Contribution of mechanical forces to structural synaptic plasticity:insights from 3D cellular motility mechanisms

Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).

Decoding molecular mechanisms:brain aging and Alzheimer's disease

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.

Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar formation.These changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health burden.Military personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military medicine.So far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart regeneration.In the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury.Insights have emerged from studies in animal models and early clinical trials.Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease.In this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

Drug resistance mechanisms in cancers:Execution of prosurvival strategies

One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

A Facile Route for the Large Scale Fabrication of Graphene Oxide Papers and Their Mechanical Enhancement by Cross-linking with Glutaraldehyde

A facile route for the large scale production of graphene oxide(GO) papers and their mechanical enhancement has been presented in this work. The novel paper-like GO made from individual GO sheets in aqueous suspension can be achieved in large scale by a simple drop casting method on hydrophobic substrates.Significant enhancement in mechanical stiffness(341%) and fracture strength(234%) of GO paper have been achieved upon modification with a small amount(less than 10 wt%) of glutaraldehyde(GA). The cross-linking reaction takes place between hydroxyl groups on the surface of GO and aldehyde groups of GA, through forming hemiacetal structure, which can result in distinct mechanical enhancement of the GO papers.

Role of methoxy and C_(α)-based substituents in electrochemical oxidation mechanisms and bond cleavage selectivity of β-O-4 lignin model compounds

In order to better understand the specific substituent effects on the electrochemical oxidation process of β-O-4 bond, a series of methoxyphenyl type β-O-4 dimer model compounds with different localized methoxyl groups, including 2-(2-methoxyphenoxy)-1-phenylethanone, 2-(2-methoxyphenoxy)-1-phenylethanol, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2-methoxyphenoxy)-1-(4-methoxyphenyl)ethanol, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanone, 2-(2,6-dimethoxyphenoxy)-1-(4-methoxyphenyl)ethanol have been selected and their electrochemical properties have been studied experimentally by cyclic voltammetry, and FT-IR spectroelectrochemistry. Combining with electrolysis products distribution analysis and density functional theory calculations, oxidation mechanisms of all six model dimers have been explored. In particular, a total effect from substituents of both para-methoxy(on the aryl ring closing to Cα) and Cα-OH on the oxidation mechanisms has been clearly observed, showing a significant selectivity on the Cα-Cβbond cleavage induced by electrochemical oxidations.

Preparation, Properties and Mechanism of Inhomogeneous Calcium Alginate Ion Cross-linking Gel Microspheres

Inhomogeneous calcium alginate ion cross\|linking gel microspheres, a novel ion absorbent, were prepared by dropping a sodium alginate solution to a calcium chloride solution via an electronic droplet generator. Calcium alginate microspheres have uniform particle sizes, a smooth surface and a microporous structure. The electrode probe reveals the inhomogeneous distribution of calcium ions with the highest concentration on the surface, and the lowest concentration in the cores of the spheres. As a novel ion adsorbent, calcium alginate gel microspheres have a lower limiting adsorption mass concentration, a higher enrichment capacity and a higher adsorption capacity for Pb 2+ than usual ion exchange resins. The highest percentage of the adsorption is 99 79%. The limiting adsorption mass concentration is 0 0426 mg/L. The adsorption capacity for Pb 2+ is 644 mg/g. Calcium alginate gel microspheres have a much faster ion exchange velocity than D418 chelating resin and D113 polyacrylate resin. The moving boundary model was employed to interpret the ion exchange kinetics process, which indicates that the ion exchange process is controlled by intraparticle diffusion of adsorbable ions. So the formation of inhomogeneous gel microspheres reduces the diffusion distance of adsorbable ions within the spheres and enhances the ion exchange velocity. Alginate has a higher selectivity for Pb 2+ than for Ca 2+ and the selectivity coefficient K Pb Ca is 316. As an ion cross\|linking gel, calcium alginate inhomogeneous microspheres can effectively adsorb heavy metal Pb 2+ at a higher selectivity and a higher adsorption velocity. It is a novel and good ion adsorbent.

