Preventing brain aging by the artificial enforcement of the unfolded protein response:future directions

As the life expectancy of the world’s population increases,age-related diseases are emerging as one of the greatest problems facing modern society.The onset of dementia and neurodegenerative diseases is strictly dependent on aging as a major risk factor and has a profound impact on various aspects of the lives of individuals and their families.

Ascertaining the influences of auxiliary qubits on the Einstein–Podolsky–Rosen steering and its directions

Einstein–Podolsky–Rosen(EPR) steering is an example of nontrivial quantum nonlocality and characteristic in the non-classical world.The directivity(or asymmetry) is a fascinating trait of EPR steering,and it is different from other quantum nonlocalities.Here,we consider the strategy in which two atoms compose a two-qubit X state,and the two atoms are owned by Alice and Bob,respectively.The atom of Alice suffers from a reservoir,and the atom of Bob couples with a bit flip channel.The influences of auxiliary qubits on EPR steering and its directions are revealed by means of the entropy uncertainty relation.The results indicate that EPR steering declines with growing time t when adding fewer auxiliary qubits.The EPR steering behaves as damped oscillation when introducing more auxiliary qubits in the strong coupling regime.In the weak coupling regime,the EPR steering monotonously decreases as t increases when coupling auxiliary qubits.The increases in auxiliary qubits are responsible for the fact that the steerability from Alice to Bob(or from Bob to Alice) can be more effectively revealed.Notably,the introductions of more auxiliary qubits can change the situation that steerability from Alice to Bob is certain to a situation in which steerability from Bob to Alice is certain.

Stability assessment of tree ring growth of Pinus armandii Franch in response to climate change based on slope directions at the Lubanling in the Funiu Mountains,China

Global warming will affect growth strategies and how trees will adapt.To compare the response of tree radial growth to climate warming in different slope directions,samples of Pinus armandii Franch were collected and treering chronologies developed on northern and western slopes from the Lubanling in the Funiu Mountains.Correlation analyses showed that two chronologies were mainly limited by temperatures in the previous June–August and the combination of temperatures and moisture in the current May–July.The difference of the climate response to slopes was small but not negligible.Radial growth of the LBL01 site on the northern slope was affected by the combined maximum and minimum temperatures,while that of the LBL02 site was affected by maximum temperatures.With regards to moisture,radial growth of the trees on the north slope was influenced by the relative humidity in the current May–July,while on the western slope,it was affected by the relative humidity in the previous June–August,the current May–July and the precipitation in the current May–July.With the change in climate,the effects of the main limiting factors on growth on different slopes were visible to a certain extent,but the differences in response of trees on different slopes gradually decreased,which might be caused by factors such as different slope directions and the change in diurnal temperature range.These results may provide information for forest protection and ecological construction in this region,and a scientific reference for future climate reconstruction.

Stability assessment of tree ring growth of Pinus armandii Franch in response to climate change based on slope directions at the Lubanling in the Funiu Mountains,China

Global warming will affect growth strategies and how trees will adapt.To compare the response of tree radial growth to climate warming in different slope directions,samples of Pinus armandii Franch were collected and tree-ring chronologies developed on northern and western slopes from the Lubanling in the Funiu Mountains.Correlation analyses showed that two chronologies were mainly limited by temperatures in the previous June-August and the com-bination of temperatures and moisture in the current May-July.The difference of the climate response to slopes was small but not negligible.Radial growth of the LBLO1 site on the northern slope was affected by the combined maximum and minimum temperatures,while that of the LBLO2 site was affected by maximum temperatures.With regards to moisture,radial growth of the trees on the north slope was influenced by the relative humidity in the current May-July,while on the western slope,it was affected by the relative humidity in the previous June-August,the current May-July and the precipitation in the current May-July.With the change in climate,the effects of the main limiting factors on growth on different slopes were visible to a certain extent,but the differences in response of trees on different slopes gradually decreased,which might be caused by factors such as different slope directions and the change in diurnal temperature range.These results may provide information for forest protection and ecological construction in this region,and a scientific reference for future climate reconstruction.

