Stress-induced Mechanisms Research Articles

Gallic acid inhibits Staphylococcus aureus RecA protein functions: role in countering antibiotic resistance in bacteria.

Recombinase RecA and its homologs play a key role in homologous recombination DNA repair and revive stalled replication fork DNA synthesis. RecA plays an essential role in the evolution of antibiotic-resistant strains via stress-induced DNA repair mechanisms during the SOS response. Accordingly, RecA has become an attractive target to slow down antibiotic resistance rates and prevent mutations in pathogenic bacterial species. We employed RecA conserved activities: DNA binding, displacement loop formation, strand exchange, ATP hydrolysis, and LexA cleavage, to elucidate the inhibitory role of gallic acid on S. aureus RecA functions. Gallic acid inhibition of the SOS response by western blot analysis and its antibacterial activity were measured. The gallic acid inhibited all the canonical activities of S. aureus RecA protein. The natural phenolic compound gallic acid interferes with RecA protein DNA complex formation and inhibits activities such as displacement loop formation, strand exchange reaction, ATP hydrolysis, and coprotease activity of S. aureus. Additionally, gallic acid can obstruct ciprofloxacin-induced RecA expression and eventually confer the inhibitory role of gallic acid in the SOS survival mechanism in S. aureus.

Multi-mechanism-based twinning evolution in machined surface induced by thermal-mechanical loads with increasing cutting speeds

Microstructural features are an important factor in the evaluation of machined surface integrity. In particular, twins and twin boundaries have a significant impact on the physical and mechanical properties of components. This study investigates twin boundary evolution mechanisms in the machined surface during orthogonal cutting of oxygen-free-high-conductivity copper with cutting speeds ranging from 125 m/min to 2000 m/min. Pertinent features including twin boundaries, grain morphologies, textures, etc. Are characterized by electron backscattered diffraction and transmission electron microscope. The results show that the machined surface is divided into the refined layer, the deformed layer, and the matrix. An abnormal gradient distribution of a 60°<111> twin boundary is discovered for the first time. Specifically, the annealing twins mostly diminish in the deformed layer and regenerate in the refined layer. In the refined layer, a temperature-dominated process of twin formation and dynamic recrystallization occur. In the deformed layer, the resolved shear stress along the twin system is calculated through a novel approach, which reveals the stress-induced detwinning mechanism. The results of this research are beneficial for understanding both the deformation mechanism of medium stacking fault energy face-centered cubic metal under extreme loading conditions and the underlying effects of twins on the mechanical properties of machined surface.

Investigation on nonequilibrium crystallization of highly undercooled Cu–Ni–Co alloys

Deep undercooling rapid solidification experiments of Cu–Ni–Co alloys were carried out using the molten glass purification cycle superheat method. 130 K, 177 K and 277 K undercooling degrees were obtained and analysed for Cu55Ni43Co2 alloy. The crystallographic information obtained by EBSD and the dynamics of the solidification front taken by high speed photography were analysed and it was concluded that both the formation of relatively rounded equiaxed grains during the first refinement and the subsequent formation of finer subcrystals were due to the release of a large amount of solidification energy during the solidification process. The re-glow stage releases a large amount of latent heat of solidification resulting in the remelting of the dendrites. TEM tests were carried out on Cu55Ni43Co2 alloy with a maximum undercooling of 277 K. It was found that part of the substructure showed a high density dislocation network. By analysing the effect of increasing undercooling on the microstructure evolution, combined with the EBSD and TEM characterisation data, it was found that the stress-induced recrystallization mechanism was the dominant factor in the grain refinement mechanism at large undercooling.

