Recovery of the injured neural system through gene delivery to surviving neurons in Parkinson’s disease

A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to address the underlying neuronal loss.This highlights that the elusive goals of halting progression and restoring damaged neurons limit the long-term impact of current approaches.Recent clinical trials using gene therapy have demonstrated the safety of various vector delivery systems,dosages,and transgenes expressed in the central nervous system,signifying tangible and substantial progress in applying gene therapy as a promising Parkinson’s disease treatment.Intriguingly,at diagnosis,many dopamine neurons remain in the substantia nigra,offering a potential window for recovery and survival.We propose that modulating these surviving dopamine neurons and axons in the substantia nigra and striatum using gene therapy offers a potentially more impactful therapeutic approach for future research.Moreover,innovative gene therapies that focus on preserving the remaining elements may have significant potential for enhancing long-term outcomes and the quality of life for patients with Parkinson’s disease.In this review,we provide a perspective on how gene therapy can protect vulnerable elements in the substantia nigra and striatum,offering a novel approach to addressing Parkinson’s disease at its core.

Regulation of sleep by astrocytes in the hypothalamic ventrolateral preoptic nucleus

Astrocytes are functionally dynamic cells that support neurons in multiple ways throughout an organism’s lifespan.The astrocytic regulation of neuronal activity has been increasingly recognized in recent years.Astrocytes are now recognized as playing a more complex role than mere bystanders in the central nervous system.However,their role in regulating the sleep neurocircuitry is not well understood.From this perspective,we highlight the role of astrocytes in sleep modulation,with a particular focus on regulatory mechanisms related to the ventrolateral preoptic nucleus(VLPO)of the hypothalamus.We briefly discuss recent literature reporting the role of VLPO astrocytes in regulating sleep-associated behaviors.

PGLYRP1 protein as a novel mediator of cellular dialogue in neuroinflammation

Neuroinflammation has been identified as a crucial element in several neurological disorders. Glial cells play a critical role in directing neuroinflammation, both in deleterious and beneficial ways.

A Multi-Center International Survey Related to the Nutritional Support after Hematopoietic Stem Cell Transplantation Endorsed by the ASIA Pacific Blood and Marrow Transplantation (APBMT)

Background: The nutritional support after hematopoietic stem cell transplantation (HSCT) has not been well established due to the scarcity of clinical trials. To conduct international clinical trials in Asia, we performed the questionnaire survey to investigate the current standard of nutritional support after HSCT. Method: We sent the questionnaire to the physicians nominated by the Asia Pacific Blood and Marrow Transplantation (APBMT) members of each country/ region. Result: We received 15 responses from 7 different countries/regions. The target calorie amount is 1.0 - 1.3 × basal energy expenditure (BEE) in 11 institutes when partial parenteral nutrition is used. When total parenteral nutrition (TPN) is used, the target calorie amount is 1.0 - 1.3 × BEE in 9 institutes and 1.3 - 1.5 × BEE in 4 institutes. Lipid emulsion is routinely used in 12 institutes. Multivitamins and trace elements are routinely added to TPN used in most institutes. It is still uncommon to use the immunonutrition. Blood glucose levels are routinely monitored in all institutes, but the target range varies (<110 in 2 institutes, <150 in 4 institutes, and <200 in 8 institutes). Conclusions: Basic nutritional support is similar in participating institutes. However, the target glucose level varies and the use of immunonutrition is rather rare. These points can be the theme of future clinical trials.

Adult neurogenesis:a real hope or a delusion?

Adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem cells.This process is restricted to neurogenic niches located in two distinct areas of the brain:the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle,where new neurons are generated and then migrate to the olfactory bulb.Neurogenesis has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem cells.Interestingly,recent years have seen tremendous progress in our understanding of adult brain neurogenesis,bridging the knowledge gap between embryonic and adult neurogenesis.Here,we discuss the current status of adult brain neurogenesis in light of what we know about neural stem cells.In this notion,we talk about the importance of intra cellular signaling molecules in mobilizing endogenous neural stem cell prolife ration.Based on the current understanding,we can declare that these molecules play a role in targeting neurogenesis in the mature brain.However,to achieve this goal,we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints,which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope.