Oral squamous cell carcinomas:state of the field and emerging directions

Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% oforal malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases werereported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ),and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oralmucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involvesgenetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeuticinterventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCCand OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors,thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC.Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitatecomprehension and provide several prospective outlooks for the fields.

GNSS array receiver faced with overloaded interferences:anti-jamming performance and the incident directions of interferences

Anti-jamming solutions based on antenna arrays enhance the anti-jamming ability and the robustness of global navigation satellite system(GNSS)receiver remarkably.However,the performance of the receiver will deteriorate significantly in the overloaded interferences scenario.We define the overloaded interferences scenario as where the number of interferences is more than or equal to the number of antenna arrays elements.In this paper,the effect mechanism of interferences with different incident directions is found by studying the anti-jamming performance of the adaptive space filter.The theoretical analysis and conclusions,which are first validated through numerical examples,reveal the relationships between the optimal weight vector and the eigenvectors of the input signal autocorrelation matrix,the relationships between the interference cancellation ratio(ICR),the signal to interference and noise power ratio(SINR)of the adaptive space filter output and the number of interferences,the eigenvalues of the input signal autocorrelation matrix.In addition,two simulation experiments are utilized to further corroborate the theoretical findings through soft anti-jamming receiver.The simulation results match well with the theoretical analysis results,thus validating the effect mechanism of overloaded interferences.The simulation results show that,for a four elements circular array,the performance difference is up to 19 dB with different incident directions of interferences.Anti-jamming performance evaluation and jamming deployment optimization can obtain more accurate and efficient results by using the conclusions.

Implications for identification of principal stress directions from acoustic emission characteristics of granite under biaxial compression experiments

The rock fracture characteristics and principal stress directions are crucial for prevention of geological disasters.In this study,we carried out biaxial compression tests on cubic granite samples of 100 mm in side length with different intermediate principal stress gradients in combination with acoustic emission(AE)technique.Results show that the fracture characteristics of granite samples change from‘sudden and aggregated’to‘continuous and dispersed’with the increase of the intermediate principal stress.The effect of increasing intermediate principal stress on AE amplitude is not significant,but it increases the proportions of high-frequency AE signals and shear cracks,which in turn increases the possibility of unstable rock failure.The difference of stress in different directions causes the anisotropy of rock fracture and thus leads to the obvious anisotropic characteristics of wave velocity variations.The anisotropy of wave velocity variations with stress difference is probable to identify the principal stress directions.The AE characteristics and the anisotropy of wave velocity variations of granite under two-dimensional stress are not only beneficial complements for rock fracture characteristic and principal stress direction identification,but also can provide a new analysis method for stability monitoring in practical rock engineering.

Practical prescribed-time tracking control for uncertain strict-feedback systems with guaranteed performance under unknown control directions

In this paper,we consider the practical prescribed-time performance guaranteed tracking control problem for a class of uncertain strict-feedback systems subject to unknown control direction.Due to the existence of unknown nonlinearities and uncertainties,it is challenging to design a controller that can ensure the stability of closed-loop system within a predetermined finite time while maintaining the specified transient performance.The underlying problem becomes further complex as the control directions are unknown.To deal with the above problems,a special translation function as well as Nussbaum type function are introduced in the prescribed performance control(PPC)framework.Finally,a PPC as well as preset finite time tracking control scheme is designed,and its effectiveness is confirmed by both theoretical analysis and numerical simulation.

LncRNAs:Current understanding,future directions,and challenges

1|CURRENT UNDERSTANDING OF LNCRNAS Long non-coding RNAs(lncRNAs)are a class of regulatory RNA molecules that have captured the attention of researchers in recent years due to their diverse roles in development,physiological and pathological processes.

