ABSTRACT
This study evaluates the impact of fertility costs and utility on the third birth intentions among working women with two children in Hainan, China. A cross-sectional survey was conducted in Hainan Island, China in 2021 using an offline survey. Among 1067 working women with two children, only 8.06 % of participants reported having a third-birth intention. After adjustment for potential confounding factors, higher economic cost (odds ratio = 1.89) and lower succession utility (odds ratio = 5.08) were significantly associated with the lack of intention to have a third child. The analysis further demonstrates that family values significantly modulate these economic and utility considerations, highlighting a strong cultural influence on fertility decisions. This finding underscores the necessity for policies that not only mitigate financial burdens but also promote family values supportive of higher fertility. Such measures are essential for creating a cultural and economic environment conducive to higher birth rates.
ABSTRACT
Arecoline, the predominant bioactive substance extracted from areca nut (AN), is the world's fourth most frequently used psychoactive material. Research has revealed that chewing AN can affect the central nervous system (CNS) and may lead to neurocognitive deficits that are possibly linked to the action of arecoline. However, the mechanism behind the neurotoxicity caused by arecoline remains unclear. This study aimed to investigate the neurotoxic effects of arecoline and its underlying mechanism. The results showed that arecoline caused cytotoxicity against HT22 cells in a dose-dependent manner and induced apoptosis by upregulating the expression of pro-apoptotic caspase and Bcl-2 family proteins. Furthermore, arecoline escalated intracellular reactive oxygen species (ROS) levels and Ca2+ concentration with increasing doses, thereby motivating endoplasmic reticulum stress (ERS) and ERS-associated apoptotic protein expression. Additionally, the study found that arecoline attenuates intracellular antioxidant defense by inhibiting the translocation of NF-E2-related factor-2 (Nrf2) into the nucleus and decreasing downstream Heme oxygenase-1 (HO-1) levels. The specific inhibitor Sodium 4-phenylbutyrate (4-PBA) can dramatically attenuate arecoline-mediated cell apoptosis and ERS-associated apoptotic pathway expression by blocking ERS. The antioxidant N-Acetylcysteine (NAC) also effectively reverses the arecoline-mediated increase of ERS-related apoptotic pathway protein levels by scavenging intracellular ROS accumulation. In conclusion, this study suggests that arecoline induces neurotoxicity in HT22 cells via ERS mediated by oxidative stress- and Ca2+ disturbance, as well as by downregulation of the Nrf2/HO-1 pathway.
Subject(s)
Apoptosis , Arecoline , Endoplasmic Reticulum Stress , Signal Transduction , Animals , Mice , Apoptosis/drug effects , Arecoline/toxicity , Calcium/metabolism , Cell Line , Down-Regulation/drug effects , Endoplasmic Reticulum Stress/drug effects , Heme Oxygenase-1/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effectsABSTRACT
The ß-relaxation is one of the major dynamic behaviors in metallic glasses (MGs) and exhibits diverse features. Despite decades of efforts, the understanding of its structural origin and contribution to the overall dynamics of MG systems is still unclear. Here two palladium-based PdâCuâP and PdâNiâP MGs are reported with distinct different ß-relaxation behaviors and reveal the structural origins for the difference using the advanced X-ray photon correlation spectroscopy and absorption fine structure techniques together with the first-principles calculations. The pronounced ß-relaxation and fast atomic dynamics in the PdâCuâP MG mainly come from the strong mobility of Cu atoms and their locally favored structures. In contrast, the motion of Ni atoms is constrained by P atoms in the PdâNiâP MG, leading to the weakened ß-relaxation peak and sluggish dynamics. The correlation of atomic dynamics with microscopic structures provides a way to understand the structural origins of different dynamic behaviors as well as the nature of aging in disordered materials.
