Persistent State Research Articles

Atomistic Origin of Microsecond Carrier Lifetimes at Perovskite Grain Boundaries: Machine Learning-Assisted Nonadiabatic Molecular Dynamics.

The polycrystalline nature of perovskites, stemming from their facile solution-based fabrication, leads to a high density of grain boundaries (GBs) and point defects. However, the impact of GBs on perovskite performance remains uncertain, with contradictory statements found in the literature. We developed a machine learning force field, sampled GB structures on a nanosecond time scale, and performed nonadiabatic (NA) molecular dynamics simulations of charge carrier trapping and recombination in stoichiometric and doped GBs. The simulations reveal long, microsecond carrier lifetimes, approaching experimental data, stemming from charge separation at the GBs and small NA coupling, 0.01-0.1 meV. Stoichiometric GBs exhibit transient trap states, which, however, are not particularly detrimental to the carrier lifetime. Halide dopants form interstitial defects in the bulk, but have a stabilizing influence on the GB structure by passivating undersaturated Pb atoms and reducing the transient trap state formation. On the contrary, excess Pb destabilizes GBs, allowing formation of persistent midgap states that trap charges. Still, the charge carrier lifetime reduces relatively little, because the midgap states decouple from the bands, and charges are more likely to escape back into bands upon a GB structural fluctuation. The atomistic study into the structural dynamics of perovskite GBs and its influence on charge carrier trapping and recombination provides valuable insights into the complex properties of perovskites and the intricate role of GBs in the material performance.

Insights and Interventions in Age-Associated Inflammation.

Aging is a systemic, complex, and heterogeneous process characterized by a progressive decline in physiological functions, rendering it a major risk factor for various chronic diseases. Chronic inflammation has emerged as both a hallmark and a driver in this complicated process. This persistent inflammatory state arises from a spectrum of stimuli, ranging from external pathogens to internal cellular remnants, to metabolic dysregulation, and to chronic stress. Here, we examine recent mechanistic advances into the driving forces behind age-related chronic inflammation, explore promising anti-inflammatory strategies to mitigate aging, and address current challenges, proposing future directions to propel this evolving field toward translational breakthrough.

Causes and management of acute oncological pain: a narrative review.

Acute pain in cancer is an important but often overlooked feature of many patients' oncological journey. Cancer-related pain is associated commonly with more persistent pain states caused by both the disease and its treatment, but there are numerous causes of acute pain which can develop in patients with cancer. This pain is frequently severe, can be challenging to manage and its suboptimal control can directly impact on oncological outcomes. This narrative review provides an overview of several causes of acute pain in patients with cancer and management approaches. A focused literature review was conducted to encompass the search terms 'acute pain', 'oncology' and 'cancer' in adult and paediatric populations. Acute pain is common in patients with cancer with a number of pain generators identified. Broadly, these are disease- and treatment-related but commonality in pain mechanisms and features are present. Importantly, these pain states do not occur in isolation; a patient may experience multiple acute pain episodes during their oncology journey. As the oncological treatment landscape shifts and increasing numbers of novel treatments are employed, the number of causes of acute pain in patients with cancer rises. This pain is often managed by non-pain specialists and suboptimal control has a variety of deleterious effects. It is important that awareness of acute pain in the oncological population is increased and treatment approaches, which adopt a biopsychosocial structure, are optimised.

Sport-specific differences in ACL injury, treatment and return to sports: Basketball.

Basketball is an intense, fast-paced game that is physically, highly demanding. Certain aspects of the game, such as the quick pivoting and cutting movements, predispose the players to serious knee injuries, including anterior cruciate ligament (ACL) tears. While an ACL tear can be a devastating condition for players, multidisciplinary management of the injury can provide the players with a reasonable chance to return to play at the pre-injury level. This article aims to review the general principles and guidelines for the management of ACL injury in basketball players. The diagnosis, surgical treatment, rehabilitation and return to sports are discussed from European and North American perspectives. With a comprehensive and multidisciplinary approach to this condition, medical professionals can provide injured basketball players with a favourable prognosis for returning to play at the pre-injury level. To return to normal life and basketball after ACL reconstruction, the proposed approach includes (1) the selection of the appropriate surgical graft and technique, (2) maintaining a healthy and persistent mental state during rehabilitation, and (3) following a scientific rehabilitation programme based on personalized recovery. LEVEL OF EVIDENCE: Level V.

