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By analogy with the construction of the Furstenberg boundary, the Stone–Čech boundary of |$\textrm {SL}(3,\mathbb {Z})$| is a fibered space over products of projective matrices. The proximal behaviour on this space is exploited to show that the preimages of certain sequences have accumulation points that belong to specific regions, defined in terms of flags. We show that the |$\textrm {SL}(3,\mathbb {Z})\times \textrm {SL}(3,\mathbb {Z})$| -quasi-invariant Radon measures supported on these regions are tempered. Thus, every quasi-invariant Radon boundary measure for |$\textrm {SL}(3,\mathbb {Z})$| is an orthogonal sum of a tempered measure and a measure having matrix coefficients belonging to a certain ideal |$c^{\prime}_0 ((\textrm {SL}(3,\mathbb {Z}) \times \textrm {SL}(3,\mathbb {Z}))$|⁠ , slightly larger than |$c_0 ((\textrm {SL}(3,\mathbb {Z}) \times \textrm {SL}(3,\mathbb {Z}))$|⁠. Hence, the left–right representation of |$C^*(\textrm {SL}(3,\mathbb {Z}) \times \textrm {SL}(3,\mathbb {Z}))$| in the Calkin algebra of |$\textrm {SL}(3,\mathbb {Z})$| factors through |$C^*_{c^{\prime}_0} (\textrm {SL}(3,\mathbb {Z}) \times \textrm {SL}(3,\mathbb {Z}))$| and the centralizer of every infinite subgroup of |$\textrm {SL}(3,\mathbb {Z})$| is amenable. [ABSTRACT FROM AUTHOR]

Homeostatic regulation of visceral organ function requires integrated processing of neural and neurohormonal sensory signals. The nucleus of the solitary tract (NTS) is the primary sensory nucleus for cranial visceral sensory afferents. Angiotensin II (ANG II) is known to modulate peripheral visceral reflexes, in part, by activating ANG II type 1A receptors (AT1AR) in the NTS. AT1AR-expressing NTS neurons occur throughout the NTS with a defined subnuclear distribution, and most of these neurons are depolarized by ANG II. In this study we determined whether AT1AR-expressing NTS neurons receive direct visceral sensory input, and whether this input is modulated by ANG II. Using AT1AR-GFP mice to make targeted whole cell recordings from AT1AR-expressing NTS neurons, we demonstrate that two-thirds (37 of 56) of AT1AR-expressing neurons receive direct excitatory, visceral sensory input. In half of the neurons tested (4 of 8) the excitatory visceral sensory input was significantly reduced by application of the transient receptor potential vallinoid type 1 receptor agonist, capsaicin, indicating AT1AR-expressing neurons can receive either C- or A-fiber-mediated input. Application of ANG II to a subset of second-order AT1AR-expressing neurons did not affect spontaneous, evoked, or asynchronous glutamate release from visceral sensory afferents. Thus it is unlikely that AT1AR-expressing viscerosensory neurons terminate on AT1AR-expressing NTS neurons. Our data suggest that ANG II is likely to modulate multiple visceral sensory modalities by altering the excitability of second-order AT1AR-expressing NTS neurons. [ABSTRACT FROM AUTHOR]

Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT1AR) most widely expressed in adult neurons. Activation of the AT1R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT1R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT1AR-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT1AR promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT1AR-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT1AR-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT1AR-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT1AR-GFP neurons and TH-GFP neurons showed similar AT1AR-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT1AR-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2011) 119, 18-26. Abstract Astrocytes are the major source of angiotensinogen in the brain and play an important role in the brain renin-angiotensin system. Regulating brain angiotensinogen production alters blood pressure and fluid and electrolyte homeostasis. In turn, several physiological and pathological manipulations alter expression of angiotensinogen in brain. Surprisingly, little is known about the factors that regulate astrocytic expression of angiotensinogen. There is evidence that angiotensinogen production in both hepatocytes and cardiac myocytes can be positively regulated via the angiotensin type 1 receptor, but this effect has not yet been studied in astrocytes. Therefore, the aim of this project was to establish whether angiotensin II modulates angiotensinogen production in brain astrocytes. Primary astrocyte cultures, prepared from neonatal C57Bl6 mice, expressed angiotensinogen measured by immunocytochemistry and real-time PCR. Using a variety of approaches we were unable to identify angiotensin receptors on cultured astrocytes. Exposure of cultured astrocytes to angiotensin II also did not affect angiotensinogen expression. When astrocyte cultures were transduced with the angiotensin type 1A receptor, using adenoviral vectors, angiotensin II induced a robust down-regulation (91.4% ± 1.8%, p < 0.01, n = 4) of angiotensinogen gene expression. We conclude that receptors for angiotensin II are present in extremely low levels in astrocytes, and that this concurs with available data in vivo. The signaling pathways activated by the angiotensin type 1A receptor are negatively coupled to angiotensinogen expression and represent a powerful pathway for decreasing expression of this protein, potentially via signaling pathways coupled to Gαq/11. [ABSTRACT FROM AUTHOR]

Angiotensin II acts through specific receptors to alter several brain functions including fluid and electrolyte control, neuroendocrine function and autonomic efferent activity. This review discusses one brain site, the rostral ventrolateral medulla, where the actions of angiotensin II have been intensively studied. The rostral ventrolateral medulla plays a critical role in the generation and regulation of sympathetic activity to the cardiovascular system and hence is important for blood pressure control. Current evidence indicates that angiotensin II activates neurons in the rostral ventrolateral medulla via the AT1A receptor. In some models of cardiovascular disease, blockade of AT1 receptors in the rostral ventrolateral medulla reduces sympathetic nerve activity and blood pressure suggesting that overactivity of the angiotensin system in this nucleus may play a role in the maintenance of high blood pressure. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This paper presents the concept of digital health, also known as e-healthcare, and discusses its current state of the art, enabling factors, and barriers. The focus is on the level of e-health literacy among the elderly population, the factors that influence it, the relevance of innovative digital health projects, the usability of digital tools, organizational models, and implications for the national health system. The study employed a research methodology consisting of two phases. A review of journal articles was conducted, followed by a longitudinal analysis of a case study of a project (TS4.0) launched by the Trentino Region. The study emphasises the need for training programmes on key IT and health technologies for underserved groups to improve the adoption of eHealth technologies by patients. Specific actions to achieve this goal are proposed, with emphasis on the crucial role of public institutions. For hospitals to fully embrace technology and become digital, healthcare facilities must undergo a business and managerial transformation that involves the use of technology. This case study highlights the importance of supporting healthcare start-ups to comprehensively improve healthcare. Although this study is limited to a single case, the results may be useful for further research in identifying other factors that enable or hinder the adoption of digitalisation in the healthcare sector. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) is a drug of abuse, which induces behavioral sensitization following repeated doses. Since METH alters blood pressure, in the present study we assessed whether systolic and diastolic blood pressure (SBP and DBP, respectively) are sensitized as well. In this context, we investigated whether alterations develop within A1/C1 neurons in the vasomotor center. C57Bl/6J male mice were administered METH (5 mg/kg, daily for 5 consecutive days). Blood pressure was measured by tail-cuff plethysmography. We found a sensitized response both to SBP and DBP, along with a significant decrease of catecholamine neurons within A1/C1 (both in the rostral and caudal ventrolateral medulla), while no changes were detected in glutamic acid decarboxylase. The decrease of catecholamine neurons was neither associated with the appearance of degeneration-related marker Fluoro-Jade B nor with altered expression of α-synuclein. Rather, it was associated with reduced free radicals and phospho-cJun and increased heat shock protein-70 and p62/sequestosome within A1/C1 cells. Blood pressure sensitization was not associated with altered arterial reactivity. These data indicate that reiterated METH administration may increase blood pressure persistently and may predispose to an increased cardiovascular response to METH. These data may be relevant to explain cardiovascular events following METH administration and stressful conditions. [ABSTRACT FROM AUTHOR]

