laparoscopic technology and a deeper understanding of intra-hepatic anatomy have led to the establishment of more precise laparoscopic hepatectomy(LH)techniques.The indocyanine green(ICG)fluorescence navi-gation technique has emerged as the most effective method for identifying hepatic regions,potentially overcoming the limitations of LH.While laparoscopic left hemihepatectomy(LLH)is a standardized procedure,there is a need for innova-tive strategies to enhance its outcomes.important anatomical markers,surgical skills,and ICG staining methods.METHODS Thirty-seven patients who underwent ICG fluorescence-guided LLH at Qujing Second People's Hospital between January 2019 and February 2022 were retrospectively analyzed.The cranial-dorsal approach was performed which involves dissecting the left hepatic vein cephalad,isolating the Arantius ligament,exposing the middle hepatic vein,and dissecting the parenchyma from the dorsal to the foot in order to complete the anatomical LLH.The surgical methods,as well as intra-and post-surgical data,were recorded and analyzed.Our hospital’s Medical Ethics Committee approved this study(Ethical review:2022-019-01).RESULTS Intraoperative blood loss during LLH was 335.68±99.869 mL and the rates of transfusion and conversion to laparotomy were 13.5%and 0%,respectively.The overall incidence of complications throughout the follow-up(median of 18 months;range 1-36 months)was 21.6%.No mortality or severe complications(level IV)were reported.CONCLUSION LLH has the potential to become a novel,standardized approach that can effectively,safely,and simply expose the middle hepatic vein and meet the requirements of precision surgery.

自旋-轨道耦合作用下极化激元凝聚中的调制不稳定性

利用线性稳定性分析方法,对存在自旋-轨道耦合(SOS)作用的二维极化激元玻色-爱因斯坦凝聚(BEC)系统中的调制不稳定性(MI)进行了研究.分析了组分内部,组分之间以及SOC相互作用对系统调制不稳定性的影响.结果显示,当系统内部不存在SOC作用,组分之间的相互作用为0,组分内部存在排斥作用时,不会出现调制不稳定性,组分内部存在吸引作用时,会出现调制不稳定性,并且调制不稳定性区间长度随吸引作用的增强而增加;组分之间相互作用不为0时,组分之间的相互作用以平方形式出现,其正负不会对调制不稳定性产生实质性影响.存在SOC相互作用时,SOC相互作用会引起增益谱曲线的不规则振荡,破坏原来的调制不稳定性区间.

双偶氮苯-二苯并[b,i]噻蒽-[2,3-b]苯-5,7,12,14-四酮衍生物分子的二阶非线性光学性质

使用密度泛函理论(DFT)M06-2X方法、采用6-311+g(d,p)基组,分别对26个双偶氮-二苯并[b,i]噻蒽-[2,3-b]苯-5,7,12,14-四酮衍生物分子进行结构优化与频率计算;使用含时密度泛函理论(TD-DFT)TD-M06-2X方法计算了a1~d6分子的前线分子轨道与电子吸收光谱,采用有效场FF方法研究了二阶非线性光学性质(NLO).研究结果表明,26个噻蒽四酮类衍生物分子的能隙在1.33—2.02 eV范围,归属于有机半导体;最低能量吸收峰波长在601.8~609.5nm范围;在增大分子的二阶非线性光学系数β_(μ)(或β_(0))值方面,含相同偶氮苯基团或含不同偶氮苯基团分别引入到二苯并[b,i]噻蒽-[2,3-b]苯-5,7,12,14-四酮分子两侧的2,10位优于2,9位,在2,10位分别端接含推、拉基团的偶氮苯优于含相同给电子基团的偶氮苯.在偶氮苯苯环对位分别端接强吸电子基(-NO_(2))与强供电子基(如-N(CH_(3))_(2)、-N(Ph)_(3)、-N-苯基咔唑等)可增强体系的二阶非线性光学性能,获得性能良好的非线性光学材料.