Mechanism of high Li-ion conductivity in poly(vinylene carbonate)-poly(ethylene oxide)cross-linked network based electrolyte revealed by solid-state NMR

Solid polymer electrolytes(SPEs)have become increasingly important in advanced lithium-ion batteries(LIBs)due to their improved safety and mechanical properties compared to organic liquid electrolytes.Cross-linked polymers have the potential to further improve the mechanical property without trading off Li-ion conductivity.In this study,focusing on a recently developed cross-linked SPE,i.e.,the one based on poly(vinylene carbonate)-poly(ethylene oxide)cross-linked network(PVCN),we used solid-state nuclear magnetic resonance(NMR)techniques to investigate the fundamental interaction between the chain segments and Li ions,as well as the lithium-ion motion.By utilizing homonuclear/heteronuclear correlation,CP(cross-polarization)kinetics,and spin-lattice relaxation experiments,etc.,we revealed the structural characteristics and their relations to lithium-ion mobilities.It is found that the network formation prevents poly(ethylene oxide)chains from crystallization,which could create sufficient space for segmental tumbling and Li-ion co nductio n.As such,the mechanical property is greatly improved with even higher Li-ion mobilities compared to the poly(vinylene carbonate)or poly(ethylene oxide)based SPE analogues.

Insights into the swelling process and drug release mechanisms from cross-linked pectin/high amylose starch matrices

Cross-linked pectin/high amylose mixtures were evaluated as a new excipient for matrix tablets formulations,since the mixing of polymers and cross-linking reaction represent rational tools to reach materials with modulated and specific properties that meet specific therapeutic needs.Objective:In this work the influence of polymer ratio and cross-linking process on the swelling and the mechanism driving the drug release from swellable matrix tablets prepared with this excipient was investigated.Methods:Cross-linked samples were characterized by their micromeritic properties(size and shape,density,angle of repose and flow rate)and liquid uptake ability.Matrix tablets were evaluated according their physical properties and the drug release rates and mechanisms were also investigated.Results:Cross-linked samples demonstrated size homogeneity and irregular shape,with liquid uptake ability insensible to pH.Cross-linking process of samples allowed the control of drug release rates and the drug release mechanism was influenced by both polymer ratio and cross-linking process.The drug release of samples with minor proportion of pectin was driven by an anomalous transport and the increase of the pectin proportion contributed to the erosion of the matrix.Conclusion:The cross-linked mixtures of high amylose and pectin showed a suitable excipient for slowing the drug release rates.

Study of action mechanisms and properties of Cr^(3+) cross-linked polymer solution with high salinity

Performance characteristics of partially hydrolyzed polyacrylamide （HPAM） and cross- linked polymer （CLP, Cr^3＋ as the cross linker） solutions have been investigated. A Brookfield viscometer, rheometer, dynamic light scattering system, and core flow device have been used to measure the viscosity, viscoelasticity, polymer coil dimensions, molecular configuration, flow characteristics, and profile modification. The results show that, under conditions of high salinity and low HPAM and Cr^3＋ concentrations, cross-linking mainly occurred between different chains of the same HPAM molecule in the presence of Cr^3＋, and a cross-linked polymer （CLP） system with a local network structure was formed. Compared with an HPAM solution of the same concentration, the apparent viscosity of the CLP solution increased slightly or remained almost unchanged, but its viscoelasticity （namely storage modulus, loss modulus, and first normal stress difference） increased, and the resistance coefficient and residual resistance coefficient increased significantly. This indicates that the CLP solution exhibits a strong capability to divert the sequentially injected polymer flood from high-permeability zones to low- permeability zones in a reservoir. Under the same HPAM concentration conditions, the dimensions of polymer coils in the CLP solution increased slightly compared with the dimensions of polymer coils in HPAM solution, which were smaller than the rock pores, indicating that the cross-linked polymer solution was well adapted to reservoir rocks. Core flood experiments show that at the same cost of reagent, the oil recovery by CLP injection （HPAM-1, Cr^3＋ as the cross linker） is 3.1% to 5.2% higher than that by HPAM- 2 injection.

