A Study on English Humor in The Ellen DeGeneres Show from the Perspective of Cooperative Principle

English humor is a popular way of communication. A pragmatic study of English humor should be based on naturally occurring humor to the greatest extent as far as possible,which makes the live talk show a best choice,and the most popular of which is in America,namely The Ellen DeGeneres Show. From the perspective of the CP,this tentative study explores the generative mech-anism of verbal humor,hoping to provide some useful suggestions to better understand the generative mechanism of verbal humor and meaningful reference for the language users.

Role of transforming growth factor-βin peripheral nerve regeneration

Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits.Unlike in the central nervous system,damaged axons in peripheral nerves can be induced to regenerate in response to intrinsic cues after reprogramming or in a growth-promoting microenvironment created by Schwann cells.However,axon regeneration and repair do not automatically result in the restoration of function,which is the ultimate therapeutic goal but also a major clinical challenge.Transforming growth factor(TGF)is a multifunctional cytokine that regulates various biological processes including tissue repair,embryo development,and cell growth and differentiation.There is accumulating evidence that TGF-βfamily proteins participate in peripheral nerve repair through various factors and signaling pathways by regulating the growth and transformation of Schwann cells;recruiting specific immune cells;controlling the permeability of the blood-nerve barrier,thereby stimulating axon growth;and inhibiting remyelination of regenerated axons.TGF-βhas been applied to the treatment of peripheral nerve injury in animal models.In this context,we review the functions of TGF-βin peripheral nerve regeneration and potential clinical applications.

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure

High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure.Our results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and fibroblasts.The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure.We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression.We found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of inflammation.This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure.These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.

Taurine: a promising nutraceutic in the prevention of retinal degeneration

Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain tissues.Taurine may be especially important for the retina.The concentration of taurine in the retina is higher than that in any other tissue in the body and taurine deficiency causes retinal oxidative stress,apoptosis,and degeneration of photoreceptors and retinal ganglion cells.Low plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective effects.Taurine has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory properties.This review summarizes the role of taurine in retinal health and disease,where it appears that taurine may be a promising nutraceutical.

ON MONOTONE TRAVELING WAVES FOR NICHOLSON'S BLOWFLIES EQUATION WITH DEGENERATE p-LAPLACIAN DIFFUSION

We study the existence and stability of monotone traveling wave solutions of Nicholson's blowflies equation with degenerate p-Laplacian diffusion.We prove the existence and nonexistence of non-decreasing smooth traveling wave solutions by phase plane analysis methods.Moreover,we show the existence and regularity of an original solution via a compactness analysis.Finally,we prove the stability and exponential convergence rate of traveling waves by an approximated weighted energy method.

Small molecules to target tau amyloid aggregation

Protein aggregation has been linked with many neurodegenerative diseases,such as Alzheimer’s disease(AD)or Parkinson’s disease.AD belongs to a group of heterogeneous and incurable neurodegenerative disorders collectively known as tauopathies.They comprise frontotemporal dementia,Pick’s disease,or corticobasal degeneration,among others.The symptomatology varies with the specific tau protein variant involved and the affected brain region or cell type.However,they share a common neuropathological hallmark-the formation of proteinaceous deposits named neurofibrillary tangles.Neurofibrillary tangles,primarily composed of aggregated tau(Zhang et al.,2022),disrupt normal neuronal functions,leading to cell death and cognitive decline.

Lower limb suspension induces threshold-specific alterations of motor units properties that are reversed by active recovery