The Effect of Zirconia Content on Physical and Mechanical Properties of Al&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt;/ZrO&lt;sub&gt;2&lt;/sub&gt; Composites

The structural, physical and mechanical properties of alumina composites reinforced with various zirconia contents were studied. Zirconia with specific stress-induced toughness mechanisms (from tetragonal to monoclinic) can improve its mechanical properties. The raw materials were commercial products of alumina (Al2O3) and zirconia (ZrO2) with gamma alumina (γ-Al2O3) and monoclinic zirconia (m-ZrO2) phases, respectively. In this study, alumina and zirconia powders containing 0, 10, 20, 30, and 40 wt% were mechanically activated and sintered at 1400°C for 3 h. Fourier transform infrared spectroscopy (FTIR) characterization was used to confirm the functional groups in the sample. Phase analysis of the sintered samples was carried out via X-ray diffraction (XRD). Composite characterization includes diameter shrinkage, density, and Vickers hardness. Corundum (α-Al2O3), monoclinic zirconia (m-ZrO2) and tetragonal zirconia (t-ZrO2) phases were the observed phases in the sintered sample. The Al2O3/ZrO2 60:40 sample had the largest shrinkage in pellet diameter, apparent density, and Vickers hardness, at 8%, 4.35 g/cm3, and 1.33 HVN, respectively.

A Molecular Mechanism of Stress-Induced Alzheimer’s Disease; Part 1

Alzheimer’s disease (AD) is a chronic but deadly neurodegenerative disorder. A significant burden on global public health, a cure for AD is still elusive. Recent clinical trials based on pathogenic theories of extra/intracellular protein aggregation resulting from oxidative stress or other environmental insults have encountered setbacks. In this first part of a series, we report a significant and serendipitous case of an AD patient. It is the first time, to our knowledge, to follow a single patient over 33 plus years (1985–2018), where AD symptoms were presented and remised repeatedly. The effects of stress resulting in numerous ailments, e.g., memory loss, brain atrophy, high blood pressure, inflammations, decrease of immunity, etc., were observed in four ‘episodes’ of severe stress, confirming that the disease is stress-induced. An anti-stress lifestyle, involving seven daily anti-stress practices, was implemented which, remarkably, led to the recovery of memory and retardation of disease progression. We discovered a relationship between stress/stress hormones, the strain effects on these stress hormones and the pathways leading to a stress-induced macro-molecular mechanism that accounts for the origin of toxic free radical species (oxidants) which derive from Amyloid beta (Aβ) and Tau proteins (antioxidants). We suggest our mechanism may also be applied to other neurodegenerative diseases related to stress effects on proteins, such as alpha-synuclein in Parkinson’s disease, superoxide dismutase in amyotrophic lateral sclerosis, IAPP amyloid in type 2 diabetes, etc. As chronic traumatic encephalopathy and post-traumatic stress disorder both lead to AD, the anti-stress program proposed here may also very well be of assistance to those impacted by the said ailments described above. Consequently, the proposed stress-induced molecular mechanism deduced from the Alzheimer disease patient’s experience, we suggest, represents a significant step forward in understanding the origins of Alzheimer’s disease and many other neurodegenerative diseases. In part 2, we will discuss the patients further AD development from 2018 to the current-time and expand our discussion of the physics of stress/strain on the macromolecules.

Stress-sensitivity analysis of geological confined pores with ultrasonics

Ultrasonics could be a promising technology to modify the geological formations for geo-energy productions, carbon geological sequestrations, monitoring of crack formation with stress and volcanic activity prediction. However, immature understanding of the post-ultrasonic geological formations seriously restricts the further applications in practices. This paper initially focuses on the in-situ geological porous media of low-permeability sandstones, analysing their stress sensitivity and relevant influential factors post-ultrasonics. Basically, the original and treated in-situ cores with and without ultrasonics were characterized through a series of experimental approaches, including permeability stress sensitivity (PSS), high-pressure mercury intrusion (HPMI), inline nuclear magnetic resonance (NMR), X-ray diffraction tests (XRD), triaxial stress test (TS) and scanning electron microscope (SEM) to explore the stress-induced rock compression mechanisms and the associated effects of pore restructures and mineral re-compositions. The experimental results reveal that the ultrasonics cause desorption of clay minerals at relatively low pressures (<5 MPa), which enlarges the pore throat and increases the permeability by 2.4 times. As the pressure increasing to 5 MPa, the porosity decreases from 8.79% to 6.13% because the plastic deformations of rock become irreversible without the cementing support (i.e., clay minerals). A further pressure increases from 5 to 25 MPa results in more porosity reduction from 6.13% to 5.77% through the rigid compressions. Overall, under the same pore pressure, the core porosity with ultrasonic treatments is usually smaller than the original ones, which thus indicates ultrasonics to some extent augment the stress sensitivity of core with compression. Hence, it is suggested to control pore pressure if the ultrasonics are introduced for geo-energy productions and carbon geological sequestrations.