Enhanced prediction of anisotropic deformation behavior using machine learning with data augmentation

Mg alloys possess an inherent plastic anisotropy owing to the selective activation of deformation mechanisms depending on the loading condition.This characteristic results in a diverse range of flow curves that vary with a deformation condition.This study proposes a novel approach for accurately predicting an anisotropic deformation behavior of wrought Mg alloys using machine learning(ML)with data augmentation.The developed model combines four key strategies from data science:learning the entire flow curves,generative adversarial networks(GAN),algorithm-driven hyperparameter tuning,and gated recurrent unit(GRU)architecture.The proposed model,namely GAN-aided GRU,was extensively evaluated for various predictive scenarios,such as interpolation,extrapolation,and a limited dataset size.The model exhibited significant predictability and improved generalizability for estimating the anisotropic compressive behavior of ZK60 Mg alloys under 11 annealing conditions and for three loading directions.The GAN-aided GRU results were superior to those of previous ML models and constitutive equations.The superior performance was attributed to hyperparameter optimization,GAN-based data augmentation,and the inherent predictivity of the GRU for extrapolation.As a first attempt to employ ML techniques other than artificial neural networks,this study proposes a novel perspective on predicting the anisotropic deformation behaviors of wrought Mg alloys.

Effect of characteristics and distribution of Mg_(17)Al_(12)precipitates on tensile and bending properties of high-Al-containing Mg alloys

This study investigates the effect of characteristics and distribution of Mg_(17)Al_(12)precipitates on the uniaxial tensile and three-point bending properties of extruded Mg alloys containing high Al contents.The extruded Mg–9Al–1Zn–0.3Mn(AZ91)alloy contains lamellar-structured Mg_(17)Al_(12)discontinuous precipitates along the grain boundaries,which are formed via static precipitation during natural air cooling.The extruded Mg–11Al–1Zn–0.3Mn(AZ111)alloy contains spherical Mg_(17)Al_(12)precipitates at the grain boundaries and inside the grains,which are formed via dynamic precipitation during extrusion.Due to inhomogeneous distribution of precipitates,the AZ111 alloy consists of two different precipitate regions:precipitate-rich region with numerous precipitates and finer grains and precipitate-scarce region with a few precipitates and coarser grains.The AZ111 alloy exhibits a higher tensile strength than the AZ91 alloy because its smaller grain size and more abundant precipitates result in stronger grain-boundary hardening and precipitation hardening effects,respectively.However,the tensile elongation of the AZ111 alloy is lower than that of the AZ91 alloy because the weak cohesion between the dynamic precipitates and the matrix facilitates the crack initiation and propagation.During bending,a macrocrack initiates on the outer surface of bending specimen in both alloys.The AZ111 alloy exhibits higher bending yield strength and lower failure bending strain than the AZ91 alloy.The bending specimens of the AZ91 alloy have similar bending formability,whereas those of the AZ111 alloy exhibit considerable differences in bending formability and crack propagation behavior,depending on the distribution and number density of precipitates in the specimen.In bending specimens of the AZ111 alloy,it is found that the failure bending strain(ε_(f,bending))is inversely proportional to the area fraction of precipitates in the outer zone of bending specimen(A_(ppt)),with a relationship ofε_(f,bending)=–0.1A_(ppt)+5.86.

Promoting dynamic recrystallization and improving strength and ductility of Mg-7Bi alloy through Al addition