Evidence of a persistent altered neural state in people with fibromyalgia syndrome during functional MRI studies and its relationship with pain and anxiety.

Altered neural signaling in fibromyalgia syndrome (FM) was investigated with functional magnetic resonance imaging (fMRI). We employed a novel fMRI network analysis method, Structural and Physiological Modeling (SAPM), which provides more detailed information than previous methods. The study involved brain fMRI data from participants with FM (N = 22) and a control group (HC, N = 18), acquired during a noxious stimulation paradigm. The analyses were supported by fMRI data from the brainstem and spinal cord in FM and HC, brain fMRI data from participants with provoked vestibulodynia (PVD), and eye-tracking data from an fMRI study of FM. The results demonstrate differences in connectivity, and in blood oxygenation-level dependent (BOLD) responses, between FM and HC. In the FM group, BOLD signals underwent a large increase during the first 40 seconds of each fMRI run, prior to the application of any stimuli, compared to much smaller increases in HC. This indicates a heightened state of neural activity in FM that is sustained during fMRI runs, and dissipates between runs. The exaggerated initial rise was not observed in PVD. Autonomic functioning differed between groups. Pupil sizes were larger in FM than in HC, and the groups exhibited pupil dilation to the same levels during noxious stimulation. The initial BOLD increase varied in relation to state and trait anxiety scores. The results indicate that people with FM enter a heightened state of neural activity associated with anxiety and autonomic functioning, during every fMRI run, concurrent with increased pupil sizes, and heightened pain sensitivity. These findings may relate to the well-known hypervigilance and global hypersensitivity of FM participants.

Longitudinal single-cell profiles of lung regeneration after viral infection reveal persistent injury-associated cell states.

Functional regeneration of the lung's gas exchange surface following injury requires the coordination of a complex series of cell behaviors within the alveolar niche. Using single-cell transcriptomics combined with lineage tracing of proliferating progenitors, we examined mouse lung regeneration after influenza injury, demonstrating an asynchronously phased response across different cellular compartments. This longitudinal atlas of injury responses has produced a catalog of transient and persistent transcriptional alterations in cells as they transit across axes of differentiation. These cell states include an injury-induced capillary endothelial cell (iCAP) that arises after injury, persists indefinitely, and shares hallmarks with developing lung endothelium and endothelial aberrations found in degenerative human lung diseases. This dataset provides a foundational resource to understand the complexity of cellular and molecular responses to injury and correlations to responses found in human development and disease.

Spatiotemporal Profiling Defines Persistence and Resistance Dynamics During Targeted Treatment of Melanoma.

Resistance of BRAF-mutant melanomas to targeted therapy arises from the ability of cells to enter a persister state, evade treatment with relative dormancy, and repopulate the tumor when reactivated. A better understanding of the temporal dynamics and specific pathways leading into and out of the persister state is needed to identify strategies to prevent treatment failure. Using spatial transcriptomics in patient-derived xenograft models, we captured clonal lineage evolution during treatment. The persister state showed increased oxidative phosphorylation, decreased proliferation, and increased invasive capacity, with central-to-peripheral gradients. Phylogenetic tracing identified intrinsic and acquired resistance mechanisms (e.g., dual specific phosphatases, reticulon-4, and CDK2) and suggested specific temporal windows of potential therapeutic susceptibility. Deep learning-enabled analysis of histopathological slides revealed morphological features correlating with specific cell states, demonstrating that juxtaposition of transcriptomics and histological data enabled identification of phenotypically distinct populations from using imaging data alone. In summary, this study defined state change and lineage selection during melanoma treatment with spatiotemporal resolution, elucidating how choice and timing of therapeutic agents will impact the ability to eradicate resistant clones.

