Systemic Spread Research Articles

Possibilities of radiological methods of diagnosis of metastatic castration-resistant prostate cancer (Review Article).

Abstract Metastatic castration-resistant prostate cancer (mCRPC) is characterized by the progression of the tumor process when it becomes unresponsive to androgen-deprivation therapy. The incidence of bone metastases in these patients reaches up to 90%. Imaging modalities play a pivotal role in the diagnosis of this oncological condition. Computed tomography (CT) and magnetic resonance imaging (MRI) offer advantages in anatomical visualization; however, they face limitations in assessing the efficacy of prostate cancer treatment. Scintigraphy is applicable in screening for skeletal bone metastatic involvement but has limitations in assessing disease progression. Positron emission tomography combined with computed tomography (PET/CT) and single-photon emission computed tomography (SPECT/CT) are utilized for early detection of local or systemic spread of prostate cancer. The assessment of quantitative data on radiopharmaceutical uptake using PSMA PET imaging is used for predicting the efficacy of antitumor therapy. With the introduction of the radiopharmaceutical 177Lu-PSMA into clinical practice, the perspective of conducting radionuclide therapy with simultaneous efficacy evaluation through hybrid imaging methods has emerged. The capabilities of imaging modalities in assessing bone metastases present a particular interest for research and systematization of the data obtained to develop optimal parameters for conducting radioligand therapy and evaluating its efficacy. Aims: To explore the capabilities of imaging modalities in diagnosing metastatic castration-resistant prostate cancer. Conclusions: The analyzed literature data indicate that imaging methods for diagnosing mCRPC vary in sensitivity and specificity, have their advantages and disadvantages, which underscores the necessity for a comprehensive approach in their utilization. The development and advancement of methods for quantitative assessment of treatment efficacy, identification of prognostic markers can influence a more informed choice of treatment tactics and radiopharmaceutical selection, potentially leading to an increase in overall survival.

A novel murine wire injury based infectious endocarditis model aggravates aortic valve stenosis

Abstract Background With mortality rates up to 40% under optimal medical treatment, infectious endocarditis (IE) remains one of the deadliest infectious diseases worldwide. In the early stages of IE, diagnosis and treatment initiation are often difficult and research is limited due to unreliable models. Most murine IE models rely on permanent prosthetic wire placement and i.v. bacterial injection, thus making it inadequate to study IE pathophysiology with the aim to reflect the course of disease in humans. Purpose To develop a reproducible murine IE model, based on aortic valve injury preceding intravenous S. aureus bacterial challenge. Methods Using a wire-injury model we induced endothelial lesions. 72h after wire injury (WI), we performed intravenous bacterial challenge using S. aureus. Echocardiography was performed to confirm bacterial vegetations and assess valvular function. Cross sections of valvular leaflets were prepared for scanning electron microscopy (SEM). Macrophage, neutrophil and S. aureus-specific immunofluorescence staining was performed and visualized by immunofluorescence microscopy. Bacterial cultivation was performed from peripheral blood and valve tissue. Systemic immune response was analyzed using flow cytometry. Results WI induced endothelial damage in all mice verified using scanning electron microscopy imaging. The combination of wire injury and injection of 10^5 and 10^6 colonies-forming-units (CFU) S. aureus reliably caused IE validated via in vivo echocardiography as well as S.aureus immunofluorescence staining and SEM imaging. Mice undergoing bacterial challenge responded with significant neutrophilia in the blood. Using 10^6 CFU S. aureus was associated with an increased mortality, liver and kidney abscess formation due to systemic bacterial spreading compared to 10^5 CFU. Peak velocity across the aortic valve and aortic valve leaflet thickness as markers for aortic valve stenosis were increased in IE compared to WI only mice. Aortic regurgitation was more prevalent after bacterial challenge mediating increased left ventricular volumes, meanwhile ejection fraction was not altered. Immunofluorescence staining revealed a pro-inflammatory milieu including increased macrophage and neutrophil infiltration in IE compared to WI only mice. Conclusion In vivo echocardiography and ex vivo histological staining revealed reliable IE induction using our new model with S. aureus concentrations of 10^5 CFU. The additional bacterial challenge causes a more severe aortic valve stenosis compared to WI only mice, potentially due to an observed increase in valvular inflammation.Fig 1 Scanning electron microscopy after

Assessment of PPMV-1 Genotype VI Virulence in Pigeons and Chickens and Protective Effectiveness of Paramyxovirus Vaccines in Pigeons.

