Subsequent Damage Research Articles

The impact of energy policy on traditional buildings: Towards a holistic decision-making framework for retrofitting: Part 2

The Energy Performance of Buildings Directive (EPBD) is the European Union’s main policy instrument for reducing the built environment’s contribution to climate change. Energy Performance Certificates (EPC) are a tool of this policy, providing buildings with a performance rating. In the UK these have become the benchmark by which the Minimum Energy Efficiency Standards (MEES) are judged, rendering residences lower than an E illegal to rent out. This has pushed property owners to undertake energy retrofitting interventions to ensure compliance. In traditional buildings this is potentially problematic. Buildings of this type rely on permeability to control moisture dynamics; the insertion of less permeable barriers can interrupt their internal hygrometry leading to condensation, damp and decay. As a result, subsequent damage to the building fabric can bring energy policy into conflict with heritage conservation. Existing frameworks that attempt to mitigate the tension within these agendas often fall short in explicitly considering the the problem holistically. This research first asks if pressure from policy is leading to incompatible retrofits. Secondly, it aims to develop a holistic framework that unites heritage and energy agendas with current policy. An inductive, pragmatic approach was undertaken. Using a historic estate’s residential portfolio as a case study, condition surveys were carried out to assess whether properties retrofitted with secondary glazing were experiencing problems with condensation. The results of this were significant, supporting the argument that energy policy is driving incompatible retrofitting interventions. Exploratory data analysis was carried out on an existing EPC dataset to highlight inconsistencies with the EPC methodology. Finally, these findings were combined with questionnaire survey results, targeted at both professionals and occupants, to inform a decision-making framework that incorporated energy efficiency, heritage values, life cycle cost analysis (LCC), building assessment, occupant behaviour, with a feedback loop promoting a bottom-up approach to policy. This issue contains Part 2 which will deal with the methodology and results. Part 1 in the previous issue set the scene.

Risk of flare and damage accrual after tapering glucocorticoids in modified serologically active clinically quiescent patients with systemic lupus erythematosus: a multinational observational cohort study

ObjectivesTo assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE).MethodsData from a 12-country longitudinal...

APOE from patient-derived astrocytic extracellular vesicles alleviates neuromyelitis optica spectrum disorder in a mouse model.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy of the central nervous system, mediated by antibodies against aquaporin-4 water channel protein (AQP4-Abs), resulting in damage of astrocytes with subsequent demyelination and axonal damage. Extracellular communication through astrocyte-derived extracellular vesicles (ADEVs) has received growing interest in association with astrocytopathies. However, to what extent ADEVs contribute to NMOSD pathogenesis remains unclear. Here, through proteomic screening of patient-derived ADEVs, we observed an increase in apolipoprotein E (APOE)-rich ADEVs in patients with AQP4-Abs-positive NMOSD. Intracerebral injection of the APOE-mimetic peptide APOE130-149 attenuated microglial reactivity, neuroinflammation, and brain lesions in a mouse model of NMOSD. The protective effect of APOE in NMOSD pathogenesis was further established by the exacerbated lesion volume in APOE-deficient mice, which could be rescued by exogenous APOE administration. Genetic knockdown of the APOE receptor lipoprotein receptor-related protein 1 (LRP1) could block the restorative effects of APOE130-149 administration. The transfusion ADEVs derived from patients with NMOSD and healthy controls also alleviated astrocyte loss, reactive microgliosis, and demyelination in NMOSD mice. The slightly larger beneficial effect of patient-derived ADEVs as compared to ADEVs from healthy controls was further augmented in APOE-/- mice. These results indicate that APOE from astrocyte-derived extracellular vesicles could mediate disease-modifying astrocyte-microglia cross-talk in NMOSD.

In vitro characterization of novel hyaluronan-antioxidant conjugates as potential topical therapeutics against hearing loss.