Sources, bioaccumulation, and toxicity mechanisms of cadmium in Chlamys farreri

The Potentially toxic elements (PTEs) cadmium (Cd) is one of the most serious stressors polluting the marine environment. Marine bivalves have specific high enrichment capacity for Cd. Previous studies have investigated the tissue distribution changes and toxic effects of Cd in bivalves, but the sources of Cd enrichment, migration regulation during growth, and toxicity mechanisms in bivalves have not been fully explained. Here, we used stable-isotope labeling to investigate the contributions of Cd from different sources to scallop tissues. We sampled the entire growth cycle of Chlamys farreri, which is widely cultured in northern China, from juveniles to adult scallops. We found tissue variability in the bioconcentration–metabolism pattern of Cd in different bound states, with Cd in the aqueous accounting for a significant contribution. The accumulation pattern of Cd in all tissues during growth was more significant in the viscera and gills. Additionally, we combined a multi-omics approach to reveal a network of oxidative stress-induced toxicity mechanisms of Cd in scallops, identifying differentially expressed genes and proteins involved in metal ion binding, oxidative stress, energy metabolism, and apoptosis. Our findings have important implications for both ecotoxicology and aquaculture. They also provide new insights into marine environmental assessment and mariculture development.

Prenatal Stress Induces Translational Disruption Associated with Myelination Deficits

Disruptions to neurodevelopment are known to be linked to behavioral disorders in childhood and into adulthood. The fetal brain is extremely vulnerable to stimuli that alter inhibitory GABAergic pathways and critical myelination processes, programing long-term neurobehavioral disruption. The maturation of the GABAergic system into the major inhibitory pathway in the brain and the development of oligodendrocytes into mature cells capable of producing myelin are integral components of optimal neurodevelopment. The current study aimed to elucidate prenatal stress-induced mechanisms that disrupt these processes and to delineate the role of placental pathways in these adverse outcomes. Pregnant guinea pig dams were exposed to prenatal stress with strobe light exposure for 2 h/day on gestational age (GA) 35, 40, 45, 50, 55, 60, and 65, and groups of fetuses and placentae were collected after the stress exposure on GA40, GA50, GA60, and GA69 (term). Fetal plasma, placental, and brain tissue were collected for allopregnanolone and cortisol quantification with ELISA. Relative mRNA expression of genes of specific pathways of interest was examined with real-time PCR in placental and hippocampal tissue, and myelin basic protein (MBP) was quantified immunohistochemically in the hippocampus and surrounding regions for assessment of mature myelin. Prenatal stress in mid-late gestation resulted in disruptions to the translational machinery responsible for the production of myelin and decreased myelin coverage in the hippocampus and surrounding regions. The male placenta showed an initial protective increase in allopregnanolone concentrations in response to maternal psychosocial stress. The male and female placentae had a sex-dependent increase in neurosteroidogenic enzymes at term following prenatal stress. Independent from exposure to prenatal stress, at gestational day 60 – a critical period for myelin development, the placentae of female fetuses had increased capability of preventing cortisol transfer to the fetus through expression of 11-beta-hydroxysteroid dehydrogenase types 1 and 2. The deficits early in the process of maturation of myelination indicate that the reduced myelination observed at childhood equivalence in previous studies begins in fetal life. This negative programing persists into childhood, potentially due to dysregulation of MBP translation processes. Expression patterns of neurosteroidogenic enzymes in the placenta at term following stress may identify at-risk fetuses that have been exposed to a stressful in utero environment.

