Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited significant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be theα,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity throughα,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Surface wave inversion with unknown number of soil layers based on a hybrid learning procedure of deep learning and genetic algorithm

Surface wave inversion is a key step in the application of surface waves to soil velocity profiling.Currently,a common practice for the process of inversion is that the number of soil layers is assumed to be known before using heuristic search algorithms to compute the shear wave velocity profile or the number of soil layers is considered as an optimization variable.However,an improper selection of the number of layers may lead to an incorrect shear wave velocity profile.In this study,a deep learning and genetic algorithm hybrid learning procedure is proposed to perform the surface wave inversion without the need to assume the number of soil layers.First,a deep neural network is adapted to learn from a large number of synthetic dispersion curves for inferring the layer number.Then,the shear-wave velocity profile is determined by a genetic algorithm with the known layer number.By applying this procedure to both simulated and real-world cases,the results indicate that the proposed method is reliable and efficient for surface wave inversion.

An efficient physics-guided Bayesian framework for predicting ground settlement profile during excavations in clay

Recently,the application of Bayesian updating to predict excavation-induced deformation has proven successful and improved prediction accuracy significantly.However,updating the ground settlement profile,which is crucial for determining potential damage to nearby infrastructures,has received limited attention.To address this,this paper proposes a physics-guided simplified model combined with a Bayesian updating framework to accurately predict the ground settlement profile.The advantage of this model is that it eliminates the need for complex finite element modeling and makes the updating framework user-friendly.Furthermore,the model is physically interpretable,which can provide valuable references for construction adjustments.The effectiveness of the proposed method is demonstrated through two field case studies,showing that it can yield satisfactory predictions for the settlement profile.

Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

Monitoring shear deformation of sliding zone via fiber Bragg grating and particle image velocimetry

Monitoring shear deformation of sliding zones is of great significance for understanding the landslide evolution mechanism,in which fiber optic strain sensing has shown great potential.However,the cor-relation between strain measurements of quasi-distributed fiber Bragg grating(FBG)sensing arrays and shear displacements of surrounding soil remains elusive.In this study,a direct shear model test was conducted to simulate the shear deformation of sliding zones,in which the soil internal deformation was captured using FBG strain sensors and the soil surface deformation was measured by particle image velocimetry(PIV).The test results show that there were two main slip surfaces and two secondary ones,developing a spindle-shaped shear band in the soil.The formation of the shear band was successfully captured by FBG sensors.A sinusoidal model was proposed to describe the fiber optic cable deformation behavior.On this basis,the shear displacements and shear band widths were calculated by using strain measurements.This work provides important insight into the deduction of soil shear deformation using soil-embedded FBG strain sensors.

Exploring the impact of economic growth and energy consumption on SO_(2) emissions in China based on the Environmental Kuznets Curve hypothesis

This study aims to analysis the influence of economic growth(EG)and energy consumption(EC)on sulfur dioxide emissions(SE)in China.Accordingly,this study explores the link between EG,EC,and SE for 30 provinces in China over the span of 2000-2019.This study also analyzes cross-sectional dependence tests,panel unit root tests,Westerlund panel cointegration tests,Dumitrescu-Hurlin(D-H)causality tests.According to the test results,there is an inverted U-shaped association between EG and SE,and the assumption of the Environmental Kuznets Curve(EKC)is verified.The signs of EG and EC in the fixed effect(FE)and random effect(RE)methods are in line with those in the dynamic ordinary least squares(DOLS),fully modified ordinary least squares(FMOLS)and autoregressive distributed lag(ARDL)estimators.Moreover,the results verified that EC can obviously positive impact the SE.To reduce SE in China,government and policymakers can improve air quality by developing cleaner energy sources and improving energy efficiency.This requires the comprehensive use of policies,regulations,economic incentives,and public participation to promote sustainable development.