Pigeon paramyxovirus serotype 1 (PPMV-1), an antigenic and host variant of avian paramyxovirus Newcastle disease virus (NDV), primarily originating from racing pigeons, has become a global panzootic. Egypt uses both inactivated PPMV-1 and conventional NDV vaccines to protect pigeons from disease and mortality. However, the impact of prevalent strains and the effectiveness of available vaccines in pigeons in Egypt are unclear. This study investigates the virulence of PPMV-1 (Pigeon/Egypt/Sharkia-19/2015/KX580988) and evaluates available paramyxovirus vaccines in protecting pigeons against a PPMV-1 challenge. Ten-day-old specific-pathogen-free (SPF) embryonated chicken eggs infected with this strain exhibited a mean death time (MDT) of 86.4 ± 5.88 h. The intracerebral pathogenicity index (ICPI) in day-old chickens was 0.8, while pigeons experienced an ICPI of 0.96 and an intravenous pathogenicity index (IVPI) of 2.11. These findings classify the strain as virulent and velogenic. Experimental infection of pigeons with this PPMV-1 strain at 106 EID50/0.1 mL resulted in a 62.5% mortality rate, displaying nervous and enteric distress. The virus caused extensive lesions in visceral organs, with strong immunohistochemistry signals in all examined organs, indicating the systemic spread of the virus concurrent to its neurotropic and viscerotropic tropism. Furthermore, vaccination using an inactivated PPMV-1 and live NDV LaSota vaccine regimen protected 100% of pigeons against mortality, while with a single NDV LaSota vaccine, it was 62.5%. The PPMV alone or combined with NDV LaSota induced protective levels of haemagglutination inhibition (HI) antibody titres and reduced virus shedding from buccal and cloacal cavities. Based on generalised linear gamma model analysis, both PPMV-1 and NDV LaSota are antigenically comparable by HI. These findings suggest that using both inactivated PPMV-1 (G-VI) and live attenuated NDV (LaSota) vaccines is an effective prophylactic regimen for preventing and controlling PPMV-1 and NDV in pigeons, thereby reducing the risk of interspecies transmission.

Physico-Chemical Characterization and Initial Evaluation of Carboxymethyl Chitosan-Hyaluronan Hydrocolloid Systems with Insulin Intended for Intranasal Administration.

The nasal route of administration can bypass the blood-brain barrier in order to obtain a higher concentration in the brain, thus offering a feasible alternative route of administration for diseases associated with the central nervous system. The advantages of the intranasal administration and the potential favorable therapeutic effects of intranasally administered insulin led to the formulation of carboxymethyl chitosan (CMC) and sodium hyaluronate (NaHA) hydrocolloidal systems with insulin for nasal administration, targeting nose-to-brain delivery and the initial assessment of these systems. The influence of the formulation variables on the response parameters defined as surface properties, rheology, and in vitro release of insulin were analyzed using experimental design and statistical programs (Modde and Minitab software). The systems recorded good wetting and adhesion capacity, allowing the spread of the hydrocolloidal systems on the nasal mucosa. The samples had a pseudoplastic flow and the rapid release of the insulin was according to our objective. According to the physico-chemical characterization and preliminary assessment, these formulations are appropriate for administration on the nasal mucosa, but further studies are necessary to demonstrate the beneficial therapeutic actions and the safety of using intranasal insulin.