ABSTRACT
Gallium-based metallic liquids, exhibiting high theoretical capacity, are considered a promising anode material for room-temperature liquid metal alkali-ion batteries. However, electrochemical performances, especially the cyclic stability, of the liquid metal anode for alkali-ion batteries are strongly limited because of the volume expansion and unstable solid electrolyte interphase film of liquid metal. Here, the bottleneck problem is resolved by designing carbon encapsulation on gallium-indium liquid metal nanoparticles (EGaIn@C LMNPs). A superior cycling stability (644 mAh g-1 after 800 cycles at 1.0 A g-1 ) is demonstrated for lithium-ion batteries, and excellent cycle stability (87 mAh g-1 after 2500 cycles at 1.0 A g-1 ) is achieved for sodium-ion batteries by carbon encapsulation of the liquid metal anode. Morphological and phase changes of EGaIn@C LMNPs during the electrochemical reaction process are revealed by in situ transmission electron microscopy measurements in real-time. The origin for the excellent performance is uncovered, that is the EGaIn@C core-shell structure effectively suppresses the non-uniform volume expansion of LMNPs from ≈160% to 127%, improves the electrical conductivity of the LMNPs, and exhibits superior electrochemical kinetics and a self-healing phenomenon. This work paves the way for the applications of room-temperature liquid metal anodes for high-performance alkali-ion batteries.
ABSTRACT
Objective@#To investigate the correlation between campus bullying and suicidal tendency symptoms comorbidity with addictive behavior among middle and high school students in Hainan Province, so as to provide a theoretical basis for health education and behavioral intervention in schools.@*Methods@#In July 2023, an anonymous questionnaire survey was conducted among 6 654 middle and high school students in Hainan Province, selected by probability proportional sampling and stratified cluster random sampling method. Campus bullying, suicidal tendency and addictive behavior were determined according to the relevant items in the questionnaire on health related behaviors of Chinese students health status and influencing factors questionnaire, and self designed questionnaire. The co occurrence of campus bullying and suicidal tendency among students was analyzed. The binary Logistic regression method was used to analyze the correlation between the co occurrence of campus bullying and suicidal tendency and the addictive behavior of middle school students.@*Results@#The report rate of campus bullying among middle and high school students in Hainan Province was 28.48%, the suicidal tendency was 15.25%, and the co occurrence of campus bullying and suicidal tendency was 8.00%. The results of Logistic regression analysis showed that middle school students and left behind students were prone to campus bullying and suicide tendency ( OR =1.55, 1.52, P <0.05), while Internet addiction, gambling and current smoking showed significant positive correlation with comorbidity of campus bullying and suicide tendency ( OR =3.14, 2.18, 2.07, P < 0.05 ).@*Conclusions@#Middle and high school students with addictive behavior have a higher possibility of comorbidity of campus bullying and suicidal tendency. The comprehensive intervention of addictive behavior can reduce the incidence of co occurrence of campus bullying and suicidal tendency, so as to improve health and wellbeing of middle school students.
ABSTRACT
Combined methamphetamine (MA) and ketamine (KET) abuse is a serious issue. At present, however, few studies have explored the mechanism underlying their combined addiction. We established a rat conditioned place preference (CPP) model. We investigated the role of dopamine (DA), 5-hydroxytryptamine (5-HT), monoamine oxidase (MAO), glutamate receptor 1 (GluR1), and glutamate receptor 2 (GluR2) in combined MA and KET addiction. The expression levels of DA, 5-HT, and MAO were detected by enzyme-linked immunosorbent assay (ELISA), and the expressions levels of GluR1 and GluR2 were detected by western blotting. Our results showed that MA and KET successfully induced CPP in rats respectively, and KET enhanced MA-induced CPP effects, although not significantly, and KET can reduce the MA-induced increase in DA, 5-HT, MAO and promoted the MA-induced increase in GluR1 and GluR2. Therefore, it suggested that DA, 5-HT, MAO, GluR1, and GluR2 expression may be involved in the mechanism underlying MA and KET-induced drug addiction in rats. Moreover, When MA and KET are used in combination, KET appears to play a dual addictive and anti-addictive role in the regulation of MA addiction.
