Reactivation Mechanisms Research Articles

Exploring frictional properties of upper plate fault reactivation in subduction zones: The Atacama Fault System in northern Chile

The Maule 2010 and Tohoku-Oki 2011 earthquakes demonstrated how dormant upper plate faults can be reactivated as normal faults by plate margin relaxation following megathrust slip. However, the reactivation mechanisms of these types of faults are yet unexplored. To provide a better understanding of these mechanisms, we collected fault core samples from fault segments of the Atacama Fault System in northern Chile. The sampled fault segments have clear morphological evidence of Quaternary reactivation as normal fault. We performed laboratory experiments to measure the fault strength, stability and dynamic weakening. We consider low-velocity tests for exploring the frictional strength and velocity dependence of friction via a double-direct shear apparatus and ii) high-velocity tests for investigating the frictional properties at seismic velocities via a rotary shear apparatus. The experiments revealed that fault cores have low frictional strength, velocity-strengthening behaviour and strong dynamic weakening. Additionally, a novel experimental procedure that simulates stress relaxation by stepwise reducing of the normal stress on the sample assembly showed: 1. Accelerating creep towards dynamic weakening in chlorite-rich gouges and 2. oscillatory sliding in fault gouges enriched in illite. By extrapolating our experimental observations to natural conditions, we conclude that stable sliding is favoured during the interseismic phase of the subduction earthquake cycle, whereas unstable sliding is favoured during the coseismic and postseismic phases. The latter occurs via normal stress reduction during the shift from interseismic compression to co- and postseismic tension at the plate margin.

Frictional Strength and Frictional Instability of Glaucophane Gouges at Blueschist Temperatures Support Diverse Modes of Fault Slip From Slow Slip Events to Moderate‐Sized Earthquakes

AbstractFluid overpressure from the water released by subducted sediments and oceanic crust is an important mechanism for generating earthquakes via brittle failure and frictional instability. If unstable, such fault materials may also host diverse fault reactivation mechanisms from slow slip events to moderate‐sized earthquakes in cold subduction zones. We examine this hypothesis for glaucophane gouge ‐ a key index minerals for blueschist facies ‐ at lower confining stresses where behavior is poorly understood. We measure friction and stability at temperatures of 100°C–500°C and effective normal stresses of 50–200 MPa, to explore the controls of temperature, stresses and excess pore fluid pressures on fault friction. The frictional coefficient of glaucophane at representative temperatures and stresses is ∼0.70, insensitive to temperature but with a slight increase at lower effective stresses. Elevating temperature promotes a transition from velocity‐strengthening to weak velocity‐weakening behavior, indicating the destabilizing effect of high temperature downdip in subduction zones. Reducing effective normal stress or concomitantly elevating pore fluid pressure further strengthens the velocity‐weakening response and would be manifest as moderate‐sized earthquakes. Our results support the potential for enhanced unstable sliding of glaucophane gouges at lower effective stresses and blueschist facies temperatures ‐ with weak to moderate velocity‐weakening responses upon fluid pressurization vital for understanding the abundance of slow slip to moderate‐sized earthquakes apparent in cold subduction zones.

Study on the chain-type failure mechanism of large-scale ancient landslides

Large-scale ancient landslides are widely distributed in Southwest China, yet their reactivation mechanisms remain complex and poorly understood. On 25 July 2020, one such landslide in Liujing Village, Wulong District, Chongqing, China, experienced reactivation. This event exhibited variable movement characteristics across different areas and times, ultimately manifesting as a chain-type failure. Combining field investigations and drilling works, this study describes the fundamental characteristics of the Zhongbao landslide and the variation rules of the seepage field and the stability by numerical simulations. The failure mechanism is preliminarily revealed, and the failure influencing factors are discussed. The results show that, the landslide’s progression was influenced by the stratigraphic lithology and the morphology of the sliding surface, resulting in two distinct turns during its movement. By analyzing the landslide’s spatial morphology, direction of sliding, material composition, extent of the accumulation area, and dynamic behavior, we have categorized the Zhongbao landslide into five principal zones. The failure process can be segmented into four stages: initiation, shear-out, acceleration, and accumulation blockage. Heavy rainfall served as the primary trigger for the landslide, while the microtopography of the sliding surface significantly influenced the failure dynamics. The insights gained from this study offer valuable guidance for understanding the reactivation mechanisms of similar chained ancient landslides in the geologically analogous regions of Southwest China.