From Single Orders to Batches: A Sensitivity Analysis of Warehouse Picking Efficiency

Currently, companies are called to meet variable market demand whilst having to comply with tighter delivery times, also due to the growing spread of e-commerce systems in the last decade. As never before, it is therefore mandatory to increase the efficiency within distribution centers to minimize operating costs and increase environmental and economical sustainability. The picking process is the most expensive task in a warehouse, both for the required resources and time for completing all the operations, which is typically carried out manually. Several policies can be identified, such as discrete or batch picking. Many studies tend to optimize both policies, treating them distinctly and integrating them with other factors including, for instance, the logic of product allocation. This article stands on a higher decision-making level: starting from a database obtained with a simulative approach that contains the average distances covered by pickers in different warehouse configurations, the aim is to provide an analysis of which factors have the greatest impact in preferring a discrete order picking policy over the batch one. The factors in question are shape factor, input–output point, routing and storage location assignment policies. Results can be useful for industrial practitioners in defining the most efficient managerial strategies.

Blocking HXA3-mediated neutrophil elastase release during S. pneumoniae lung infection limits pulmonary epithelial barrier disruption and bacteremia.

Streptococcus pneumoniae (Sp), a leading cause of community-acquired pneumonia, can spread from the lung into the bloodstream to cause septicemia and meningitis, with a concomitant threefold increase in mortality. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that target pathogenic immune processes. Polymorphonuclear leukocytes (PMNs) are essential for infection control but can also promote tissue damage and pathogen spread. The major Sp virulence factor, pneumolysin, triggers acute inflammation by stimulating the 12-lipoxygenase (12-LOX) eicosanoid synthesis pathway in epithelial cells. This pathway is required for systemic spread in a mouse pneumonia model and produces a number of bioactive lipids, including hepoxilin A3 (HXA3), a hydroxy epoxide PMN chemoattractant that has been hypothesized to facilitate breach of mucosal barriers. To understand how 12-LOX-dependent inflammation promotes dissemination during Sp lung infection and dissemination, we utilized bronchial stem cell-derived air-liquid interface cultures that lack this enzyme to show that HXA3 methyl ester (HXA3-ME) is sufficient to promote basolateral-to-apical PMN transmigration, monolayer disruption, and concomitant Sp barrier breach. In contrast, PMN transmigration in response to the non-eicosanoid chemoattractant N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP) did not lead to epithelial disruption or bacterial translocation. Correspondingly, HXA3-ME but not fMLP increased the release of neutrophil elastase (NE) from Sp-infected PMNs. Pharmacologic blockade of NE secretion or activity diminished epithelial barrier disruption and bacteremia after pulmonary challenge of mice. Thus, HXA3 promotes barrier-disrupting PMN transmigration and NE release, pathological events that can be targeted to curtail systemic disease following pneumococcal pneumonia.IMPORTANCEStreptococcus pneumoniae (Sp), a leading cause of pneumonia, can spread from the lung into the bloodstream to cause systemic disease. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that limit pathologic host immune responses to Sp. Excessive polymorphonuclear leukocyte (PMN) infiltration into Sp-infected airways promotes systemic disease. Using stem cell-derived respiratory cultures that reflect bona fide lung epithelium, we identified eicosanoid hepoxilin A3 as a critical pulmonary PMN chemoattractant that is sufficient to drive PMN-mediated epithelial damage by inducing the release of neutrophil elastase. Inhibition of the release or activity of this protease in mice limited epithelial barrier disruption and bacterial dissemination, suggesting a new host-directed treatment for Sp lung infection.

Interferometric Radars for Bridge Monitoring: Comparison among X-Bands, Ku-Bands, and W-Bands

Interferometric radars are widely used sensors for structural health monitoring. They are able to perform dynamic measurements of displacement with sub-millimeter precision. Today, the Ku-band is the most common, due to the spread of commercial systems operating in this band. At the same time, the W-band sensors are gaining ever more interest. Other popular systems work in the X-band. Since the characteristics of the measurements dramatically depend on the operative frequency, it is essential to highlight their differences. For instance, higher frequency allows for high displacement resolution, but it is more subject to phase wrapping and decorrelation effects. In this paper, a direct comparison between radars operating in X, Ku, and W-band for bridge monitoring is carried out. The radars provide frequency-modulated continuous-wave signals. Experimental campaigns were performed both in controlled and realistic scenarios (a stayed bridge). The results of the experiments demonstrate that all the three sensors are suitable for performing dynamic structure monitoring despite their differences. It is worth noting that this comparative analysis has highlighted the role of amplitude variation in phase/displacement measurement. Regarding this point, the three different bands exhibit significant differences.