Arterial hypertension (HTN) is one of the major global contributors to cardiovascular diseases and premature mortality, particularly due to its impact on vital organs and the coexistence of various comorbidities such as chronic renal disease, diabetes, cerebrovascular diseases, and obesity. Regardless of the accessibility of several well-established pharmacological treatments, the percentage of patients achieving adequate blood pressure (BP) control is still significantly lower than recommended levels. Therefore, the pharmacological and non-pharmacological management of HTN is currently the major focus of healthcare systems. Various strategies are being applied, such as the development of new pharmacological agents that target different underlying physiopathological mechanisms or associated comorbidities. Additionally, a novel group of interventional techniques has emerged in recent years, specifically for situations when blood pressure is not properly controlled despite the use of multiple antihypertensives in maximum doses or when patients are unable to tolerate or desire not to receive antihypertensive medications. Nonetheless, reducing the focus on antihypertensive medication development by the pharmaceutical industry and increasing recognition of ineffective HTN control due to poor drug adherence demands ongoing research into alternative approaches to treatment. The aim of this review is to summarize the potential novel pharmacological targets for the treatment of arterial hypertension as well as the future perspectives of the treatment strategy. [ABSTRACT FROM AUTHOR]

L'évacuation des blessés, partiqulièrement dans la zone comprise entre la ligne de combat et les hôpitaux de camp de corps d'armée (zone de première évacuation), atteignit, dans le premier conflit, une importance et une gravité nouvelles et imprévues, de sorte que, les premiers temps, les services sanitaires des diverses armées belligérantes se trouvèrent plus ou moins bien préparés. [ABSTRACT FROM PUBLISHER]

The development, differentiation, and function of immune cells are precisely regulated by transcription factors. The E26 transformation-specific (ETS) transcription factor family is involved in various physiological and pathological processes by regulating cell proliferation, differentiation, and apoptosis. Emerging evidence has suggested that ETS family proteins are intimately involved in the development and function of immune cells. This review summarizes the role of the ETS family in immune cells and immune-related disorders. Seven transcription factors within the ETS family, including PU.1, ETV5, ETV6, ETS1/2, ELK3, and ELF1, play essential roles in the development and function of T cells, B cells, macrophages, neutrophils, and dendritic cells. Furthermore, they are involved in the occurrence and development of immune-related diseases, including tumors, allergies, autoimmune diseases, and arteriosclerosis. This review is conducive to a comprehensive overview of the role of the ETS family in immune cells, and thus is informative for the development of novel therapeutic strategies targeting the ETS family for immune-related diseases. [ABSTRACT FROM AUTHOR]

Leptin is a hormone produced by the small intestines and adipose tissue that promotes feelings of satiety. Leptin receptors (LepRs) are highly expressed in the hypothalamus, enabling central neural control of hunger. Interestingly, LepRs are also expressed in several other regions of the body and brain, notably in the cerebral cortex and hippocampus. These brain regions mediate higher-order sensory, motor, cognitive, and memory functions, which can be profoundly altered during periods of hunger and satiety. However, LepR expression in these regions has not been fully characterized on a cell-type-specific basis, which is necessary to begin assessing their potential functional impact. Consequently, we examined LepR expression on neurons and glia in the forebrain using a LepR-Cre transgenic mouse model. LepR-positive cells were identified using a 'floxed' viral cell-filling approach and co-labeling immunohistochemically for cell-type-specific markers, i.e., NeuN, VGlut2, GAD67, parvalbumin, somatostatin, 5-HT3R, WFA, S100β, and GFAP. In the cortex, LepR-positive cells were localized to lower layers (primarily layer 6) and exhibited non-pyramidal cellular morphologies. The majority of cortical LepR-positive cells were neurons, while the remainder were identified primarily as astrocytes or other glial cells. The majority of cortical LepR-positive neurons co-expressed parvalbumin, while none expressed somatostatin or 5-HT3R. In contrast, all hippocampal LepR-positive cells were neuronal, with none co-expressing GFAP. These data suggest that leptin can potentially influence neural processing in forebrain regions associated with sensation and limbic-related functions. [ABSTRACT FROM AUTHOR]