一种面向柔性离子电子学的超强韧、可拉伸的多功能离子凝胶

Ionogels have attracted much attention in recent years because of their good thermal stability, high ionic conductivity, and non-volatility. However, there is a trade-off between the mechanical strength and stretchability of ionogels, which results in unsatisfactory mechanical performance. Herein, strong polymer crystallization and weak ion-dipole interaction are combined to prepare an ultra-tough and super-stretchable ionogel. The crystalline region can dissipate the energy through the stress-induced disaggregation mechanism in the stretching process and toughen the gel, while the reversible formation and dissociation of the ion-dipole interaction between amorphous polymer chains and ionic liquids can provide elasticity for large strain. These ionogels have high toughness, strong tensile strength, large Young’s modulus, and good stretchability. Furthermore, the ionogels also possess other properties like good fatigue resistance, quick self-recovery, high transparency, recyclability, self-healing ability, high ionic conductivity, and wide electrochemical window. This ionogel exhibits great potential in several iontronic devices, such as triboelectric nanogenerators, ionic thermoelectric materials, and strain sensors. This study develops a new method to guide the preparation of high-performance ionogels by combining reversible strong and weak interactions.

Contact Stress-Induced Wear Mechanism Transitions of PcBN/Al2O3 Under Vacuum and Air Conditions

Abstract Since the millennium, incremental breakthroughs in aerospace have attracted widespread attention from countries around the world on deep space exploration. Technological innovations in ceramic and superhard materials have also played a key role in deep space exploration. Inspired by this, a tribological ball-disk experiment of polycrystalline cubic boron nitride (PcBN) sliding against aluminum oxide (Al2O3) was implemented in air and vacuum conditions, in order to evaluate the friction and wear properties of PcBN based on drilling in the deep space environment. The results prove that the coefficient of friction (CoF) is interrelated with load and wear conditions, where CoFs gradually decrease with load growth in both air and vacuum. When the loads keep increasing, however, the wear mechanisms finally change under the high Hertz contact stress and lead to the CoF lift. Detailed characterizations were made to verify the tribological behaviors of the microscopic surface and chemical composition. Finally, by analyzing the surface topographies and chemical residues, it is certain that the wear mechanisms change due to the high Hertz contact stress. As a result, abrasive wear and adhesive wear turn to furrow wear in air and three-body wear in vacuum. These results can influence actual work in deep space by reducing large stress loads to avoid the impact of severe vibrations on precision instruments during work and improving cutting removal efficiency by selecting the appropriate loading.

Formation of CuO whiskers and facet-controlled oxidation during the oxidation of Au-Cu nanoparticles fabricated by solid-state dewetting

The fabrication of cupric oxide (CuO) nanowires from Cu particles via thermal oxidation provides a simple and scalable method to produce hierarchical structures. A stress-induced growth mechanism is believed to account for the nanowire formation while a slow oxidation rate is favored to sustain the driving force. Here, CuO whiskers are grown from Au-Cu nanoparticles because the formation of Au-Cu phases decreases the Cu diffusion rate and in turn slows down the oxidation rate. The driving force for the whisker growth is attributed to the compressive stress imposed by the CuO shell on the Au-Cu core, which is induced by the significantdifference in their linear thermal expansion coefficients. The contribution of the compressive stress is proved by the calculation. Moreover, preferred oxidation is observed and it is related to the crystalline structures of different facets existing on the surface of Au-Cu nanoparticles. The more compact the plane, the slower the diffusion rate through the plane, resulting in the formation of thinner CuO on the relevant facet. The results open a cost-effect way to fabricate hybrid nanostructures consisting of Cu-based core–shell nanoparticles attached with CuO whiskers and bring new insights into the oxidation behaviors of Cu on different crystal planes.