Data analysis of average glandular dose in mammography toward revision of the diagnostic reference level of Japan.

Diagnostic reference level (DRL) for mammography for 2015 and 2020 has been published by J-RIME. More new dose studies are needed to revise the next DRL. In preparation for the next revision of the DRL for mammography, this study investigated data from the Japan Central Organization on Quality Assurance of Breast Cancer Screening on the mean average glandular dose (AGD) for institutional image accreditation in 2019-2023 and the relationship between the average at eligible institutions to date and the type of breast X-ray system. The 95th percentile values of the AGD distributions for the Computed Radiography (CR) and Flat Panel Detector (FPD) systems were 2.5mGy and 2.0mGy, respectively. Moreover, it is assumed that AGD is decreasing due to the spread of FPD systems, and it is expected that the further spread of FPD systems and systems with W/Rh target/filter will reduce AGD in future.

Vascular network-mediated systemic spread of Pseudomonas syringae pv. actinidiae causes the bacterial canker of kiwifruit

Pseudomonas syringae pv. actinidiae (Psa) causes destructive kiwifruit bacterial canker by invading vascular tissues across multiple plant organs. However, the cellular mechanism underlying its systemic transmission and cell-to-cell movement within these specialized vascular conduits remains unclear. In this study, a Psa-GFP strain and various microscopic techniques were used to investigate the interaction between kiwifruit and Psa. Our results reveal that Psa strategically exploits host vascular conduits for systemic movement, with the xylem vessel being the predominant avenue. In the phloem, Psa exhibits adaptive alteration in bacterial shape to traverse sieve pores, facilitating its systemic spread along sieve tubes and inducing phloem necrosis. Within the xylem, Psa breaches pit membranes to migrate between adjacent vessels. Furthermore, phloem fibers act as an initial barrier at the early stages of infection, delaying Psa's entry into vascular tissues during its journey to the xylem. Additionally, at the junctions of stem–stem or stem-leaf, branch trace or leaf trace mediates the bacterial organ-to-organ translocation, thus facilitating the systemic progression of disease. In conclusion, our findings shed light on the cellular mechanism employed by Psa to exploit the woody plant's vascular network for infection, thereby enhancing a better understanding of the biology of this poorly defined bacterium. These insights carry implications for the pathogenesis of Psa and other vascular pathogens, offering theoretical guidance for effective control strategies.

Mapping Human Immunity and the Education of Waldeyer's Ring.

The development and deployment of single-cell genomic technologies have driven a resolution revolution in our understanding of the immune system, providing unprecedented insight into the diversity of immune cells present throughout the body and their function in health and disease. Waldeyer's ring is the collective name for the lymphoid tissue aggregations of the upper aerodigestive tract, comprising the palatine, pharyngeal (adenoids), lingual, and tubal tonsils. These tonsils are the first immune sentinels encountered by ingested and inhaled antigens and are responsible for mounting the first wave of adaptive immune response. An effective mucosal immune response is critical to neutralizing infection in the upper airway and preventing systemic spread, and dysfunctional immune responses can result in ear, nose, and throat pathologies. This review uses Waldeyer's ring to demonstrate how single-cell technologies are being applied to advance our understanding of the immune system and highlight directions for future research.

Sex-based difference in immune responses and efficacy of the pneumococcal conjugate vaccine.

Vaccine-mediated protection and susceptibility to Streptococcus pneumoniae (pneumococcus) infections are influenced by biological sex. The incidence of invasive pneumococcal disease remains higher in males compared to females even after the introduction of the pneumococcal conjugate vaccine (PCV). However, sex-based differences in the immune response to this conjugate vaccine remain unexplored. To investigate those differences, we vaccinated adult male and female mice with PCV and assessed cellular and humoral immune responses. Compared to females, male mice displayed lower levels of T follicular helper cells, germinal center B cells and plasmablasts, which are all required for antibody production following vaccination. This was linked to lower IgG and IgM levels against pneumococci and lower isotype switching to IgG3 in vaccinated males. Due to lower antibody levels, sera of vaccinated male mice had lower efficacy in several anti-pneumococcal functions including neutralization of bacterial binding to pulmonary epithelial cells as well as direct cytotoxicity against S. pneumoniae. Importantly, while the vaccine was highly protective in females, vaccinated males succumbed to infection more readily and were more susceptible to both lung-localized infection and systemic spread following S. pneumoniae challenge. These findings identify sex-based differences in immune responses to PCV that can inform future vaccine strategies.