A Numerical Study of Fault Reactivation Mechanisms in CO2 Storage.

Due to extensive industrialization and ongoing fossil fuel consumption, CO2 emissions have significantly contributed to climate change and rising greenhouse gas levels. The collection and storage of CO2 in subsurface geological formations have been proposed as a feasible alternative. The well-documented In Salah storage site is the subject of the chosen case study. For the numerical analysis, a two-dimensional finite element simulation of fault reactivation processes was conducted in the context of the CO2 storage. The goal of this research is to conduct a mechanistic numerical analysis of a typical CO2 storage condition. The selected analysis domain is 4 km (width) × 2 km (depth) and includes all important domains and formations (overburden, main caprock, lower caprock, and underburden) of the In Salah site. The simulation results indicate that the influence of fault reactivation under 32 MPa of base injection pressure results in peak vertical deformation of 0.044 m in the caprock and a vertical displacement magnitude of 0.015-0.020 m at the surface level (Z = 0 m). The derived vertical deformation findings at the surface level are in agreement with the data obtained from the in situ InSAR monitoring system in 2009. The effects of the changes in the fault dip angle, key caprock mechanical parameters, and in situ stress ratio on the displacement profile are evaluated within the parametric study. In comparison to the benchmark numerical run, the scenario ratio of k = 0.5 led to a significant reduction in the displacement. The simulation in which the fault dip angle was 30° produced a more pessimistic result with a larger displacement field. This could be an indication of heightened fault reactivation risks associated with low-angle faults in storage sites with strong horizontal stress regimes due to the combined effect of increased shear stress and reduced inherent frictional resistance on the fault plane. Considering that a vertical fault dip angle (90°) and an additional three 20 m long vertical fractures above the reservoir produced similar vertical displacement observed with the fault dipping at a 60° angle, this indicated that the vertical faults in the vicinity of the storage site pose limited safety risks to the integrity of the sealing rock.

Advances in 2,3-Dimethylmaleic Anhydride (DMMA)-Modified Nanocarriers in Drug Delivery Systems.

Cancer represents a significant threat to human health. The cells and tissues within the microenvironment of solid tumors exhibit complex and abnormal properties in comparison to healthy tissues. The efficacy of nanomedicines is inhibited by the presence of substantial and complex physical barriers in the tumor tissue. The latest generation of intelligent drug delivery systems, particularly nanomedicines capable of charge reversal, have shown promise in addressing this issue. These systems can transform their charge from negative to positive upon reaching the tumor site, thereby enhancing tumor penetration via transcytosis and promoting cell internalization by interacting with the negatively charged cell membranes. The modification of nanocarriers with 2,3-dimethylmaleic anhydride (DMMA) and its derivatives, which are responsive to weak acid stimulation, represents a significant advance in the field of charge-reversal nanomedicines. This review provides a comprehensive examination of the recent insights into DMMA-modified nanocarriers in drug delivery systems, with a particular focus on their potential in targeted therapeutics. It also discusses the synthesis of DMMA derivatives and their role in charge reversal, shell detachment, size shift, and ligand reactivation mechanisms, offering the prospect of a tailored, next-generation therapeutic approach to overcome the diverse challenges associated with cancer therapy.

Origin of deactivation of aqueous Na–CO2 battery and mitigation for long-duration energy storage

The development of long-duration energy storage technology is crucial to facilitate the efficient utilization of renewable energy sources while mitigating carbon dioxide production. In this study, we investigate the deactivation and reactivation mechanisms of the aqueous Na–CO2 battery during extended cycling. We have designed the cathode to include non-precious intermetallic catalysts. As the cell undergoes repeated cycles, the voltage polarization during discharge progressively rises, eventually leading to the cell's deactivation and formation of decomposition products clogging the electrode surface. Results obtained from comprehensive characterization techniques, including conductive atomic force microscopy (cAFM), Raman spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and inductively coupled plasma-mass spectrometry provide insight into the decomposition products. We also showcase an electrochemical approach for regeneration of these aqueous cells. Our findings, along with the insights we have gained, provide a path toward creating long-duration systems with self-healing properties.