Subject(s)
Ketamine , Methamphetamine , Substance-Related Disorders , Rats , Animals , Methamphetamine/pharmacology , Ketamine/pharmacology , Serotonin/metabolism , Receptors, Glutamate , Dopamine/metabolism , Neurotransmitter Agents , Monoamine OxidaseABSTRACT
The mechanical properties of high-entropy alloys (HEAs) can be regulated by altering the stacking fault energy (SFE) through compositional modulation. The Co-rich HEAs, exhibiting deformation twinning and even strain-induced martensitic transformation at room temperature, suffer from insufficient ductility at high strength. In this work, we developed Co-rich (Co40Fe25Cr20Ni15)100-xAlx (x = 0 and 5 at.%) HEAs and investigated their tensile behaviors at room temperature. The addition of Al resulted in a massive improvement in the strength-ductility product, even at similar grain sizes, and also altered the fracture mode from quasi-cleavage to ductile dimple fracture. Interestingly, both alloys were deformed by mechanical twinning, which was also verified by molecular dynamics (MD) simulations. The MD simulations revealed the SFE increased upon Al addition; however, the slip energy barrier was reduced, which favored the mobility of dislocations and twinning propensity to prolong strain hardening. The present findings provide further insights into the regulation of mechanical properties of HEAs by Al-alloying.
ABSTRACT
KIF4A has been demonstrated to play a crucial function in the pathogenesis of a broad number of tumors and have close association with PI3K/AKT pathway. The aim of this study was to explore the potential function of KIF4A in lung cancer progression by targeting PI3K/AKT pathway and P21 combination with doxorubicin. A549 cell lines were transfected with siRNA against KIF4A and negative control siRNA (si-NC). MTT assay and trypan blue staining were used to evaluate the effect of si-KIF4A on the doxorubicin cytotoxicity. The mRNA and protein expression levels of KIF4A and p21 were assessed by qRT-PCR and Western blotting. Apoptosis was measured by cell death ELISA kit. Our result revealed that KIF4A silencing decreased cellular proliferation in A549 lung cancer cells. Doxorubicin in combination with si-KIF4A led to significant reduction in the survival rate of A549 cell. KIF4A silencing upregulated p21. In conclusion, our results demonstrate that KIF4A inhibition sensitizes A549 cells to doxorubicin by targeting p21 and PI3K/AKT pathway, indicating a significant role for KIF4A in lung cancer chemotherapy.
Subject(s)
Lung Neoplasms , Proto-Oncogene Proteins c-akt , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction , Cell Line, Tumor , Lung Neoplasms/metabolism , Doxorubicin/pharmacology , Cell Proliferation , Apoptosis , RNA, Small Interfering/pharmacology , Gene Expression Regulation, Neoplastic , Kinesins/genetics , Kinesins/metabolism , Kinesins/pharmacologyABSTRACT
@#Abstract: Objective To further investigate the underreporting of mortality surveillance data among permanent residents in Hainan Province in 2020, and to explore the application of Application of the Analysis of National Causes of Death for Action (ANACONDA) in the quality analysis of mortality surveillance. Methods The data were collected from the Death Information Monitoring and Management System of Hainan Center for Disease Control and Prevention, and mainly included 33 418 deaths reported from 19 cities and counties in Hainan Province from January 1, 2020 to December 31, 2020. All the data were analyzed by the application of ANACONDA, and the causes of death were classified by the International Classification of Diseases, 10th Revision (ICD-10). Results A total of 33 418 deaths were reported in Hainan Province in 2020, with a crude mortality rate of 3.6‰. The proportion of deaths in males under 85 years old was higher than that in females, while the proportion of deaths in 85 years old and above was opposite. The quality analysis of cause of death surveillance showed that there was under-reporting of death surveillance in Hainan Province in 2020, with an under-reporting rate of 30.1%. There were differences in the age composition and GBD regional composition ratio of deaths of the three major categories of diseases, and the misreporting of causes of death in the middle and high age groups was more significant. The Vital Statistics Performance Index (VSPI) score of death data in Hainan Province in 2020 was 52.8, the score of cause of death reporting quality was 85.5, and the score of specific cause of death level that could be used was 88.4. The completeness of death reports in the priority action areas for improving cause of death data quality accounted for the largest share, followed by the quality of cause of death reports. There was a difference in the proportion of specific causes of death between males and females after the survey, but the change in order was not obvious. Conclusions The data integrity of cause-of-death surveillance is low in Hainan Province in 2020. It is suggested to improve the completeness of reporting data, strengthen the training of cause-of-death surveillance system, and regularly evaluate and supervise the system.