PolyGA targets the ER stress-adaptive response by impairing GRP75 function at the MAM in C9ORF72-ALS/FTD

ER stress signaling is linked to the pathophysiological and clinical disease manifestations in amyotrophic lateral sclerosis (ALS). Here, we have investigated ER stress-induced adaptive mechanisms in C9ORF72-ALS/FTD, focusing on uncovering early endogenous neuroprotective mechanisms and the crosstalk between pathological and adaptive responses in disease onset and progression. We provide evidence for the early onset of ER stress-mediated adaptive response in C9ORF72 patient-derived motoneurons (MNs), reflected by the elevated increase in GRP75 expression. These transiently increased GRP75 levels enhance ER–mitochondrial association, boosting mitochondrial function and sustaining cellular bioenergetics during the initial stage of disease, thereby counteracting early mitochondrial deficits. In C9orf72 rodent neurons, an abrupt reduction in GRP75 expression coincided with the onset of UPR, mitochondrial dysfunction and the emergence of PolyGA aggregates, which co-localize with GRP75. Similarly, the overexpression of PolyGA in WT cortical neurons or C9ORF72 patient-derived MNs led to the sequestration of GRP75 within PolyGA inclusions, resulting in mitochondrial calcium (Ca2+) uptake impairments. Corroborating these findings, we found that PolyGA aggregate-bearing human post-mortem C9ORF72 hippocampal dentate gyrus neurons not only display reduced expression of GRP75 but also exhibit GRP75 sequestration within inclusions. Sustaining high GRP75 expression in spinal C9orf72 rodent MNs specifically prevented ER stress, normalized mitochondrial function, abrogated PolyGA accumulation in spinal MNs, and ameliorated ALS-associated behavioral phenotype. Taken together, our results are in line with the notion that neurons in C9ORF72-ALS/FTD are particularly susceptible to ER–mitochondrial dysfunction and that GRP75 serves as a critical endogenous neuroprotective factor. This neuroprotective pathway, is eventually targeted by PolyGA, leading to GRP75 sequestration, and its subsequent loss of function at the MAM, compromising mitochondrial function and promoting disease onset.

Spatial variation of crustal anisotropy in the Arunachal Himalaya inferred from splitting of local S waveforms

• A large spatial variability in crustal deformation is found beneath the western and eastern parts of the Arunachal Himalaya. • Small delay times and large scattering in the fast axis of anisotropy characterize the western part. • Crustal anisotropy beneath the western part is due to a combination of structure- and stress-induced mechanisms. • Correlation of local S and XK(K)S measurements in the central part suggests coherent deformation. • Combined delay times from the central and eastern parts show a correlation with depth. Shear wave anisotropy of the crust beneath the Arunachal Himalaya is investigated by analysing the splitting of steeply incident (i c ≤ 45°) direct S-phases of 396 local earthquakes, recorded at 32 stations. The 76 well constrained splitting measurements reveal that the delay times between fast and slow waves range from 0.02 to 0.30 s, clustered around 0.07 s. A large variation in the orientation of fast polarization directions (FPDs) is found. The smallest delay times (mostly < 0.10 s) and large variation in the orientation of FPDs are found at stations located in the western part of the Arunachal Himalaya. This is likely associated with heterogeneities in the lithological properties and a combined effect of stress-induced and structure-induced anisotropy. For a small crustal block in the central part of Arunachal, the FPDs are parallel to the strike of the Himalayan arc and are associated with structure-induced anisotropy. In this region, the FPDs representing the upper mantle are also found to be parallel to the strike of the Himalayan arc, suggesting a coherent deformation. In the eastern part, a variation in the FPDs is observed from north to south, being parallel to the strike of the Siang river in the former and mostly parallel to the average maximum horizontal stress in the latter. The delay times show a correlation with depth when the observations in the central and eastern parts of the Arunachal Himalaya are combined.