This study investigated the influence of the addition of Al to a Mg-7Bi(B7,wt%)alloy,particularly its recrystallization behavior during extrusion and its resulting mechanical properties.The addition of 2 wt%Al to the B7 alloy resulted in a lower grain size,a reduction in the number density of fine Mg3Bi2 particles,and a higher area fraction of relatively coarse Mg3Bi2 particles in the extrusion billet.These microstructural changes increased the nucleation sites for recrystallization,reduced the Zener pinning effect,and enhanced particle-stimulated nucleation,all of which promoted dynamic recrystallization behavior during extrusion.As a result,the area fraction of recrystallized grains in the extruded alloy increased from 77%to 94%.The extruded B7 alloy exhibited a strong<10-10>fiber texture,whereas the extruded Mg-7Bi-2Al(BA72)alloy had a weak<10-10>-<2-1-10>texture,which was attributed to the minimal presence of unrecrystallized grains and the dispersed orientation of the recrystallized grains.The tensile yield strength(TYS)of the extruded BA72 alloy was higher than that of the extruded B7 alloy(170 and 124 MPa,respectively),which resulted from the enhanced grain-boundary and solid-solution strengthening effects.The tensile elongation(EL)of the BA72 alloy also exceeded that of the B7 alloy(20.3%and 6.1%,respectively),the result of the uniform formation of fine twins under tension in the former and the formation of a few coarse twins among the unrecrystallized grains in the latter.Consequently,the addition of a small amount of Al to the B7 alloy significantly improved both the strength and ductility of the extruded alloy,resulting in a remarkable increase in the product of the TYS and EL from 756 to 3451 MPa%and expanding its potential range of applications as a lightweight extruded structural component.

Effect of pre-deformation on precipitation behavior of AZ80 alloy:Comparison of slip-and twinning-dominant deformation

This study investigates the effect of the deformation mode on the precipitation behavior of an extruded Mg-8.0Al-0.5Zn-0.2Mn(AZ80)alloy.The alloy samples are compared after the application of 3.5%tension and 3.5%compression along the extrusion direction to induce slip-dominant and twinning-dominant deformation modes,respectively.The pre-compressed(PC)sample,which contained numerous{10-12}tension twins,has a reduced grain size and a higher internal strain than the pre-tensioned(PT)sample,which is attributed to the inherent internal strain that occurs during the formation and growth of the twins.As a result,the precipitation behavior of the PC sample is accelerated,leading to its short peak aging time of 32 h,which is lower than those of the PT and as-extruded samples(48 and 100 h,respectively).Furthermore,fine continuous precipitates(CPs)rapidly form within the{10-12}twins,contributing to the enhanced hardness.Discontinuous precipitates(DPs),which have a hardness comparable to the CP-containing twinned regions,in the PC sample experience less coarsening during aging than those in the PT sample due to growth inhibition by the{10-12}twins.Ultimately,the{10-12}twins generated under the twinning-dominant deformation condition lead to enhanced precipitation behaviors,including the preferential formation and refinement of CPs and the suppressed coarsening of DPs.Consequently,pre-deformation that occurs{10-12}twinning exhibits more pronounced effects on precipitation acceleration and microstructural modification than slip-inducing pre-deformation.

Effect of atractylenolide Ⅲ on zearalenone-induced Snail1-mediated epithelial–mesenchymal transition in porcine intestinal epithelium

Background The intestinal epithelium performs essential physiological functions,such as nutrient absorption,and acts as a barrier to prevent the entry of harmful substances.Mycotoxins are prevalent contaminants found in ani-mal feed that exert harmful effects on the health of livestock.Zearalenone(ZEA)is produced by the Fusarium genus and induces gastrointestinal dysfunction and disrupts the health and immune system of animals.Here,we evaluated the molecular mechanisms that regulate the effects of ZEA on the porcine intestinal epithelium.Results Treatment of IPEC-J2 cells with ZEA decreased the expression of E-cadherin and increased the expression of Snai1 and Vimentin,which induced Snail1-mediated epithelial-to-mesenchymal transition(EMT).In addition,ZEA induces Snail-mediated EMT through the activation of TGF-βsignaling.The treatment of IPEC-J2 cells with atractyle-nolideⅢ,which were exposed to ZEA,alleviated EMT.Conclusions Our findings provide insights into the molecular mechanisms of ZEA toxicity in porcine intestinal epi-thelial cells and ways to mitigate it.