Elucidating the Subcellular Localization of GLRaV-3 Proteins Encoded by the Unique Gene Block in N. benthamiana Suggests Implications on Plant Host Suppression.

Grapevine leafroll-associated virus 3 (GLRaV-3) is a formidable threat to the stability of the global grape and wine industries. It is the primary etiological agent of grapevine leafroll disease (GLD) and significantly impairs vine health, fruit quality, and yield. GLRaV-3 is a member of the genus Ampelovirus, Closteroviridae family. Viral genes within the 3' proximal unique gene blocks (UGB) remain highly variable and poorly understood. The UGBs of Closteroviridae viruses include diverse open reading frames (ORFs) that have been shown to contribute to viral functions such as the suppression of the host RNA silencing defense response and systemic viral spread. This study investigates the role of GLRaV-3 ORF8, ORF9, and ORF10, which encode the proteins p21, p20A, and p20B, respectively. These genes represent largely unexplored facets of the GLRaV-3 genome. Here, we visualize the subcellular localization of wildtype and mutagenized GLRaV-3 ORFs 8, 9, and 10, transiently expressed in Nicotiana benthamiana. Our results indicate that p21 localizes to the cytosol, p20A associates with microtubules, and p20B is trafficked into the nucleus to carry out the suppression of host RNA silencing. The findings presented herein provide a foundation for future research aimed at the characterization of the functions of these ORFs. In the long run, it would also facilitate the development of innovative strategies to understand GLRaV-3, mitigate its spread, and impacts on grapevines and the global wine industry.

Commensal Yeast Promotes Salmonella Typhimurium Virulence.

Enteric pathogens engage in complex interactions with the host and the resident microbiota to establish gut colonization. Although mechanistic interactions between enteric pathogens and bacterial commensals have been extensively studied, whether and how commensal fungi affect pathogenesis of enteric infections remains largely unknown. Here we show that colonization with the common human gut commensal fungus Candida albicans worsened infections with the enteric pathogen Salmonella enterica serovar Typhimurium. Presence of C. albicans in the mouse gut increased Salmonella cecum colonization and systemic dissemination. We investigated the underlying mechanism and found that Salmonella binds to C. albicans via Type 1 fimbriae and uses its Type 3 Secretion System (T3SS) to deliver effector proteins into C. albicans . A specific effector, SopB, was sufficient to manipulate C. albicans metabolism, triggering increased arginine biosynthesis in C. albicans and the release of millimolar amounts of arginine into the extracellular environment. The released arginine, in turn, induced T3SS expression in Salmonella , increasing its invasion of epithelial cells. C. albicans deficient in arginine production was unable to increase Salmonella virulence in vitro or in vivo . In addition to modulating pathogen invasion, arginine also directly influenced the host response to infection. Arginine-producing C. albicans dampened the inflammatory response during Salmonella infection, whereas C. albicans deficient in arginine production did not. Arginine supplementation in the absence of C. albicans increased the systemic spread of Salmonella and decreased the inflammatory response, phenocopying the presence of C. albicans . In summary, we identified C. albicans colonization as a susceptibility factor for disseminated Salmonella infection, and arginine as a central metabolite in the cross-kingdom interaction between fungi, bacteria, and host.