Transcriptomic Analysis of Fusarium oxysporum Stress-Induced Pathosystem and Screening of Fom-2 Interaction Factors in Contrasted Melon Plants.

Fusarium wilt is one of the most destructive and less controllable diseases in melon, which is usually caused by fusarium oxysporum. In this study, transcriptome sequencing and Yeast Two-Hybrid (Y2H) methods were used for quantification of differentially expressed genes (DEGs) involved in fusarium oxysporum (f. sp. melonis race 1) stress-induced mechanisms in contrasted melon varieties (M4-45 “susceptible” and MR-1 “resistant”). The interaction factors of Fom-2 resistance genes were also explored in response to the plant-pathogen infection mechanism. Transcriptomic analysis exhibited total 1,904 new genes; however, candidate DEGs analysis revealed a total of 144 specific genes (50 upregulated and 94 downregulated) for M4-45 variety and 104 specific genes (71 upregulated and 33 downregulated) for MR-1 variety, respectively. The analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway depicted some candidate DEGs, including Phenylalanine metabolism, phenylpropane biosynthesis, plants-pathogen interaction, and signal transduction of plant hormones, which were mainly involved in disease resistance metabolic pathways. The weighted gene co-expression network analysis (WGCNA) analysis revealed a strong correlation module and exhibited the disease resistance-related genes encoding course proteins, transcription factors, protein kinase, benzene propane biosynthesis path, plants-pathogen interaction pathway, and glutathione S-transferase. Meanwhile, the resistance-related specific genes expression was relatively abundant in MR-1 compared to the M4-45, and cell wall-associated receptor kinases (MELO3C008452 and MELO3C008453), heat shock protein (Cucumis_melo_newGene_172), defensin-like protein (Cucumis_melo_newGene_5490), and disease resistance response protein (MELO3C016325), activator response protein (MELO3C021623), leucine-rich repeat receptor protein kinase (MELO3C024412), lactyl glutathione ligase (Cucumis_melo_newGene_36), and unknown protein (MELO3C007588) were persisted by exhibiting the upregulated expressions. At the transcription level, the interaction factors between the candidate genes in response to the fusarium oxysporum induced stress, and Y2H screening signified the main contribution of MYB transcription factors (MELO3C009678 and MELO3C014597), BZIP (MELO3C011839 and MELO3C019349), unknown proteins, and key enzymes in the ubiquitination process (4XM334FK014). The candidate genes were further verified in exogenously treated melon plants with f. oxysporum (Fom-2, Race 1), Abscisic acid (ABA), Methyl Jasmonite (MeJA), and Salicylic acid (SA), using the fluorescence quantitative polymerase chain reaction (qRT-PCR) analysis. The overall expression results indicated that the SA signal pathway is involved in effective regulation of the Fom-2 gene activity.

Evolutionary Divergence of Marinobacter Strains in Cryopeg Brines as Revealed by Pangenomics

Marinobacter spp. are cosmopolitan in saline environments, displaying a diverse set of metabolisms that allow them to competitively occupy these environments, some of which can be extreme in both salinity and temperature. Here, we introduce a distinct cluster of Marinobacter genomes, composed of novel isolates and in silico assembled genomes obtained from subzero, hypersaline cryopeg brines, relic seawater-derived liquid habitats within permafrost sampled near Utqiaġvik, Alaska. Using these new genomes and 45 representative publicly available genomes of Marinobacter spp. from other settings, we assembled a pangenome to examine how the new extremophile members fit evolutionarily and ecologically, based on genetic potential and environmental source. This first genus-wide genomic analysis revealed that Marinobacter spp. in general encode metabolic pathways that are thermodynamically favored at low temperature, cover a broad range of organic compounds, and optimize protein usage, e.g., the Entner–Doudoroff pathway, the glyoxylate shunt, and amino acid metabolism. The new isolates contributed to a distinct clade of subzero brine-dwelling Marinobacter spp. that diverged genotypically and phylogenetically from all other Marinobacter members. The subzero brine clade displays genomic characteristics that may explain competitive adaptations to the extreme environments they inhabit, including more abundant membrane transport systems (e.g., for organic substrates, compatible solutes, and ions) and stress-induced transcriptional regulatory mechanisms (e.g., for cold and salt stress) than in the other Marinobacter clades. We also identified more abundant signatures of potential horizontal transfer of genes involved in transcription, the mobilome, and a variety of metabolite exchange systems, which led to considering the importance of this evolutionary mechanism in an extreme environment where adaptation via vertical evolution is physiologically rate limited. Assessing these new extremophile genomes in a pangenomic context has provided a unique view into the ecological and evolutionary history of the genus Marinobacter, particularly with regard to its remarkable diversity and its opportunism in extremely cold and saline environments.