Purpose:This study aimed to non-invasively test the hypothesis that(a) short-term lower limb unloading would induce changes in the neural control of force production(based on motor units(MUs) properties) in the vastus lateralis muscle and(b) possible changes are reversed by active recovery(AR).Methods:Ten young males underwent 10 days of unilateral lower limb suspension(ULLS) followed by 21 days of AR.During ULLS,participants walked exclusively on crutches with the dominant leg suspended in a slightly flexed position(15°-20°) and with the contralateral foot raised by an elevated shoe.The AR was based on resistance exercise(leg press and leg extension) and executed at 70% of each participant’s 1repetition maximum,3 times/week.Maximal voluntary isometric contraction(MVC) of knee extensors and MUs properties of the vastus lateralis muscle were measured at baseline,after ULLS,and after AR.MUs were identified using high-density electromyography during trapezoidal isometric contractions at 10%,25%,and 50% of the current MVC,and individual MUs were tracked across the 3 data collection points.Results:We identified 1428 unique MUs,and 270 of them(18.9%) were accurately tracked.After ULLS,MVC decreased by 29.77%,MUs absolute recruitment/derecruitment thresholds were reduced at all contraction intensities(with changes between the 2 variables strongly correlated),while discharge rate was reduced at 10% and 25% but not at 50% MVC.Impaired MVC and MUs properties fully recovered to baseline levels after AR.Similar changes were observed in the pool of total as well as tracked MUs.Conclusion:Our novel results demonstrate,non-invasively,that 10 days of ULLS affected neural control predominantly by altering the discharge rate of lower-threshold but not of higher-threshold MUs,suggesting a preferential impact of disuse on motoneurons with a lower depolarization threshold.However,after 21 days of AR,the impaired MUs properties were fully restored to baseline levels,highlighting the plasticity of the components involved in neural control.

Astrocyte syncytium:from neonatal genesis to aging degeneration

Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in December of 1906 in Stockholm where Santiago Ramon y Cajal(the proponent of the neuronal doctrine)and Camillo Golgi(who advocated the syncytial reticular organization of neural networks)delivered their Noble prize lectures(Verkhratsky,2009).

Actin(g) toward a revised understanding of the role of cytoskeletal dynamics in neuronal bioenergetics

Neurons are energy-demanding cells.Disruptions in energy metabolism can quickly interrupt neuronal function,leading to cell death and neurodegeneration.For instance,ischemia rapidly depletes adenosine triphosphate(ATP)thereby disrupting energy-dependent cellular processes crucial for homeostasis,and axon degeneration is preceded by a collapse of axonal ATP levels.

Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following injury.At the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to regenerate.Recent works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of regeneration.The role of glia in neuron regeneration has long been studied.

A new perspective on intervertebral disc calcification—from bench to bedside

Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

Unraveling the potential of acute intermittent hypoxia as a strategy for inducing robust repair in multiple sclerosis

Multiple sclerosis(MS)is a debilitating inflammatory disease of the central nervous system characterized by immune-mediated segmental demyelination and variable degrees of axonal and neuronal degeneration that contribute to disability.Inducing efficient and effective repair programs following demyelination is a major goal and challenge in MS.Conventional MS therapies focus largely on modulating the immune aspects of the disease contributing to lesions.While this alleviates some symptoms and mitigates damage,it does not tackle the fundamental challenge of effective remyelination,which few MS patients experience,especially in the progressive phase of the disease.

Giant Magneto-Optical Effect in van der Waals Room-Temperature Ferromagnet Fe_(3)GaTe_(2)

The discovery of ferromagnetic two-dimensional(2D)van der Waals(vdWs)materials provides an opportunity to explore intriguing physics and to develop innovative spin electronic devices.However,the main challenge for practical applications of vd Ws ferromagnetic crystals lies in the weak intrinsic ferromagnetism and small perpendicular magnetic anisotropy(PMA)above room temperature.Here,we report the intrinsic vd Ws ferromagnetic crystal Fe_(3)GaTe_(2),synthesized by the self-flux method,exhibiting a Curie temperature(TC)of 370 K,a high saturation magnetization of 33.47 emu/g,and a large PMA energy density of approximately 4.17×10^(5)J/m^(3).Furthermore,the magneto-optical effect is systematically investigated in Fe_(3)GaTe_(2).The doubly degenerate E_(2g)(Γ)mode reverses the helicity of incident photons,indicating the existence of pseudoangular-momentum(PAM)and chirality.Meanwhile,the non-degenerate non-chiral A_(1g)(Γ)phonon exhibits a significant magneto-Raman effect under an external out-of-plane magnetic field.These results lay the groundwork for studying phonon chirality and magneto-optical phenomena in 2D magnetic materials,providing the feasibility for further fundamental research and applications in spintronic devices.