Artifacts-free lensless on-chip tomography empowered by three-dimensional deconvolution

A lensless holographic microscope based on in-line holograms and optical diffraction tomography is an ideal imaging system for label-free 3D biological samples and can achieve large-volume imaging with single-cell resolution in a convenient way. However, due to the phase information loss and the missing cone problem, the imaging quality is significantly degraded by the reconstructed artifacts of twin images and out-of-focus images, which severely hinders the identification and interpretation of the objects. We propose an artifacts-free lensless on-chip tomography certified by three-dimensional deconvolution, which facilitates the extraction of real object morphology through straightforward yet effective computation. Initially, a globally valid systemic point spread function (PSF) is generated by simulating the imaging output of an ideal point light source positioned at the origin of the object space coordinate. Subsequently, an iterative three-dimensional deconvolution process is applied to the primitive imaging outcome of the lensless on-chip tomography using this PSF. Through rapid iterations, the optimized imaging result is swiftly obtained. Both the simulated and experimental results indicate that the artifacts-free lensless on-chip tomography can effectively circumvent the reconstructed artifacts and retrieve the real object morphology, which is critical for detailed observation and further quantitative analysis. In addition, we anticipate that the proposed approach has the potential to be transferred to other 3D imaging systems in systemic artifacts removal after corresponding modifications.

Investigating Exosomes in SARS-CoV-2 Infection: A Potential Partner for Coronavirus Reinfection/Reactivation

Virus-infected cells secrete exosomes and other extracellular vesicles which could deliver viral components, including structural proteins and viral derived-ribonucleic acids to other cells. Released extracellular vesicles carry virus-specific receptors that increase the sensitivity of the target cells to viral infection. Exosomes may contribute to the systemic spreading of SARS-CoV-2 virus by transferring essential receptors, such as angiotensin-converting enzyme 2 and CD9 that promote the ability of the virus to dock into the target cells. Subsequently, the SARS-CoV-2 virus might also enter into the exosomal pathway to use this system for packaging their components into exosomes for secretion. This study suggests that one of the potential explanations for the relapse and persistence of the SARS-CoV-2 virus infection could be an endocytic transport pathway related to the secretion of COVID-19-loaded extracellular vesicles.

Surgical Management of Iatrogenic Mercury Poisoning From Subcutaneous Injection Into the Arm.

Mercury, an element with threats of severe toxic insult to humans and no biological function, has a surprisingly extensive record of human exposure. Regardless of hesitancies toward its harmfulness, it has been historically identified with an almost supernatural power to provide protection from evil and sickness, give good fortune, lend aid in athletic undertakings, or even allow one to achieve immortality. Mercury poisoning is an iatrogenic disease even today as people attempt to achieve these effects through volitional injections into their body by practitioners. Although an uncommon practice in the United States, awareness of patient presentation after volitional injections of elemental mercury is necessary for appropriate treatment of these patients. We aim to increase awareness of the cultural practice of subcutaneous injections of mercury, as it is uncommonly seen in the United States, to contribute a broader understanding to the patient's medical presentation and describe an approach and the impact of medical and surgical intervention. In this report, we describe a rare case of elemental mercury poisoning secondary to volitional subcutaneous injection to the arm. Initial management of care through chelation therapy and monitoring of renal and serum mercury levels in addition to symptoms of systemic spread was overseen by an internal medicine physician and poison control. Surgical intervention via full-thickness excision of the visible mercury to the right arm followed by local flap and skin grafting reconstruction was performed. Mercury poisoning from intentional subcutaneous administration is an uncommon patient presentation in the United States; however, knowledge of management of this rare condition is important for effective management of iatrogenic mercury toxicity.

Trophic microRNA: Post-transcriptional regulation of target genes and larval development impairment in Plutella xylostella upon precursor and mature microRNA ingestion.

MicroRNAs (miRNAs) are post-transcriptional gene regulators. In the miRNA pathway's cytoplasmic part, the miRNA is processed from a hairpin-structured precursor to a double-stranded (ds) mature RNA and ultimately to a single-stranded mature miRNA. In insects, ingesting these two ds forms can regulate the target gene expression; this inspired the trophic miRNA's use as a functional genomics and pest management tool. However, systematic studies enabling comparisons of pre- and mature forms, dosages, administration times and instar-wise effects on target transcripts and phenotypes, which can help develop a miRNA administration method, are unavailable due to the different focuses of the previous investigations. We investigated the impact of trophically delivered Px-let-7 miRNA on the lepidopteran pest Plutella xylostella, to compare the efficacies of its pre- and ds-mature forms. Continuous feeding on the miRNA-supplemented diet suppressed expressions of FTZ-F1 and E74, the target ecdysone pathway genes. Both the pre-let-7 and mature let-7 miRNA forms similarly downregulated the target transcripts in all four larval instars. Pre-let-7 and let-7 ingestions decreased larval mass and instar duration and increased mortality in all instars, exhibiting adverse effects on larval growth and development. miRNA processing Dicer-1 and AGO-1's upregulations upon miRNA ingestion denoted the systemic miRNA spread in larval tissues. The scrambled sequence controls did not affect the target transcripts, suggesting the sequence-specific targeting by the mature miRNA and hairpin cassette's non-involvement in the target downregulation. This work provides a framework for miRNA and target gene function analyses and potentiates the trophic miRNA's utility in pest management.