A meta-analysis of experienced incivility and its correlates: Exploring the dual path model of experienced workplace incivility.

The present study proposes and examines a theoretical Dual Path Model of Experienced Workplace Incivility using meta-analytic relationships (k = 246; N = 145, 008) between experienced incivility and frequent correlates. The stress-induced mechanism was supported with perceived stress mediating the meta-analytical relationship between experienced incivility and occupational health (i.e., emotional exhaustion and somatic complaints). The commitment-induced mechanism was also supported with affective commitment to the organization mediating the relationship between experienced incivility and organizational correlates (i.e., job satisfaction and turnover intentions). However, these paths were not able to explain the strong relationship between experienced and enacted workplace incivility. Moderating analysis revealed that the experienced-enactment link is stronger between coworkers, in comparison to incivility experienced from supervisors; experienced incivility is more strongly related to organizational correlates, when incivility is enacted by supervisors in comparison to coworkers, and in human service samples when compared to samples comprised of mixed occupations. We discuss theoretical and practical implications as well as directions for future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neuronal circuits of stress and their dynamic interactions: a biopsychological framework

Stress alters neuroendocrine, autonomic, and behavioral processes to cope well with perceived threats that compromise subjective wellbeing. Just as the perception of risk can change the structure and function of brain circuitry, which may result in enduring behavioral changes. There needs to be a greater understanding of how the brain reacts to stress-related disorders and discern how the adaptation mechanisms of the central nervous system under acute stress, as well as how stressinduced adaptation mechanisms are altered under chronic stress conditions that may induce plasticity-related changes in the brain. During this interaction, the brain becomes more capable of resolving stress in a way that is either adaptive or maladaptive, leaving the most critical deficit in the emotion regulation associated with risk for pathological conditions. The essence of this associated risk involves the reciprocal influence between hypothalamic-pituitary-adrenal function, the relay nucleus within the amygdala reactivation, and the hippocampus as essential structures associated with the forebrain pathways mediating stress-induced hormones, and the gammaaminobutyric acid neurotransmitter system as key mechanisms of regulating stress. Understanding how related emotional experiences occur on the neural level and their impact on cognition and behavior entail tracing the interaction between the hypothalamic-pituitary-adrenal axis, the hormones released by these structures, and the neuroendocrine system's reactivity to stress. The interaction between threat-sensitive brain circuitry and the neuroendocrine stress system is crucial to understanding how related emotions arise on the neural level and their impact on cognition and behavior. The hypothalamicpituitary-adrenal axis is critical in regulating the synthesis and release of endocrine hormones through its interactions with these structures, collectively referred to as the stress response. The stress system is described in its anatomy and physiology and connections to other brain areas and endocrine systems. We explore the current evidence linking stress with pathophysiologic mechanisms implicated in stressful conditions affecting the neuronal circuitry between endocrine, metabolic, gastrointestinal, and immune systems. Examining the biopsychological contributions provides a conceptual framework for understanding the emergence of emotions and stress-related behaviors.

