Ferroptosis mechanism and Alzheimer's disease

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

Efficacy of exercise rehabilitation for managing patients with Alzheimer's disease

Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progression are currently unavailable, a plethora of studies have highlighted the potential advantages of exercise rehabilitation for managing this condition. Those studies show that exercise rehabilitation can enhance cognitive function and improve the quality of life for individuals affected by AD. Therefore, exercise rehabilitation has been regarded as one of the most important strategies for managing patients with AD. Herein, we provide a comprehensive analysis of the currently available findings on exercise rehabilitation in patients with AD, with a focus on the exercise types which have shown efficacy when implemented alone or combined with other treatment methods, as well as the potential mechanisms underlying these positive effects. Specifically, we explain how exercise may improve the brain microenvironment and neuronal plasticity. In conclusion, exercise is a cost-effective intervention to enhance cognitive performance and improve quality of life in patients with mild to moderate cognitive dysfunction. Therefore, it can potentially become both a physical activity and a tailored intervention. This review may aid the development of more effective and individualized treatment strategies to address the challenges imposed by this debilitating disease, especially in low-and middle-income countries.

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

The future of artificial hibernation medicine:protection of nerves and organs after spinal cord injury

Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hibernation techniques,mild hypothermia has preliminarily confirmed its clinical effect on spinal cord injury.However,its technical defects and barriers,along with serious clinical side effects,restrict its clinical application for spinal cord injury.Artificial hibernation is a futureoriented disruptive technology for human life support.It involves endogenous hibernation inducers and hibernation-related central neuromodulation that activate particular neurons,reduce the central constant temperature setting point,disrupt the normal constant body temperature,make the body adapt"to the external cold environment,and reduce the physiological resistance to cold stimulation.Thus,studying the artificial hibernation mechanism may help develop new treatment strategies more suitable for clinical use than the cooling method of mild hypothermia technology.This review introduces artificial hibernation technologies,including mild hypothermia technology,hibernation inducers,and hibernation-related central neuromodulation technology.It summarizes the relevant research on hypothermia and hibernation for organ and nerve protection.These studies show that artificial hibernation technologies have therapeutic significance on nerve injury after spinal co rd injury through inflammatory inhibition,immunosuppression,oxidative defense,and possible central protection.It also promotes the repair and protection of res pirato ry and digestive,cardiovascular,locomoto r,urinary,and endocrine systems.This review provides new insights for the clinical treatment of nerve and multiple organ protection after spinal cord injury thanks to artificial hibernation.At present,artificial hibernation technology is not mature,and research fa ces various challenges.Neve rtheless,the effort is wo rthwhile for the future development of medicine.

An NMOS output-capacitorless low-dropout regulator with dynamic-strength event-driven charge pump

In this paper,an NMOS output-capacitorless low-dropout regulator(OCL-LDO)featuring dual-loop regulation has been proposed,achieving fast transient response with low power consumption.An event-driven charge pump(CP)loop with the dynamic strength control(DSC),is proposed in this paper,which overcomes trade-offs inherent in conventional structures.The presented design addresses and resolves the large signal stability issue,which has been previously overlooked in the event-driven charge pump structure.This breakthrough allows for the full exploitation of the charge-pump structure's poten-tial,particularly in enhancing transient recovery.Moreover,a dynamic error amplifier is utilized to attain precise regulation of the steady-state output voltage,leading to favorable static characteristics.A prototype chip has been fabricated in 65 nm CMOS technology.The measurement results show that the proposed OCL-LDO achieves a 410 nA low quiescent current(IQ)and can recover within 30 ns under 200 mA/10 ns loading change.

Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

New advances of adiponectin in regulating obesity and related metabolic syndromes

Obesity and related metabolic syndromes have been recognized as important disease risks,in which the role of adipokines cannot be ignored.Adiponectin(ADP)is one of the key adipokines with various beneficial effects,including improving glucose and lipid metabolism,enhancing insulin sensitivity,reducing oxidative stress and inflammation,promoting ceramides degradation,and stimulating adipose tissue vascularity.Based on those,it can serve as a positive regulator in many metabolic syndromes,such as type 2 diabetes(T2D),cardiovascular diseases,non-alcoholic fatty liver disease(NAFLD),sarcopenia,neurodegenerative diseases,and certain cancers.Therefore,a promising therapeutic approach for treating various metabolic diseases may involve elevating ADP levels or activating ADP receptors.The modulation of ADP genes,multimerization,and secretion covers the main processes of ADP generation,providing a comprehensive orientation for the development of more appropriate therapeutic strategies.In order to have a deeper understanding of ADP,this paper will provide an all-encompassing review of ADP.

A short overview of the lead iodide residue impact and regulation strategies in perovskite solar cells

Lead iodide(PbI2) is a vital raw material for preparing perovskite solar cells(PSCs),and it not only takes part in forming the light absorption layer but also remains in the grain boundary as a passivator.In other words,the PbI2 content in the precursor and as formed film will affect the efficiency and stability of the PSCs.With moderate residual PbI2,it passivates the bulk/surface defects of perovskite,reduces the interfacial recombination,promotes the perovskite stability,minimizes the device hysteresis,and so on.Deficient PbI2 residue will reduce the interfacial passivation effect and device performance.In addition to facilitating the non-radiative recombination,over PbI2 residue can also lead to electronic insulation in the grain boundary and deteriorate the device performance.However,the impact and regulation of PbI2 residue on the device performance and stability is still not fully understood.Herein,a comprehensive and detailed review is presented by discussing the PbI2 residue impact and its regulation strategies(i.e., elimination,facilitation and conversion of the residue PbI2) to manipulate the PbI2 content,distribution and forms.Finally,we also show future outlooks in this field,with an aim to help further the progression of high-efficiency and stable PSCs.

Dynamic regulation of the irrigation-nitrogen-biochar nexus for the synergy of yield,quality,carbon emission and resource use efficiency in tomato

Integrated water and fertilizer management is important for promoting sustainable development of facility agriculture,and biochar plays an important role in guaranteeing food production,as well as alleviating water shortages and the overuse of fertilizers.The field experiment had twelve treatments and a control(CK)trial including two irrigation amounts(I1,100%ETm;I2,60%ETm;where ETm is the maximum evapotranspiration),two nitrogen applications(N1,360 kg ha^(−1);N2,120 kg ha^(−1))and three biochar application levels(B1,60 t ha^(−1);B_(2),30 t ha^(−1)and B3,0 t ha^(−1)).A multi-objective synergistic irrigation-nitrogen-biochar application system for improving tomato yield,quality,water and nitrogen use efficiency,and greenhouse emissions was developed by integrating the techniques of experimentation and optimization.First,a coupled irrigation-nitrogen-biochar plot experiment was arranged.Then,tomato yield and fruit quality parameters were determined experimentally to establish the response relationships between irrigation-nitrogen-biochar dosage and yield,comprehensive quality of tomatoes(TCQ),irrigation water use efficiency(IWUE),partial factor productivity of nitrogen(PFPN),and net greenhouse gas emissions(NGE).Finally,a multi-objective dynamic optimization regulation model of irrigation-nitrogen-biochar resource allocation at different growth stages of tomato was constructed which was solved by the fuzzy programming method.The results showed that the application of irrigation and nitrogen to biochar promoted increase in yield,IWUE and PFPN,while it had an inhibitory effect on NGE.In addition,the optimal allocation amounts of water and fertilizer were different under different scenarios.The yield of the S1 scenario increased by 8.31%compared to the B_(1)I_(1)N_(2) treatment;TCQ of the S2 scenario increased by 5.14%compared to the B_(2)I_(2)N_(1) treatment;IWUE of the S3 scenario increased by 10.01%compared to the B1I2N2 treatment;PFPN of the S4 scenario increased by 9.35%compared to the B_(1)I_(1)N_(2) treatment;and NGE of the S5 scenario decreased by 11.23%compared to the B_(2)I1N1 treatment.The optimization model showed that the coordination of multiple objectives considering yield,TCQ,IWUE,PFPN,and NGE increased on average from 4.44 to 69.02%compared to each treatment when the irrigation-nitrogen-biochar dosage was 205.18 mm,186 kg ha^(−1)and 43.31 t ha^(−1),respectively.This study provides a guiding basis for the sustainable management of water and fertilizer in greenhouse tomato production under drip irrigation fertilization conditions.