Virtual source approach for maximizing resolution in high-penetration gamma-ray imaging

High-energy gamma-ray radiography has exceptional penetration ability and has become an indispensable nondestructive testing(NDT)tool in various fields.For high-energy photons,point projection radiography is almost the only feasible imaging method,and its spatial resolution is primarily constrained by the size of the gamma-ray source.In conventional industrial applications,gamma-ray sources are commonly based on electron beams driven by accelerators,utilizing the process of bremsstrahlung radiation.The size of the gamma-ray source is dependent on the dimensional characteristics of the electron beam.Extensive research has been conducted on various advanced accelerator technologies that have the potential to greatly improve spatial resolution in NDT.In our investigation of laser-driven gamma-ray sources,a spatial resolution of about 90μm is achieved when the areal density of the penetrated object is 120 g/cm^(2).A virtual source approach is proposed to optimize the size of the gamma-ray source used for imaging,with the aim of maximizing spatial resolution.In this virtual source approach,the gamma ray can be considered as being emitted from a virtual source within the convertor,where the equivalent gamma-ray source size in imaging is much smaller than the actual emission area.On the basis of Monte Carlo simulations,we derive a set of evaluation formulas for virtual source scale and gamma-ray emission angle.Under optimal conditions,the virtual source size can be as small as 15μm,which can significantly improve the spatial resolution of high-penetration imaging to less than 50μm.

Debate on direct-anterior vs posterior approach for hip hemiarthroplasty:The authors’insights

We read and discussed the study entitled“Complication rates after direct anterior vs posterior approach for Hip Hemiarthroplasty in elderly individuals with femoral neck fractures”with great interest.The authors have done justice to the topic of comparison of anterior and posterior surgical approaches for bipolar hemiarthroplasty which has been an everlasting debate in the existing literature.However,there are certain aspects of this study that need clarification from the authors.

“Instruction-Category” Approach of Test Suite Construction for Oven Embedded System

Being different from testing for popular GUI software, the “instruction-category” approach is proposed for testing embedded system. This approach is constructed by three steps including refining items, drawing instruction-brief and instruction-category, and constructing test suite. Consequently, this approach is adopted to test oven embedded system, and detail process is deeply discussed. As a result, the factual result indicates that the “instruction-category” approach can be effectively applied in embedded system testing as a black-box method for conformity testing.

Optimizing PID controller parameters for robust automatic voltage regulator system through indirect design approach-2

Automatic voltage regulators(AVR)are designed to manipulate a synchronous generator’s voltage level automatically.Proportional integral derivative(PID)controllers are typically used in AVR systems to regulate voltage.Although advanced PID tuning methods have been proposed,the actual voltage response differs from the theoretical predictions due to modeling errors and system uncertainties.This requires continuous fine tuning of the PID parameters.However,manual adjustment of these parameters can compromise the stability and robustness of the AVR system.This study focuses on the online self-tuning of PID controllers called indirect design approach-2(IDA-2)in AVR systems while preserving robustness.In particular,we indirectly tune the PID controller by shifting the frequency response.The new PID parameters depend on the frequency-shifting constant and the previously optimized PID parameters.Adjusting the frequency-shifting constant modifies all the PID parameters simultaneously,thereby improving the control performance and robustness.We evaluate the robustness of the proposed online PID tuning method by comparing the gain margins(GMs)and phase margins(PMs)with previously optimized PID parameters during parameter uncertainties.The proposed method is further evaluated in terms of disturbance rejection,measurement noise,and frequency response analysis during parameter uncertainty calculations against existing methods.Simulations show that the proposed method significantly improves the robustness of the controller in the AVR system.In summary,online self-tuning enables automated PID parameter adjustment in an AVR system,while maintaining stability and robustness.

An isogeometric analysis approach for dynamic response of doubly-curved magneto electro elastic composite shallow shell subjected to blast loading

For the first time, the isogeometric analysis(IGA) approach is used to model and analyze free and forced vibrations of doubly-curved magneto-electro-elastic(MEE) composite shallow shell resting on the visco-Pasternak foundation in a hygro-temperature environment. The doubly-curved MEE shallow shell types include spherical shallow shell, cylindrical shallow shell, saddle shallow shell, and elliptical shallow shell subjected to blast load are investigated. The Maxwell equation and electromagnetic boundary conditions are used to determine the vary of the electric and magnetic potentials. The MEE shallow shell's equations of motion are derived from Hamilton's principle and refined higher-order shear theory. Then, the IGA method is used to derive the laws of natural frequencies and dynamic responses of the shell under various boundary conditions. The accuracy of the model and method is verified through reliable numerical comparisons. Aside from this, the impact of the input parameters on the free and forced vibration of the doubly-curved MEE shallow shell is examined in detail. These results may be useful in the design and manufacture of military structures such as warships, fighter aircraft, drones and missiles.