Development Characteristics and Reactivation Mechanism of a Large-Scale Ancient Landslide in Reservoir Area

The intricate geological conditions of reservoir banks render them highly susceptible to destabilization and damage from fluctuations in water levels. The study area, the Cheyipin section of the Huangdeng Hydroelectric Station, is characterized by numerous ancient landslides of varying scales and ages. In June 2019, during the reservoir filling process of the Huangdeng Hydroelectric Station, a large-scale reactivation of ancient landslides occurred in this area, posing severe threats to riverside infrastructure and human safety, including ground cracking, house cracking, foundation settlement, and road collapse. The reactivation mechanism of ancient landslides at reservoir banks is highly complex due to fluid dynamics. This study conducted field investigations in the Cheyipin landslide area, monitored surface and subsurface deformations using GNSS and inclinometers, and analyzed the distribution characteristics, destruction features, and reactivation mechanisms of the landslides through correlation analysis and numerical calculations. The results indicate that the instability pattern of the slopes manifests as traction-type sliding failure. The slopes do not slide along the ancient sliding surface but along a newly formed arcuate sliding surface, with the direct impact area mainly concentrated near the waterline. The stability of the slopes in this project is closely related to the reservoir water level. It can be assumed that the lowering of the reservoir water level triggered the reactivation of the ancient landslides in the Cheyipin section, while the influence of rainfall can be ignored. To prevent the reactivation of ancient landslides, attention should be focused on the changes in reservoir water level, avoiding rapid adjustments in water level during the initial lowering and final raising of the water level.

A macrophage-cell model of HIV latency reveals the unusual importance of the bromodomain axis

BackgroundAlthough macrophages are now recognized as an essential part of the HIV latent reservoir, whether and how viral latency is established and reactivated in these cell types is poorly understood. To understand the fundamental mechanisms of viral latency in macrophages, there is an urgent need to develop latency models amenable to genetic manipulations and screening for appropriate latency-reversing agents (LRAs). Given that differentiated THP-1 cells resemble monocyte-derived macrophages in HIV replication mechanisms, we set out to establish a macrophage cell model for HIV latency using THP-1 cells.MethodsWe created single-cell clones of THP-1 cells infected with a single copy of the dual-labeled HIVGKO in which a codon switched eGFP (csGFP) is under the control of the HIV-1 5’ LTR promoter, and a monomeric Kusabira orange 2 (mKO2) under the control of cellular elongation factor one alpha promoter (EF1α). Latently infected cells are csGFP−, mKO2+, while cells with actively replicating HIV (or reactivated virus) are csGFP+,mKO2+. After sorting for latently infected cells, each of the THP-1 clones with unique integration sites for HIV was differentiated into macrophage-like cells with phorbol 12-myristate 13-acetate (PMA) and treated with established LRAs to stimulate HIV reactivation. Monocyte-derived macrophages (MDMs) harboring single copies of HIVGKO were used to confirm our findings.ResultsWe obtained clones of THP-1 cells with latently infected HIV with unique integration sites. When the differentiated THP-1 or primary MDMs cells were treated with various LRAs, the bromodomain inhibitors JQ1 and I-BET151 were the most potent compounds. Knockdown of BRD4, the target of JQ1, resulted in increased reactivation, thus confirming the pharmacological effect. The DYRK1A inhibitor Harmine and lipopolysaccharide (LPS) also showed significant reactivation across all three MDM donors. Remarkably, LRAs like PMA/ionomycin, bryostatin-1, and histone deacetylase inhibitors known to potently reactivate latent HIV in CD4 + T cells showed little activity in macrophages.ConclusionsOur results indicate that this model could be used to screen for appropriate LRAs for macrophages and show that HIV latency and reactivation mechanisms in macrophages may be distinct from those of CD4 + T cells.

