Stress Migration Research Articles

Sourcing of the Oligocene to Pliocene sediments of the Ningnan Basin: Evidence for Tibetan Plateau growth and local faulting unravelled by detrital apatite fission‐track and U–Pb double dating

AbstractThe Cenozoic topographic growth of the Tibetan Plateau is a pulsed, polyphase process that still requires more constraints. The Cenozoic sedimentary record of the Ningnan Basin, a continental basin located adjacent to the northeastern margin of the Tibetan Plateau, is a key archive for recording the surface evolution of the Tibetan Plateau. This work reports new provenance data (apatite fission‐track, apatite U–Pb dating, and trace element analysis on the same individual grains) from the Oligocene–Pliocene sedimentary sequence that filled the Ningnan Basin. The data set shows variations in provenance patterns through the Miocene which are related to the tectonic evolution of the northeastern margin of the Tibetan Plateau. In contrast to a primary provenance from the Western Ordos Block (WOB) during the Oligocene, the Miocene sediments were mostly derived from the recycling of Mesozoic successions that occur along the northwestern Haiyuan Fault, documenting it was active in the last ca. 15 Myr. These sediments, in turn, were derived from different orogenic blocks but mainly from different segments of the Qilian Mountains. We show that the Late Miocene–Pliocene sediments were primarily derived from transpressional uplift along the Haiyuan Fault, which affected regions such as the Liupan Mountains. Progressive northeastward migration of tectonic stress since the Middle Miocene has induced extensive regional deformation in the northeastern Tibetan Plateau, particularly along the Haiyuan Fault. The provenance record of the neighbouring Cenozoic basins is a key archive for deciphering this tectonic evolution.

Predictive model for the instability of flexible formwork concrete wall in secondary mining of non-pillar coal mining

The secondary mining movement in non-pillar coal extraction causes significant overrun damage to flexible formwork concrete walls, leading to extensive deformation of roadway roof and bottom plates. This adversely affects working face efficiency and safety. The engineering context focuses on the non-pillar gob-side retaining walls in the 1315 working face of Zhaozhuang Coal Mine and the 23107 working face of Xiegou Coal Mine. Through on-site investigation, numerical simulation, theoretical analysis, and testing, we explore the stress migration law and destabilizing mechanism of the flexible formwork concrete wall influenced by the secondary mining movement of the coal-free pillar along the hollow wall. The research results showed that: (1) During the mining back process, the concrete wall formed with flexible formwork may experience stress concentration, leading to excessive damage and compromising mining safety. (2) Developing a predictive stress model for the concrete wall with flexible formwork is essential. If the stress surpasses the ultimate compressive strength during mining back, reinforcement becomes necessary.3) The length of damage overrun in the flexible formwork concrete wall exhibits two distinct stages as the distance back to mining increases. The first stage shows nearly linear growth, while the second stage indicates a decreasing growth rate, ultimately stabilizing. The application of Z6 concrete reinforcing agent effectively strengthens the flexible formwork concrete wall.

Dynamic stress characterization and instability risk identification using multisource acoustic signals in cut-and-fill stopes

The quantitative characterization of rock mass and stress changes induced by mining activities is crucial for structural stability monitoring and disaster early warning. This paper investigates the time–space–intensity distribution of microseismic sources during the pillar-free large-area continuous extraction. Furthermore, it explores a method involving collaborative evolution patterns of the velocity field and spatial b-value to identify stress and structural changes at the panel stope. Results show that anomalous zones in wave velocities and b-values form at the intersections of extraction drifts, strike drifts, cross drifts, and connection roadways influenced by mining activities, as well as in footwall ore-rock contacts, often accompanied by the nucleation of microseismic events. The synergistic use of wave velocity fields and spatial b-value models reveals the relationship between stress migration behavior and stope structure changes due to mining disturbances. The velocity field primarily reflects macroscopic changes in the structure and stress distribution, while spatial b-values further explain stress gradients in specific areas. Additionally, we have advanced the identification of an instability disaster at the connection roadway and cross drift intersection based on increases in wave velocity and abnormal changes in b-value. This paper demonstrates the potential of risk identification using the proposed method, providing insights into predicting geotechnical engineering disasters in complex stress environments.