Trastornos neuropsiquiátricos asociados al Covid persistente

Persistent COVID (PC) is the term used to describe a multisystemic and multifactorial entity, which follows acute SARS-CoV-2 infection. Symptoms must persist for three months or more to define this disorder. The clinical manifestations are variable and nonspecific, but have a great impact on the quality of life of patients. Neuropsychiatric symptoms are commonly reported in CP, mostly chronic fatigue, cognitive disorders, attention disorders, among others. The pathophysiological mechanisms are not fully known, but the most described are hypoxia related neuronal damage, microvascular lesions, a persistent proinflammatory state, activation of latent viral infections, and alteration of the blood-brain barrier. There are no specific complementary tests to confirm the diagnosis of CP. There is also no specific treatment to date and most therapies are aimed at relieving symptoms and improving quality of life. This article provides a comprehensive bibliographic review of the most common neuropsychiatric manifestations of CP, including its probable pathophysiological mechanisms and the therapies proposed to date.

Neuroprotective Effects of Dexamethasone in a Neuromelanin-Driven Parkinson’s Disease Model

Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra that primarily affects movement control. Neuroinflammation plays a pivotal role in driving the disease’s progression. The persistent inflammatory state in the brain exacerbates neuronal damage, creating a cycle that perpetuates the neurodegenerative process. Glucocorticoids, such as dexamethasone, have potent anti-inflammatory properties and have been studied for their neuroprotective potential in different neurodegenerative diseases. However, their specific impact on PD remains unclear. This study aimed to evaluate the impact of dexamethasone on a neuromelanin (NM)-driven model of PD. We demonstrated that dexamethasone administration significantly improved motor function and preserved dopaminergic neuron compared to untreated controls in our study. These neuroprotective effects were mediated, at least in part, by suppressing reactive microglia and reducing the infiltration of peripheral immune cells into the brain. Our findings underscore the potential therapeutic benefits of dexamethasone in mitigating neuroinflammation and maintaining neuronal integrity in a NM-driven model of PD. These results advocate for further investigation into glucocorticoid-based therapies as adjunctive treatments for PD, particularly in scenarios where neuroinflammation contributes prominently to disease progression.

Persistent ferromagnetic ground state in pristine and Ni-doped Fe3GaTe2 flakes

Room-temperature magnetism and its stability upon miniaturization are essential characteristics required for materials for spintronic devices and information storage. Among various candidates, Fe3GaTe2 stands out due to its high Curie temperature and strong perpendicular magnetic anisotropy (PMA), recently gaining large attention as one of the promising candidate materials for spintronics applications. In this study, we measured the thickness-dependent ferromagnetic properties of Fe3GaTe2 and (Fe1 − xNix)3GaTe2 (with x = 0.1) flakes. We observed that both pristine and Ni-doped Fe3GaTe2 exhibit persistent ferromagnetism, with only a minor decrease in TC as the thickness is reduced to a few tens of nanometers. This capacity to retain robust ferromagnetic properties at reduced dimensions is highly advantageous for thin-film applications, which is crucial for the scaling of spintronic devices. Understanding and controlling thickness-dependent magnetic properties is fundamental to harnessing the full potential of Fe3GaTe2 in van der Waals magnetic heterostructures and advanced spintronic technologies.

Perspectives on why DanGer Shock is the first positive trial on mechanical circulatory support in cardiogenic shock.

Cardiogenic shock related to acute myocardial infarction (AMI-CS) remains a severe condition associated with a high risk of mortality despite increased availability of primary percutaneous coronary intervention and improvements in pharmacologic and device-based therapy. The results of the DanGer Shock trial stand out compared with the outcomes of the previous trials and mark the first mechanical circulatory support (MCS) strategy to show a benefit in patients with AMI-CS, a population that has always been challenging to study. Notably, negative findings from previous trials may mask positive treatment effects in specific subgroups and patient category. We systematically reviewed the design of all contemporary randomized controlled AMI-CS trials and identified four distinct features, which likely provide reasons why DanGer Shock became the first positive randomized controlled trial to support MCS in AMI-CS. DanGer Shock was the first RCT that established MCS in the context of AMI-CS. Key features were (1) patient phenotype that 1)includes STEMI and 2)excludes severe RV failure and persistent comatose state after out-of-hospital cardiac arrest; (3) optimal timing of MCS deployment, as soon as possible (lower SCAI stage) and before revascularization efforts; and (4) rigorous intensive care management protocols on hemodynamic and MCS monitoring.