ABSTRACT
Soft devices, especially capacitive stress (or strain) sensors, are important for applications, including wearable medical monitoring, electronic skin, and soft robotics. The incorporation of liquid metal particles (LMPs) into highly deformable elastomers as inclusions ameliorates the mechanical compliance caused by a rigid filler. The high dielectric constant and liquid feature of LMPs are suitable for soft sensors with high sensitivity and a large real-time dynamic detection range. Here, a class of LM-elastomer composites are introduced with elastic and high dielectric properties, making them uniquely suitable for the application of soft stress sensors. The prepared stretchable soft stress sensor can detect the bending degree of the finger, monitor physiological signals in real time, and distinguish the vibration from the pronunciation of different letters. The nanoscale X-ray computational tomography (nano-CT) measurements indeed detect the changes of LMPs under stress, i.e., LMPs in the matrix distribute from uneven to relatively uniform, agglomerate, and even connect each other to have a conduction path in the composition with high LMP contents, which cause the changes in the physical properties of devices under operation. The cognition of LMP changes in composites under stress is instructive for promoting their further applications in the field of soft devices.
Subject(s)
Elastomers , Wearable Electronic Devices , Electronics , Metals , Monitoring, PhysiologicABSTRACT
This study demonstrates the enantioselective removal dynamics and mechanisms of the chiral herbicide metolachlor in a hydroponic system of Phragmites australis. It presents the first work to elucidate plant-microbial driven enantioselective degradation processes of chiral chemicals. The results showed a degradation efficiency of up to 95.07 ± 2.81% in the hydroponic system driven by a notably high degradation rate constant of 0.086 d-1. P. australis was demonstrated to rapidly increase the contribution of biodegradation pathways in the hydroponic system to 82.21 ± 4.81% within 4 d with an enantiomeric fraction (EF) drop to 0.26 ± 0.02 to favour the enantioselective degradation of S-Metolachlor (kS-Metolachlor = 0.568 d-1 and kR-Metolachlor = 0.147 d-1). Comparatively, the biodegradation pathways in the control constituted less than 25%, with an EF value of circa 0.5. However, the enantioselective biodegradation pathways exhibited complete reversal after about 4 d to favour R-Metolachlor. Plants promoted the degradation of R-Metolachlor, evidenced by an increase in EF to 0.59 ± 0.03. Nonetheless, metolachlor showed an inhibitory effect on plants reflected by the reduction of plant growth rate, chlorophyll content, and electron transport rate to -7.85 ± 1.52%, 1.33 ± 0.43 mg g-1, 4.03 ± 1.33 µmol (m2 s)-1, respectively. However, rhizosphere microorganisms aided plants to catalyze excessive reactive oxygen species production by the antioxidant enzymes to protect plants from oxidative damage and restore their physiological activities. High-throughput analysis of microbial communities demonstrated the enrichment of Massilia (40.63%) and Pseudomonas (8.16%) in the initial stage to promote the rapid degradation of S-Metolachlor. By contrast, the proliferation of Brevundimonas (32.29%) and Pseudarthrobacter (11.03%) in the terminal stage was closely associated with the degradation of R-Metolachlor. Moreover, as symbiotic bacteria of plants, these bacteria aided plants protection from reactive oxygen damages and promoted the recovery of plant metabolic functions and photosynthesis. Overall, these results demonstrate biodegradation mediated by plant-microbe mechanisms as the main driver for the enantioselective degradation of metolachlor in hydroponic systems.