Phloridzin Docosahexaenoate, an Omega-3 Fatty Acid Ester of a Flavonoid Precursor, Inhibits Angiogenesis by Suppressing Endothelial Cell Proliferation, Migration, and Differentiation.

Angiogenesis is a normal physiological process that also contributes to diabetic retinopathy-related complications and facilitates tumor metastasis by promoting the hematogenic dissemination of malignant cells from solid tumors. Here, we investigated the in vitro, ex vivo, and in vivo anti-angiogenic activity of phloridzin docosahexaenoate (PZ-DHA), a novel ω-3 fatty acid ester of a flavonoid precursor. Human umbilical vein endothelial cells (HUVEC) and human dermal microvascular endothelial cells (HMVEC) treated with a sub-cytotoxic concentration of PZ-DHA to assess in vitro anti-angiogenic activity showed impaired tubule formation on a Matrigel matrix. Ex vivo angiogenesis was measured using rat thoracic aortas, which exhibited reduced vessel sprouting and tubule formation in the presence of PZ-DHA. Female BALB/c mice bearing VEGF165- and basic fibroblast growth factor-containing Matrigel plugs showed a significant reduction in blood vessel development following PZ-DHA treatment. PZ-DHA inhibited HUVEC and HMVEC proliferation, as well as the migration of HUVECs in gap closure and trans-well cell migration assays. PZ-DHA inhibited upstream and downstream components of the Akt pathway and vascular endothelial growth factor (VEGF165)-induced overexpression of small molecular Rho GTPases in HUVECs, suggesting a decrease in actin cytoskeletal-mediated stress fiber formation and migration. Taken together, these findings reveal the potential of combined food biomolecules in PZ-DHA to inhibit angiogenesis.

Epistemic Reciprocity Through a Decolonial Crip Literacy in Accommodated Language Education for Adults

Abstract This linguistic ethnography was conducted in accommodated language education in Sweden, aimed at adult learners with deafness, hearing impairment, post-traumatic stress disorder, migration stress, or intellectual disability, here, focusing on the latter group, who attended Swedish language learning courses. We empirically investigate a decolonial crip literacy, by connecting language education to epistemic reciprocity. The decolonial lens is understood with regard to the marginalized and dis-abled body, under-represented in Applied Linguistics. More specifically, we focus on teacher positionality and ethical stance-taking among three of the teachers, to contribute an in-depth and situated account of a decolonial crip literacy, as counteracts of ableism and linguicism, and an orientation toward epistemic justice. Based on our linguistic ethnographic data, we suggest that the decolonial crip literacy project engages with disability-as-difference, positioning the dis-abled body as knower, via epistemic reciprocity, which is communicated through a multiplicity of communicative resources, materialities, and creativity. The paper contributes both to the theorizing of injustice in language education and to alternatives in pedagogical practice.

War as A Socio-Cultural Phenomenon: A Criminological Perspective and Conceptualization with Empirical Study in Ukraine

This research delves into the sociocultural phenomenon of war, focusing on Russia's illegal invasion of Ukraine. It examines war through a criminological lens, aiming to understand its short and long-term effects on society. Through empirical analysis of Ukraine's management of the crisis, the study evaluates how the socio-cultural perspective influences war handling. Destructive consequences such as increased stress levels and migration, alongside constructive factors, are identified. The research highlights the criminogenic potential of war trauma and post-war syndrome. Despite various methods and hypotheses, socio-cultural effects persist, posing a complex challenge for Ukraine. War is portrayed as a multifaceted phenomenon influenced by demographic, economic, and ideological factors, as well as historical legacies. Ultimately, the conclusion underscores the irreparable impact of war on the environment, populations, and international relations. This suggests a pressing need for comprehensive efforts to mitigate the long-term consequences of war and foster stable post-conflict societies.