Enhancement of vertical phase separation in sequentially deposited organic photovoltaics through the independent processing of additives

Herein,the impact of the independent control of processing additives on vertical phase separation in sequentially deposited (SD) organic photovoltaics (OPVs) and its subsequent effects on charge carrier kinetics at the electron donor-acceptor interface are investigated.The film morphology exhibits notable variations,significantly depending on the layer to which 1,8-diiodooctane (DIO) was applied.Grazing incidence wide-angle X-ray scattering analysis reveals distinctly separated donor/acceptor phases and vertical crystallinity details in SD films.Time-of-flight secondary ion mass spectrometry analysis is employed to obtain component distributions in diverse vertical phase structures of SD films depending on additive control.In addition,nanosecond transient absorption spectroscopy shows that DIO control significantly affects the dynamics of separated charges in SD films.In SD OPVs,DIO appears to act through distinct mechanisms with minimal restriction,depending on the applied layer.This study emphasizes the significance of morphological optimization in improving device performance and underscores the importance of independent additive control in the advancement of OPV technology.

Synthesis of crystalline g-C_(3)N_(4) with rock/molten salts for efficient photocatalysis and piezocatalysis

Graphitic carbon nitride(g-C_(3)N_(4))is emerging as a promising visible-light photocatalyst while the low crystallinity with sluggish charge separation/migration dynamics significantly restricts its practical applications.Currently,synthesizing highly crystalline g-C_(3)N_(4) with sufficient surface activities still remains challenging.Herein,different from using alkali molten salts which is commonly reported,we propose an approach for synthesis of highly crystalline g-C_(3)N_(4) with FeCl3/KCl rock/molten mixed salts.The rock salt can serve as the structure-directing template while molten salt provides the required liquid medium for re-condensation.Intriguingly,the synthesized photocatalyst showed further enhanced crystallinity and improved surface area along with high p/p*excitation compared with crystalline C_(3)N_(4) prepared from conventional molten-salt methods.These catalytically advantageous features lead to its superior photocatalytic and piezocatalytic activities with a high reactivity for overall water splitting that is not commonly reported for C_(3)N_(4).This work provides an effective strategy for structural optimization of organic semiconductor based materials and may inspire new ideas for the design of advanced photocatalysts.

Review on inorganic and polymeric materials-coordinated metal-organic-framework photocatalysts for green hydrogen evolution

Metal-organic frameworks(MOFs)possess a distinct advantage over conventional heterogeneous photocatalysts because of their carefully defined architecture and particular pores,which facilitate the targeted incorporation of other efficient cocatalysts or semiconductor materials.The integration of MOFs with other materials has resulted in significant breakthroughs,as the coupled materials improve the performance due to the combined effect.The unique MOF structures allow them to host foreign materials,which results in harvesting the visible region of the solar spectrum and effectively mitigating charge recombination by promoting charge separation.The review presents an evaluation of the latest developments in the utilization of surface and/or pore chemistry of MOF-supported heterojunctions for photocatalytic green-hydrogen generation with a basic understanding of the mechanism involved.The review begins with the basic principles of photocatalysis,the significance of MOFs,their optical properties,the methods used for synthesizing MOFs,and their coordination with other inorganic and polymeric materials.Furthermore,methods to increase photocatalytic H2 evolution using MOF-supported heterojunction have been proposed as standard practice.Lastly,to address environmental challenges,we highlight the future potential of MOF-supported heterojunctions for use in green-energy production.We hope that this review provides guidance to researchers in the development of effective heterojunctions based on MOFs to address challenges in energy applications and catalytic processes.

Understanding of the Relationship between the Properties of Cu(In,Ga)Se_(2) Solar Cells and the Structure of Ag Network Electrodes

The relation between the structure of the silver network electrodes and the properties of Cu(In,Ga)Se_(2)(CIGS)solar cells is systemically investigated.The Ag network electrode is deposited onto an Al:ZnO(AZO)thin film,employing a self-forming cracked template.Precise control over the cracked template's structure is achieved through careful adjustment of temperature and humidity.The Ag network electrodes with different coverage areas and network densities are systemically applied to the CIGS solar cells.It is revealed that predominant fill factor(FF)is influenced by the figure of merit of transparent conducting electrodes,rather than sheet resistance,particularly when the coverage area falls within the range of 1.3–5%.Furthermore,a higher network density corresponds to an enhanced FF when the coverage areas of the Ag networks are similar.When utilizing a thinner AZO film,CIGS solar cells with a surface area of 1.0609 cm^(2)exhibit a notable performance improvement,with efficiency increasing from 10.48%to 11.63%.This enhancement is primarily attributed to the increase in FF from 45%to 65%.These findings underscore the considerable potential for reducing the thickness of the transparent conductive oxide(TCO)in CIGS modules with implications for practical applications in photovoltaic technology.