Noise-induced hearing loss affects roughly 430 million people worldwide. Current treatment options often require invasive medical procedures, and to date, there are no FDA-approved drug therapies. While the causes can be diverse, noise induced hearing loss is unequivocally associated with oxidative stress and inflammation, and subsequent damage to the inner ear structures. Several studies have shown that various antioxidants such as glutathione, cysteine, and methionine can be used to mitigate oxidative damage from reactive oxygen species; however, these studies relied on invasive or systemic drug delivery methods. This study focused on the development and characterization of a novel series of antioxidant compounds that would be suitable for non or minimally invasive topical inner ear delivery and could mitigate reactive oxygen species associated cellular damage. Specifically, a series of covalent conjugates were synthesized by using hyaluronan as a drug carrier, and methionine, cysteine or glutathione as antioxidant drugs. The conjugates were tested for their ability to readily permeate though in vitro round window membrane and tympanic membrane permeation models, as well as their in vitro internalization into cochlear cells. Our data revealed interdependence between the molecular weight of the hyaluronan carrier, and the tissue and cellular membrane permeation capacity. Subsequent screening of the adequately sized conjugates in in vitro acellular assays revealed the strongest antioxidant activity for the cysteine and glutathione conjugates. These oxidative stress protective effects were further confirmed in cellular in vitro assays. Collectively, the data herein showcase the potential value of these conjugates as therapeutics against oxidative-stress-mediated cellular damage specific to noise-induced hearing loss.

A Comparative Study: Cardioprotective Effects of High-Intensity Interval Training Versus Ischaemic Preconditioning in Rat Myocardial Ischaemia-Reperfusion.

(1) Background: Years of research have identified ischemic preconditioning (IPC) as a crucial endogenous protective mechanism against myocardial ischemia-reperfusion injury, enhancing the myocardial cell's tolerance to subsequent ischemic damage. High-intensity interval training (HIIT) is promoted by athletes because it reduces exercise duration and improves metabolic response and cardiopulmonary function. Our objective was to evaluate and compare whether HIIT and IPC could reduce myocardial ischemia and reperfusion injury in rats. (2) Methods: Male Sprague-Dawley rats were divided into four groups: sham surgery, coronary artery occlusion (CAO), high-intensity interval training (HIIT), and ischemic preconditioning (IPC). The CAO, HIIT, and IPC groups experienced 40 min of coronary artery occlusion followed by 3 h of reperfusion to induce myocardial ischemia-reperfusion injury. Subsequently, the rats were sacrificed, and blood samples along with cardiac tissues were examined. The HIIT group received 4 weeks of training before surgery, and the IPC group underwent preconditioning before the ischemia-reperfusion procedure. (3) Results: The HIIT and IPC interventions significantly reduced the extent of the myocardial infarction size and the levels of serum troponin I and lactate dehydrogenase. Through these two interventions, serum pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, were significantly decreased, while the anti-inflammatory cytokine IL-10 was increased. Furthermore, the expression of pro-apoptotic proteins PTEN, caspase-3, TNF-α, and Bax in the myocardium was reduced, and the expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) was increased, ultimately reducing cellular apoptosis in the myocardium. In conclusion, both HIIT and IPC demonstrated effective strategies with potential for mitigating myocardial ischemia-reperfusion injury for the heart.

Mechanism of Efferocytosis in Determining Ischaemic Stroke Resolution-Diving into Microglia/Macrophage Functions and Therapeutic Modality.

After ischaemic cerebral vascular injury, efferocytosis-a process known as the efficient clearance of apoptotic cells (ACs) by various phagocytes in both physiological and pathological states-is crucial for maintaining central nervous system (CNS) homeostasis and regaining prognosis. The mechanisms of efferocytosis in ischaemic stroke and its influence on preventing inflammation progression from secondary injury were still not fully understood, despite the fact that the fundamental process of efferocytosis has been described in a series of phases, including AC recognition, phagocyte engulfment, and subsequent degradation. The genetic reprogramming of macrophages and brain-resident microglia after an ischaemic stroke has been equated by some researchers to that of the peripheral blood and brain. Based on previous studies, some molecules, such as signal transducer and activator of transcription 6 (STAT6), peroxisome proliferator-activated receptor γ (PPARG), CD300A, and sigma non-opioid intracellular receptor 1 (SIGMAR1), were discovered to be largely associated with aspects of apoptotic cell elimination and accompanying neuroinflammation, such as inflammatory cytokine release, phenotype transformation, and suppressing of antigen presentation. Exacerbated stroke outcomes are brought on by defective efferocytosis and improper modulation of pertinent signalling pathways in blood-borne macrophages and brain microglia, which also results in subsequent tissue inflammatory damage. This review focuses on recent researches which contain a number of recently discovered mechanisms, such as studies on the relationship between benign efferocytosis and the regulation of inflammation in ischaemic stroke, the roles of some risk factors in disease progression, and current immune approaches that aim to promote efferocytosis to treat some autoimmune diseases. Understanding these pathways provides insight into novel pathophysiological processes and fresh characteristics, which can be used to build cerebral ischaemia targeting techniques.