Lassa virus (LASV) is an enveloped, negative-sense RNA virus that causes Lassa hemorrhagic fever. Successful entry of LASV requires the viral glycoprotein 1 (GP1) to undergo a receptor switch from its primary receptor alpha-dystroglycan (α-DG) to its endosomal receptor lysosome-associated membrane protein 1 (LAMP1). A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor switch. To test the hypothesis that other non-conserved residues also contribute to receptor switch, we constructed a series of mutant LASV GP1 proteins and tested them for binding to LAMP1. Four residues, L84, K88, L107, and H170, were identified as critical for receptor switch. Substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus (LCMV) residue (L84 N, K88E, L10F, and H170S) reduced the binding affinity of LASV GP1 for LAMP1. Moreover, all mutations caused decreases in glycoprotein precursor (GPC)-mediated membrane fusion at both pH 4.5 and 5.2. The infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types, while L107F and H170S had only mild effects on infectivity. Using biolayer light interferometry assay, we found that all four mutants had decreased binding affinity to LAMP1, in the order of binding affinity being L84 N > L107F > K88E > H170S. The four amino acid loci identified for the first time in this study have important reference significance for the in-depth investigation of the mechanism of receptor switching and immune escape of LASV occurrence and the development of reserve anti-LASV infection drugs. [ABSTRACT FROM AUTHOR]

Beginning in 2022, following widespread infection and vaccination among the global population, the SARS-CoV-2 virus mainly evolved to evade immunity derived from vaccines and past infections. This review covers the convergent evolution of structural, nonstructural, and accessory proteins in SARS-CoV-2, with a specific look at common mutations found in long-lasting infections that hint at the virus potentially reverting to an enteric sarbecovirus type. [ABSTRACT FROM AUTHOR]

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Background: Medication errors and associated adverse drug events (ADE) are a major cause of morbidity and mortality worldwide. In recent years, the prevention of medication errors has become a high priority in healthcare systems. In order to improve medication safety, computerized Clinical Decision Support Systems (CDSS) are increasingly being integrated into the medication process. Accordingly, a growing number of studies have investigated the medication safety-related effectiveness of CDSS. However, the outcome measures used are heterogeneous, leading to unclear evidence. The primary aim of this study is to summarize and categorize the outcomes used in interventional studies evaluating the effects of CDSS on medication safety in primary and long-term care. Methods: We systematically searched PubMed, Embase, CINAHL, and Cochrane Library for interventional studies evaluating the effects of CDSS targeting medication safety and patient-related outcomes. We extracted methodological characteristics, outcomes and empirical findings from the included studies. Outcomes were assigned to three main categories: process-related, harm-related, and cost-related. Risk of bias was assessed using the Evidence Project risk of bias tool. Results: Thirty-two studies met the inclusion criteria. Almost all studies (n = 31) used process-related outcomes, followed by harm-related outcomes (n = 11). Only three studies used cost-related outcomes. Most studies used outcomes from only one category and no study used outcomes from all three categories. The definition and operationalization of outcomes varied widely between the included studies, even within outcome categories. Overall, evidence on CDSS effectiveness was mixed. A significant intervention effect was demonstrated by nine of fifteen studies with process-related primary outcomes (60%) but only one out of five studies with harm-related primary outcomes (20%). The included studies faced a number of methodological problems that limit the comparability and generalizability of their results. Conclusions: Evidence on the effectiveness of CDSS is currently inconclusive due in part to inconsistent outcome definitions and methodological problems in the literature. Additional high-quality studies are therefore needed to provide a comprehensive account of CDSS effectiveness. These studies should follow established methodological guidelines and recommendations and use a comprehensive set of harm-, process- and cost-related outcomes with agreed-upon and consistent definitions. Prospero registration: CRD42023464746 [ABSTRACT FROM AUTHOR]