Accelerated Decay due to Operator Spreading in Bulk-Dissipated Quantum Systems.

Markovian open many-body quantum systems display complicated relaxation dynamics. The spectral gap of the Liouvillian characterizes the asymptotic decay rate towards the stationary state, but it has recently been pointed out that the spectral gap does not necessarily determine the overall relaxation time. Our understanding on the relaxation process before the asymptotically long-time regime is still limited. We here present a collective relaxation dynamics of autocorrelation functions in the stationary state. As a key quantity in the analysis, we introduce the instantaneous decay rate, which characterizes the transient relaxation and converges to the conventional asymptotic decay rate in the long-time limit. Our theory predicts that a bulk-dissipated system generically shows an accelerated decay before the asymptotic regime due to the scrambling of quantum information associated with the operator spreading.

Impaired ATP hydrolysis in blood plasma contributes to age-related neutrophil dysfunction

BackgroundThe function of polymorphonuclear neutrophils (PMNs) decreases with age, which results in infectious and inflammatory complications in older individuals. The underlying causes are not fully understood. ATP release and autocrine stimulation of purinergic receptors help PMNs combat microbial invaders. Excessive extracellular ATP interferes with these mechanisms and promotes inflammatory PMN responses. Here, we studied whether dysregulated purinergic signaling in PMNs contributes to their dysfunction in older individuals.ResultsBacterial infection of C57BL/6 mice resulted in exaggerated PMN activation that was significantly greater in old mice (64 weeks) than in young animals (10 weeks). In contrast to young animals, old mice were unable to prevent the systemic spread of bacteria, resulting in lethal sepsis and significantly greater mortality in old mice than in their younger counterparts. We found that the ATP levels in the plasma of mice increased with age and that, along with the extracellular accumulation of ATP, the PMNs of old mice became increasingly primed. Stimulation of the formyl peptide receptors of those primed PMNs triggered inflammatory responses that were significantly more pronounced in old mice than in young animals. However, bacterial phagocytosis and killing by PMNs of old mice were significantly lower than that of young mice. These age-dependent PMN dysfunctions correlated with a decrease in the enzymatic activity of plasma ATPases that convert extracellular ATP to adenosine. ATPases depend on divalent metal ions, including Ca2+, Mg2+, and Zn2+, and we found that depletion of these ions blocked the hydrolysis of ATP and the formation of adenosine in human blood, resulting in ATP accumulation and dysregulation of PMN functions equivalent to those observed in response to aging.ConclusionsOur findings suggest that impaired hydrolysis of plasma ATP dysregulates PMN function in older individuals. We conclude that strategies aimed at restoring plasma ATPase activity may offer novel therapeutic opportunities to reduce immune dysfunction, inflammation, and infectious complications in older patients.

Out of time order correlation of the Hubbard model with random local disorder.

The out-of-time-order correlator (OTOC) serves as a powerful tool for investigating quantum information spreading and chaos in complex systems. We present a method employing non-equilibrium dynamical mean-field theory and coherent potential approximation combined with diagrammatic perturbation on the Schwinger-Keldysh contour to calculate the OTOC for correlated fermionic systems subjected to both random disorder and electron interaction. Our key finding is that random disorder enhances the OTOC decay in the Hubbard model for the metallic phase in the weakly interacting limit. However, the current limitation of our perturbative solver restricts the applicability to weak interaction regimes.