Application of different fiber structures and arrangements by electrospinning in triboelectric nanogenerators

In recent years,nanogenerators(NGs)have attracted wide attention in the energy field,among which triboelectric nanogenerators(TENGs)have shown superior performance.Multiple reports of electrospinning(ES)-based TENGs have been reported,but there is a lack of deep analysis of the designing method from microstructure,limiting the creative of new ES-based TENGs.Most TENGs use polymer materials to achieve corresponding design,which requires structural design of polymer materials.The existing polymer molding design methods include macroscopic molding methods,such as injection,compression,extrusion,calendering,etc.,combined with liquid-solid changes such as soluting and melting;it also includes micro-nano molding technology,such as melt-blown method,coagulation bath method,ES method,and nanoimprint method.In fact,ES technology has good controllability of thickness dimension and rich means of nanoscale structure regulation.At present,these characteristics have not been reviewed.Therefore,in this paper,we combine recent reports with some microstructure regulation functions of ES to establish a more general TENGs design method.Based on the rich microstructure research results in the field of ES,much more new types of TENGs can be designed in the future.

Analysis of the optimal target node to reduce seizure-like discharge in networks

Network approaches have been widely accepted to guide surgical strategy and predict outcome for epilepsy treatment.This study starts with a single oscillator to explore brain activity,using a phenomenological model capable of describing healthy and epileptic states.The ictal number of seizures decreases or remains unchanged with increasing the speed of oscillator excitability and in each seizure,there is an increasing tendency for ictal duration with respect to the speed.The underlying reason is that the strong excitability speed is conducive to reduce transition behaviors between two attractor basins.Moreover,the selection of the optimal removal node is estimated by an indicator proposed in this study.Results show that when the indicator is less than the threshold,removing the driving node is more possible to reduce seizures significantly,while the indicator exceeds the threshold,the epileptic node could be the removal one.Furthermore,the driving node is such a potential target that stimulating it is obviously effective in suppressing seizure-like activity compared to other nodes,and the propensity of seizures can be reduced 60%with the increased stimulus strength.Our results could provide new therapeutic ideas for epilepsy surgery and neuromodulation.

Epigenetic control on transcription of vernalization genes and whole-genome gene expression profile induced by vernalization in common wheat

Vernalization is necessary for winter wheat to flower.However,it is unclear whether vernalization is also required for spring wheat,which is frequently sown in fall,and what molecular mechanisms underlie the vernalization response in wheat varieties.In this study,we examined the molecular mechanisms that regulate vernalization response in winter and spring wheat varieties.For this purpose,we determined how major vernalization genes(VRN1,VRN2,and VRN3)respond to vernalization in these varieties and whether modifications to histones play a role in changes in gene expression.We also identified genes that are differentially regulated in response to vernalization in winter and spring wheat varieties.We found that in winter wheat,but not in spring wheat,VRN1 expression decreases when returned to warm temperature following vernalization.This finding may be associated with differences between spring and winter wheat in the levels of tri-methylation of lysine 27 on histone H3(H3K27me3)and tri-methylation of lysine 4 on histone H3(H3K4me3)at the VRN1 gene.Analysis of winter wheat transcriptomes before and after vernalization revealed that vernalization influences the expression of several genes,including those involved in leucine catabolism,cysteine biosynthesis,and flavonoid biosynthesis.These findings provide new candidates for further study on the mechanism of vernalization regulation in wheat.