Debris flow runout behaviors considering the influences of densely populated buildings

Debris flows pose serious risks to communities in mountainous areas,often resulting in large losses of human life and property.The impeding presence of urban buildings often affects the runout behavior and deposition of debris flows.But the impact of different building densities and sizes on debris flow dynamics has yet to be quantified to guide urban planning in debris flow risk zones.This study focused on a debris flow that occurred in Zhouqu County,Gansu Province,China on August 7th,2010,which was catastrophic and destroyed many buildings.The FLO-2D software was used to simulate this debris flow in two scenarios,i.e.the presence and the absence of buildings,to obtain debris-flow intensity parameters.The developed model was then used to further analyze the influence of large buildings and narrow channels within the urban environment.The simulation results show that considering the presence of buildings in the simulation is essential for accurate assessment of debris flow intensity and deposition distribution.The layout of buildings in the upstream urban area,such as large buildings or parallel buildings which form narrow channels,can affect the flow velocity and depth of debris flow heading towards downstream buildings.To mitigate damage to downstream buildings,the relative spacing(d/a)between upstream and downstream buildings should not exceed a value of two and should ideally be even lower.These findings provide valuable insights for improving the resistance of mountainous cities to urban debris flows.

Enhancing the Performance of Perovskite Light-Emitting Diodes via Synergistic Effect of Defect Passivation and Dielectric Screening

Metal halide perovskites,particularly the quasi-two-dimensional perovskite subclass,have exhibited considerable potential for next-generation electroluminescent materials for lighting and display.Nevertheless,the presence of defects within these perovskites has a substantial influence on the emission efficiency and durability of the devices.In this study,we revealed a synergistic passivation mechanism on perovskite films by using a dual-functional compound of potassium bromide.The dual functional potassium bromide on the one hand can passivate the defects of halide vacancies with bromine anions and,on the other hand,can screen the charged defects at the grain boundaries with potassium cations.This approach effectively reduces the probability of carriers quenching resulting from charged defects capture and consequently enhances the radiative recombination efficiency of perovskite thin films,leading to a significant enhancement of photoluminescence quantum yield to near-unity values(95%).Meanwhile,the potassium bromide treatment promoted the growth of homogeneous and smooth film,facilitating the charge carrier injection in the devices.Consequently,the perovskite light-emitting diodes based on this strategy achieve a maximum external quantum efficiency of~21%and maximum luminance of~60,000 cd m^(-2).This work provides a deeper insight into the passivation mechanism of ionic compound additives in perovskite with the solution method.

Ganoderma lucidum:a comprehensive review of phytochemistry,efficacy,safety and clinical study

Ganoderma lucidum,one of the most well-known edible fungi,is believed to be very beneficial for longevity and vitality.A long usage history suggests that G.lucidum has various clinical therapeutic effects.And experimental studies have confirmed that G.lucidum has multiple pharmacological effects,including antitumor,anti-microbial,anti-HIV protease,and antidiabetic activity and so on.With the deepening of research,more than 300 compounds have been isolated from G.lucidum.There is an increasing population of G.lucidum-based products,and its international development is expanding.Currently,G.lucidum has drawn much attention to its chemical composition,therapeutic effect,clinical value,and safety.This paper provides a comprehensive review of these aspects to enhance the global promotion of G.lucidum.

Optical Properties of GaAs/AlGaAs Nanowires Grown on Pre-etched Si Substrates

GaAs-based nanomaterials are essential for near-infrared nano-photoelectronic devices due to their exceptional optoelectronic properties.However,as the dimensions of GaAs materials decrease,the development of GaAs nanowires(NWs)is hindered by type-Ⅱquantum well structures arising from the mixture of zinc blende(ZB)and wurtzite(WZ)phases and surface defects due to the large surface-to-volume ratio.Achieving GaAs-based NWs with high emission efficiency has become a key research focus.In this study,pre-etched silicon substrates were combined with GaAs/AlGaAs core-shell heterostructure to achieve GaAs-based NWs with good perpendicularity,excellent crystal structures,and high emission efficiency by leveraging the shadowing effect and surface passivation.The primary evidence for this includes the prominent free-exciton emission in the variable-temperature spectra and the low thermal activation energy indicated by the variable-power spectra.The findings of this study suggest that the growth method described herein can be employed to enhance the crystal structure and optical properties of otherⅢ-Ⅴlow-dimensional materials,potentially paving the way for future NW devices.