Deep tectonics and seismogenic mechanisms of the seismic source zone of the Jishishan M_(s)6.2 earthquake on December 18,2023,at the northeast margin of the Tibetan Plateau

On December 18,2023,an M_(s)6.2 earthquake occurred in Jishishan,Gansu Province,China.This earthquake happened in the eastern region of the Qilian Orogenic Belt,which is situated at the forefront of the NE margin of the Tibetan Plateau(i.e.,Qinghai-Tibet Plateau),encompassing a rhombic-shaped area that intersects the Qilian-Qaidam Basin,Alxa Block,Ordos Block,and South China Block.In this study,we analyzed the deep tectonic pattern of the Jishishan earthquake by incorporating data on the crustal thickness,velocity structure,global navigation satellite system(GNSS)strain field,and anisotropy.We discovered that the location of the earthquake was related to changes in the crustal structure.The results showed that the Jishishan M_(s)6.2 earthquake occurred in a unique position,with rapid changes in the crustal thickness,Vp/Vs,phase velocity,and S-wave velocity.The epicenter of the earthquake was situated at the transition zone between high and low velocities and was in proximity to a low-velocity region.Additionally,the source area is flanked by two high-velocity anomalies from the east and west.The principal compressive strain orientation near the Lajishan Fault is primarily in the NNE and NE directions,which align with the principal compressive stress direction in this region.In some areas of the Lajishan Fault,the principal compressive strain orientations show the NNW direction,consistent with the direction of the upper crustal fast-wave polarization from local earthquakes and the phase velocity azimuthal anisotropy.These features underscore the relationship between the occurrence of the Jishishan M_(s)6.2 earthquake and the deep inhomogeneous structure and deep tectonic characteristics.The NE margin of the Tibetan Plateau was thickened by crustal extension in the process of northeastward expansion,and the middle and lower crustal materials underwent structural deformation and may have been filled with salt-containing fluids during the extension process.The presence of this weak layer makes it easier for strong earthquakes to occur through the release of overlying rigid crustal stresses.However,it is unlikely that an earthquake of comparable or larger magnitude would occur in the short term(e.g.,in one year)at the Jishishan east margin fault.

Interplay between temperature-dependent strengthening mechanisms and mechanical stability in high-performance austenitic stainless steels

The effects of deformation temperature on the transformation-induced plasticity(TRIP)-aided 304L,twinning-induced plasti-city(TWIP)-assisted 316L,and highly alloyed stable 904L austenitic stainless steels were compared for the first time to tune the mechan-ical properties,strengthening mechanisms,and strength-ductility synergy.For this purpose,the scanning electron microscopy(SEM),electron backscattered diffraction(EBSD),X-ray diffraction(XRD),tensile testing,work-hardening analysis,and thermodynamics calcu-lations were used.The induced plasticity effects led to a high temperature-dependency of work-hardening behavior in the 304L and 316L stainless steels.As the deformation temperature increased,the metastable 304L stainless steel showed the sequence of TRIP,TWIP,and weakening of the induced plasticity mechanism;while the disappearance of the TWIP effect in the 316L stainless steel was also observed.However,the solid-solution strengthening in the 904L superaustenitic stainless steel maintained the tensile properties over a wide temper-ature range,surpassing the performance of 304L and 316L stainless steels.In this regard,the dependency of the total elongation on the de-formation temperature was less pronounced for the 904L alloy due to the absence of additional plasticity mechanisms.These results re-vealed the importance of solid-solution strengthening and the associated high friction stress for superior mechanical behavior over a wide temperature range.

A molecular dynamics study on mechanical performance and deformation mechanisms in nanotwinned NiCo-based alloys with nano-precipitates under high temperatures

Molecular dynamics simulations are performed to investigate the mechanical behavior of nanotwinned NiCo-based alloys containing coherent L12 nano-precipitates at different temperatures,as well as the interactions between the dislocations and nano-precipitates within the nanotwins.The simulation results demonstrate that both the yield stress and flow stress in the nanotwinned NiCo-based alloys with nano-precipitates decrease as the temperature rises,because the higher temperatures lead to the generation of more defects during yielding and lower dislocation density during plastic deformation.Moreover,the coherent L12 phase exhibits excellent thermal stability,which enables the hinderance of dislocation motion at elevated temperatures via the wrapping and cutting mechanisms of dislocations.The synergistic effect of nanotwins and nano-precipitates results in more significant strengthening behavior in the nanotwinned NiCo-based alloys under high temperatures.In addition,the high-temperature mechanical behavior of nanotwinned NiCo-based alloys with nano-precipitates is sensitive to the size and volume fraction of the microstructures.These findings could be helpful for the design of nanotwins and nano-precipitates to improve the high-temperature mechanical properties of NiCo-based alloys.

