Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Stress tensor determination by modified hydraulic tests on pre-existing fractures:Method and stress constraints

The hydraulic testing of pre-existing fractures(HTPF)is one of the most promising in situ stress measurement methods,particularly for three-dimensional stress tensor determination.However,the stress tensor determination based on the HTPF method requires at least six tests or a minimum of 14-15 tests(under different conditions)for reliable results.In this study,we modified the HTPF method by considering the shear stress on each pre-existing fracture,which increased the number of equations for the stress tensor determination and decreased the number of tests required.Different shear stresses were attributed to different fractures by random sampling;therefore,the stress tensors were obtained by searching for the optimal solution using the least squares criterion based on the Monte Carlo method.Thereafter,we constrained the stress tensor based on the tensile strength criterion,compressive strength criterion,and vertical stress constraints.The inverted stress tensors were presented and analyzed based on the tensorial nature of the stress using the Euclidean mean stress tensor.Two stress-measurement campaigns in Weifang(Shandong Province,China)and Mercantour road tunnel(France)were implemented to highlight the validity and efficiency of the modified HTPF(M-HTPF)method.The results showed that the M-HTPF method can be applied for stress tensor inversion using only three to four tests on pre-existing fractures,neglecting the stress gradient.The inversion results were confined to relatively small distribution dispersions and were significantly reliable and stable due to the shear stresses on the fractures and the stress constraints employed.The M-HTPF method is highly feasible and efficient for complete stress tensor determination in a single borehole.

A continuous and long-term in-situ stress measuring method based on fiber optic. Part I: Theory of inverse differential strain analysis

A method for in-situ stress measurement via fiber optics was proposed. The method utilizes the relationship between rock mass elastic parameters and in-situ stress. The approach offers the advantage of long-term stress measurements with high spatial resolution and frequency, significantly enhancing the ability to measure in-situ stress. The sensing casing, spirally wrapped with fiber optic, is cemented into the formation to establish a formation sensing nerve. Injecting fluid into the casing generates strain disturbance, establishing the relationship between rock mass properties and treatment pressure.Moreover, an optimization algorithm is established to invert the elastic parameters of formation via fiber optic strains. In the first part of this paper series, we established the theoretical basis for the inverse differential strain analysis method for in-situ stress measurement, which was subsequently verified using an analytical model. This paper is the fundamental basis for the inverse differential strain analysis method.

Effects of Intermittent Hypoxia Exposure on Symptoms of Chronic Fatigue Syndrome in Repeated Restraint Stress and Forced Swimming Induced-Mouse Model

Background: Chronic fatigue syndrome (CFS) shows as its main symptoms debilitating fatigue that is not relieved by physiological rest, depression, inflammation, learning disability and memory impairment. But, intermittent hypoxia, consisting of alternating exposure to hypoxia and normoxia, plays a very important role in improving CFS. However, the essential components for improving learning and memory in CFS patients as well as their mechanism are largely unknown. Objectives: This study aims to analyze the effects of 12% and 15% hypoxia on the expression of alpha tumor necrosis factor (TNF-α) and nuclear factor kappa B (NF-κB) in CFS induced-mouse model for clarifying the effects on the learning and memory function. Methods: A total of 48 type IC mice were used. The CFS mouse model was established using restrained stress and repeated forced swimming. Treatment of CFS was done by exposing CFS mice to intermittent hypoxia at 12% and 15%. The effects of intermittent hypoxia on learning and memory as well as its mechanism of action on inflammation were tested respectively with the Morris test, the SDS page, the immunohistochemistry technique and the Nissl staining. Results: We found that 12% and 15% intermittent hypoxia exposure improved learning capacity and memory of CFS induced-mice. SDS page showed that CFS caused higher TNF-α expression. By exposing CFS mice to 12% and 15% intermittent hypoxia, TNF-α expression decreased significantly, with a much better effect at 15%. Both TNF-α and NF-κB increased in CFS state and decreased after treatment with intermittent hypoxia. Conclusion: Intermittent hypoxia improves learning capacity and memory. It acted by decreasing NF-κB come to down-regulating TNF-α and ameliorates learning capacity and memory impairment in CFS mice.