Subject(s)
Herbicides , Acetamides , Antioxidants , Biodegradation, Environmental , Chlorophyll , Herbicides/chemistry , Hydroponics , Oxygen , Plants/metabolism , Reactive Oxygen SpeciesABSTRACT
Inspired by gradient materials in nature, advanced engineering components with controlled structural gradients have attracted substantial research interests due to their exceptional combinations of properties. However, it remains challenging to generate structural gradients that penetrate through bulk materials, which is essential for achieving enhanced mechanical properties in metallic materials. Here, we report practical strategies to design controllable structural gradients in bulk metallic glasses (BMGs). By adjusting processing conditions, including holding time and/or controlling temperatures, of cryogenic thermal cycling and fast cooling, two different types of gradient metallic glasses (GMGs) with spatially gradient-distributed free volume contents can be synthesized. Both mechanical testing and atomistic simulations demonstrate that the spatial gradient can endow GMGs with extra plasticity. Such an enhanced mechanical property is governed by the gradient-induced deflection of shear deformation that fundamentally suppresses the unlimited shear localization on a straight plane that would be expected in BMGs without such a gradient.
ABSTRACT
This study demonstrates the stereoselective degradation patterns and biodegradation mechanisms of metolachlor (MET) and napropamide (NAP) in integrated vertical flow constructed wetlands (IVCW). The higher interphase transferability of NAP resulted in higher degradation rates of 90.60 ± 4.09%. The enantiomeric fraction (EF) values of 0.38 ± 0.02 and 0.54 ± 0.03, respectively, recorded for the enantiomers S-MET and R-NAP, with higher herbicidal activities, demonstrated their highly selective biodegradation patterns. The antioxidant enzyme activities and fluorescence parameters of plants showed positive correlations with the degradation efficiency and enantioselectivity of MET and NAP. Adaptive regulations by plants promoted the proliferation of microbial genera like Enterobacter and unclassified_Burkholderiales, which could facilitate plant growth. Moreover, enrichment of the herbicide-degrading functional bacteria Terrimonas (5.10%), Comamonas (4.05%) Pseudoxanthomonas (4.49%) and Mycobacterium (1.42%) demonstrably promoted the preferential degradation of S-MET and R-NAP. Furthermore, the abundance of Ferruginibacter favored the use of R-NAP as carbon source to achieve co-removal of R-NAP and NO3--N.
Subject(s)
Herbicides , Wetlands , Amides , Bacteria/metabolism , Biodegradation, Environmental , Herbicides/metabolism , Plants/metabolismABSTRACT
RATIONALE: Adaptive alteration of dopamine (DA) system in mesocorticolimbic circuits is an extremely intricate and dynamic process, which contributes to maintaining methamphetamine (METH)-related disorders. There are no approved pharmacotherapies for METH-related disorders. Cannabidiol (CBD), a major non-psychoactive constituent of cannabis, has received attention for its therapeutic potential in treating METH-related disorders. However, the major research obstacles of CBD are the yet to be clarified mechanisms behind its therapeutic potential. Recent evidence showed that DA system may be active target of CBD. CBD could be a promising dopaminergic medication for METH-related disorders. OBJECTIVES: We investigated the role of the DA receptor D1 (DRD1)-methyl-CpG-binding protein 2 (MeCP2)-brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling pathway in DA release induced by METH. Investigating the intervention effects of CBD on the DRD1-MeCP2-BDNF-TrkB signaling pathway could help clarify the underlying mechanisms and therapeutic potential of CBD in METH-related disorders. RESULTS: METH (400 µM) significantly increased DA release from primary neurons in vitro, which was blocked by CBD (1 µM) pretreatment. METH (400 µM) significantly increased the expression levels of DRD1, BDNF, and TrkB, but decreased the expression of MeCP2 in the neurons, whereas CBD (1 µM) pretreatment notably inhibited the protein changes induced by METH. In addition, DRD1 antagonist SCH23390 (10 µM) inhibited the DA release and protein change induced by METH in vitro. However, DRD1 agonist SKF81297 (10 µM) induced DA release and protein change in vitro, which was also blocked by CBD (1 µM) pretreatment. METH (2 mg/kg) significantly increased the DA level in the nucleus accumbens (NAc) of rats with activation of the DRD1-MeCP2-BDNF-TrkB signaling pathway, but these changes were blocked by CBD (40 or 80 mg/kg) pretreatment. CONCLUSIONS: This study indicates that METH induces DA release via the DRD1-MeCP2-BDNF-TrkB signaling pathway. Furthermore, CBD significantly inhibits DA release induced by METH through modulation of this pathway.