Influence of carbon layer hardness characteristics on RCF performance of carburized bearing steel and optimization of heat treatment process

Being a pivotal element within high-speed train transmission systems, the mechanical attributes of bearings are of great significance to ensure the quality and safety of train operation. In this study, the rolling contact fatigue performance of bearing materials was tested to investigate the effects of different carbon layer characteristics on the rolling contact fatigue behavior. Combined with the thickness of carburizing layer, the elastoplastic coupling model of rolling contact fatigue damage of G20CrNi2MoA carburizing bearing steel was established. The model revealed the relationship between the number of load cycles and the degree of subsequent material damage. The model was used to calculate and predict the loading frequency of G20CrNi2MoA carburized bearing steel with excellent fatigue characteristics, which was 2.02 × 108 times before spalling. In addition, the carburizing heat treatment process for bearings was optimized based on the hardness gradient curves obtained, which provided valuable insights for improving the actual production process.

Methodology to generate earthquake-tsunami fragility surfaces for community resilience modeling

Community resilience analysis and performance-based tsunami design methods typically use separate fragility curves for earthquake and near-field tsunami hazards to predict damage, neglecting the direct cascading effects of the earthquake damage on the subsequent tsunami damage analysis for coastal communities. This paper presents an improved two-phase successive analysis that can incorporate the most significant sources of uncertainties in structural modeling and hazards. However, generating multi-hazard 3D fragility surfaces that fully incorporate uncertainties through Monte Carlo Simulation requires millions of successive nonlinear analyses, which can be computationally intensive. To address this issue, a multi-distributed and parallel processing architecture was used and summarized herein. This methodology has been applied to a 4-story RC building as an illustrative example and demonstrated to be highly efficient and scalable in generating near-continuous fragility surfaces for earthquake and tsunami hazards, reducing the expected computational time by over 98%. Due to their near-continuous characteristic, these surfaces are easier to implement in resilience frameworks and applications. The fragility surfaces also feature earthquake-only and tsunami-only 2D fragility curves along the intensity measure axis boundaries, making them versatile for use in resilience frameworks that focus on a single hazard or both earthquake and tsunami hazards. Therefore, the proposed method is scalable making it helpful in developing fragility models for building portfolios to be used at the community resilience modeling of full coastal cities.

Predictors of Organ Damage in Systemic Lupus Erythematosus in the Asia Pacific Region: A Systematic Review.

Irreversible organ damage is common in patients with systemic lupus erythematosus (SLE). Despite evidence of increased prevalence and severity of SLE in Asia Pacific, organ damage is less well studied in this region. This systematic review aims to identify predictors of organ damage in SLE in the Asia Pacific region. We searched Medline, PubMed, Embase, and Web of Science for observational studies on organ damage in adult patients with SLE in Asia Pacific from August 31, to September 5, 2022. Study selection and data extraction were completed by two independent reviewers using Covidence systematic review software. Risk of bias was assessed using the Newcastle-Ottawa Scale and Joanna Briggs Institute tool. Significant results from univariable and multivariable analyses were synthesized from included studies. Thirty-eight eligible studies were selected from 1999 to 2022; 22 (58%) of these reported organ damage at study enrollment and 19 (50%) reported damage accrual, as measured by the Systemic Lupus International Collaborating Clinic/American College of Rheumatology Damage Index. Factors predictive of organ damage included older age, glucocorticoid use, longer disease duration, and disease activity. Lupus nephritis was a risk factor for renal and overall damage accrual. Hydroxychloroquine was protective against overall organ damage. Predictors of organ damage in SLE in Asia Pacific are similar to other regions. Although glucocorticoid use is a modifiable risk factor for organ damage, the impact of immunosuppressives and biologic therapies needs further investigation. Effective strategies in early disease are needed to minimize initial organ damage as it predicts subsequent damage accrual.