Photobiomodulation studies on diabetic wound healing: An insight into the inflammatory pathway in diabetic wound healing.

Diabetes mellitus remains a global challenge to public health as it results in non-healing chronic ulcers of the lower limb. These wounds are challenging to heal, and despite the different treatments available to improve healing, there is still a high rate of failure and relapse, often necessitating amputation. Chronic diabetic ulcers do not follow an orderly progression through the wound healing process and are associated with a persistent inflammatory state characterised by the accumulation of pro-inflammatory macrophages, cytokines and proteases. Photobiomodulation has been successfully utilised in diabetic wound healing and involves illuminating wounds at specific wavelengths using predominantly light-emitting diodes or lasers. Photobiomodulation induces wound healing through diminishing inflammation and oxidative stress, among others. Research into the application of photobiomodulation for wound healing is current and ongoing and has drawn the attention of many researchers in the healthcare sector. This review focuses on the inflammatory pathway in diabetic wound healing and the influence photobiomodulation has on this pathway using different wavelengths.

Dynamics of localized waves and interactions in a [formula omitted]-dimensional equation from combined bilinear forms of Kadomtsev–Petviashvili and extended shallow water wave equations

This work investigates new exact solutions within a unique (2+1)-dimensional problem by combining the Hirota bilinear forms of the Kadomtsev–Petviashvili and the Shallow Water Wave equations. We obtain resonant Y-type and X-type soliton, breather, and lump waves by introducing novel limitations on the N-soliton. Additionally, it generates various types of solutions (bulk-soliton, fissionable soliton-lump, breather-lump, and soliton-breather-lump) based on velocity and module resonance conditions. Furthermore, we investigate the lump wave’s paths interacting with the waves prior to and following collision using the long-wave limit approach. We show that the lump wave either avoids collision with other waves or maintains a persistent state of collision with them by applying additional limitations. Specifically, we provide a series of figures depicting all solutions, comprehensively capturing their dynamical behavior and interactions.

Enhancing photocatalytic hydrogen generation by achieving long-lasting shallow trapping states in distorted covalent triazine frameworks

Short-lived shallow trapping states in photocatalysts created from polymeric semiconductors impedes the effective use of charge carriers, leading to a decrease in the solar-to-hydrogen conversion efficiency of covalent triazine frameworks (CTF). In this study, methylene-modified covalent triazine frameworks (M−CTF) with increased structural distortion were synthesized through a dynamic trimerization reaction of cyano groups using the precursors of 1,4-terephthalonitrile and 1,4-phenylenediacetonitrile. The optimal M−CTF catalyst obtained in this approach showed persistent shallow trapping states through n-π* electronic transitions, leading to a noticeable red-shift in the light absorption edge to 600 nm. Femtosecond transient absorption spectroscopy verified the existence of shallow trapping states with extended lifetimes (1103.8 ps) in M−CTF. The distorted structure promote increased involvement of photo-induced electrons in reducing water to generate H2, leading to a substantial improvement in the ability of M−CTF to catalyze the production of H2. M−CTF sample loaded with Pt cocatalysts exhibited an impressive efficiency of 10.1 mmol·g−1·h −1 in producing H2 via photocatalysis under visible light (λ > 420 nm), marking a tenfold improvement compared to the original CTF. The findings underscore the significance of structural distortion in CTF for achieving long-lasting shallow trapping states, leading to improved photocatalytic efficiency.

Occurrence and Phenotypic Characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) in Emergency Medical Service Ambulances as a Potential Threat to Medical Staff and Patients.

