Photobiomodulation:a novel approach to promote trans-differentiation of adipose-derived stem cells into neuronal-like cells

Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infrared light promotes adipose stem cell proliferation and affects adipose stem cell migration,which is necessary for the cells homing to the site of injury.In this in vitro study,we explored the potential of adipose-derived stem cells to differentiate into neurons for future translational regenerative treatments in neurodegenerative disorders and brain injuries.We investigated the effects of various biological and chemical inducers on trans-differentiation and evaluated the impact of photobiomodulation using 825 nm near-infrared and 525 nm green laser light at 5 J/cm2.As adipose-derived stem cells can be used in autologous grafting and photobiomodulation has been shown to have biostimulatory effects.Our findings reveal that adipose-derived stem cells can indeed trans-differentiate into neuronal cells when exposed to inducers,with pre-induced cells exhibiting higher rates of proliferation and trans-differentiation compared with the control group.Interestingly,green laser light stimulation led to notable morphological changes indicative of enhanced trans-differentiation,while near-infrared photobiomodulation notably increased the expression of neuronal markers.Through biochemical analysis and enzyme-linked immunosorbent assays,we observed marked improvements in viability,proliferation,membrane permeability,and mitochondrial membrane potential,as well as increased protein levels of neuron-specific enolase and ciliary neurotrophic factor.Overall,our results demonstrate the efficacy of photobiomodulation in enhancing the trans-differentiation ability of adipose-derived stem cells,offering promising prospects for their use in regenerative medicine for neurodegenerative disorders and brain injuries.

Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke

It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke.Indeed,previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue.Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke,but its specific role and mechanism are currently unclear.To simulate stroke in vivo,a middle cerebral artery occlusion rat model was established,with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke.We found that in the early stage(within 24 hours)of ischemic stroke,neutrophils produced a large amount of hypochlorous acid,while in the recovery phase(10 days after stroke),microglia were activated and produced a small amount of hypochlorous acid.Further,in acute stroke in rats,hypochlorous acid production was prevented using a hypochlorous acid scavenger,taurine,or myeloperoxidase inhibitor,4-aminobenzoic acid hydrazide.Our results showed that high levels of hypochlorous acid(200μM)induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation.However,in the recovery phase of the middle cerebral artery occlusion model,a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes.This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury.Lower levels of hypochlorous acid(5 and 100μM)promoted nuclear translocation ofβ-catenin.By transfection of single-site mutation plasmids,we found that hypochlorous acid induced chlorination of theβ-catenin tyrosine 30 residue,which promoted nuclear translocation.Altogether,our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Tanyu Tongzhi formula attenuates atherosclerotic plaque vulnerability by inhibiting CD40^(+) monocyte differentiation

Background:Atherosclerosis(AS)is a chronic progressive inflammatory disease,and plaque stability plays a critical role in preventing acute events.Tanyu Tongzhi formula(TTF),a traditional Chinese medicine,has potential therapeutic effects on AS.Methods:We used an AS animal model to examine the effects of TTF on atherosclerotic plaque vulnerability and CD40^(+)monocyte differentiation.AS plaque area,collagen content,and lipid area were assessed using histological staining.AS plaque-related biomarkers(monocyte chemoattractant protein 1(MCP-1),monocyte plus macrophage(MOMA-2),von Willebrand factor(vWF),CD31,and alpha-smooth muscle actin(α-SMA))were detected using immunohistochemistry.Inflammatory cytokines were determined using enzyme-linked immunosorbent assay.CD40 mRNA expression was detected by real-time quantitative PCR.CD40^(+)monocyte differentiation was evaluated by flow cytometry analysis in ApoE-/-mice and peripheral blood mononuclear cells(PBMCs).AMPK/NF-κB signaling pathways-related protein expression was investigated through western blotting.Results:TTF treatment reduced AS plaque area,collagen content,and lipid area in AS model mice.Levels of MCP-1,MOMA-2,vWF,and CD31 were decreased,whileα-SMA level was increased by TTF in model mice.TTF reduced inflammatory cytokines levels,including tumor necrosis factor receptor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6).TTF inhibited CD40^(+)monocyte differentiation and decreased the number of CD40^(+)/CD40-and Ly6C^(+)/Ly6C-cells and M1/M2 ratio in AS model mice and human PBMCs.Additionally,TTF modulated the AMPK/NF-κB signaling pathway in human PBMCs.Conclusion:TTF attenuates atherosclerotic plaque vulnerability by inhibiting CD40^(+)monocyte differentiation,possibly through the regulation of the AMPK/NF-κB signaling pathway.These findings suggest that TTF could be a potential therapeutic agent for preventing plaque rupture and subsequent cardiovascular events in patients with AS.