Solid-state NMR of vulcanized natural rubber/butadiene rubber blends:Local organization and cross-linking heterogeneities This article is part of the virtual special issue“Solid-state NMR studies on polymers and biological solids”

Elastomer blends,among which natural rubber(NR)and butadiene rubber(BR),are involved in many components of the automotive/tire industry.A comprehensive understanding of their mechanical behavior requires,among other features,a detailed description of the crosslink density in these mixtures.In the case of vulcanized immiscible blends,the distribution of the cross-link density within each of the NR-and BR-rich domains is key information,but difficult to determine using the conventional approaches used for one-component crosslinked elastomers.In this study,the vulcanization within NR/BR blends is investigated using a robust^(1)H double-quantum(DQ)MAS recoupling experiment,BaBa-xy16.Two kinds of cross-linked NR/BR blends were considered with two different microstructures for the BR component.The bulk organization of the resulting blends was first probed by analyzing the^(1)H spin-lattice relaxation behavior.In a second step,BaBa-xy16 was used to investigate,in a selective way,the cross-link heterogeneities within NR/BR blends.In particular,for immiscible NR/BR mixtures,the distribution of the cross-link density between both phases was compared and the observed differences were discussed.

Early changes in corneal densitometry after FS-LASIK combined with accelerated corneal cross-linking for correction of high myopia

AIM:To observe the effects of femtosecond laserassisted excimer laser in situ keratomileusis combined with accelerated corneal cross-linking(FS-LASIK Xtra)on corneal densitometry after correcting for high myopia.METHODS:In this prospectively study,130 patients underwent FS-LASIK or FS-LASIK Xtra for high myopia.Their right eyes were selected for inclusion in the study,of which 65 cases of 65 eyes in the FS-LASIK group,65 patients with 65 eyes in the FS-LASIK Xtra group.Patients were evaluated for corneal densitometry at 1,3,and 6mo postoperatively using Pentacam Scheimpflug imaging.RESULTS:Preoperative differences in corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups in different ranges were not statistically significant(P>0.05).Layer-by-layer analysis revealed statistically significant differences in the anterior(120μm),central,and total layer corneal densitometry between the FS-LASIK and FS-LASIK Xtra groups at 1 and 3mo postoperatively(all P<0.05),the FS-LASIK Xtra group is higher than that of the FS-LASIK group.Analysis of different diameter ranges showed statistically significant differences between the FS-LASIK group and the FS-LASIK Xtra group at 1mo postoperatively in the ranges of 0–2,2–6,and 6–10 mm(both P<0.05);At 3mo postoperatively,the FS-LASIK Xtra group is higher than that of the FS-LASIK group in the ranges of 0–2 and 2–6 mm(P<0.05).At 6mo postoperatively,there were no statistically significant differences in corneal densitometry between the FS-LASIK group and the FS-LASIK Xtra group in different diameter ranges(all P>0.05).CONCLUSION:There is an increase in internal corneal densitometry during the early postoperative period after FS-LASIK Xtra for correction of high myopia.However,the densitometry values decreased to the level of conventional FS-LASIK at 6mo after surgery,with the most significant changes observed in the superficial central zone.

Activity-dependent mechanisms of neuroprotection:promising avenues against dementia

The study of the brain and its complex functions is highly fascinating and,at the same time,extremely important.Indeed,furthering our understanding of the biology of neurons and synapses is a prerequisite to uncover the mechanisms involved in memory formation and the coordination of movement as well as their alterations occurring in several neurological disorders.

Wnt/β-catenin signaling components and mechanisms in bone formation,homeostasis,and disease

Wnts are secreted,lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways,which control various biological processes throughout embryonic development and adult life.Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses.

Obituary:Prof.Yun Zhang(1963-2023)-A scientist focused on toxins and their underlying mechanisms to decipher human diseases

Prof.Yun Zhang was born on 9 July 1963 in Kunming,Yunnan,China,during a tumultuous period which he often referenced.Throughout his life,he harbored a steadfast belief in using knowledge to unravel the mysteries of human diseases.His educational journey was marked by frequent changes in schools due to his parents’occupational relocations.However,despite these challenges,he consistently displayed diligence and was admitted to the East China University of Science and Technology,Shanghai,after completing high school in 1980.He remained an active and loyal member of the School of Biotechnology at the university.