Insulin resistance and metabolic diseases - a review

Introduction: This review paper aims to discuss the effects of insulin resistance, and its association with various metabolic diseases. Insulin resistance (IR), characterized by diminished tissue responsiveness to physiological insulin levels, is a key component in various metabolic diseases, including type 2 diabetes, cardiovascular disorders (CVDs), obesity, and non-alcoholic fatty liver disease (NAFLD).
 State of knowledge The consequences of IR are profound; in type 2 diabetes, it hinders glucose utilization by muscle cells, leading to hyperglycemia, muscle damage, and loss of mass and strength. IR also plays a central role in NAFLD, promoting lipid accumulation, hepatic inflammation, fibrosis, and cell death.
 Materials and methods: A review of chosen literature in the PubMed and Google Scholar databases was conducted, using the following key words: „Insulin resistane”, „Insulin resistance in obesity”, „Obesity”, „Insulin resistance NAFLD”, „Diebetes”, „Insulin resistance CVD”
 Summary: The consequences of insulin resistance are far-reaching. In the context of type 2 diabetes, it impedes glucose utilization by muscle cells, resulting in hyperglycemia and subsequent muscle cell damage, contributing to loss of mass and strength. Insulin resistance is also a central player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), fostering lipid accumulation, hepatic inflammation, and, ultimately, fibrosis and cell death.
 Conclusions: In conclusion, understanding insulin resistance is paramount in addressing the rising prevalence of metabolic diseases globally Controlling insulin resistance emerges as a crucial aspect of managing these metabolic disorders and their complications. Further research into the mechanisms of IR formation and effective intervention strategies is imperative for improving public health outcomes.

Hyaluronic acid-ibuprofen conjugation: a novel ototherapeutic approach protecting inner ear cells from inflammation-mediated damage.

There is a substantial need of effective drugs for the treatment of hearing loss, which affects nearly 500 million individuals globally. Hearing loss can be the result of intense or prolonged noise exposure, ototoxic drugs, infections, and trauma, which trigger inflammatory signaling cascades that lead to irreversible damage to cochlear structures. To address this, we developed and characterized a series of covalent conjugates of anti-inflammatory drugs to hyaluronic acid (HA), for potential use as topical ototherapeutics. These conjugates were tested in in vitro assays designed to mirror physiological processes typically observed with acoustic trauma. Intense noise exposure leads to macrophage recruitment to the cochlea and subsequent inflammatory damage to sensory cells. We therefore first tested our conjugates' ability to reduce the release of inflammatory cytokines in macrophages. This anti-inflammatory effect on macrophages also translated to increased cochlear cell viability. In our initial screening, one conjugate, ibuprofen-HA, demonstrated significantly higher anti-inflammatory potential than its counterparts. Subsequent cytokine release profiling of ibuprofen-HA further confirmed its ability to reduce a wider range of inflammatory markers, to a greater extent than its equivalent unconjugated drug. The conjugate's potential as a topical therapeutic was then assessed in previously developed tympanic and round window membrane tissue permeation models. As expected, our data indicate that the conjugate has limited tympanic membrane model permeability; however, it readily permeated the round window membrane model and to a greater extent than the unconjugated drug. Interestingly, our data also revealed that ibuprofen-HA was well tolerated in cellular and tissue cytocompatibility assays, whereas the unconjugated drug displayed significant cytotoxicity at equivalent concentrations. Moreover, our data highlighted the importance of chemical conjugation of ibuprofen to HA; the conjugate had improved anti-inflammatory effects, significantly reduced cytotoxicity, and is more suitable for therapeutic formulation. Overall, this work suggests that ibuprofen-HA could be a promising safe and effective topical ototherapeutic for inflammation-mediated cochlear damage.