NEW MECHANISM OF LIMITED-SLIP DIFFERENTIAL

According to property requirement of differential, create a new mechanism, which is a combination of a paralleogram linkage and a inverse parallelogram linkage,to replace conventional bevel gears of differential and point out that using the new mechanism the differential can meet the needs of the requirements of torque and speed of the two axle shafts. The instantaneous speed ratio (ISR) which is the left and right half-shaft with respect to differential shell is variable. The calculating result of the locking factor of the new mechanism is up to 3. The limited-slip capability increase twice. The mechanism is an ideal new type of mechanism of differential.

NEW TYPE OF LIMITED-SLIP DIFFERENTIAL WITH THREE-PITCH FLUCTUATING SPEED RATIO

A type of three-pitch fluctuating speed ratio limited-slip differential （TPLSD） is presented for the first time, analyzed its working principle, introduced the tooth profile design method of using non-involute tooth profile and separated tooth profile design along the pitch line. Performance comparison between vehicles equipped with three-pitch fluctuating speed ratio limited-slip differential and common open differefitial is finished. The data from experiments prove that three-pitch fluctuating speed ratio limited-slip differential can increase the traction of a vehicle, improve its acceleration performance, decrease braking distance and limit sideslip. The basic structure of new differential is the same of open differential, the only difference is that they have different tooth profile, so the new differential has a high performance price.

Modeling joints with clearance and friction in multibody dynamic simulation of automotive differentials

Defects in kinematic joints can sometimes highly influence the simulation response of the whole multibody system within which these joints are included. For instance, the clearance, the friction, the lubrication and the flexibility affect the transient behaviour, reduce the component life and produce noise and vibration for classical joints such as prismatics, cylindrics or universal joints.In this work, a new 3D cylindrical joint model which accounts for the clearance, the misalignment and the friction is presented. This formulation has been used to represent the link between the planet gears and the planet carrier in an automotive differential model. C 2013 The Chinese Society of Theoretical and Applied Mechanics. [doi：10.1063/2.1301303]

Star-shaped Differentiable Functions and Star-shaped Differentials

Based on the isomorphism between the space of star-shaped sets and the space of continuous positively homogeneous real-valued functions, the star-shaped differential of a directionally differentiable function is defined. Formulas for star-shaped differential of a pointwise maximum and a pointwise minimum of a finite number of directionally differentiable functions, and a composite of two directionaUy differentiable functions are derived. Furthermore, the mean-value theorem for a directionaUy differentiable function is demonstrated.

Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma

Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation.Ki-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine tumors.However,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains uncertain.Methods:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were examined.Grade of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was evaluated.Results:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS.The GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic factors.The tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and RFS.Conclusions:Ki-67 is a valuable prognostic indicator for PDAC.Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

Spatial-temporal differentiation and influencing factors of rural settlements in mountainous areas: an example of Liangshan Yi Autonomous Prefecture, Southwestern China

Rural settlement is the basic spatial unit for compact communities in rural area. Scientific exploration of spatial-temporal differentiation and its influencing factors is the premise of spatial layout rationalization. Based on land use data of Liangshan Yi Autonomous Prefecture(hereinafter referred to as Liangshan Prefecture) in Sichuan Province, China from 1980 to 2020, compactness index, fractal dimension, imbalance index, location entropy and the optimal parameters-based geographical detector(OPGD) model are used to analyze the spatial-temporal evolution of the morphological characteristics of rural settlements, and to explore the influence of natural geographical factors, socioeconomic factors, and policy factors on the spatial differentiation of rural settlements. The results show that:(1) From 1980 to 2020, the rural settlements area in Liangshan Prefecture increased by 15.96 km^(2). In space, the rural settlements are generally distributed in a local aggregation, dense in the middle and sparse around the periphery. In 2015, the spatial density and expansion index of rural settlements reached the peak.(2) From 1980 to 2020, the compactness index decreased from 0.7636 to 0.7496, the fractal dimension increased from 1.0283 to 1.0314, and the fragmentation index decreased from 0.1183 to 0.1047. The spatial morphological structure of rural settlements tended to be loose, the shape contour tended to be complex, the degree of fragmentation decreased, and the spatial distribution was significantly imbalanced.(3) The results of OPGD detection in 2015 show that the influence of each factor is slope(0.2371) > traffic accessibility(0.2098) > population(0.1403) > regional GDP(0.1325) > elevation(0.0987) > poverty alleviation(0). The results of OPGD detection in 2020 show that the influence of each factor is slope(0.2339) > traffic accessibility(0.2198) > population(0.1432) > regional GDP(0.1219) > poverty alleviation(0.0992) > elevation(0.093). Natural geographical factors(slope and elevation) are the basic factors affecting the spatial distribution of rural settlements, and rural settlements are widely distributed in the river valley plain and the second half mountain area. Socioeconomic factors(traffic accessibility, population, and regional GDP) have a greater impact on the spatial distribution of rural settlements, which is an important factor affecting the spatial distribution of rural settlements. Policy factors such as poverty alleviation relocation have an indispensable impact on the spatial distribution of rural settlements. The research results can provide decisionmaking basis for the spatial arrangement of rural settlements in Liangshan Prefecture, and optimize the implementation of rural revitalization policies.