Metabolic Profiling, in vitro Cytotoxicity and in silico Investigation of Lycium shawii Roem. Extract

Background: Breast cancer is a prevalent global health concern. Traditional medicine often incorporates the use of medicinal plants to address various diseases. Methods: The cytotoxicity, oxidative stress and cell migration effects of saponin and phenol extracts were evaluated through MTT assay, ROS analysis and wound-healing assay. Following the identification of the active extract, it underwent GC-MS analysis and in silico investigations. Result: Our results revealed significant inhibition of cell proliferation in MDA-MB-231 (IC50:407.3 μg/mL) and HUVECs (IC50:500 μg/mL), which was achieved only with the ethyl acetate extract (Fraction 2). Fraction 2 extract induced notable morphological changes and significantly inhibited time-dependent migration in MDA-MB-231 cells. Additionally, it elevated cellular ROS levels compared to the control cells. In molecular docking analysis, out of the 51 chosen secondary metabolites from L. shawii, stigmast-5-en-3-ol, (3α,24S) (-10.0 kcal/mol) and lup-20(29)-ene-3,28-diol (-9.5 kcal/mol) were found to be the best docked to their respective targets-6CHZ and 4MAN, respectively. Therefore, this plant holds promise as a potential therapeutic agent for breast cancer treatment.

Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming.

JOURNAL/nrgr/04.03/01300535-202504000-00032/figure1/v/2024-07-06T104127Z/r/image-tiff Microglia, the primary immune cells within the brain, have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system, including Parkinson's disease. Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity, but also exhibit remarkable anti-inflammatory properties. However, the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood. In this study, we developed perfluoropentane-based oxygen-loaded nanodroplets (PFP-OLNDs) and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo, and suppressed microglial activation in a mouse model of Parkinson's disease. Microglial suppression led to a reduction in the inflammatory response, oxidative stress, and cell migration capacity in vitro. Consequently, the neurotoxic effects were mitigated, which alleviated neuronal degeneration. Additionally, ultrahigh-performance liquid chromatography-tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming. We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1α pathway. Collectively, our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

Mechanistic insights into the antitumoral potential and in vivo antiproliferative efficacy of a silver-based core@shell nanosystem

This study delves into the biomolecular mechanisms underlying the antitumoral efficacy of a hybrid nanosystem, comprised of a silver core@shell (Ag@MSNs) functionalized with transferrin (Tf). Employing a SILAC proteomics strategy, we identified over 150 de-regulated proteins following exposure to the nanosystem. These proteins play pivotal roles in diverse cellular processes, including mitochondrial fission, calcium homeostasis, endoplasmic reticulum (ER) stress, oxidative stress response, migration, invasion, protein synthesis, RNA maturation, chemoresistance, and cellular proliferation. Rigorous validation of key findings substantiates that the nanosystem elicits its antitumoral effects by activating mitochondrial fission, leading to disruptions in calcium homeostasis, as corroborated by RT-qPCR and flow cytometry analyses. Additionally, induction of ER stress was validated through western blotting of ER stress markers. The cytotoxic action of the nanosystem was further affirmed through the generation of cytosolic and mitochondrial reactive oxygen species (ROS). Finally, in vivo experiments using a chicken embryo model not only confirmed the antitumoral capacity of the nanosystem, but also demonstrated its efficacy in reducing cellular proliferation. These comprehensive findings endorse the potential of the designed Ag@MSNs-Tf nanosystem as a groundbreaking chemotherapeutic agent, shedding light on its multifaceted mechanisms and in vivo applicability.

Kinase PIM1 governs ferroptosis to reduce retinal microvascular endothelial cell dysfunction triggered by high glucose.