Watson-Jones Anatomical Approach for Open Reduction and Internal Fixation of Proximal Femoral Fractures without Image Intensifier in a Low-Resource Setting

Introduction: Standard procedures for surgical fixation of proximal femoral fractures (PFF) require an image intensifier which in developing countries remains a luxury. We hypothesized that, with a well-codified technique, the Watson Jones approach (WJA) without image intensifier nor traction table, can allow open reduction and internal fixation (ORIF) of PFF using Dynamic hip screw (DHS), with satisfactory outcome. Patients and methods: Forty one consecutive patients (mean age 59.5 ± 21.6 years, 61% males) who were followed in a Teaching Hospital for PFF treated by ORIF using the WJA and DHS from January 2016 to December 2020 were reassessed. The outcome measures were the quality of the reduction, the positioning of the implants, the tip-apex distance (TAD), the rate and delay of consolidation, the functional results using Postel Merle d’Aubigné (PMA) score, the rate of surgical site infection (SSI) and the overall mortality. Logistic regression was used to determine factors associated with mechanical failure. Results: The mean follow-up period was 33.8 ± 15.0 months. Fracture reduction was good in 31 (75.6%) cases and acceptable in 8(19.5%) cases. Implant position was fair to good in 37 (90.2%) patients. The mean TAD was 26.1 ± 3.9 mm. Three patients developed SSI. Consolidation was achieved in 38 (92.6%) patients. The functional results were good to excellent in 80.5% of patients. The overall mortality rate was 7.3%. There were an association between mechanical failure and osteoporosis (p = 0.04), fracture reduction (p = 0.003), and TAD (p = 0.025). In multivariate logistic regression, no independent factors were predictive of mechanical failure. Conclusion: This study shows that ORIF using DHS for PFF via the Watson-Jones approach without an image intensifier can give satisfactory anatomical and functional outcomes in low-resource settings. It provides and validates a reliable and reproducible technique that deserves to be diffused to surgeons in austere areas over the world.

Relaxed Stability Criteria for Time-Delay Systems:A Novel Quadratic Function Convex Approximation Approach

This paper develops a quadratic function convex approximation approach to deal with the negative definite problem of the quadratic function induced by stability analysis of linear systems with time-varying delays.By introducing two adjustable parameters and two free variables,a novel convex function greater than or equal to the quadratic function is constructed,regardless of the sign of the coefficient in the quadratic term.The developed lemma can also be degenerated into the existing quadratic function negative-determination(QFND)lemma and relaxed QFND lemma respectively,by setting two adjustable parameters and two free variables as some particular values.Moreover,for a linear system with time-varying delays,a relaxed stability criterion is established via our developed lemma,together with the quivalent reciprocal combination technique and the Bessel-Legendre inequality.As a result,the conservatism can be reduced via the proposed approach in the context of constructing Lyapunov-Krasovskii functionals for the stability analysis of linear time-varying delay systems.Finally,the superiority of our results is illustrated through three numerical examples.

Development of a DFN-based probabilistic block theory approach for bench face angle design in open pit mining

In open pit mining,uncontrolled block instabilities have serious social,economic and regulatory consequences,such as casualties,disruption of operation and increased regulation difficulties.For this reason,bench face angle,as one of the controlling parameters associated with block instabilities,should be carefully designed for sustainable mining.This study introduces a discrete fracture network(DFN)-based probabilistic block theory approach for the fast design of the bench face angle.A major advantage is the explicit incorporation of discontinuity size and spatial distribution in the procedure of key blocks testing.The proposed approach was applied to a granite mine in China.First,DFN models were generated from a multi-step modeling procedure to simulate the complex structural characteristics of pit slopes.Then,a modified key blocks searching method was applied to the slope faces modeled,and a cumulative probability of failure was obtained for each sector.Finally,a bench face angle was determined commensurate with an acceptable risk level of stability.The simulation results have shown that the number of hazardous traces exposed on the slope face can be significantly reduced when the suggested bench face angle is adopted,indicating an extremely low risk of uncontrolled block instabilities.