Abstract 1927: Resistance to RAS-GTP inhibition in models of pancreatic ductal adenocarcinoma arises downstream of RAS effectors

Abstract More than 90% of pancreatic ductal adenocarcinoma (PDAC) cases are driven by activating mutations in KRAS that drive it into an active, GTP-bound state (KRAS(ON)), producing excessive signaling via MAPK and other effector pathways. RMC-7977 is a potent inhibitor of GTP-bound RAS proteins (RAS(ON)), including both wild type and mutant variants of KRAS, NRAS, and HRAS. The related investigational agent, RMC-6236, is a first-in-class, potent, orally bioavailable, RASMULTI(ON) inhibitor currently in Phase 1/1b clinical trials (NCT05379985). Exposure to RMC-7977 suppressed the MAPK biomarker p-ERK, reduced cell growth, and induced apoptosis in multiple human RAS-addicted cancer cell lines. Assessment of RMC-7977 in a series of PDAC preclinical model systems revealed broad anti-tumor activity and treatment was well tolerated at translatable doses. The K-rasLSL.G12D/+, p53LSL.R172H/+, Pdx1Cretg/+ (KPC) autochthonous mouse model was utilized to study the effects of Ras-GTP inhibition in both tumor and normal tissues. At doses that drove anti-tumor activity, RMC-7977 dosing produced a metronomic effect on RAS signaling in tumor and normal tissue, with full pathway inhibition at 4 h post treatment that was restored by 24 h. This pattern yielded tumor-selective effects on apoptosis and proliferation, consistent with RAS oncogene addition in PDAC. RMC-7977 treatment drove regressions and an unprecedented ~3-fold extension of overall survival in KPC mice. After an initial response, all tumors eventually developed resistance on treatment, affording the opportunity to study acquired resistance mechanisms to RAS-GTP inhibition. Strikingly, in all resistant tumors, acute inhibition of MAPK and PI3K signaling was still apparent following treatment. These results indicate that RAS signaling re-activation mechanisms that have been reported as clinical mechanisms of resistance to mutant-selective KRASG12C inhibitors (e.g. second-site mutations or upregulation of upstream RTK) may be insufficient to confer resistance to a compound that inhibits all RAS isoforms. Rather, in this model we observed activation of alternative oncogenic mechanisms downstream of RAS effector signaling, including frequent focal amplification of Myc, focal amplification of Jun, and/or activation of Yap/Taz/Tead signaling in most resistant KPC tumors. Together these results demonstrate preclinical activity of RMC-7977 at tolerable doses, producing unprecedented responses even in highly chemoresistant PDAC models such as the KPC mouse. The observed range of potential resistance mechanisms suggests that RAS-GTP inhibition imposes a narrow evolutionary path to the development of acquired resistance in this context. These preclinical findings may help inform the ongoing development of investigational RAS inhibitors and the design of potential combinatorial treatment strategies to forestall resistance. Citation Format: Urszula N. Wasko, Jingjing Jiang, Yingyun Wang, Lorenzo Tomassoni, Lingyan Jiang, Marie Menard, Alvaro Curiel-Garcia, Tanner C. Dalton, Margo Orlen, Cole Edwards, Clint Stalnecker, Julien Dilly, Stephanie Chang, Stephen A. Sastra, Carmine F. Palermo, Timour Baslan, Sha Tian, Matthew Holderfield, Elsa Quintana, Zhengping Wang, Jacqueline A. Smith, Andrea Califano, David Wildes, Andrew J. Aguirre, Robert H. Vonderheide, Ben Z. Stanger, Scott W. Lowe, Channing J. Der, Mallika Singh, Kenneth P. Olive. Resistance to RAS-GTP inhibition in models of pancreatic ductal adenocarcinoma arises downstream of RAS effectors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1927.

Evolution Process of Ancient Landslide Reactivation under the Action of Rainfall: Insights from Model Tests

Under rapid global climate change, the risk of ancient landslide reactivation induced by rainfall infiltration is increasing significantly. The contribution of cracks to the reactivation of ancient landslides, as an evolutionary product, is a topic that deserves attention; however, current research on this issue remains insufficient. In this study, taking the Woda landslide in the upper Jinsha River as a case study, we investigated the reactivation mechanisms of ancient landslides with and without cracks under rainfall based on model tests. The study showed that cracks influence the reactivation range and depth of ancient landslide. In cases where no cracks develop on ancient landslides, rainfall can only cause shallow sliding with failure concentrated at its front edge. Conversely, when cracks develop on ancient landslides, rainwater can quickly infiltrate into the sliding zone along the cracks and induce overall reactivation of the ancient landslide. Furthermore, the reactivation mechanism of ancient landslides without cracks is that the failure of ancient landslide foot results in progressive failure at the front of the ancient landslide. When cracks have developed at ancient landslides, the reactivation mechanism of which involves mid-rear ancient landslide creeping, tensile cracks develop on the mid-rear ancient landslide, with localized sliding at the front edge, tensile cracks extending, local sliding range extending, accelerated creeping, and progressive failure of the mid-rear ancient landslide. These findings shed light on how cracks influence rainfall-induced mechanisms of ancient landslide reactivation and hold great significance for advancing our understanding regarding these mechanisms.