Previous studies have implicated targeting Pim-1 proto-oncogene, serine/threonine kinase (PIM1) as a preventive measure against high glucose-induced cellular stress and apoptosis. This study aimed to reveal the potential role and regulatory mechanism of PIM1 in diabetic retinopathy. Human retinal microvascular endothelial cells (hRMECs) underwent high glucose induction, and fluctuations in PIM1 levels were assessed. By overexpressing PIM1, its effects on the levels of inflammatory factors, oxidative stress indicators, migration and tube formation abilities, tight junction protein expression levels, and ferroptosis in hRMECs were identified. Afterwards, hRMECs were treated with the ferroptosis-inducing agent erastin, and the effect of erastin on the above PIM1 regulatory functions was focused on. PIM1 was downregulated upon high glucose, and its overexpression inhibited the inflammatory response, oxidative stress, cell migration, and tube formation potential in hRMECs, whereas elevated tight junction protein levels. Furthermore, PIM1 overexpression reduced intracellular iron ion levels, lipid peroxidation, and levels of proteins actively involved in ferroptosis. Erastin treatment reversed the impacts of PIM1 on hRMECs, suggesting the mediation of ferroptosis in PIM1 regulation. The current study has yielded critical insights into the role of PIM1 in ameliorating high glucose-induced hRMEC dysfunction through the inhibition of ferroptosis.

Grain boundaries-dominated migration failure of copper interconnect under multiphysics field: Insight from theoretical modeling and finite element analysis

As the feature size of Cu interconnects in microelectronic devices are miniaturized into micro- and even nano-scale, the effects of grain boundaries (GBs) on the electromigration (EM) failure become more and more obvious. It is of fundamentally importance to investigate the grain boundaries dominated failure mechanism and lifetime of Cu interconnects. In this work, the interconnection models containing different grain boundaries were constructed by using finite element simulations. The simulation results indicate that the current density at Cu grain boundaries is lower, but the current will be increased locally, when it is almost perpendicular to grain boundaries. However, the temperature is higher locally at grain boundaries. In the early stage of atomic diffusion, thermal migration and stress migration also occur near grain boundaries, resulting in significant atomic segregation near grain boundaries, particularly at the intersection of grain boundaries and near the inclined grain boundaries with small angles to the current direction. The atomic diffusion is considerably accelerated as the density of grain boundaries is increased, but is slowed down by poorly connected columnar grain boundaries.

Knockdown of Hyaluronan synthase 2 suppresses liver fibrosis in mice via induction of transcriptomic changes similar to 4MU treatment.

Hepatic fibrosis remains a significant clinical challenge due to ineffective treatments. 4-methylumbelliferone (4MU), a hyaluronic acid (HA) synthesis inhibitor, has proven safe in phase one clinical trials. In this study, we aimed to ameliorate liver fibrosis by inhibiting HA synthesis. We compared two groups of mice with CCl4-induced fibrosis, treated with 4-methylumbelliferone (4MU) and hyaluronan synthase 2 (HAS2) targeting siRNA (siHAS2). The administration of 4MU and siHAS2 significantly reduced collagen and HA deposition, as well as biochemical markers of hepatic damage induced by repeated CCl4 injections. The transcriptomic analysis revealed converging pathways associated with downstream HA signalling. 4MU- and siHAS2-treated fibrotic livers shared 405 upregulated and 628 downregulated genes. These genes were associated with xenobiotic and cholesterol metabolism, mitosis, endoplasmic reticulum stress, RNA processing, and myeloid cell migration. The functional annotation of differentially expressed genes (DEGs) in siHAS2-treated mice revealed attenuation of extracellular matrix-associated pathways. In comparison, in the 4MU-treated group, DEGs were related to lipid and bile metabolism pathways and cell cycle. These findings confirm that HAS2 is an important pharmacological target for suppressing hepatic fibrosis using siRNA.

HRD1 reduction promotes cholesterol-induced vascular smooth muscle cell phenotypic change via endoplasmic reticulum stress.