Indication and surgical approach for reconstruction with endoprosthesis in bone-associated soft tissue sarcomas:Appropriate case management is vital

It is important for surgeons performing sarcoma surgery to know that bone resection and tumor prosthesis applications in soft tissue sarcomas(STS)have unique features in terms of indication,surgical approach and follow-up,in terms of the management of these cases.Some STS are associated with bone and major neurovascular structures.Bone-associated STS are generally relatively large and relatively deep-seated.Additionally,the tendency for metastasis is high.In some cases,the decision about which structures to resect is difficult.These cases are often accompanied by poor oncological and surgical outcomes.Management of cases should be done by a multidisciplinary team in advanced centers specialized in this field.The surgical team must have sufficient knowledge and experience in the field of limb-sparing surgery.Preoperative evaluation and especially good planning of bone and soft tissue reconstruction are vital.

Accelerated Primal-Dual Projection Neurodynamic Approach With Time Scaling for Linear and Set Constrained Convex Optimization Problems

The Nesterov accelerated dynamical approach serves as an essential tool for addressing convex optimization problems with accelerated convergence rates.Most previous studies in this field have primarily concentrated on unconstrained smooth con-vex optimization problems.In this paper,on the basis of primal-dual dynamical approach,Nesterov accelerated dynamical approach,projection operator and directional gradient,we present two accelerated primal-dual projection neurodynamic approaches with time scaling to address convex optimization problems with smooth and nonsmooth objective functions subject to linear and set constraints,which consist of a second-order ODE(ordinary differential equation)or differential conclusion system for the primal variables and a first-order ODE for the dual vari-ables.By satisfying specific conditions for time scaling,we demonstrate that the proposed approaches have a faster conver-gence rate.This only requires assuming convexity of the objective function.We validate the effectiveness of our proposed two accel-erated primal-dual projection neurodynamic approaches through numerical experiments.

Regional Brand and High-quality Development of Fruits in Ethnic Areas of the Yangtze River Economic Belt under the Greater Food Approach

Establishing the Greater Food Approach and promoting the Yangtze River Economic Belt s national major regional development strategy can better support and serve the agricultural power and Chinese-style modernization.This paper introduces the characteristics of fruit industry in 16 autonomous prefectures and 47 autonomous counties under the jurisdiction of the Yangtze River Economic Belt.It studies the intellectual property resources of brand marks from the aspects of geographical indications,collective trademarks,certification trademarks,well-known trademarks in China and national design patents,and analyzes the main problems of brand and high-quality development of fruit industry in these ethnic autonomous areas.Finally,it puts forward some strategies,such as improving the protection of intellectual property rights of geographical indications,using intellectual property rights of brand signs,building modern seed industry upgrading project,drawing lessons from the experience of thousand villages demonstration project,ensuring that large-scale poverty does not occur,and building a diversified food supply system.

Multi-disciplinary Pathways to Computing:A Scalable and Col aborative Approach to Capitalize on the Demand for Computer Science Education

The number of students demanding computer science(CS)education is rapidly rising,and while faculty sizes are also growing,the traditional pipeline consisting of a CS major,a CS master’s,and then a move to industry or a Ph.D.program is simply not scalable.To address this problem,the Department of Computing at the University of Illinois has introduced a multidisciplinary approach to computing,which is a scalable and collaborative approach to capitalize on the tremendous demand for computer science education.The key component of the approach is the blended major,also referred to as“CS+X”,where CS denotes computer science and X denotes a non-computing field.These CS+X blended degrees enable win-win partnerships among multiple subject areas,distributing the educational responsibilities while growing the entire university.To meet the demand from non-CS majors,another pathway that is offered is a graduate certificate program in addition to the traditional minor program.To accommodate the large number of students,scalable teaching tools,such as automatic graders,have also been developed.

A Novel Inverse-Free Neurodynamic Approach for Solving Absolute Value Equations

We propose a novel inverse-free neurodynamic approach (NIFNA) for solving absolute value equations (AVE). The NIFNA guarantees global convergence and notably improves convergence speed by achieving fixed-time convergence. To validate the theoretical findings, numerical simulations are conducted, demonstrating the effectiveness and efficiency of the proposed NIFNA.

Solving Neumann Boundary Problem with Kernel-Regularized Learning Approach

We provide a kernel-regularized method to give theory solutions for Neumann boundary value problem on the unit ball. We define the reproducing kernel Hilbert space with the spherical harmonics associated with an inner product defined on both the unit ball and the unit sphere, construct the kernel-regularized learning algorithm from the view of semi-supervised learning and bound the upper bounds for the learning rates. The theory analysis shows that the learning algorithm has better uniform convergence according to the number of samples. The research can be regarded as an application of kernel-regularized semi-supervised learning.