Precursory Signals to Injection Induced Fault Reactivation in the Laboratory Using Active Ultrasonic Monitoring Methods

AbstractInduced earthquakes are still highly unpredictable, and often caused by variations in pore fluid pressure. Monitoring and understanding the mechanisms of fluid‐induced fault slip is essential for seismic risk mitigation and seismicity forecasting. Fluid‐induced slip experiments were performed on critically stressed faulted sandstone samples, and the evolution of the actively sent ultrasonic waves throughout the experiment was measured. Two different fault types were used: smooth saw‐cut fault samples at a 35° angle, and a rough fault created by in situ faulting of the samples. Variations in the seismic slip velocity and friction along the fault plane were identified by the coda of the ultrasonic waves. Additionally, ultrasonic amplitudes show precursory signals to laboratory fault reactivation. Our results show that small and local variations in stress before fault failure can be inferred using coda wave interferometry for time‐lapse monitoring, as coda waves are more sensitive to small perturbations in a medium than direct waves. Hence, these signals can be used as precursors to laboratory fault slip and to give insight into reactivation mechanisms. Our results show that time‐lapse monitoring of coda waves can be used to monitor local stress changes associated with fault reactivation in this laboratory setting of fluid‐induced fault reactivation. This is a critical first step toward a method for continuous monitoring of natural fault zones, contributing to seismic risk mitigation of induced and natural earthquakes.

Deformation Behavior and Reactivation Mechanism of the Dandu Ancient Landslide Triggered by Seasonal Rainfall: A Case Study from the East Tibetan Plateau, China

In recent years, numerous ancient landslides initially triggered by historic earthquakes on the eastern Tibetan Plateau have been reactivated by fault activity and heavy rainfall, causing severe human and economic losses. Previous studies have indicated that short-term heavy rainfall plays a crucial role in the reactivation of ancient landslides. However, the deformation behavior and reactivation mechanisms of seasonal rainfall-induced ancient landslides remain poorly understood. In this paper, taking the Dandu ancient landslide as an example, field investigations, ring shear experiments, and interferometric synthetic aperture radar (InSAR) deformation monitoring were performed. The cracks in the landslide, formed by fault creeping and seismic activity, provide pathways for rainwater infiltration, ultimately reducing the shear resistance of the slip zone and causing reactivation and deformation of the Dandu landslide. The deformation behavior of landslides is very responsive to seasonal rainfall, with sliding movements beginning to accelerate sharply during the rainy season and decelerating during the dry season. However, this response generally lags by several weeks, indicating that rainfall takes time to infiltrate into the slip zone. These research results could help us better understand the reactivation mechanism of ancient landslides triggered by seasonal rainfall. Furthermore, these findings explain why many slope failures take place in the dry season, which typically occurs approximately a month after the rainy season, rather than in the rainy season itself.

Severe acute respiratory syndrome coronavirus-2 Alpha variant (B.1.1.7), original wild-type severe acute respiratory syndrome coronavirus 2, and cytomegalovirus co-infection in a young adult with acute lymphoblastic leukemia, case report, and review of the possible cytomegalovirus reactivation mechanisms