Phenotypic change of vascular smooth muscle cells (VSMCs) is the main contributor of vascular pathological remodeling in atherosclerosis. The endoplasmic reticulum (ER) is critical for maintaining VSMC function through elimination of misfolded proteins that impair VSMC cellular function. ER-associated degradation (ERAD) is an ER-mediated process that controls protein quality by clearing misfolded proteins. One of the critical regulators of ERAD is HRD1, which also plays a vital role in lipid metabolism. However, the function of HRD1 in VSMCs of atherosclerotic vessels remains poorly understood. The level of HRD1 expression was analyzed in aortic tissues of mice fed with a high-fat diet (HFD). The H&E and EVG (VERHOEFF'S VAN GIESON) staining were used to demonstrate pathological vascular changes. IF (immunofluorescence) and WB (western blot) were used to explore the signaling pathways in vivo and in vitro. The wound closure and transwell assays were also used to test the migration rate of VSMCs. CRISPR gene editing and transcriptomic analysis were applied in vitro to explore the cellular mechanism. Our data showed significant reduction of HRD1 in aortic tissues of mice under HFD feeding. VSMC phenotypic change and HRD1 downregulation were detected by cholesterol supplement. Transcriptomic and further analysis of HRD1-KO VSMCs showed that HRD1 deficiency induced the expression of genes related to ER stress response, proliferation and migration, but reduced the contractile-related genes in VSMCs. HRD1 deficiency also exacerbated the proliferation, migration and ROS production of VSMCs induced by cholesterol, which promoted the VSMC dedifferentiation. Our results showed that HRD1 played an essential role in the contractile homeostasis of VSMCs by negatively regulating ER stress response. Thus, HRD1 in VSMCs could serve as a potential therapeutic target in metabolic disorder-induced vascular remodeling.

Formoterol Exerts Anti-Cancer Effects Modulating Oxidative Stress and Epithelial-Mesenchymal Transition Processes in Cigarette Smoke Extract Exposed Lung Adenocarcinoma Cells.

Lung cancer frequently affects patients with Chronic Obstructive Pulmonary Disease (COPD). Cigarette smoke (CS) fosters cancer progression by increasing oxidative stress and by modulating epithelial-mesenchymal transition (EMT) processes in cancer cells. Formoterol (FO), a long-acting β2-agonist widely used for the treatment of COPD, exerts antioxidant activities. This study explored in a lung adenocarcinoma cell line (A549) whether FO counteracted the effects of cigarette smoke extract (CSE) relative to oxidative stress, inflammation, EMT processes, and cell migration and proliferation. A549 was stimulated with CSE and FO, ROS were evaluated by flow-cytometry and by nanostructured electrochemical sensor, EMT markers were evaluated by flow-cytometry and Real-Time PCR, IL-8 was evaluated by ELISA, cell migration was assessed by scratch and phalloidin test, and cell proliferation was assessed by clonogenic assay. CSE significantly increased the production of ROS, IL-8 release, cell migration and proliferation, and SNAIL1 expression but significantly decreased E-cadherin expression. FO reverted all these phenomena in CSE-stimulated A549 cells. The present study provides intriguing evidence that FO may exert anti-cancer effects by reverting oxidative stress, inflammation, and EMT markers induced by CS. These findings must be validated in future clinical studies to support FO as a valuable add-on treatment for lung cancer management.

Abstract 13116: Profiling the Role of Gut Microbiota-Derived Trimethylamine- N -Oxide in Cardiac Fibrosis — Evidence From a Primary Human in vitro Model

Introduction: The gut derived trimethylamine- N -oxide (TMAO) is correlated with increased atrial inflammation and fibrosis and associated with atrial fibrillation, heart failure, and stroke. However, the mechanisms mediating these links remain unresolved. Hypothesis: TMAO and its precursor metabolite L-carnitine (LCART) induce the transformation of atrial fibroblasts into pro-fibrotic phenotypes. Aim: To characterise the association between TMAO and cardiac fibrosis. Methods: Primary human cardiac (atrial) fibroblasts (hCFs) were sourced from healthy donors. hCFs were starved for 24 h and treated with PBS (control), 20 ng/mL transforming growth factor beta 1 (TGFβ1), 10 mM TMAO, or 1.0 mM LCART for 72 h (n=6 in each), then analysed by flow cytometry for α-smooth muscle actin (αSMA) expression. Unbiased proteomics was performed using LC-MS/MS to determine protein expression profile. Results: Analysis of αSMA expression revealed 3 hCF states: quiescent (Fbs), quiescent-to-myofibroblast (intermediate [Fbs-myoFbs]), and fully activated myofibroblast (myoFbs), (Fig-A). Compared to controls, there was no difference in the intermediate state after TGFβ1, TMAO, or LCART treatment (p=0.30). TMAO and LCART resulted in a significant induction of myofibroblast states compared to controls and TGFβ1 group. Unbiased proteomics identified 92, 65, and 43 proteins to be overexpressed and 84, 46, and 78 proteins downregulated following TGFβ1, TMAO, and LCART treatments (Fig-B). Both TGFβ1 and TMAO demonstrated shared enrichment for oxidative stress-regulated ferroptosis pathway (fold enrichment [FE] 31.8 and 22.2, p <.01 and 0.03); LCART showed enrichment for cell motility (FE 3.8, p=0.03). Conclusions: TMAO and its precursor L-carnitine are associated with activation of pro-fibrotic states, which may be due to oxidative stress and abnormal cell migration related mechanisms.