Preparation of Manganese Oxide and Its Adsorption Properties

The in-situ oxidation of manganese sulfate solution with H2O_(2),sodium hypochlorite,potassium permanganate and oxygen as oxidants was investigated by means of SEM,EDS,XRD,BET and infrared analysis,and the effects of different oxidants on the morphology,phase composition,surface properties and specific surface area of manganese oxides were investigated.The experimental results show that the diameter of manganese oxide particles prepared with H_(2)O_(2)is the smallest,about 50 nm,and the specific surface area is the largest,63.8764 m^(2)/g.It has the advantages of abundant surface hydroxyl groups,no introduction of other impurities and large adsorption potential.It is most suitable to be used as an oxidant for oxidizing manganese sulfate solution to prepare manganese oxide by in-situ oxidation.Nano manganese oxide prepard by H_(2)O_(2)in-situ oxidation method is used as adsorbent to adsorb cobalt and nickel impurities in manganese sulfate.When the reaction pH is 6,the reaction time is 30min and the amount of adsorbent is 1.0 g,the adsorption rates of cobalt and nickel impurities in 100ml manganese sulfate solution are 97.59%and 97.67%,respectively.The residual amounts of cobalt and nickel meet the industrial process standard of first-class products(Co,Ni w/%≤0.005)of high-purity manganese sulfate(Hg/t4823-2015)for batteries.The study plays a guiding role in the preparation and regulation of manganese oxide,and provides a new method with high efficiency,purity and adsorbent availability for the preparation of high-purity manganese sulfate solution.

Structural Engineering of Anode Materials for Low-Temperature Lithium-Ion Batteries:Mechanisms,Strategies,and Prospects

The severe degradation of electrochemical performance for lithium-ion batteries(LIBs)at low temperatures poses a significant challenge to their practical applications.Consequently,extensive efforts have been contributed to explore novel anode materials with high electronic conductivity and rapid Li^(+)diffusion kinetics for achieving favorable low-temperature performance of LIBs.Herein,we try to review the recent reports on the synthesis and characterizations of low-temperature anode materials.First,we summarize the underlying mechanisms responsible for the performance degradation of anode materials at subzero temperatures.Second,detailed discussions concerning the key pathways(boosting electronic conductivity,enhancing Li^(+)diffusion kinetics,and inhibiting lithium dendrite)for improving the low-temperature performance of anode materials are presented.Third,several commonly used low-temperature anode materials are briefly introduced.Fourth,recent progress in the engineering of these low-temperature anode materials is summarized in terms of structural design,morphology control,surface&interface modifications,and multiphase materials.Finally,the challenges that remain to be solved in the field of low-temperature anode materials are discussed.This review was organized to offer valuable insights and guidance for next-generation LIBs with excellent low-temperature electrochemical performance.

A novel histone methyltransferase gene Cg SDG40 positively regulates carotenoid biosynthesis during citrus fruit ripening

The flesh color of pummelo(Citrus maxima)fruits is highly diverse and largely depends on the level of carotenoids,which are beneficial to human health.It is vital to investigate the regulatory network of carotenoid biosynthesis to improve the carotenoid content in pummelo.However,the molecular mechanism underlying carotenoid accumulation in pummelo is not fully understood.In this study,we identified a novel histone methyltransferase gene,CgSDG40,involved in carotenoid regulation by analyzing the flesh transcriptome of typical white-fleshed pummelo,red-fleshed pummelo and extreme-colored F1 hybrids from a segregated pummelo population.Expression of CgSDG40 corresponded to flesh color change and was highly coexpressed with CgPSY1.Interestingly,CgSDG40 and CgPSY1 are located physically adjacent to each other on the chromosome in opposite directions,sharing a partially overlapping promoter region.Subcellular localization analysis indicated that CgSDG40 localizes to the nucleus.Overexpression of CgSDG40 significantly increased the total carotenoid content in citrus calli relative to that in wild type.In addition,expression of CgPSY1 was significantly activated in overexpression lines relative to wild type.Taken together,our findings reveal a novel histone methyltransferase regulator,CgSDG40,involved in the regulation of carotenoid biosynthesis in citrus and provide new strategies for molecular design breeding and genetic improvement of fruit color and nutritional quality.