BackgroundLike other viral infections, severe acute respiratory syndrome coronavirus-2 infection could affect different human body systems, including host immune responses. Three years after its pandemic, we learn more about this novel coronavirus. As we expected, different co-infections with various organisms, such as viruses, bacteria, and even fungi, have been reported. However, concurrent infection with two severe acute respiratory syndrome coronavirus-2 strains and cytomegalovirus is extremely unusual. We have only a rudimentary understanding of such co-infections and their long-term consequences for patients with cancer.Case presentationAn 18-year-old young Iranian adult with acute lymphoblastic leukemia presented with abdominal pain, diarrhea, nausea, and vomiting following a recent history of severe acute respiratory syndrome coronavirus-2 infection. The patient never experienced respiratory symptoms, and the chest imaging study was normal on admission. His primary laboratory investigation revealed prerenal azotemia and severe abnormal liver function tests (blood urea nitrogen 32 mg/dL, creatinine 1.75 mg/dL, prothrombin time 66 s, partial thromboplastin time 44.5 s, international normalized ratio 5.14, total bilirubin 2.9 mg/dL, and direct bilirubin 2.59 mg/dL). Cytomegalovirus disease was diagnosed by polymerase chain reaction in his blood and stool samples. The patient’s gastrointestinal signs and symptoms improved shortly after receiving intravenous ganciclovir treatment. His gastrointestinal symptoms continued intermittently for weeks despite maintenance valganciclovir prescription, necessitating frequent hospitalizations. The patient was complicated by the recurrence of gastrointestinal symptoms during the sixth hospitalization, even though he had no respiratory symptoms, and the nasopharyngeal test revealed severe acute respiratory syndrome coronavirus-2 Wuhan strain for the first time. Remdesivir and valganciclovir were administrated due to persistent enteritis and evidence of intestinal tissue invasion by severe acute respiratory syndrome coronavirus 2 and cytomegalovirus on multiple intestinal biopsies, which led to partial clinical responses. Cytomegalovirus and severe acute respiratory syndrome coronavirus-2 fecal shedding continued for more than 6 months despite repeated antiviral therapy, and the Wuhan and Alpha strains were also detected in his nasopharyngeal samples through repeated sampling (confirmed by four nasopharyngeal sampling and multiple stool specimens and several intestinal biopsies). Finally, during the Delta-variant (B.1.617.2) outbreak in Iran, the patient was admitted again with febrile neutropenia and decreased level of consciousness, necessitating respiratory support and mechanical ventilation. During the Delta-variant peak, the patient’s nasopharyngeal sample once more tested positive for severe acute respiratory syndrome coronavirus 2. The patient died a few days later from cardiopulmonary arrest.ConclusionThe coronavirus disease 2019 pandemic has encountered patients with cancer with critical diagnostic and treatment challenges. Patients who are immunocompromised may co-infect with multiple severe acute respiratory syndrome coronavirus-2 strains and cytomegalovirus, and even with timely diagnosis and treatment, the prognosis may be poor.

Novel uncharged triazole salicylaldoxime derivatives as potential acetylcholinesterase reactivators: comprehensive computational study, synthesis and in vitro evaluation.

The present study aims to design and synthesise novel uncharged aldoximes and explore their reactivation abilities, structures, descriptors, and mechanisms of action, as well as assessing the interactions and stabilities in the active site of paraoxon-inhibited acetylcholinesterase enzyme using computational studies and in vitro assay. The comprehensive computational studies including quantum chemical, molecular dynamics simulations and molecular docking were conducted on paraoxon-inhibited human acetylcholinesterase to investigate the reactivation ability of the novel aldoximes and compare them with pralidoxime as a reactivator model molecule.

G protein coupled pattern recognition receptors expressed in neutrophils: Recognition, activation/modulation, signaling and receptor regulated functions.

Neutrophils, the most abundant white blood cell in human blood, express receptors that recognize damage/microbial associated pattern molecules of importance for cell recruitment to sites of inflammation. Many of these receptors belong to the family of G protein coupled receptors (GPCRs). These receptor-proteins span the plasma membrane in expressing cells seven times and the down-stream signaling rely in most cases on an activation of heterotrimeric G proteins. The GPCRs expressed in neutrophils recognize a number of structurally diverse ligands (activating agonists, allosteric modulators, and inhibiting antagonists) and share significant sequence homologies. Studies of receptor structure and function have during the last 40 years generated important information on GPCR biology in general; this knowledge aids in the overall understanding of general pharmacological principles, governing regulation of neutrophil function and inflammatory processes, including novel leukocyte receptor activities related to ligand recognition, biased/functional selective signaling, allosteric modulation, desensitization, and reactivation mechanisms as well as communication (receptor transactivation/cross-talk) between GPCRs. This review summarizes the recent discoveries and pharmacological hallmarks with focus on some of the neutrophil expressed pattern recognition GPCRs. In addition, unmet challenges, including recognition by the receptors of diverse ligands and how biased signaling mediate different biological effects are described/discussed.