Establishment of a chicken intestinal organoid culture system to assess deoxynivalenol‑induced damage of the intestinal barrier function

Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in livestock.Since DON-contaminated feedstuff is absorbed in the gastrointestinal tract,we used chicken organoids to assess the DON-induced dysfunction of the small intestine.Results We established a culture system using chicken organoids and characterized the organoids at passages 1 and 10.We confirmed the mRNA expression levels of various cell markers in the organoids,such as KI67,leucine-rich repeat containing G protein-coupled receptor 5(Lgr5),mucin 2(MUC2),chromogranin A(CHGA),cytokeratin 19(CK19),lysozyme(LYZ),and microtubule-associated doublecortin-like kinase 1(DCLK1),and compared the results to those of the small intestine.Our results showed that the organoids displayed functional similarities in permeability compared to the small intestine.DON damaged the tight junctions of the organoids,which resulted in increased permeability.Conclusions Our organoid culture displayed topological,genetic,and functional similarities with the small intes-tine cells.Based on these similarities,we confirmed that DON causes small intestine dysfunction.Chicken organoids offer a practical model for the research of harmful substances.

Interfacial engineering through lead binding using crown ethers in perovskite solar cells

In the domain of perovskite solar cells(PSCs),the imperative to reconcile impressive photovoltaic performance with lead-related issue and environmental stability has driven innovative solutions.This study pioneers an approach that not only rectifies lead leakage but also places paramount importance on the attainment of rigorous interfacial passivation.Crown ethers,notably benzo-18-crown-6-ether(B18C6),were strategically integrated at the perovskite-hole transport material interface.Crown ethers exhibit a dual role:efficiently sequestering and immobilizing Pb^(2+)ions through host-guest complexation and simultaneously establishing a robust interfacial passivation layer.Selected crown ether candidates,guided by density functional theory(DFT)calculations,demonstrated proficiency in binding Pb2+ions and optimizing interfacial energetics.Photovoltaic devices incorporating these materials achieved exceptional power conversion efficiency(PCE),notably 21.7%for B18C6,underscoring their efficacy in lead binding and interfacial passivation.Analytical techniques,including time-of-flight secondary ion mass spectrometry(ToF-SIMS),ultraviolet photoelectron spectroscopy(UPS),time-resolved photoluminescence(TRPL),and transient absorption spectroscopy(TAS),unequivocally affirmed Pb^(2+)ion capture and suppression of non-radiative recombination.Notably,these PSCs maintained efficiency even after enduring 300 h of exposure to 85%relative humidity.This research underscores the transformative potential of crown ethers,simultaneously addressing lead binding and stringent interfacial passivation for sustainable PSCs poised to commercialize and advance renewable energy applications.

Chemical and mechanical properties of stainless, environment-friendly, and nonflammable Mg alloys (SEN alloys): A review

This review article provides overall understanding of stainless,environment-friendly,and nonflammable Mg alloys(SEN alloys)recently developed at the Korea Institute of Materials Science.SEN alloys are produced by adding small amounts of Ca and Y(each<1 wt%)into commercial Mg–Al based alloys,resulting in exceptional ignition and corrosion resistances and impressive mechanical properties.Their main advantages of SEN alloys are as follows.(1)A dense multi-oxide layer of SEN alloys comprising MgO,CaO,and Y_(2)O_(3) impedes the outward dispersion of Mg vapor and the inward penetration of O_(2) during oxidation,thereby enhancing the oxidation and ignition resistances.(2)The presence of Ca-and Y-based second-phase particles in SEN alloys can enhance their corrosion resistance because Ca-containing particles prevent the spread of corrosion,and the replacement of Al-containing particles with less noble ones containing Y(e.g.,Al–Mn–Y or Al–Y particles)retards corrosion.(3)The addition of minor amounts of Ca and Y renders excellent mechanical properties due to improved strengthening effects.These enhanced properties are attributed to more pronounced dynamic recrystallization and grain refining behaviors caused by the second-phase particles during extrusion.(4)Despite the presence of various types of second-phase particles,the fatigue properties of SEN9 alloys are similar to those of commercial AZ91 alloys.(5)Simultaneous introduction of Ca and Y suppresses the formation of Mg17Al12 discontinuous precipitates during aging,leading to the enhanced elongation of aged SEN alloys.(6)Adding mischmetal into the SEN9 alloy leads to a six-fold enhancement in extrudability.Consequently,the studies conducted on SEN alloys demonstrate their excellent ignition and corrosion resistances and mechanical properties,which broaden the industrial applications of Mg alloys by addressing their inherent weaknesses.