Remote sensing of air pollution incorporating integrated-path differential-absorption and coherent-Doppler lidar

An innovative complex lidar system deployed on an airborne rotorcraft platform for remote sensing of atmospheric pollution is proposed and demonstrated.The system incorporates integrated-path differential absorption lidar(DIAL) and coherent-doppler lidar(CDL) techniques using a dual tunable TEA CO_(2)laser in the 9—11 μm band and a 1.55 μm fiber laser.By combining the principles of differential absorption detection and pulsed coherent detection,the system enables agile and remote sensing of atmospheric pollution.Extensive static tests validate the system’s real-time detection capabilities,including the measurement of concentration-path-length product(CL),front distance,and path wind speed of air pollution plumes over long distances exceeding 4 km.Flight experiments is conducted with the helicopter.Scanning of the pollutant concentration and the wind field is carried out in an approximately 1 km slant range over scanning angle ranges from 45°to 65°,with a radial resolution of 30 m and10 s.The test results demonstrate the system’s ability to spatially map atmospheric pollution plumes and predict their motion and dispersion patterns,thereby ensuring the protection of public safety.

Monopoly Causes Inter-industry Wage Differentials

Inter-industry wage differentials in China, measured in terms of average employment earnings by industry, are significant and have been increasing since 1988. The coefficient of variables measuring inter-industry average earning differentials is apparently on the rise along with the subdivision of industry. A theoretical analysis of the labour market indicates that inter-industry wage differentials are mainly due to human capital variation among the employees of different industries and the likelihood of monopoly rent sharing. An empirical study finds that employee characteristics such as sex, age and education can only explain 60 percent of CVs in the period 2003 to 2005 and the rest may be due to the effect of monopoly rent sharing in certain industries. A residual analysis of wage equation proves that the monopoly industries of technology or knowledge share a small proportion of rents with employment, whereas non-competitive monopoly industries generally garner an abnormal share of rents, as much as half of their above-average earnings for their industries. Such abnormal rents and benefits are mainly the result of low cost natural resources, the use of state-owned assets, the misappropriation of consumer welfare and the seeking of fiscal or social subsidy for cost inflation. So, China should deal with the non-competitive monopoly industries by reforming their monopoly power and primary social distribution mechanism to structure a fair income distribution order.

Derivatives and differentials for multiplicative intuitionistic fuzzy information

By using the unsymmetrical scale instead of the symmetrical scale,the multiplicative intuitionistic fuzzy sets(MIFSs) reflect our intuition more objectively.Each element in a MIFS is expressed by an ordered pair which is called a multiplicative intuitionistic fuzzy number(MIFN)and is based on the unbalanced scale(i.e.,Saaty’s 1-9 scale).In order to describe the derivatives and differentials for multiplicative intuitionistic fuzzy information more comprehensively,in this paper,we firstly propose two new basic operational laws for MIFNs,which are the subtraction law and the division law.Secondly,we describe the change values of MIFNs when considering them as variables,classify these change values based on the basic operational laws for MIFNs,and depict the convergences of sequences of MIFNs by the subtraction and division laws.Finally,we focus on the multiplicative intuitionistic fuzzy functions and derive some basic results related to their continuities,derivatives and differentials,and also give their application in selecting the configuration of a computer.

Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

Strong/weak limits and strong/weak differentials of multi-variable indeterminate forms. I: Deduction and geometric illustration

Strong and weak limits as well as strong and weak differentials of multi-variable indeterminate forms are discussed based on the thorough exploration of differentiation to solve the strong and weak limits and differentials of unitary indeterminate forms. The fruit of this work is going to be reported in three parts. The first part presents the standard analysis on this subject which supplements, systematizes and advances L. Hospital抯 principles on differential calculus by applying special ,general, and limit guaranteeing theories together with K(t) and XhK0 theories. The combination of theoretical analysis and geometric signification makes the derivation intuitional, visual and easy to perceive.

Diagnosis of poorly differentiated adenocarcinoma of the stomach by confocal laser endomicroscopy:A case report

BACKGROUND In recent years,confocal laser endomicroscopy(CLE)has become a new endoscopic imaging technology at the microscopic level,which is extensively performed for real-time in vivo histological examination.CLE can be performed to distinguish benign from malignant lesions.In this study,we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma.CASE SUMMARY A 63-year-old woman was diagnosed with gastric mucosal lesions,which may be gastric cancer,in the small curvature of the stomach by gastroscopy.She consented to undergo CLE for morphological observation of the gastric mucosa.Through the combination of CLE diagnosis and postoperative pathology,the intraoperative CLE diagnosis was considered to be reliable.According to our experience,CLE can be performed as the first choice for the diagnosis of gastric cancer.CONCLUSION CLE has several advantages over pathological diagnosis.We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.

Crosstalk between Wnt and bone morphogenetic protein signaling during osteogenic differentiati

Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic development.Osteogenesis is the process by which new bones are formed;it also aids in bone remodeling.Wnt/β-catenin and bone morphogenetic protein(BMP)signaling pathways are involved in many cellular processes and considered to be essential for life.Wnt/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the body.Recent studies have indicated that these two signaling pathways contribute to osteogenic differen-tiation.Active Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling pathway.Here,we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation,emphasizing the canonical pathways.This review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch-and extracellular-regulated kinases in osteogenic differentiation and bone development.

How mesenchymal stem cells transform into adipocytes:Overview of the current understanding of adipogenic differentiation

Mesenchymal stem cells(MSCs)are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts,chondrocytes and adipocytes.The transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes,in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into adipocytes.Previous studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in adipogenesis.However,the mechanism underlying the adipogenic differentiation of MSCs is not fully understood.Here,the current knowledge of adipogenic differentiation in MSCs is reviewed,focusing on signaling pathways,noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC differentiation.Finally,the relationship between maladipogenic differentiation and diseases is briefly discussed.We hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.

Reaction of Sorghum Differentials to Grain Mold Infection in Puerto Rico

Grain mold, associated with many fungi, is the most important disease of sorghum, causing both yield and quality losses. In this study, 23 sorghum differentials used in pathotype characterization of anthracnose and head smut pathogens were evaluated for grain mold resistance under favorable conditions in Isabela, Puerto Rico. Lines BTx643 and IS18760 exhibited the lowest grain mold severity, indicating that these two may possess genes for grain mold resistance. These two lines also recorded the highest germination rates 94.7% and 97.6%, respectively, and their seed weight was among the heaviest. In conclusion, these two lines can be utilized in breeding programs to develop grain mold-resistant hybrid lines.

A No—Go Theorem for Compatibility Between Involutions of First Order Differentials on a Lattice and Continuum Limit

We prove that the following three properties cannot match each other on a lattice, that differentials of coordinate functions are algebraically dependent on their involutive conjugates, that the involution on a lattice is an antihomomorphism, and that differential calculus has a natural continuum limit.

Classification and Analysis of Electric-Powered Lateral Torque-Vectoring Differentials with Six Elements

The principle of improving the torque amplification factor of E-TVDs with six elements is illustrated in this paper.A velocity diagram is used to study speed and torque relationships.The results reveal that the torque amplification factor is the linear combination of the ratio of the differentials of the four elements and the ratio of planetary gear units,and its maximum value is easily more than 10.The E-TVDs with six elements are classified into three types,and there are six different configurations for each type.The torque amplification factor and the speed of interconnection between two planetary gear units are employed to evaluate the different characteristics of each E-TVD with six elements.The feasible configurations of a differential with four elements are also presented by the analysis of velocity level and planarity.This paper helps to further the understanding of the complex interconnection of the planetary gear units in E-TVDs with six elements and the differences of their characteristics.