Probabilistic-Ellipsoid Hybrid Reliability Multi-Material Topology Optimization Method Based on Stress Constraint

This paper proposes a multi-material topology optimization method based on the hybrid reliability of the probability-ellipsoid model with stress constraint for the stochastic uncertainty and epistemic uncertainty of mechanical loads in optimization design.The probabilistic model is combined with the ellipsoidal model to describe the uncertainty of mechanical loads.The topology optimization formula is combined with the ordered solid isotropic material with penalization(ordered-SIMP)multi-material interpolation model.The stresses of all elements are integrated into a global stress measurement that approximates the maximum stress using the normalized p-norm function.Furthermore,the sequential optimization and reliability assessment(SORA)is applied to transform the original uncertainty optimization problem into an equivalent deterministic topology optimization(DTO)problem.Stochastic response surface and sparse grid technique are combined with SORA to get accurate information on the most probable failure point(MPP).In each cycle,the equivalent topology optimization formula is updated according to the MPP information obtained in the previous cycle.The adjoint variable method is used for deriving the sensitivity of the stress constraint and the moving asymptote method(MMA)is used to update design variables.Finally,the validity and feasibility of the method are verified by the numerical example of L-shape beam design,T-shape structure design,steering knuckle,and 3D T-shaped beam.

An Artificial Intelligence‑Assisted Flexible and Wearable Mechanoluminescent Strain Sensor System

The complex wiring,bulky data collection devices,and difficulty in fast and on-site data interpretation significantly limit the practical application of flexible strain sensors as wearable devices.To tackle these challenges,this work develops an artificial intelligenceassisted,wireless,flexible,and wearable mechanoluminescent strain sensor system(AIFWMLS)by integration of deep learning neural network-based color data processing system(CDPS)with a sandwich-structured flexible mechanoluminescent sensor(SFLC)film.The SFLC film shows remarkable and robust mechanoluminescent performance with a simple structure for easy fabrication.The CDPS system can rapidly and accurately extract and interpret the color of the SFLC film to strain values with auto-correction of errors caused by the varying color temperature,which significantly improves the accuracy of the predicted strain.A smart glove mechanoluminescent sensor system demonstrates the great potential of the AIFWMLS system in human gesture recognition.Moreover,the versatile SFLC film can also serve as a encryption device.The integration of deep learning neural network-based artificial intelligence and SFLC film provides a promising strategy to break the“color to strain value”bottleneck that hinders the practical application of flexible colorimetric strain sensors,which could promote the development of wearable and flexible strain sensors from laboratory research to consumer markets.

Correlation between the rock mass properties and maximum horizontal stress:A case study of overcoring stress measurements

Understanding the mechanical properties of the lithologies is crucial to accurately determine the horizontal stress magnitude.To investigate the correlation between the rock mass properties and maximum horizontal stress,the three-dimensional(3D)stress tensors at 89 measuring points determined using an improved overcoring technique in nine mines in China were adopted,a newly defined characteristic parameter C_(ERP)was proposed as an indicator for evaluating the structural properties of rock masses,and a fuzzy relation matrix was established using the information distribution method.The results indicate that both the vertical stress and horizontal stress exhibit a good linear growth relationship with depth.There is no remarkable correlation between the elastic modulus,Poisson's ratio and depth,and the distribution of data points is scattered and messy.Moreover,there is no obvious relationship between the rock quality designation(RQD)and depth.The maximum horizontal stress σ_(H) is a function of rock properties,showing a certain linear relationship with the C_(ERP)at the same depth.In addition,the overall change trend of σ_(H) determined by the established fuzzy identification method is to increase with the increase of C_(ERP).The fuzzy identification method also demonstrates a relatively detailed local relationship betweenσ_H and C_(ERP),and the predicted curve rises in a fluctuating way,which is in accord well with the measured stress data.