Parameterization and Explicit Modeling of Cloud Microphysics:Approaches, Challenges, and Future Directions

Cloud microphysical processes occur at the smallest end of scales among cloud-related processes and thus must be parameterized not only in large-scale global circulation models(GCMs)but also in various higher-resolution limited-area models such as cloud-resolving models(CRMs)and large-eddy simulation(LES)models.Instead of giving a comprehensive review of existing microphysical parameterizations that have been developed over the years,this study concentrates purposely on several topics that we believe are understudied but hold great potential for further advancing bulk microphysics parameterizations:multi-moment bulk microphysics parameterizations and the role of the spectral shape of hydrometeor size distributions;discrete vs“continuous”representation of hydrometeor types;turbulence-microphysics interactions including turbulent entrainment-mixing processes and stochastic condensation;theoretical foundations for the mathematical expressions used to describe hydrometeor size distributions and hydrometeor morphology;and approaches for developing bulk microphysics parameterizations.Also presented are the spectral bin scheme and particle-based scheme(especially,super-droplet method)for representing explicit microphysics.Their advantages and disadvantages are elucidated for constructing cloud models with detailed microphysics that are essential to developing processes understanding and bulk microphysics parameterizations.Particle-resolved direct numerical simulation(DNS)models are described as an emerging technique to investigate turbulence-microphysics interactions at the most fundamental level by tracking individual particles and resolving the smallest turbulent eddies in turbulent clouds.Outstanding challenges and future research directions are explored as well.

BUILDING A SECURE AND PROSPEROUS LMC COMMUNITY WITH A SHARED FUTURE The Global Security Initiative will expand cooperation among Lancang- Mekong countries in new directions and with new momentum

This year marks the seventh anniversary of the launch of the Lancang-Mekong Cooperation(LMC)mechanism and the first year of the Five-Year Plan of Action on the Lancang-Mekong Cooperation(2023-2027).Theseventh LMC Foreign Ministers’Meeting in July 2022 formally proposed jointly building the region into a pilot zone for the Global Security Initiative(GSI).Recently,China officially released the“The Global Security Initiative Concept Paper,”which again clearly stated that it supports“efforts to promote cooperation in non-traditional security areas under the framework of the LMC,striving to foster a pilot zone for the GSI.”In the future,the GSI will expand cooperation among Lancang-Mekong countries in new directions and with new momentum,at both conceptual and practical levels.

Printability disparities in heterogeneous material combinations via laser directed energy deposition:a comparative study

Additive manufacturing provides achievability for the fabrication of bimetallic and multi-material structures;however,the material compatibility and bondability directly affect the parts’formability and final quality.It is essential to understand the underlying printability of different material combinations based on an adapted process.Here,the printability disparities of two common and attractive material combinations(nickel-and iron-based alloys)are evaluated at the macro and micro levels via laser directed energy deposition(DED).The deposition processes were captured using in situ high-speed imaging,and the dissimilarities in melt pool features and track morphology were quantitatively investigated within specific process windows.Moreover,the microstructure diversity of the tracks and blocks processed with varied material pairs was comparatively elaborated and,complemented with the informative multi-physics modeling,the presented non-uniformity in mechanical properties(microhardness)among the heterogeneous material pairs was rationalized.The differences in melt flow induced by the unlike thermophysical properties of the material pairs and the resulting element intermixing and localized re-alloying during solidification dominate the presented dissimilarity in printability among the material combinations.This work provides an in-depth understanding of the phenomenological differences in the deposition of dissimilar materials and aims to guide more reliable DED forming of bimetallic parts.

Neonatal Direct Rigid Laryngoscopy and Bronchoscopy: A Near Miss

Airway management is a skill necessary for healthcare providers who manage patients. Intubation is a skill that both anesthesiologists and intensivists use daily. We present a case of a neonate that developed significant worsening stridor after a successful intubation for a hernia repair. After 4 intubation attempts, with easy visualization of the vocal cords and unsuccessful placement of the endotracheal tube, the patient was emergently brought to the operating room for evaluation.

MSD-Net: Pneumonia Classification Model Based on Multi-Scale Directional Feature Enhancement