While alkaline Zn batteries, like traditional rechargeable aqueous batteries, boast an advantage in terms of energy density, their progress has been hampered by concerns related to the anode. These concerns include issues like Zn dendrites, self‐corrosion, passivation, shape change, and the hydrogen evolution reaction (HER). To tackle these challenges, we have introduced a nanostructuring approach for the anode, employing carbon‐coated ZnO nanoparticles (ZnO@C) as the active material. In this study, we synthesized ZnO@C nanoparticles in an environmentally sustainable and scalable manner to address passivation and dissolution issues jointly. Nanoscale ZnO particles effectively prevent passivation, while carbon shell slows down the dissolution of zincate. The Zn anode exhibits a significant performance boost when compared to Zn foil and bare ZnO nanoparticles, even when subjected to demanding conditions (without the use of ZnO‐saturated electrolyte). This rechargeable Zn anode marks a significant step toward the realization of practical, high‐energy rechargeable aqueous batteries, such as Zn‐air batteries. [ABSTRACT FROM AUTHOR]

Veterinary oncology has experienced significant evolution over the last few decades, with chemotherapy being currently applied to several neoplasms with therapeutic success. Traditionally, chemotherapy protocols are based on classic cytostatic drugs under the concept of maximum tolerated dose (MTD), which has been associated with a greater risk of toxicity and resistance. Thus, new therapeutic alternatives have emerged, such as metronomic chemotherapy (MC), introducing a new paradigm in cancer treatment. MC consists of administering low doses of chemotherapy drugs continuously over a long period of time, modulating the tumour microenvironment (TME) due to the combination of cytotoxic, antiangiogenic and immunomodulatory effects. This multi-targeted therapy has been described as a treatment option in several canine and feline cancers since 2007, with positive results already published in the literature, particularly in mammary carcinomas and soft tissue sarcomas in dogs. The aim of this review article is to describe the current knowledge about the use of MC in small animal oncology, with emphasis on its mechanisms of action, the most commonly used drugs and clinical outcome. [ABSTRACT FROM AUTHOR]

Chemical reactions are by definition dynamical. Reactants move towards each other, collide and products separate again. Therefore, it is important to look beyond the stationary description, and look at how molecules rearrange and how energy is partitioned during a reactive collision. Chemical reactions are complex and often involve competing chemical and/or atomistic pathways whose dominance depends on several factors as for example the involved quantum states or collision energy. Here, we focus on ion molecule reactions which play an important role in gaseous environments even though their steady-state abundance is often much lower than that of their neutral counterparts. We present the use of angle and energy differential cross sections from crossed beam imaging experiments to disentangle competing reaction pathways. The general term pathways includes different effects of specific reactant quantum states on the atomistic mechanism to the competition of different product channels. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic has heightened concerns about immunological protection, especially for individuals with inborn errors of immunity (IEI). While COVID-19 vaccines elicit strong immune responses in healthy individuals, their effectiveness in IEI patients remains unclear, particularly against new viral variants and vaccine formulations. This uncertainty has led to anxiety, prolonged self-isolation, and repeated vaccinations with uncertain benefits among IEI patients. Despite some level of immune response from vaccination, the definition of protective immunity in IEI individuals is still unknown. Given their susceptibility to severe COVID-19, strategies such as immunoglobulin replacement therapy (IgRT) and monoclonal antibodies have been employed to provide passive immunity, and protection against both current and emerging variants. This review examines the efficacy of COVID-19 vaccines and antibody-based therapies in IEI patients, their capacity to recognize viral variants, and the necessary advances required for the ongoing protection of people with IEIs. [ABSTRACT FROM AUTHOR]

Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about the possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories of broadly neutralizing antibodies (bnAbs) that retain prominent effectiveness against emerging variants including Omicron sub-lineages. The molecular characteristics, epitope conservation, and resistance mechanisms of these antibodies are further detailed, aiming to offer suggestion or direction for the development of therapeutic antibodies, and facilitate the design of vaccines with broad-spectrum potential. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease on haemodialysis (HD) were given priority COVID-19 vaccination due to increased disease risk. The immune response to COVID-19 vaccination in patients on HD was diminished compared to healthy individuals in 2-dose studies. This study aimed to evaluate seroconversion rate, neutralizing antibody (nAB) levels and longitudinal antibody dynamics to 3-dose heterologous vaccination against COVID-19 in a cohort of HD patients compared to healthy controls and assess patient factors associated with antibody levels. Methods: This study was a case–control longitudinal evaluation of nAB dynamics in 74 HD patients compared to 37 healthy controls in a low/middle income setting. Corresponding samples were obtained from the two cohorts at time-points (TP) 1–1-month post 2nd dose of AZD1222 vaccine, TP2- 4 months post 2nd dose, TP4- 2 weeks post 3rd dose with BNT162b2 vaccine, TP5-5 months post 3rd dose and TP6-12 months post 3rd dose. Additional data is available at TP0- pre 2nd dose and TP3- 6 months post 2nd dose in HC and HD cohorts respectively. Anti-SARS-CoV-2 nAB were detected using Genscript cPassTM pseudoviral neutralization kit. Demographic and clinical details were obtained using an interviewer administered questionnaire. Results: Cohorts were gender matched while mean age of the HD cohort was 54.1yrs (vs HCs mean age, 42.6yrs, p < 0.05). Percentage seroconverted and mean/median antibody level (MAB) in the HD cohort vs HCs at each sampling point were, TP1-83.7% vs 100% (p < 0.05), MAB-450 IU/ml vs 1940 IU/ml (p < 0.0001); TP2-71.4% vs 100%, (p < 0.001), MAB- 235 IU/ml vs 453 IU/ml, (p < 0.05); TP4-95.2% vs 100% (p > 0.05), MAB-1029 IU/ml vs 1538 IU/ml (p < 0.0001); TP5-100% vs 100%, MAB-1542 IU/ml vs 1741IU/ml (p > 0.05); TP6-100% vs 100%, MAB-1961 IU/ml vs 2911 IU/ml (p > 0.05). At TP2, patients aged < 60 years (p < 0.001) were associated with maintaining seropositivity compared to patients > 60 years. Conclusion: Two dose vaccination of haemodialysis patients provided poor nAB levels which improved markedly following 3rd dose vaccination, the effect of which was long- lasting with high nAB levels in both patients and controls detectable at 1 year follow-up. [ABSTRACT FROM AUTHOR]

The sympathetic nervous system modulates arterial blood pressure. Individuals with obstructive sleep apnea (OSA) experience numerous nightly hypoxic episodes and exhibit elevated sympathetic activity to the cardiovascular system leading to hypertension. This suggests that OSA disrupts normal respiratorysympathetic coupling. This study investigates the role of the postinspiratory complex (PiCo) and preBötzinger complex (preBötC) in respiratory-sympathetic coupling under control conditions and following exposure to chronic intermittent hypoxia (CIH) for 21 days (5% O2-80 bouts/day). The surface of the ventral brainstem was exposed in urethane (1.5 g/kg) anesthetized, spontaneously breathing adult mice. Cholinergic (ChAT), glutamatergic (Vglut2), and neurons that co-express ChAT and Vglut2 at PiCo, as well as Dbx1 and Vglut2 neurons at preBötC, were optogenetically stimulated while recording activity from the diaphragm (DIA), vagus nerve (cVN), and cervical sympathetic nerve (cSN). Following CIH exposure, baseline cSN activity increased, breathing frequency increased, and expiratory time decreased. In control mice, stimulating PiCo specific cholinergic-glutamatergic neurons caused a sympathetic burst during all phases of the respiratory cycle, whereas optogenetic activation of cholinergicglutamatergic PiCo neurons in CIH mice increased sympathetic activity only during postinspiration and late expiration. Stimulation of glutamatergic PiCo neurons increased cSN activity during the postinspiratory phase in control and CIH mice. Optogenetic stimulation of ChAT containing neurons in the PiCo area did not affect sympathetic activity under control or CIH conditions. Stimulating Dbx1 or Vglut2 neurons in preBötC evoked an inspiration and a concomitant cSN burst under control and CIH conditions. Taken together, these results suggest that PiCo and preBötC contribute to respiratory-sympathetic coupling, which is altered by CIH, and may contribute to the hypertension observed in patients with OSA. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 virus has infected more than 660 million people and caused nearly seven million deaths worldwide. During the pandemic, a number of SARS-CoV-2 vaccines were rapidly developed, and several are currently licensed for use in Europe. However, the optimization of vaccination regimens is still ongoing, particularly with regard to booster vaccinations. At the same time, the emergence of new virus variants poses an ongoing challenge to vaccine efficacy. In this study, we focused on a comparative analysis of the neutralization capacity of vaccine-induced antibodies against four different variants of concern (i.e., Alpha, Beta, Delta, and Omicron) after two and three doses of COVID-19 vaccine. We were able to show that both two (prime/boost) and three (prime/boost/boost) vaccinations elicit highly variable levels of neutralizing antibodies. In addition, we did not observe a significant difference in antibody levels after two and three vaccinations. We also observed a significant decrease in the neutralization susceptibility of all but one SARS-CoV-2 variants to vaccine-induced antibodies. In contrast, a SARS-CoV-2 breakthrough infection between the second and third vaccination results in overall higher levels of neutralizing antibodies with a concomitant improved neutralization of all virus variants. Titer levels remained highly variable across the cohort but a common trend was observed. This may be due to the fact that at the time of this study, all licensed vaccines were still based exclusively on wild-type SARS-CoV-2, whereas infections were caused by virus variants. Overall, our data demonstrate the importance of (booster) vaccinations, but at the same time emphasize the need for the continued adaptation of vaccines to induce a protective immune response against virus variants in order to be prepared for future (seasonal) SARS-CoV-2 outbreaks. [ABSTRACT FROM AUTHOR]