Subject(s)
Cannabidiol , Methamphetamine , Animals , Brain-Derived Neurotrophic Factor/metabolism , Cannabidiol/pharmacology , Dopamine/metabolism , Methamphetamine/pharmacology , Methyl-CpG-Binding Protein 2/metabolism , Rats , Receptor, trkB , Receptors, Dopamine D1 , Signal TransductionABSTRACT
High-entropy alloys (HEAs), as an emerging class of materials, have pointed a pathway in developing alloys with interesting property combinations. Although they are not exempted from the strength-ductility trade-off, they present a standing chance in overcoming this challenge. Here, we report results for a precipitation-strengthening strategy, by tuning composition to design a CoNiV-based face-centered cubic/B2 duplex HEA. This alloy sustains ultrahigh gigapascal-level tensile yield strengths and excellent ductility from cryogenic to elevated temperatures. The highest specific yield strength (~150.2 MPa·cm3/g) among reported ductile HEAs is obtained. The ability of the alloy presented here to sustain this excellent strength-ductility synergy over a wide temperature range is aided by multiple deformation mechanisms i.e., twins, stacking faults, dynamic strain aging, and dynamic recrystallization. Our results open the avenue for designing precipitation-strengthened lightweight HEAs with advanced strength-ductility combinations over a wide service temperature range.
ABSTRACT
Amorphous alloys (AAs) are promising materials due to their unique properties and have been applied in various biomaterial coatings and micro-electro-mechanical systems. However, they have seldom been applied in the optical nano-device. Here, we systematically investigate morphology, microstructure, mechanical and optical properties of an Au-Cu-Si AA and successfully design and fabricate a broadband optical absorber using the Au-Cu-Si AA. Such device achieves an average absorption up to about 95% from 500 to 1500 nm with a thickness less than 300 nm. This is of significance for exploration the feasibility of AAs application in the field of optical nano-devices.
ABSTRACT
Gallium-based liquid alloys are attractive due to their unique properties, and they can potentially be applied in the field of flexible electronics as coolant materials for nuclear and liquid batteries, due to the high thermal conductivity and excellent fluid properties of liquid metals. However, it is still challenging to fabricate gallium-based liquid alloy nanodroplets with uniform and small size. Here, we performed a systematical study on the influence of various factors affecting the size of nanodroplets. Liquid metal nanodroplets with an average size of 74 nm and narrow size distribution were successfully fabricated. Li-ion half-cells were assembled with eutectic GaIn (eGaIn) nanodroplets as anode active materials, which showed higher specific capacity than the bulk eGaIn alloy under the same testing conditions.