First report of the histopathological effect of electrocautery using on the urethral taste rosea during glans penis injury by incision in rabbits

Objective:Currently,electrocautery devices have frequently been used in penile surgical procedures.We hypothesized that electrocautery using during penile surgical procedures may harm the taste rosea and the dorsal nerve of the penis or clitoris.Methods:Eighteen young age male New Zealand rabbits were studied:five in the control(Group I,n=5),five in the penile surgery without using electrocautery(sham group,Group II,n=5),eight in the monopolar cautery(study group,Group III,n=8)groups under general anesthesia.The animals were followed for 3 weeks and sacrificed.Penile tissue—pudendal nerve root complexes and dorsal root ganglion of sacral 3 level were examined using stereological methods.The results were compared statistically.Results:The live and degenerated taste bud-like structures and degenerated neuron densities of pudendal ganglia(mean±standard deviation,n/mm^(3))were estimated as 198±24/mm^(3),4±1/mm^(3),and 5±1/mm^(3) in Group I;8±3/mm^(3),174±21/mm^(3),and 24±7/mm^(3) in Group II;and 21±5/mm^(3),137±14/mm^(3),and 95±12/mm^(3) in Group III,respectively.Neurodegeneration of taste buds and pudendal ganglia was significantly different between groups.Conclusion:Intact spinal cord and normal parasympathetic and thoracolumbar sympathetic networks are crucial for human sexual function.The present study indicates that the glans penis injury by using electrocautery may lead to pudendal ganglia degeneration.Iatrogenic damage to taste rosea and retrograde degeneration of the pudendal nerve may be the cause of sexual dysfunction responsible mechanism.

Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration

Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.

Nondegenerate Soliton Solutions of(2+1)-Dimensional Multi-Component Maccari System

For a multi-component Maccari system with two spatial dimensions,nondegenerate one-soliton and two-soliton solutions are obtained with the bilinear method.It can be seen by drawing the spatial graphs of nondegenerate solitons that the real component of the system shows a cross-shaped structure,while the two solitons of the complex component show a multi-solitoff structure.At the same time,the asymptotic analysis of the interaction behavior of the two solitons is conducted,and it is found that under partially nondegenerate conditions,the real and complex components of the system experience elastic collision and inelastic collision,respectively.

MAP4K inhibition as a potential therapy for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis(ALS)is a rare neurological disease,featuring gradual loss of muscle controls due to degeneration of motor neurons.Unfortunately,there is currently no cure for ALS.The available therapies only offer a limited extension of survival by several months,begging for more options of therapeutics.

Targeting cholesterol trafficking to mitigate axonal degeneration in hereditary spastic paraplegia

Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extremities.HSP is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.

Niosome-encapsulated auraptene reduced the mRNA expression of VEGF-A and PDGFs genes in human retinaderived RPE cell line

AIM:To evaluate the effect of auraptene(AUR)treatment in forms of free and encapsulated in niosome nanoparticles by investigating the mRNA expression level of vascular endothelium growth factor(VEGF)-A and platelet-derived growth factors(PDGFs)in human retinal pigment epithelium(RPE)cell line.METHODS:Niosome nanocarriers were produced using two surfactants Span 60 and Tween 80.RPE cell line was treated with both free AUR and niosome-encapsulated.Optimum dosage of treatments was calculated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Expression of VEGF-A and PDGF-A,PDGF-B,PDGF-C,PDGF-D genes was measured after total RNA extraction and cDNA synthesis,using real-time polymerase chain reaction(RT-PCR).RESULTS:The highest entrapment efficiency(EE)was achieved by Span 60:cholesterol(1:1)with 64.3%.The half maximal inhibitory concentration(IC50)of free and niosome-encapsulated AUR were 38.5 and 27.78µg/mL,respectively.Release study revealed that niosomal AUR had more gradual delivery to the cells.RT-PCR results showed reduced expression levels of VEGF-A,PDGF-A,PDGF-B,PDGF-C,and PDGF-D after treatment with both free and niosomal AUR.CONCLUSION:Niosomal formulation of Span 60:cholesterol(1:1)is an effective drug delivery approach to transfer AUR to RPE cells.VEGF-A,PDGF-A,PDGF-B,PDGF-C,and PDGF-D are four angiogenic factors,inhibiting which by niosomal AUR may be effective in age-related macular degeneration.