Bioinspired Ultrasensitive Flexible Strain Sensors for Real‑Time Wireless Detection of Liquid Leakage

Liquid leakage of pipeline networks not only results in considerableresource wastage but also leads to environmental pollution and ecological imbalance.In response to this global issue, a bioinspired superhydrophobic thermoplastic polyurethane/carbon nanotubes/graphene nanosheets flexible strain sensor (TCGS) hasbeen developed using a combination of micro-extrusion compression molding andsurface modification for real-time wireless detection of liquid leakage. The TCGSutilizes the synergistic effects of Archimedean spiral crack arrays and micropores,which are inspired by the remarkable sensory capabilities of scorpions. This designachieves a sensitivity of 218.13 at a strain of 2%, which is an increase of 4300%. Additionally, it demonstrates exceptional durability bywithstanding over 5000 usage cycles. The robust superhydrophobicity of the TCGS significantly enhances sensitivity and stability indetecting small-scale liquid leakage, enabling precise monitoring of liquid leakage across a wide range of sizes, velocities, and compositionswhile issuing prompt alerts. This provides critical early warnings for both industrial pipelines and potential liquid leakage scenariosin everyday life. The development and utilization of bioinspired ultrasensitive flexible strain sensors offer an innovative and effectivesolution for the early wireless detection of liquid leakage.

Flexible Strain Sensors with Ultra‑High Sensitivity and Wide Range Enabled by Crack‑Modulated Electrical Pathways

This study presents a breakthrough in flexible strain sensor technology with the development of an ultrahigh sensitivity and wide-range sensor,addressing the critical challenge of reconciling sensitivity with measurement range.Inspired by the structure of bamboo slips,we introduce a novel approach that utilises liquid metal to modulate the electrical pathways within a cracked platinum fabric electrode.The resulting sensor demonstrates a gauge factor greater than 108 and a strain measurement capability exceeding 100%.The integration of patterned liquid metal enables customisable tuning of the sensor’s response,while the porous fabric structure ensures superior comfort and air permeability for the wearer.Our design not only optimises the sensor’s performance but also enhances the electrical stability that is essential for practical applications.Through systematic investigation,we reveal the intrinsic mechanisms governing the sensor’s response,offering valuable insights for the design of wearable strain sensors.The sensor’s exceptional performance across a spectrum of applications,from micro-strain to large-strain detection,highlights its potential for a wide range of real-world uses,demonstrating a significant advancement in the field of flexible electronics.

Dip2a regulates stress susceptibility in the basolateral amygdala

Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

Acquired sensorineural hearing loss,oxidative stress,and microRNAs

Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.

Posttraumatic stress symptoms among Chinese university students during the COVID-19 pandemic:Prevalence,correlates,and mental health help-seeking

BACKGROUND Revisiting the epidemiology of posttraumatic stress symptoms(PTSSs)among university students during the coronavirus disease 2019(COVID-19)pandemic as well as understanding the mental health help-seeking behavior of individuals with PTSSs has critical implications for public mental health strategies in future medical pandemics.AIM To investigate the prevalence and correlates of PTSSs among university students during the first wave of the COVID-19 pandemic in China and to examine mental health help-seeking behaviors among these students.METHODS A total of 2507 Chinese university students were recruited via snowball sampling.The students completed the Seven-item Screening Scale for Post-traumatic Stress Disorder during the first wave of the COVID-19 pandemic in China.Sociodemo-graphic characteristics,pandemic-related characteristics,and mental health help-seeking behaviors of students with PTSSs were also collected.RESULTS The prevalence of PTSSs among the participants was 28.0%.Seven significant correlates of PTSSs were identified(odds ratio=1.23-3.65,P≤0.024):Female sex,being 19 years old or older,living with others or alone,a low level of family economic status,fair or poor interpersonal relationships,severe or very severe local pandemic,and having family members diagnosed with COVID-19.However,only 3.28%of the students with PTSSs reported seeking help from mental health specialists.Among the 23 students who sought help from mental health specialists,13 opted for online or telephone-based psychological consultation.CONCLUSION Our data suggest that there was a high risk of PTSSs among university students and a high level of unmet mental health needs during the COVID-19 pandemic.The delivery of mental health services online or via telephone is a promising approach to address these unmet needs.

Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary behaviors.The preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion repair.In the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats.Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws.Dorsal von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve transections.Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex.Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats.Following sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury.However,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats.Furthermore,PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recove ry compared with those without Sciatic Functional Index recovery,suggesting a correlation between successful PEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries.This correlation was independent of the sex or strain of the rat.Furthermore,our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths.No chronic hypersensitivity developed in any rat up to 12 weeks.All these data suggest that PEG-fusion repair of transection peripheral nerve injuries co uld have important clinical benefits.

Relationship between parenting stress and behavioral and emotional problems in preschool children: A mediation effect analysis

BACKGROUND Emotional reactions,such as anxiety,irritability,and aggressive behavior,have attracted clinical attention as behavioral and emotional problems in preschool-age children.AIM To investigate the current status of family rearing,parental stress,and behavioral and emotional problems of preschool children and to analyze the mediating effect of the current status of family rearing on parental stress and behavioral/emo-tional problems.METHODS We use convenience sampling to select 258 preschool children in the physical examination center of our hospital from October 2021 to September 2023.The children and their parents were evaluated using a questionnaire survey.Pearson's correlation was used to analyze the correlation between child behavioral and emotional problems and parental stress and family rearing,and the structural equation model was constructed to test the mediating effect.RESULTS The score for behavioral/emotional problems of 258 preschool children was(27.54±3.63),the score for parental stress was(87.64±11.34),and the score for parental family rearing was(31.54±5.24).There was a positive correlation between the behavioral and emotional problems of the children and the“hostile/mandatory”parenting style;meanwhile,showed a negative correlation with the“support/participation”parenting style(all P<0.05).The intermediary effect value between the family upbringing of parents in parental stress and children's behavior problems was 29.89%.CONCLUSION Parental family upbringing has a mediating effect between parental stress and behavioral and emotional problems of children.Despite paying attention to the behavioral and emotional problems of preschool-age children,clinical medical staff should provide correct and reasonable parenting advice to their parents to promote the mental health of preschool-age children.

Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion injury.Autophagy occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains unclear.In this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion injury.We found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced autophagy.Furthermore,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating autophagy.Blocking autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion injury.Findings from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

MicroRNAs as potential biomarkers for diagnosis of post-traumatic stress disorder

Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.

Diabetes mellitus and glymphatic dysfunction:Roles for oxidative stress,mitochondria,circadian rhythm,artificial intelligence,and imaging

Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.

Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

Advances in the Research Application of Ultrasound Non-Invasive Stress-Strain Loop Technology in Cardiovascular Diseases

The ultrasound pressure-strain loop (PSL) technique is a non-invasive method of examining myocardial work, which takes into account the effect of cardiac afterload on deformation and combines the overall longitudinal strain force of the left ventricle with the changes in the left ventricular pressure, allowing earlier detection of possible subclinical cardiac damage in patients, and a more accurate and non-invasive assessment of the patient’s myocardial work performance. In this article, we will discuss the progress of PSL applications in cardiovascular diseases.

Constitutive equations for high temperature flow stress prediction of 6063 Al alloy considering compensation of strain

In order to develop the appropriate constitutive equation which can precisely model high temperature flow stress of 6063 Al alloy, a series of isothermal hot compression tests were performed at temperatures from 573 to 773 K and strain rates from 0.5 to 50 s?1 on a Gleeble?1500 thermo-simulation machine. Zener–Hollomon parameter in an exponent-type equation was used to describe the combined effects of temperature and strain rate on hot deformation behaviour of 6063 Al alloy, whereas the influence of strain was incorporated in the developed constitutive equation by considering material constants (α,n,Q andA) to be 4th order polynomial functions of strain. The results show that the developed constitutive equation can accurately predict high temperature flow stress of 6063 Al alloy, which demonstrates that it can be suitable for simulating hot deformation processes such as extrusion and forging, and for properly designing the deformation parameters in engineering practice.