Introduction: An ambulance used by an emergency medical service team is the workplace of specialised medical personnel, providing daily transportation for patients in life-threatening conditions, from all walks of life, with numerous diseases and injuries. MRSA (methicillin-resistant Staphylococcus aureus) strains are classified as Gram-positive cocci, characterised primarily by their multidrug resistance. Infections caused by S. aureus have a low treatment success rate and are associated with persistent carrier state. This study aimed to isolate MRSA and MSSA (methicillin-sensitive Staphylococcus aureus) in the emergency vehicle and determine drug resistance of these isolates. Materials and Methods: This study involved an ambulance vehicle operated in central Poland. A total of 39 swabs were taken and evaluated from inside the ambulance on permanent duty. The isolates were analysed using catalase and coagulase assays, Gram staining, culturing on Chapman medium, growth evaluation on agar with 5% sheep blood, and assessing the strains' sensitivities to selected antibiotics. Material was collected from 13 designated points located in the medical compartment and driver's cabin. Results:S. aureus bacteria were detected in 51.28% of the samples, 40% of which were MRSA strains. Despite the application of high disinfection standards for the interior of the ambulance, it was not possible to kill all S. aureus strains, which may be because the pathogens in question produce a biofilm that effectively allows them to survive on various surfaces, including those disinfected. Almost 100% of the MRSA isolates were resistant to antibiotics from the β-lactam group (penicillin, ticarcillin, cefotaxime, and cefoxitin), the macrolide group (erythromycin) and the lincosamide group (clindamycin). However, only a few MRSA strains proved resistant to streptomycin (12.5%) and ciprofloxacin (37.5%). β-lactam antibiotics, such as cefotaxime (100% resistant strains) and penicillin (58% resistant strains), were also ineffective against MSSA. Although MSSA isolates showed slight resistance to ticarcillin and erythromycin (33.3%) and clindamycin (25%), the remaining antibiotics proved effective (no resistant strains). Conclusions: Among the isolated strains, the greatest resistance to β-lactam antibiotics and erythromycin was observed. Multidrug-resistant strains of S. aureus were found in the emergency medical system. Even the MSSA strains detected in the studied ambulance showed resistance to some of the antibiotics used. The prevalence of S. aureus strains within ambulances indicates the need for a high hygiene level in daily prehospital work with patients.

Tailoring Cathode Materials: Al2O3 Coating for Advanced Sodium-Ion Batteries

The attractive combination of sodium-ion battery's (SIB) homogeneous profusion in earth and LIB's identical intercalation chemistry makes it possible drop-in replacement for lithium-ion battery (LIB) technology in the ever-growing energy storage market. Layered transition metal oxide cathodes are the most sought-after for SIB cathodes because of their superior sodium storage capabilities, increased energy density, and straightforward synthesis process. However, these intercalation materials are prone to severe capacity decline and pose several safety concerns. In addition to safety concerns, several explanations of this capacity fading have been proposed, including structural instability, metal ion solubility in the electrolyte due to HF generation, and degradation of the electrolyte at higher cutoff voltages (>4.3 V). Metal oxide coatings are viable owing to their cost-effectiveness and ease of application. The inactivity of the metal during electrochemical reactions is attributed to its persistent valance state; consequently, cathodes adorned with such coatings experience a decline in ion conductivity. In this research, a thin layer of coating is employed upon titanium and vanadium doped sodium iron manganese oxide () via sol-gel process followed by a solid-state ball milling method in order to improve the rate capability and long term cyclic stability. The thickness and uniformity of the coating layer is verified from the SEM and EDS images. Furthermore, the XRD analysis is performed to see whether any modification has occurred in the cathode lattice due to the coating. Following that, the electrochemical performance of uncoated P2-electrodes is compared to that of coated P2- electrodes via electrochemical analyses such as galvanostatic charge-discharge test, CV and EIS which validate the efficacy of coating on ). This straightforward surface modulation technique will open up a potential route for the synthesis of superior cathode materials for sodium-ion batteries.

Combating Tuberculosis via Restoring the Host Immune Capacity by Targeting M. tb Kinases and Phosphatases.