Computer-aided diagnosis of pneumonia based on deep learning is a research hotspot.However,there are some problems that the features of different sizes and different directions are not sufficient when extracting the features in lung X-ray images.A pneumonia classification model based on multi-scale directional feature enhancement MSD-Net is proposed in this paper.The main innovations are as follows:Firstly,the Multi-scale Residual Feature Extraction Module(MRFEM)is designed to effectively extract multi-scale features.The MRFEM uses dilated convolutions with different expansion rates to increase the receptive field and extract multi-scale features effectively.Secondly,the Multi-scale Directional Feature Perception Module(MDFPM)is designed,which uses a three-branch structure of different sizes convolution to transmit direction feature layer by layer,and focuses on the target region to enhance the feature information.Thirdly,the Axial Compression Former Module(ACFM)is designed to perform global calculations to enhance the perception ability of global features in different directions.To verify the effectiveness of the MSD-Net,comparative experiments and ablation experiments are carried out.In the COVID-19 RADIOGRAPHY DATABASE,the Accuracy,Recall,Precision,F1 Score,and Specificity of MSD-Net are 97.76%,95.57%,95.52%,95.52%,and 98.51%,respectively.In the chest X-ray dataset,the Accuracy,Recall,Precision,F1 Score and Specificity of MSD-Net are 97.78%,95.22%,96.49%,95.58%,and 98.11%,respectively.This model improves the accuracy of lung image recognition effectively and provides an important clinical reference to pneumonia Computer-Aided Diagnosis.

Effects of cooling rate on microstructure and microhardness of directionally solidified Galvalume alloy

The influences of cooling rate on the phase constitution,microstructural length scale,and microhardness of directionally solidified Galvalume(Zn-55Al-1.6Si)alloy were investigated by directional solidification experiments at different withdrawal speeds(5,10,20,50,100,200,and 400μm·s^(-1)).The results show that the microstructure of directionally solidified Galvalume alloys is composed of primary Al dendrites,Si-rich phase and(Zn-Al-Si)ternary eutectics at the withdrawal speed ranging from 5 to 400μm·s^(-1).As the withdrawal speed increases,the segregation of Si element intensifies,resulting in an increase in the area fraction of the Si-rich phase.In addition,the primary Al dendrites show significant refinement with an increase in the withdrawal speed.The relationship between the primary dendrite arm spacing(λ_(1))and the thermal parameters of solidification is obtained:λ_(1)=127.3V^(-0.31).Moreover,as the withdrawal speed increases from 5 to 400μm·s^(-1),the microhardness of the alloy increases from 90 HV to 151 HV.This is a combined effect of grain refinement and second-phase strengthening.

Efficient Direct Decomposition of NO over La_(0.8)A_(0.2)NiO_(3)(A=K, Ba, Y) Catalysts under Microwave Irradiation

La_(0.8)A_(0.2)NiO_(3) (A=K,Ba,Y) catalysts supported on the microwave-absorbing ceramic heating carrier were prepared by the sol-gel method.The crystalline phase and the catalytic activity of the La_(0.8)A_(0.2)NiO_(3)catalysts were characterized by XRD and H_(2) temperature-programmed reduction (TPR).The effects of reaction temperature,oxygen concentration,and gas flow rate on the direct decomposition of nitric oxide over the synthesized catalysts were studied under microwave irradiation (2.45 GHz).The XRD results indicated that the La_(0.8)A_(0.2)NiO_(3) catalysts formed an ABO_(3) perovskite structure,and the H_(2)-TPR results revealed that the relative reducibility of the catalysts increased in the order of La_(0.8)K_(0.2)NiO_(3)>La_(0.8)Ba_(0.2)NiO_(3)>La_(0.8)Y_(0.2)Ni O_(3).Under microwave irradiation,the highest NO conversion amounted to 98.9%,which was obtained with the La_(0.8)K_(0.2)NiO_(3) catalyst at 400℃.The oxygen concentration did not inhibit the NO decomposition on the La_(0.8)A_(0.2)NiO_(3) catalysts,thus the N_(2) selectivity exceeded 99.8%under excess oxygen at 550℃.The NOconversion of the La_(0.8)A_(0.2)NiO_(3) catalysts decreased linearly with the increase in the gas flow rate.

Unraveling the Impact of Direct-Acting Antivirals on Hepatitis-Linked Cirrhosis: A Comprehensive Analysis of Fibrosis, Child Score, and Disease Progression

The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).