Study on load distributing function of square slab surface under the action of underwater close‐in blast loading

AbstractThe mode and magnitude of the blast load are the main cause of damage to the structure. Most current studies have simplified the blast load into a bilinear form that differs greatly from the actual time history curve and is applied directly to the structure, avoiding the fluid–solid coupling interaction between the water fluid and the structure. The simplified blast load for near‐explosion or internal explosion will bring a big error to the calculation results. To quickly determine the load on the structure surface under the action of underwater near the explosion, this study studies the interaction between water hammer wave and structure through the verified full coupling model, and puts forward the explosion load distribution function on the square plate surface under the action of underwater explosion, and establishes a simplified prediction formula for the explosion load parameters (peak pressure and positive reflection impulse) at the center of the plate surface, using these formulas, a general method for constructing the explosion load at any point on the structural surface is proposed, which lays a foundation for subsequent structural damage and failure analysis.

Experimental investigation of freeze injury temperatures in trees and their contributing factors based on electrical impedance spectroscopy.

In trees, injuries resulting from subfreezing temperatures can cause damage to the cellular biofilm system, metabolic functions, and fibrous reticulum, and even cell death. Investigating the occurrence of freezing damage and its contributing factors could help understand the mechanisms underlying freezing injury and prevent the subsequent damage in trees. To achieve this, a laboratory experiment was conducted using cut wood samples from Korean pine (Pinus koraiensis Siebold & Zucc) and Simon poplar (Populus simonii Carr.), and the effects of environmental freezing factors, including freezing temperatures, freezing duration, and cooling rate, on the temperature at which freezing injuries occur were examined using the electrical impedance spectroscopy (EIS) method. The semi-lethal temperature (LT50), as an indicator of freezing injury in wood tissue, was theoretically deduced based on the measured extracellular resistance (r e) using EIS. The contributory factors to changes in LT50 were determined and their relationship was established. The results revealed that all freezing factors exhibited significant effects on electrical impedance characteristics (r e, r i, and τ), significantly influencing the LT50 of the wood. Random forest (RF) and support vector machine (SVM) models were used to assess the contribution of the freezing factors and moisture content (MC). Among the factors examined, freezing duration had the greatest impact on LT50, followed by the MC, whereas the contribution of the cooling rate was minimal. The model accuracies were 0.89 and 0.86 for Korean pine and Simon poplar, respectively. The findings of our study illustrate that the occurrence of freezing injury in trees is primarily influenced by the duration of freezing at specific subzero temperatures. Slow cooling combined with prolonged freezing at low subzero temperatures leads to earlier and more severe freezing damage.

Restoration of the Mucosal IgA Response by Improving CD4+ T Pyroptosis Fails to Attenuate Gut Bacterial Translocation and Organ Damage After LPS Attack.

Currently, the mechanisms of impaired gut mucosal immunity in sepsis remain unclear. Gut immunoglobulin A (IgA) is an important defense mechanism against invasive pathogens, and CD4+ T cells regulate the IgA response. We aimed to verify the hypothesis indicating that CD4+ T pyroptosis induced by lipopolysaccharide (LPS) leads to an impaired gut IgA response and subsequent bacterial translocation and organ damage. Cultured CD4+ T cells and mice were manipulated with LPS, and pyroptosis was improved by A438079 or adoptive CD4+ T cell transfer. The changes demonstrated in pyroptosis-related molecules, cytotoxicity and CD4+ T cells were examined to determine CD4+ T pyroptosis. The changes demonstrated in IgA+ B cells, AID (key enzyme for immunoglobulins) and IgA production and function were examined to evaluate the IgA response. Serum biomarkers, bacterial colonies and survival analysis were detected for bacterial translocation and organ damage. LPS attack induced CD4+ T pyroptosis, as evidenced by increased expression of P2X7, Caspase-11 and cleaved GSDMD, which elevated cytotoxicity and decreased CD4+ T cells. Decreased CD4+ T subsets (Foxp3+ T and Tfh cells) influenced the IgA response, as evidenced by lower AID expression, which decreased IgA+ B cells and IgA production and function. A438079 or cell transfer improved the IgA response but failed to reduce the translocation of gut pathogens, damage to the liver and kidney, and mortality of mice. LPS attack results in CD4+ T pyroptosis. Improvement of pyroptosis restores the mucosal IgA response but fails to ameliorate bacterial translocation and organ damage.