Achieving dynamic privacy measurement and protection based on reinforcement learning for mobile edge crowdsensing of IoT

With the maturity and development of 5G field,Mobile Edge CrowdSensing(MECS),as an intelligent data collection paradigm,provides a broad prospect for various applications in IoT.However,sensing users as data uploaders lack a balance between data benefits and privacy threats,leading to conservative data uploads and low revenue or excessive uploads and privacy breaches.To solve this problem,a Dynamic Privacy Measurement and Protection(DPMP)framework is proposed based on differential privacy and reinforcement learning.Firstly,a DPM model is designed to quantify the amount of data privacy,and a calculation method for personalized privacy threshold of different users is also designed.Furthermore,a Dynamic Private sensing data Selection(DPS)algorithm is proposed to help sensing users maximize data benefits within their privacy thresholds.Finally,theoretical analysis and ample experiment results show that DPMP framework is effective and efficient to achieve a balance between data benefits and sensing user privacy protection,in particular,the proposed DPMP framework has 63%and 23%higher training efficiency and data benefits,respectively,compared to the Monte Carlo algorithm.

A critical review of direct laser additive manufacturing ceramics

The urgent need for integrated molding and sintering across various industries has inspired the development of additive manu-facturing(AM)ceramics.Among the different AM technologies,direct laser additive manufacturing(DLAM)stands out as a group of highly promising technology for flexibly manufacturing ceramics without molds and adhesives in a single step.Over the last decade,sig-nificant and encouraging progress has been accomplished in DLAM of high-performance ceramics,including Al_(2)O_(3),ZrO_(2),Al_(2)O_(3)/ZrO_(2),SiC,and others.However,high-performance ceramics fabricated by DLAM face challenges such as formation of pores and cracks and resultant low mechanical properties,hindering their practical application in high-end equipment.Further improvements are necessary be-fore they can be widely adopted.Methods such as field-assisted techniques and post-processing can be employed to address these chal-lenges,but a more systematic review is needed.This work aims to critically review the advancements in direct selective laser sintering/melting(SLS/SLM)and laser directed energy deposition(LDED)for various ceramic material systems.Additionally,it provides an overview of the current challenges,future research opportunities,and potential applications associated with DLAM of high-perform-ance ceramics.

High-performance magnesium/sodium hybrid ion battery based on sodium vanadate oxide for reversible storage of Na^(+)and Mg^(2+)

Magnesium ion batteries(MIBs)are a potential field for the energy storage of the future but are restricted by insufficient rate capability and rapid capacity degradation.Magnesium-sodium hybrid ion batteries(MSHBs)are an effective way to address these problems.Here,we report a new type of MSHBs that use layered sodium vanadate((Na,Mn)V_(8)O_(20)·5H_(2)O,Mn-NVO)cathodes coupled with an organic 3,4,9,10-perylenetetracarboxylic diimide(PTCDI)anode in Mg^(2+)/Na^(+)hybrid electrolytes.During electrochemical cycling,Mg^(2+)and Na^(+)co-participate in the cathode reactions,and the introduction of Na^(+)promotes the structural stability of the Mn-NVO cathode,as cleared by several ex-situ characterizations.Consequently,the Mn-NVO cathode presents great specific capacity(249.9 mA h g^(−1)at 300 mA g^(−1))and cycling(1500 cycles at 1500 mA g^(−1))in the Mg^(2+)/Na^(+)hybrid electrolytes.Besides,full battery displays long lifespan with 10,000 cycles at 1000 mA g^(−1).The rate performance and cycling stability of MSHBs have been improved by an economical and scalable method,and the mechanism for these improvements is discussed.