Estimation of the anisotropy of hydraulic conductivity through 3D fracture networks using the directional geological entropy

With an extension of the geological entropy concept in porous media,the approach called directional entrogram is applied to link hydraulic behavior to the anisotropy of the 3D fracture networks.A metric called directional entropic scale is used to measure the anisotropy of spatial order in different directions.Compared with the traditional connectivity indexes based on the statistics of fracture geometry,the directional entropic scale is capable to quantify the anisotropy of connectivity and hydraulic conductivity in heterogeneous 3D fracture networks.According to the numerical analysis of directional entrogram and fluid flow in a number of the 3D fracture networks,the hydraulic conductivities and entropic scales in different directions both increase with spatial order(i.e.,trace length decreasing and spacing increasing)and are independent of the dip angle.As a result,the nonlinear correlation between the hydraulic conductivities and entropic scales from different directions can be unified as quadratic polynomial function,which can shed light on the anisotropic effect of spatial order and global entropy on the heterogeneous hydraulic behaviors.

Effect of hot isostatic pressure on the microstructure and tensile properties of γ'-strengthened superalloy fabricated through induction-assisted directed energy deposition

The microstructure characteristics and strengthening mechanism of Inconel738LC(IN-738LC) alloy prepared by using induction-assisted directed energy deposition(IDED) were elucidated through the investigation of samples subjected to IDED under 1050℃ preheating with and without hot isostatic pressing(HIP,1190℃,105 MPa,and 3 h).Results show that the as-deposited sample mainly consisted of epitaxial columnar crystals and inhomogeneously distributed γ’ phases in interdendritic and dendritic core regions.After HIP,grain morphology changed negligibly,whereas the size of the γ’ phase became increasingly even.After further heat treatment(HT,1070℃,2 h + 845℃,24 h),the γ’ phase in the as-deposited and HIPed samples presented a bimodal size distribution,whereas that in the as-deposited sample showed a size that remained uneven.The comparison of tensile properties revealed that the tensile strength and uniform elongation of the HIP + HTed sample increased by 5% and 46%,respectively,due to the synergistic deformation of bimodal γ’phases,especially large cubic γ’ phases.Finally,the relationship between phase transformations and plastic deformations in the IDEDed sample was discussed on the basis of generalized stability theory in terms of the trade-off between thermodynamics and kinetics.

Post-transcriptional mechanisms controlling neurogenesis and direct neuronal reprogramming

Neurogenesis is a tightly regulated process in time and space both in the developing embryo and in adult neurogenic niches.A drastic change in the transcriptome and proteome of radial glial cells or neural stem cells towards the neuronal state is achieved due to sophisticated mechanisms of epigenetic,transcriptional,and post-transcriptional regulation.Understanding these neurogenic mechanisms is of major importance,not only for shedding light on very complex and crucial developmental processes,but also for the identification of putative reprogramming factors,that harbor hierarchically central regulatory roles in the course of neurogenesis and bare thus the capacity to drive direct reprogramming towards the neuronal fate.The major transcriptional programs that orchestrate the neurogenic process have been the focus of research for many years and key neurogenic transcription factors,as well as repressor complexes,have been identified and employed in direct reprogramming protocols to convert non-neuronal cells,into functional neurons.The post-transcriptional regulation of gene expression during nervous system development has emerged as another important and intricate regulatory layer,strongly contributing to the complexity of the mechanisms controlling neurogenesis and neuronal function.In particular,recent advances are highlighting the importance of specific RNA binding proteins that control major steps of mRNA life cycle during neurogenesis,such as alternative splicing,polyadenylation,stability,and translation.Apart from the RNA binding proteins,microRNAs,a class of small non-coding RNAs that block the translation of their target mRNAs,have also been shown to play crucial roles in all the stages of the neurogenic process,from neural stem/progenitor cell proliferation,neuronal differentiation and migration,to functional maturation.Here,we provide an overview of the most prominent post-transcriptional mechanisms mediated by RNA binding proteins and microRNAs during the neurogenic process,giving particular emphasis on the interplay of specific RNA binding proteins with neurogenic microRNAs.Taking under consideration that the molecular mechanisms of neurogenesis exert high similarity to the ones driving direct neuronal reprogramming,we also discuss the current advances in in vitro and in vivo direct neuronal reprogramming approaches that have employed microRNAs or RNA binding proteins as reprogramming factors,highlighting the so far known mechanisms of their reprogramming action.