Test Setup for Investigating the Impact Behavior of Biaxially Prestressed Composite Laminates

Instrumented impact testing and compression-after-impact testing are important to adequately qualify material behavior and safely design composite structures. However, the stresses to which fiber-reinforced plastic components are typically subjected in practice are not considered in the impact test methods recommended in guidelines or standards. In this paper, a test setup for investigating the impact behavior of composite specimens under plane uniaxial and biaxial preloading is presented. For this purpose, a special test setup consisting of a biaxial testing machine and a specially designed drop-weight tower was developed. The design decisions were derived from existing guidelines and standards with the aim of inducing barely visible impact damage in laminated carbon fiber-reinforced plastic specimens. Several measurement systems have been integrated into the setup to allow comprehensive observation of the impact event and specimen behavior. A feasibility test was performed with biaxially prestressed carbon fiber-reinforced plastic specimens in comparison with unstressed reference tests. The compressive-tensile prestressing resulted in lower maximum contact forces, higher maximum deflections, higher residual deflections and a different damage pattern, which was investigated by light microscopic analysis. Finally, the functionality of the experimental setup is discussed, and the results seem to indicate that the test setup and parameters were properly chosen to investigate the effect of prestresses on the impacts behavior of composite structures, in particular for barely visible subsequent damages.

A Narrative Review on the Management of Severe COVID-19 Infection Using Stem Cell-based therapies with a Focus on the Registered Clinical Trials

The emergence of SARS-CoV-2 has led to a concerning global pandemic. The severity of COVID-19 symptoms may be enhanced due to underlying medical conditions. Several studies demonstrated severe COVID-19 infection can lead to innate and adaptive immune dysregulation, cytokine storms as well and the formation of fibromyxoid exudate in the respiratory alveolar, ultimately resulting in pulmonary fibrosis and ARDS as the leading cause of mortality and morbidity. Currently, there is a widespread global endeavor in finding efficient drugs or vaccines to manage COVID-19. Although some FDA-approved treatments have been introduced for COVID-19, alternative therapies might decrease the mortality rates. Various sources of pluripotent and mesenchymal stem cells as cell-based therapies have been applied on moderate to severe COVID-19 patients with acute respiratory distress syndrome, leading to positive results. Cell-based therapies by modulating the cytokine cascades and cellular apoptosis can probably inhibit tissue remodeling and subsequent end-organ damage. The present review aims to discuss the advantages of stem cell-based therapies in the treatment of COVID-19 patients and the possible challenges associated with their application.

Experimental Study on Dynamic Modulus of High Content Rubber Asphalt Mixture

Currently, the research on the mechanical properties of rubber-modified asphalt mixtures primarily focuses on small-scale investigations, with insufficient exploration into the performance of rubber particles and their relationship with the mechanism and properties of modified asphalt mixtures. Limited studies have been conducted on large-scale rubber modification in asphalt mixtures. Due to frequent use and subsequent high damage to existing asphalt pavements, incorporating rubber-modified asphalt mixtures can partially alleviate premature deterioration. Dynamic modulus tests were conducted using MTS equipment under unconfined conditions to investigate the viscoelastic behavior of rubber-modified asphalt mixtures with high rubber content and elucidate the influence of rubber particle content on the elastic deformation and recovery capability. The dynamic mechanical properties of the mixtures were determined at different loading rates, temperatures, and types of rubber-modified asphalt mixtures. Based on the test data, variations in the dynamic modulus, phase angle, storage modulus, loss modulus, loss factor, and rut factor of the rubber-modified asphalt mixtures under different loading frequencies, temperatures, and types were analyzed. The results demonstrate the pronounced viscoelastic behavior of rubber-modified asphalt mixtures. The mixtures exhibit enhanced elasticity at low temperatures and high frequencies, while their viscosity becomes more prominent at high temperatures and low frequencies. Under constant test temperatures, an increase in load loading frequency leads to a higher dynamic modulus; conversely, a decrease in dynamic modulus is observed with increasing test temperatures. The dynamic modulus of ARHM-25 at a frequency of 10 Hz is found to be 12.99 times higher at 15 °C compared to that at 60 °C, while at 30 °C, the dynamic modulus at 25 Hz is observed to be 2.72 times greater than that at 0.1 Hz. Furthermore, the rutting resistance factors of the asphalt mixtures increase with loading frequency but decrease with temperature. The rutting factor for ARHM-13 at a frequency of 10 Hz is found to be 22.98 times higher at 15 °C compared to that at 60 °C, while at a temperature of 30 °C, the rutting factor for this material is observed to be 3.09 times greater at a frequency of 25 Hz than at 0.1 Hz. These findings suggest that rutting is most likely when vehicles drive at low speeds in hot weather conditions.