OsPPG encodes a pseudouridine-5'-phosphate glycosidase and regulates rice spikelet development

Florets are the basic structural units of spikelets,and their morphogenesis determines the yield and quality of rice grains.However,whether and how pseudouridine-5’-phosphate glycosidase participates in rice spikelet development remains an open question.In this study,we identified a novel gene,OsPPG,which encodes a peroxisome-localized pseudouridine-5’-phosphate glycosidase and regulates the development of rice spikelets.osppg mutants exhibited abnormal sterile lemma,lemma,palea,lodicule,stamens,and pistils;male sterility;shorter panicles;and reduced plant height.OsPPG was found to regulate several OsMADS genes,thereby affecting the morphogenesis of rice spikelets.Furthermore,metabolomics revealed that the OsPPG gene was involved in the decomposition of pseudouridine via the pyrimidine metabolism pathway and may affect the jasmonic acid signaling pathway.These results suggest that OsPPG is a key regulator of rice spikelet development.

Molecular Mechanism of Rice Necrotic Lesion for Optimized Yield and Disease Resistance

How to balance rice resistance and yield is an important issue in rice breeding.Plants with mutated necrotic lesion genes often have persistent broad-spectrum resistance,but this broad-spectrum resistance usually comes at the expense of yield.Currently,many necrotic lesion mutants in rice have been identified,and these genes are involved in disease resistance pathways.This review provides a detailed introduction to the characteristics,classification,and molecular mechanisms of necrotic lesion formation.Additionally,we review the molecular regulatory pathways of genes involved in rice disease resistance.Concurrently,we summarize the relationship between resistance and yield in rice using newly developed gene editing methods.We discuss a rational and precise breeding strategy to better utilize molecular design technology for breeding disease-resistant and high-yield rice varieties.

Rice melatonin deficiency causes premature leaf senescence via DNA methylation regulation

In a study of DNA methylation changes in melatonin-deficient rice mutants,mutant plants showed premature leaf senescence during grain-filling and reduced grain yield.Melatonin deficiency led to transcriptional reprogramming,especially of genes involved in chlorophyll and carbon metabolism,redox regulation,and transcriptional regulation,during dark-induced leaf senescence.Hypomethylation of mCG and mCHG in the melatonin-deficient rice mutants was associated with the expression change of both protein-coding genes and transposable element-related genes.Changes in gene expression and DNA methylation in the melatonin-deficient mutants were compensated by exogenous application of melatonin.A decreased S-adenosyl-L-methionine level may have contributed to the DNA methylation variations in rice mutants of melatonin deficiency under dark conditions.

Compartmentalized regulation of organelle integrity in neurodegenerative diseases:lessons from the Drosophila motor neuron

Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).

Investigation on mechanical properties regulation of rock-like specimens based on 3D printing and similarity quantification

3D printing is widely adopted to quickly produce rock mass models with complex structures in batches,improving the consistency and repeatability of physical modeling.It is necessary to regulate the mechanical properties of 3D-printed specimens to make them proportionally similar to natural rocks.This study investigates mechanical properties of 3D-printed rock analogues prepared by furan resin-bonded silica sand particles.The mechanical property regulation of 3D-printed specimens is realized through quantifying its similarity to sandstone,so that analogous deformation characteristics and failure mode are acquired.Considering similarity conversion,uniaxial compressive strength,cohesion and stress–strain relationship curve of 3D-printed specimen are similar to those of sandstone.In the study ranges,the strength of 3D-printed specimen is positively correlated with the additive content,negatively correlated with the sand particle size,and first increases then decreases with the increase of curing temperature.The regulation scheme with optimal similarity quantification index,that is the sand type of 70/140,additive content of 2.5‰and curing temperature of 81.6℃,is determined for preparing 3D-printed sandstone analogues and models.The effectiveness of mechanical property regulation is proved through uniaxial compression contrast tests.This study provides a reference for preparing rock-like specimens and engineering models using 3D printing technology.