Fyn-Mediated Paxillin Tyrosine 31 Phosphorylation Regulates Migration and Invasion of Breast Cancer Cells.

Metastasis is the leading cause of death in breast cancer patients due to the lack of effective therapies. Elevated levels of paxillin expression have been observed in various cancer types, with tyrosine phosphorylation shown to play a critical role in driving cancer cell migration. However, the specific impact of the distinct tyrosine phosphorylation events of paxillin in the progression of breast cancer remains to be fully elucidated. Here, we found that paxillin overexpression in breast cancer tissue is associated with a patient's poor prognosis. Paxillin knockdown inhibited the migration and invasion of breast cancer cells. Furthermore, the phosphorylation of paxillin tyrosine residue 31 (Tyr31) was significantly increased upon the TGF-β1-induced migration and invasion of breast cancer cells. Inhibiting Fyn activity or silencing Fyn decreases paxillin Tyr31 phosphorylation. The wild-type and constitutively active Fyn directly phosphorylate paxillin Tyr31 in an in vitro system, indicating that Fyn directly phosphorylates paxillin Tyr31. Additionally, the non-phosphorylatable mutant of paxillin at Tyr31 reduces actin stress fiber formation, migration, and invasion of breast cancer cells. Taken together, our results provide direct evidence that Fyn-mediated paxillin Tyr31 phosphorylation is required for breast cancer migration and invasion, suggesting that targeting paxillin Tyr31 phosphorylation could be a potential therapeutic strategy for mitigating breast cancer metastasis.

Experimental investigation on stress distribution and migration of the overburden during the mining process in deep coal seam mining

Coal mining has a significant impact on the movement of the overburden, leading to potential safety hazards in the working face. In this paper, a similarity simulation experiment was conducted to investigate the migration of overburden during the mining process of a specific working face in the Liuzhuang Coal Mine located in southern China. Sand and gravel were used to simulate the geological environment of each rock stratum. The deformation of the stratum was monitored using strain gauges, the fracture and displacement changes of the overburden stratum were recorded using cameras, and the characteristics of roof collapse was monitored using infrared thermal imager. The experimental model fully simulated the situation of the working face, and the actual working face size was obtained by enlarging the model by 100 times. The experiment found that during the initial stage of mining, there was no significant subsidence of the roof. In the course of the advancement of the working face, the primary roof intermittently fractured behind the working face, with subsequent propagation of upper cracks in an upward direction. The overburden rock layer above the goaf experienced continuous compaction, leading to the gradual closure of the separation layer. Simultaneously, new cracks constantly emerged in front of the working face, resulting in the progressive stabilization of the height of the crack zone. The stress measurements at each point exhibit a pattern of initial increased, followed by decrease, and ultimately stabilization. By considering the stress variation law of the overburden rock, the stress changes in key layers of the bedrock during mining could be categorized into four zones: the stress stable zone, stress increasing zone, stress reducing zone, and compaction stable zone. During the initial phase of coal seam mining, the presence of rock layers provided support, resulting in minimal subsidence of the overburden rock. However, as the mining operation progressed, the disturbance force and collapse of the overburden rock leaded to further downward subsidence. When the working face reached the stop line, the collapsed overburden rock gradually consolidates, resulting in a deceleration of energy release and the formation of a pressure relief zone. Consequently, the overburden rock above the working face underwent a slight additional subsidence, reaching its maximum level. A short cantilever rock beam structure was formed in the experiment. This study will provide valuable reference for future coal mining and serve as a vital theoretical basis for roof control in deep coal seam mining.