Targeting KDM4 family epigenetically triggers antitumour immunity via enhancing tumour-intrinsic innate sensing and immunogenicity.

Despite the remarkable clinical efficacy of cancer immunotherapy, considerable patients fail to benefit from it due to primary or acquired resistance. Tumours frequently hijack diverse epigenetic mechanisms to evade immune detection, thereby highlighting the potential for pharmacologically targeting epigenetic regulators to restore the impaired immunosurveillance and re-sensitise tumours to immunotherapy. Herein, we demonstrated that KDM4-targeting chemotherapeutic drug JIB-04, epigenetically triggered the tumour-intrinsic innate immune responses and immunogenic cell death (ICD), resulting in impressive antitumour effects. Specifically, JIB-04 induced H3K9 hypermethylation through specific inhibition of the KDM4 family (KDM4A-D), leading to impaired DNA repair signalling and subsequent DNA damage. As a result, JIB-04 not only activated the tumour-intrinsic cyclic GMP-AMP synthase (cGAS)-STING pathway via DNA-damage-induced cytosolic DNA accumulation, but also promoted ICD, releasing numerous damage-associated molecular patterns. Furthermore, JIB-04 induced adaptive resistance through the upregulation of programmed death-ligand 1 (PD-L1), which could be overcome with additional PD-L1 blockade. In human tumours, KDM4B expression was negatively correlated with clinical outcomes, type I interferon signatures, and responses to immunotherapy. In conclusion, our results demonstrate that targeting KDM4 family can activate tumour-intrinsic innate sensing and immunogenicity, and synergise with immunotherapy to improve antitumour outcomes.

Literature review : Hyperthermia outcome on intracerebral hemorrhage

Hyperthermia occurs in up to 30–40% of patients with ICH and is associated with the highest morbidity and mortality rates. Primary ICH accounts for 85% of all ICH cases and is associated with high morbid­ity and mortality rates. ICH can lead to primary or secondary brain injury. The purpose of the study was to identify outcome related to hyperthermia on intracerebral haemorraghe. This literature review described four peer-reviewed journals based on inclusion criteria. The results of the analysis of the literature review found that outcome of hyperthermia are mortality and morbidity. Fever can contribute to subsequent brain damage following ICH, hyperthermia to worse outcomes in both ischemic and hemorrhagic stroke patients at 3 months, but the underlying mechanism may differ. Fever is prevalent in people with ICH and is seldom linked with a definite infectious cause

Gut Microbiome Mediates Ferroptosis Resistance for Colorectal Cancer Development.

Colorectal cancer is a prevalent cancer type in the United States, affecting both genders and influenced by genetics and environmental factors. The role of the gut microbiome in colorectal cancer development and therapy response is a burgeoning field of study. A recent study uncovered that trans-3-indoleacrylic acid (IDA), a microbial metabolite from P. anaerobius, promotes colorectal cancer by inhibiting ferroptosis, a type of nonapoptotic cell death driven by unrestricted lipid peroxidation and subsequent membrane damage. IDA activates aryl hydrocarbon receptor (AHR), a nuclear transcription factor, leading to the expression of aldehyde dehydrogenase 1 family member A3 (ALDH1A3). ALDH1A3, known for aldehyde detoxification, also contributes to ferroptosis resistance by generating reduced nicotinamide adenine dinucleotide (NADH), critical for the synthesis of reduced coenzyme Q10 (COQH10), by apoptosis-inducing factor mitochondria-associated 2 (AIFM2, also known as FSP1). Knocking out AHR, AIFM2, or ALDH1A3 reverses the inhibitory effect of IDA on ferroptosis and IDA-mediated tumor growth. Significantly, P. anaerobius is enriched in patients with colorectal cancer, and supplementing IDA or P. anaerobius accelerates colorectal cancer progression in spontaneous or orthotopic mouse models. Taken together, these findings suggest that targeting P. anaerobius-mediated ferroptosis resistance emerges as a promising strategy to combat colorectal cancer development.