Inhibiting the phase transition of WO_(3)for highly stable aqueous electrochromic battery

Aqueous electrochromic battery(ECB)has shown intense potential for achieving energy storage and saving simultaneously.While tungsten oxide(WO_(3))is the most promising EC material for commercialization,the cycling stability of WO_(3)-based aqueous ECBs is currently unsatisfactory due to the repeated phase transition during the redox process and the corrosion by acidic electrolytes.Herein,we present a titanium-tungsten oxide alloy(Ti-WO_(3))with controllable morphology and crystal phase synthesized by a facile hot injection method to overcome the challenges.In contrast to conventional monoclinic WO_(3),the Ti-WO_(3)nanorods can stably maintain their cubic crystal phase during the redox reaction in an acidic electrolyte,thus leading to dramatically enhanced response speed and cycling stability,Specifically,when working in a well-matched hybrid Al^(3+)/Zn^(2+)aqueous electrolyte,our phasetransition-free cubic Ti-WO_(3)exhibits an ultra-high cycling stability(>20000 cycles),fast response speed(3,95 s/4,65 s for bleaching/coloring),as well as excellent discharge areal capacity of 214.5 mA h m^(-2),We further fabricate a fully complementa ry aqueous electrochromic device,for the first time,using a Ti-WO_(3)/Prussian blue device architecture.Remarkably,the complementary ECB shows>10000 stable operation cycles,attesting to the feasibility of our Ti-WO_(3)for practical applications.Our work validates the significance of inhibiting the phase transitions of WO_(3)during the electrochromic process for realizing highly cyclable aqueous ECB,which can possibly provide a generalized design guidance for other high-quality metallic oxides for electrochemical applications.

Progress in Research on the Impact of Religious Psychological Coping on the Holistic Well-Being of Cancer Patients and Relevant Factors

This study reviews the historical development,current applications,and multifaceted impacts of religious psychological coping on the physical and mental health of cancer patients.As a method for coping with life’s pressures through religious beliefs or activities,religious psychological coping has been proven to alleviate the negative emotions of cancer patients and enhance their spiritual well-being and quality of life(QOL).Research indicates that religious faith can alleviate the physical symptoms of cancer patients,extend survival time,reduce the fear of death,assist in coping with treatment side effects,and improve self-efficacy and overall quality of life.Additionally,this study explores factors influencing religious psychological coping,including demographic and sociological characteristics,the faith status of caregivers,types of religion,the relationship between the course of the disease and the duration of belief,and psychological factors.Considering the cultural differences between China and other countries,this study calls for further research into the real experiences of cancer patients with religious beliefs and provides theoretical guidance for clinical nursing practices to achieve holistic care for the body,mind,and spirit of cancer patients.

Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization

BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine.Stem cells can self-organise into microsized organ units,partially modelling tissue function and regeneration.Dental pulp organoids have been used to recapitulate the processes of tooth development and related diseases.However,the lack of vasculature limits the utility of dental pulp organoids.AIM To improve survival and aid in recovery after stem cell transplantation,we demonstrated the three-dimensional(3D)self-assembly of adult stem cell-human dental pulp stem cells(hDPSCs)and endothelial cells(ECs)into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium(CM).METHODS During culture,primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and CM.The hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp organoids.The biological characteristics of the organoids were analysed,and the regulatory pathways associated with angiogenesis were studied.RESULTS The combination of these two agents resulted in prevascularized human dental pulp organoids(Vorganoids)that more closely resembled dental pulp tissue in terms of morphology and function.Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with angiogenesis.The biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of Vorganoids.CONCLUSION In this innovative study,we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration,facilitating the development of clinical treatment strategies.