ABSTRACT
Synergistic impairment of the blood-brain barrier (BBB) induced by methamphetamine (METH) and HIV-Tat protein increases the risk of HIV-associated neurocognitive disorders (HAND) in HIV-positive METH abusers. Studies have shown that oxidative stress plays a vital role in METH- and HIV-Tat-induced damage to the BBB but have not clarified the mechanism. This study uses the human brain microvascular endothelial cell line hCMEC/D3 and tree shrews to investigate whether the transient receptor potential melastatin 2 (TRPM2) channel, a cellular effector of the oxidative stress, might regulate synergistic damage to the BBB caused by METH and HIV-Tat. We showed that METH and HIV-Tat damaged the BBB in vitro, producing abnormal cell morphology, increased apoptosis, reduced protein expression of the tight junctions (TJ) including Junctional adhesion molecule A (JAMA) and Occludin, and a junctional associated protein Zonula occludens 1 (ZO1), and increased the flux of sodium fluorescein (NaF) across the hCMEC/D3 cells monolayer. METH and HIV-Tat co-induced the oxidative stress response, reducing catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) activity, as well as increased reactive oxygen species (ROS) and malonaldehyde (MDA) level. Pretreatment with n-acetylcysteine amide (NACA) alleviated the oxidative stress response and BBB damage characterized by improving cell morphology, viability, apoptosis levels, TJ protein expression levels, and NaF flux. METH and HIV-Tat co-induced the activation and high protein expression of the TRPM2 channel, however, early intervention using 8-Bromoadenosine-5'-O-diphosphoribose (8-Br-ADPR), an inhibitor of TPRM2 channel, or TRPM2 gene knockdown attenuated the BBB damage. Oxidative stress inhibition reduced the activation and high protein expression of the TRPM2 channel in the in vitro model, which in turn reduced the oxidative stress response. Further, 8-Br-ADPR attenuated the effects of METH and HIV-Tat on the BBB in tree shrews-namely, down-regulated TJ protein expression and increased BBB permeability to Evans blue (EB) and NaF. In summary, the TRPM2 channel can regulate METH- and HIV-Tat-induced oxidative stress and BBB injury, giving the channel potential for developing drug interventions to reduce BBB injury and neuropsychiatric symptoms in HIV-infected METH abusers.
ABSTRACT
Many individuals infected with human immunodeficiency virus (HIV) are also afflicted with HIV-associated neurocognitive disorders (HANDs). Methamphetamine (METH) abuse puts HIV-1 patients at risk for HANDs because METH and HIV-1 proteins, such as trans-activator of transcription (Tat), can synergistically damage the blood-brain barrier (BBB). However, the underlying mechanism of METH- and HIV-Tat-induced BBB damage remains unclear. In this study, male adult tree shrews and human brain capillary endothelial cells were treated with HIV-Tat, METH, and gastrodin. We used western blotting to examine the expressions of glucose transporters (GLUT1 and GLUT3), tight junctions, and junctional adhesion molecule A (JAMA) and to evaluate the damage and detect Evans blue (EB) and fluorescein sodium in the brain to assess BBB permeability to study the effect of METH and the HIV-1 Tat protein on BBB function in vitro and in vivo. The results showed that the group treated with Tat and METH experienced a significant change at the ultrastructural level of the tree shrew cerebral cortex, decreased protein levels of occluding, claudin-5, Zonula occludens 1 (ZO1), and JAMA in vitro and in vivo, and increased levels of EB and fluorescein sodium in the tree shrew cerebral cortex. The protein levels of GLUT1 and GLUT3 was downregulated in patients with Tat- and METH-induced BBB damage. Pretreatment with gastrodin significantly increased the levels of EB and fluorescein sodium in the tree shrew cerebral cortex and increased the expressions of occluding, ZO1, JAMA, and GLUT1 and GLUT. These results indicate that gastrodin may offer a potential therapeutic option for patients with HANDs.
ABSTRACT
We use the pulse current thermoplastic forming technique based on joule heating to rejuvenate the atomic structure of a La62Al14Ag2.34Ni10.83Co10.83 bulk metallic glass (BMG). The pulse-formed sample exhibits more pronounced ß-relaxation than the as-cast one due to the increased free volume. Instead, the sub-Tg annealing clearly weakens the ß-relaxation and also makes it more isolated from the α-relaxation, showing contributions from free volume and preferred structure. However, both treatments exhibit little influence on the following α-relaxation and high temperature crystallization kinetics. Our results open an effective way to rejuvenate the structure of BMGs and provide an in-depth understanding of the relationship between structural relaxations and crystallization kinetics of BMGs.