Atomically Adjustable Rhodium Catalyst Synthesis with Outstanding Mass Activity via Surface-Li mi ted Cation Exchange

Rh has been widely studied as a catalyst for the promising hydrazine oxidation reaction that can replace oxygen evolution reactions for boosting hydrogen production from hydrazine-containing wastewater.Despite Rh being expensive,only a few studies have examined its electrocatalytic mass activity.Herein,surface-limited cation exchange and electrochemical activation processes are designed to remarkably enhance the mass activity of Rh.Rh atoms were readily replaced at the Ni sites on the surface of NiOOH electrodes by cation exchange,and the resulting RhOOH compounds were activated by the electrochemical reduction process.The cation exchange-derived Rh catalysts exhibited particle sizes not exceeding 2 nm without agglomeration,indicating a decrease in the number of inactive inner Rh atoms.Consequently,an improved mass activity of 30 A mg_(Rh)^(-1)was achieved at 0.4 V versus reversible hydrogen electrode.Furthermore,the two-electrode system employing the same CE-derived Rh electrodes achieved overall hydrazine splitting over 36 h at a stable low voltage.The proposed surface-limited CE process is an effective method for reducing inactive atoms of expensive noble metal catalysts.

Enhancing ChatGPT’s Querying Capability with Voice-Based Interaction and CNN-Based Impair Vision Detection Model

This paper presents an innovative approach to enhance the querying capability of ChatGPT,a conversational artificial intelligence model,by incorporating voice-based interaction and a convolutional neural network(CNN)-based impaired vision detection model.The proposed system aims to improve user experience and accessibility by allowing users to interact with ChatGPT using voice commands.Additionally,a CNN-based model is employed to detect impairments in user vision,enabling the system to adapt its responses and provide appropriate assistance.This research tackles head-on the challenges of user experience and inclusivity in artificial intelligence(AI).It underscores our commitment to overcoming these obstacles,making ChatGPT more accessible and valuable for a broader audience.The integration of voice-based interaction and impaired vision detection represents a novel approach to conversational AI.Notably,this innovation transcends novelty;it carries the potential to profoundly impact the lives of users,particularly those with visual impairments.The modular approach to system design ensures adaptability and scalability,critical for the practical implementation of these advancements.Crucially,the solution places the user at its core.Customizing responses for those with visual impairments demonstrates AI’s potential to not only understand but also accommodate individual needs and preferences.

Real-Time Object Detection and Face Recognition Application for the Visually Impaired

The advancement of navigation systems for the visually impaired has significantly enhanced their mobility by mitigating the risk of encountering obstacles and guiding them along safe,navigable routes.Traditional approaches primarily focus on broad applications such as wayfinding,obstacle detection,and fall prevention.However,there is a notable discrepancy in applying these technologies to more specific scenarios,like identifying distinct food crop types or recognizing faces.This study proposes a real-time application designed for visually impaired individuals,aiming to bridge this research-application gap.It introduces a system capable of detecting 20 different food crop types and recognizing faces with impressive accuracies of 83.27%and 95.64%,respectively.These results represent a significant contribution to the field of assistive technologies,providing visually impaired users with detailed and relevant information about their surroundings,thereby enhancing their mobility and ensuring their safety.Additionally,it addresses the vital aspects of social engagements,acknowledging the challenges faced by visually impaired individuals in recognizing acquaintances without auditory or tactile signals,and highlights recent developments in prototype systems aimed at assisting with face recognition tasks.This comprehensive approach not only promises enhanced navigational aids but also aims to enrich the social well-being and safety of visually impaired communities.