Shear stress migration in a tapered girder with trapezoidal corrugated steel webs

This study conducted a comprehensive investigation into the shear stress migration of a tapered prestressed concrete (PC) continuous box girder bridge with trapezoidal corrugated steel webs (TCSWs) throughout the entire construction process, including cantilever construction, structural system transformation and external prestressing tendon tensioning. The results revealed that the basic assumptions, which state that TCSWs bear all the shear force and that only the vertical component of the external prestressing contributes to shear stress when considering its contribution, are not valid for the shear design of tapered PC girder bridges with TCSWs. The horizontal component of the external prestressing and bending moments can cause additional shear forces via the Resal effect, which results in the migration of the shear stresses between the curved bottom concrete slabs and TCSWs. This study investigated the mechanism through which the Resal effect and external prestressing influence the migration of shear stress in the entire construction process. The results revealed that within continuous girders, the Resal effect exhibits both positive and negative implications. Specifically, the negative Resal effect exerts an unfavorable influence, resulting in an increase in the shear stress experienced by the TCSWs. Moreover, this study introduced a modified shear method that that takes into account the influence of bending moments and the horizontal component of external prestressing. In contrast to basic shear methods, this approach provides notably heightened accuracy.

Effect of differential deprivation of nutrients on cellular proliferation, oxidative stress, mitochondrial function, and cell migration in MDA-MB-231, HepG2, and HeLa cells.

The online version contains supplementary material available at 10.1007/s13205-023-03759-w.

Anti-inflammatory effects of Arnica montana (mother tincture and homeopathic dilutions) in various cell models

Ethnopharmacological relevanceThe plant Arnica montana L. has been shown to alleviate inflammation, pain and swelling associated with trauma, and post-operative clinical conditions, yet the mechanism of action is not well understood. Aim of the studyThe study was designed to investigate the effect of Arnica montana (A. montana) mother tincture and homeopathic dilutions on inflammation markers, oxidative stress and cell migration in diverse cell culture models. Materials and methodsWe tested A. montana mother tincture and a range of homeopathic dilutions in different human and murine cell culture models to demonstrate their anti-inflammatory properties by measuring the inflammatory markers: tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule (ICAM-1), reactive oxygen species (ROS) and cell migration. The inflammatory markers were measured by ELISA assays. The intracellular oxidative stress (ROS) in microglial cells was measured using Deep Red CellROX probe. The cell migration was examined by wound healing using the Oris Cell migration assay. ResultsThese data showed the ability of A. montana (mother tincture and mainly 1C dilution) to significantly reduce TNFα production in inflamed macrophages compared with vehicle (control). They significantly reduced both IL-6 and MCP-1 in inflamed human microglial cells and significantly decreased COX-2 expression in inflamed murine fibroblasts. Moreover, A. montana mother tincture reduced the cell migration whereas 9C dilution significantly enhanced the migration of fibroblast cells compared with vehicle. The expression of ICAM-1 was significantly reduced with A. montana mother tincture and 1C, 3C, 5C, and 9C dilutions in inflamed human endothelial cells compared with vehicle. A. montana mother tincture and 1C, 3C, 5C and 9C dilutions induced a significant and consistent effect on ROS production in inflamed murine microglial cells. A. montana 1C had the largest impact on ROS production. ConclusionsMother tincture and 1C dilution of A. montana showed anti-inflammatory properties assessed by measurement of several markers (pro-inflammatory cytokines, adhesion molecule, ROS) in various human and murine cell models. In addition, A. montana 3C, 5C, 9C dilutions have anti-inflammatory and antioxidant effects as highlighted on both primary endothelial cells and murine microglial cells.