Stress Hormones Epinephrine and Corticosterone Selectively Reactivate HSV-1 and HSV-2 in Sympathetic and Sensory Neurons.

Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) establish latency in sensory and autonomic neurons, from which they can reactivate to cause recurrent disease throughout the life of the host. Stress is strongly associated with HSV recurrences in humans and animal models. However, the mechanisms through which stress hormones act on the latent virus to cause reactivation are unknown. We show that the stress hormones epinephrine (EPI) and corticosterone (CORT) induce HSV-1 reactivation selectively in sympathetic neurons, but not sensory or parasympathetic neurons. Activation of multiple adrenergic receptors is necessary for EPI-induced HSV-1 reactivation, while CORT requires the glucocorticoid receptor. In contrast, CORT, but not EPI, induces HSV-2 reactivation in both sensory and sympathetic neurons through either glucocorticoid or mineralocorticoid receptors. Reactivation is dependent on different transcription factors for EPI and CORT, and coincides with rapid changes in viral gene expression, although genes differ for HSV-1 and HSV-2, and temporal kinetics differ for EPI and CORT. Thus, stress-induced reactivation mechanisms are neuron-specific, stimulus-specific and virus-specific. These findings have implications for differences in HSV-1 and HSV-2 recurrent disease patterns and frequencies, as well as development of targeted, more effective antivirals that may act on different responses in different types of neurons.

Exploration of the Specific Pathology of HXMM Tablet Against Retinal Injury Based on Drug Attack Model to Network Robustness.

Retinal degenerative diseases are related to retinal injury because of the activation of the complement cascade, oxidative stress-induced cell death mechanisms, dysfunctional mitochondria, chronic neuroinflammation, and production of the vascular endothelial growth factor. Anti-VEGF therapy demonstrates remarkable clinical effects and benefits in retinal degenerative disease patients. Hence, new drug development is necessary to treat patients with severe visual loss. He xue ming mu (HXMM) tablet is a CFDA-approved traditional Chinese medicine (TCM) for retinal degenerative diseases, which can alleviate the symptoms of age-related macular degeneration (AMD) and diabetic retinopathy (DR) alone or in combination with anti-VEGF agents. To elucidate the mechanisms of HXMM, a quantitative evaluation algorithm for the prediction of the effect of multi-target drugs on the disturbance of the disease network has been used for exploring the specific pathology of HXMM and TCM precision positioning. Compared with anti-VEGF agents, the drug disturbance of HXMM on the functional subnetwork shows that HXMM reduces the network robustness on the oxidative stress subnetwork and inflammatory subnetwork to exhibit the anti-oxidation and anti-inflammation activity. HXMM provides better protection to ARPE-19 cells against retinal injury after H2O2 treatment. HXMM can elevate GSH and reduce LDH levels to exhibit antioxidant activity and suppress the expression of IL-6 and TNF-α for anti-inflammatory activity, which is different from the anti-VEGF agent with strong anti-VEGF activity. The experimental result confirmed the accuracy of the computational prediction. The combination of bioinformatics prediction based on the drug attack on network robustness and experimental validation provides a new strategy for precision application of TCM.

Implications of Oxidative Stress in the Pathogenesis and Treatment of Hyperpigmentation Disorders.

Oxidative stress represents an imbalance between the generation of reactive oxygen and nitrogen species and the ability of antioxidant systems to decompose those products. Oxidative stress is implicated in the pathogenesis of hyperpigmentation, hypopigmentation, melanoma, and other skin diseases. Regulatory networks involving oxidative stress and related pathways are widely represented in hypopigmentation diseases, particularly vitiligo. However, there is no complete review into the role of oxidative stress in the pathogenesis of hyperpigmentation disorders, especially regarding associations involving oxidative stress and cellular signaling pathways. Here, we review oxidative and antioxidant systems, oxidative stress-induced signal transduction mechanisms, and effects of antioxidant drugs used in preclinical and clinical settings in hyperpigmentation disorders.