ТРОМБОЗ ВОРОТНОЙ ВЕНЫ КАК ОСЛОЖНЕНИЕ COVID-19 У ПАЦИЕНТА С ЭПШТЕЙНА-БАРР/ЦИТОМЕГАЛОВИРУСНОЙ-ИНФЕКЦИЕЙ

Portal vein thrombosis is a partial or complete occlusion of blood flow through the portal vein, resulting from the presence of a thrombus in its lumen. The etiology of portal vein thrombosis is often multifactorial, a combination of local and systemic factors being possible. It is necessary to conduct a wide diagnostic search in order to identify the causes of thrombosis, including liver diseases, malignant neoplasms, infectious diseases, etc. The clinical picture of portal vein thrombosis can vary from low-symptomatic manifestations to an acute course. Chronic portal vein thrombosis can also manifest with nonspecific symptoms. It is known that COVID-19 is associated with increased blood clotting and the development of thromboembolic complications. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is considered as a trigger factor for the reactivation mechanisms of other viral infections in the patient's body, in particular the herpes group. This article presents a clinical case of COVID-19, complicated by portal vein thrombosis in a patient with EBV/CMV infection.

Formation and reactivation mechanisms of large-scale ancient landslides in the Longwu River basin in the northeast Tibetan Plateau, China

Formation and reactivation mechanisms of large-scale ancient landslides in the Longwu River basin in the northeast Tibetan Plateau, China

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.

Thermal annealing ambiance effect on phosphorus passivation and reactivation mechanisms in silicon-based Schottky diodes hydrogenated by MW-ECR plasma

The main objective of this work is to investigate the effect of thermal annealing in forming gas atmosphere on the mechanism of deactivation and reactivation of phosphorus in silicon-based Schottky diodes. Firstly, the microwave plasma power, initial phosphorus concentration in the samples and hydrogen flux were fixed as 650 W, 1015 cm–3, and 30 sccm, respectively, to investigate the behavior of different working parameters of diodes, specifically the duration and temperature of hydrogenation. Secondly, few samples hydrogenated at 400 °C for 1 h were annealed under the forming gas (10% H2 + 90% N2) within the temperature range from 100 to 700 °C for 1 h. The profiles of active phosphorus concentration were monitored by evaluating the change in concentration of phosphorus after hydrogenation or thermal annealing in a forming gas environment through capacitance-voltage measurements. The obtained results depict the temperature and duration of hydrogenation, which ultimately reveals the complex behavior of phosphorous and hydrogen in silicon. However, the phosphorus passivation rate is homogeneous over all the depths measured at 400 °C. The thermal annealing in a forming gas indicates the increase in passivation rate of phosphorus as a function of annealing temperature, till the passivation rate attains saturation in the sample annealed at 400 °C. At higher temperatures, a decrease in the concentration of phosphorous-hydrogen complexes is observed due to the dissociation of these complexes and reactivation of phosphorus under thermal effect.

Presence and clinical impact of human herpesvirus-6 infection in patients with moderate to critical coronavirus disease-19.

Human herpesvirus‐6 (HHV‐6) may cause serious diseases in immunocompromised individuals. SARS‐CoV‐2/HHV‐6 coinfection has been emphasized in previous works, mostly case reports, small series, or epidemiological studies, but few are known about its real clinical outcomes. Here we present a real‐world pilot study aiming to understand the frequency and the clinical impact of HHV‐6 coinfection in moderate to critically ill patients hospitalized due to COVID‐19. SARS‐CoV‐2 and HHV‐6 were evaluated in nasopharyngeal samples at the hospital admission of suspected COVID‐19 patients. From 173 consecutive cases, 60 were SARS‐CoV‐2 positive and 13/60 (21.7%) were HHV‐6 positive after identified as the HHV‐6B species by a Sanger sequencing. The SARS‐CoV‐2+/HHV‐6+ group was younger but not significant for cardiovascular diseases, diabetes, obesity, and cancer, but significant among therapeutic immunosuppressed patients (as systemic lupus erythematosus and kidney transplant patients). In the medical records, only sparse data on cutaneous or neurological manifestations were found. Biochemical and hematological data showed only a trend towards hyperferritinemic status and lymphopenia. In conclusion, despite the impressive high frequency of HHV‐6 coinfection in SARS‐CoV‐2 positive cases, it did not impact general mortality. We suggest larger future prospective studies to better elucidate the influence of HHV‐6 reactivation in cases of COVID‐19, designed to specific assessment of clinical outcomes and viral reactivation mechanisms.