Chromosome-level genome assembly of the glass catfish(Kryptopterus vitreolus)reveals molecular clues to its transparent phenotype

Glass catfish(Kryptopterus vitreolus)are notable in the aquarium trade for their highly transparent body pattern.This transparency is due to the loss of most reflective iridophores and light-absorbing melanophores in the main body,although certain black and silver pigments remain in the face and head.To date,however,the molecular mechanisms underlying this transparent phenotype remain largely unknown.To explore the genetic basis of this transparency,we constructed a chromosome-level haplotypic genome assembly for the glass catfish,encompassing 32 chromosomes and 23344 protein-coding genes,using PacBio and Hi-C sequencing technologies and standard assembly and annotation pipelines.Analysis revealed a premature stop codon in the putative albinism-related tyrp1b gene,encoding tyrosinase-related protein 1,rendering it a nonfunctional pseudogene.Notably,a synteny comparison with over 30 other fish species identified the loss of the endothelin-3(edn3b)gene in the glass catfish genome.To investigate the role of edn3b,we generated edn3b^(−/−)mutant zebrafish,which exhibited a remarkable reduction in black pigments in body surface stripes compared to wild-type zebrafish.These findings indicate that edn3b loss contributes to the transparent phenotype of the glass catfish.Our high-quality chromosome-scale genome assembly and identification of key genes provide important molecular insights into the transparent phenotype of glass catfish.These findings not only enhance our understanding of the molecular mechanisms underlying transparency in glass catfish,but also offer a valuable genetic resource for further research on pigmentation in various animal species.

Vocational Identity and Agency of Chinese College Students: Effects of Filial Piety and Implications in Career Education

Balancing family obligations and personal aspirations is crucial for college students in making life decisions.This critical review examined empirical studies on the effects of filial piety on college students’vocational identity and agency.According to identity capital theory,college students need a sense of agency to construct identity consciously and adapt to adulthood.Filial piety may profoundly influence this process as the core value and internalized social structure for the role of being an adult child in a Chinese family.However,no studies have been conducted from the identity capital perspective.This review found that filial piety had direct effects on college students'vocational identity and also indirect effects by shaping specific agency competencies.The impact of filial piety on the agency was more likely to occur through providing normative guidance about adult roles,influencing how college students view family as a supportive resource,and perpetuating parenting experiences.Based on these findings,this article suggested further examining the mediating role of agency between filial piety and identity development,as well as the effects of filial piety on the psychological foundation of agency development.This review suggested enhancing the agency of college students and encouraging reflections on filial piety in career education.

The Aesthetic Connotation of Ancient Calligraphy

From the origin of writing to the formation of the writing system,the names and aesthetics of calligraphy have been evolving with time.Calligraphy has different mainstream writing styles across different eras and has been assigned different names,which also maps the aesthetic orientation of the times.Not only is calligraphy the evolution of the designation of successive generations but also in the continuous pursuit of“name”and“reality”of the unity of the ancient connotation of calligraphy and the era of aesthetic integration.This paper discusses the flavorful meaning behind the concept of ancient calligraphy,as well as its various forms of expression.

A Study of a Moral Dilemma Stories Teaching Model Focusing on the Development of Higher-Order Thinking --"Synthetic polymers" as an example

Cultivating students'higher-order thinking is one of the important goals of modern education,and innovative teaching model is an effective way to achieve this goal.Aiming at the inadequacy of the existing moral dilemma stories approach in the transformation of knowledge and behavior,this research constructs a new Project Based Learning-Ethical Dilemma Stories(PBL-EDS)Teaching Model applicable to China's secondary education stage based on the innovative features of the moral dilemma stories approach on the core competencies,taking the chemistry subject as an example to carry out practice,and puts forward suggestions for the implementation of the teaching model.Chemistry as an example to carry out the practice,and suggestions are made for the implementation of the teaching model.