Mycobacterium tuberculosis (M. tb) is a remarkably versatile pathogen that possesses a unique ability to counteract the host's defence mechanisms to control the infection. Several mycobacterial protein kinases and phosphatases were found to play a key role in impeding phagosome maturation in macrophages and accordingly blocking the phagosome-lysosome fusion, therefore allowing the bacteria to survive. During phagocytosis, both M. tb and the host's phagocytic cells develop mechanisms to fight each other, resulting in pathogen elimination or survival. In this respect, M. tb uses a phosphorylation-based signal transduction mechanism, whereby it senses extracellular signals from the host and initiates the appropriate adaptation responses. Indeed, the ability of M. tb to exist in different states in the host (persistent quiescent state or actively replicating mode) is mainly mediated through protein phosphorylation/dephosphorylation signalling. The M. tb regulatory and defensive responses coordinate different aspects of the bacilli's physiology, for instance, cell wall components, metabolic activity, virulence, and growth. Herein, we will discuss the implication of M. tb kinases and phosphatases in hijacking the host immune system, perpetuating the infection. In addition, the role of PknG, MPtpA, MPtpB, and SapM inhibitors in resetting the host immune system will be highlighted.

Targeting ErbB and tankyrase1/2 prevent the emergence of drug-tolerant persister cells in ALK-positive lung cancer

Targeting the drug tolerant persister (DTP) state in cancer cells should prevent further development of resistance mechanisms. This study explored combination therapies to inhibit alectinib-induced DTP cell formation from anaplastic lymphoma kinase–positive non-small cell lung cancer (ALK + NSCLC) patient–derived cells. After drug-screening 3114 compounds, pan-HER inhibitors (ErbB pathway) and tankyrase1/2 inhibitors (Wnt/β-catenin signaling) emerged as top candidates to inhibit alectinib-induced DTP cells growth. We confirmed knockdown of both TNKS1/2 in DTP cells recovered the sensitivity to alectinib. Further, our study suggested knockdown of TNKS1/2 increased stability of Axin1/2, which induced β-catenin degradation and decreased its nuclear translocation, thereby suppressing transcription of antiapoptotic and proliferation-related genes (survivin, c-MYC). Targeting both pathways with alectinib+pan-HER inhibitor and alectinib+TNKS1/2 inhibitor suppressed alectinib-induced DTP cells, and the triple combination almost completely prevented the appearance of DTP cells. In conclusion, combination with ALK-TKI, pan-HER and TNKS1/2 inhibitors has the potential to prevent the emergence of DTP in ALK + NSCLC.

Molecular ladder polymer network enables scalable and robust solar water oxidation

Organic polymers with tunable band structures and light absorption properties offer a versatile alternative to inorganic materials for solar energy conversion. However, advancing organic polymers for efficient solar water oxidation has been hindered by challenges in charge separation and transport. Here we develop a molecular strategy to achieve an apparent quantum yield of 22 % for solar water oxidation by using a ladder polymer network coupled with a FeNi catalyst. Solar irradiation of the photocatalytic network produces high-flux excited states capable for catalyst activation, generating persistent charge-separated states available for water oxidation. The network exhibits high robustness during 125-hour solar water oxidation, showing negligible decrease in the photocatalytic activity. Owing to improved charge transport, the photocatalytic network is scaled up from 1.0 cm2 to 25 cm2 without sacrificing the quantum efficiency. Our findings herald the potential of ladder polymer networks toward scalable manufacturing of high-efficiency and cost-effective organic photocatalysts.

Olfactory bulb tracks breathing rhythms and place in freely behaving mice.

Vertebrates sniff to control the odor samples that enter their nose. These samples can not only help identify odorous objects, but also locations and events. However, there is no receptor for place or time. Therefore, to take full advantage of olfactory information, an animal's brain must contextualize odor-driven activity with information about when, where, and how they sniffed. To better understand contextual information in the olfactory system, we captured the breathing and movements of mice while recording from their olfactory bulb. In stimulus- and task-free experiments, mice structure their breathing into persistent rhythmic states which are synchronous with statelike structure in ongoing neuronal population activity. These population states reflect a strong dependence of individual neuron activity on variation in sniff frequency, which we display using "sniff fields" and quantify using generalized linear models. In addition, many olfactory bulb neurons have "place fields" that display significant dependence of firing on allocentric location, which were comparable with hippocampal neurons recorded under the same conditions. At the population level, a mouse's location can be decoded from olfactory bulb with similar accuracy to hippocampus. Olfactory bulb place sensitivity cannot be explained by breathing rhythms or scent marks. Taken together, we show that the mouse olfactory bulb tracks breathing rhythms and self-location, which may help unite internal models of self and environment with olfactory information as soon as that information enters the brain.