This paper presents a summary of and introduction to research on high-altitude and subatmospheric combustion concerning turbine and scramjet engines. The investigation includes theoretical analysis, experimental studies, and numerical simulations. The analysis encompasses the flow field structure, fuel atomization, and combustion performance. Subsequently, recent research on the combustion performance of liquid fuels, solid fuels, and gaseous fuels under high-altitude and low-pressure plateau environments is reviewed. This includes an evaluation of flame height, flame temperature, combustion rate, fire spread rate, and heat radiation flux. Additionally, combustion performance prediction models for high-altitude environments based on experimental and theoretical analysis have been introduced. Lastly, issues in subatmospheric combustion in the aerospace and plateau fire fields are presented based on the current research. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is associated with a poor prognosis despite multimodal treatments. To improve the efficacy of radiotherapy, the use of nanoscintillators is emerging. Made of high‐Z elements, they absorb X‐rays more efficiently than tissues and can locally enhance the radiation dose provided they have accumulated near tumor cells. This study focuses on the role of the coating, a key parameter that controls both in vitro and in vivo properties of nanoparticles, including their internalization, biocompatibility, and therapeutic efficacy. Polyethylene glycol and tripolyphosphate molecules are used to coat lanthanum fluoride nanoscintillators, and their properties are evaluated on pancreatic cancer models. The experiments demonstrate a higher internalization of the nanoparticles when coated with tripolyphosphate, in both 2D and 3D culture models, correlating with greater efficacy under X‐rays, which may be associated with higher radiation dose‐enhancement. The nanoparticles are also injected intravenously in healthy or tumor‐bearing mice in order to study their toxicity, pharmacokinetics, and biodistribution. Despite a strong liver and spleen accumulation, especially for the tripolyphosphate‐coated nanoparticles, no toxicity is observed for either coating. Because they show promising radiation dose‐enhancement in vitro in both culture models and a limited toxicity in vivo, polyethylene glycol‐coated nanoparticles are good candidates for biomedical applications. [ABSTRACT FROM AUTHOR]

About four years have passed since the detection of the first cases of COVID-19 in China. During this lethal pandemic, millions of people have lost their lives around the world. Since the first waves of COVID-19 infection, various pharmacotherapeutic agents have been examined in the management of COVID-19. Despite all these efforts in pharmacotherapy, drug repurposing, and design and development of new drugs, multiple organ involvement and various complications occurred during COVID-19. Some of these complications became chronic and long-lasting which led to the "long COVID" syndrome appearance. Therefore, the best way to eradicate this pandemic is prophylaxis through mass vaccination. In this regard, various vaccine platforms including inactivated vaccines, nucleic acid-based vaccines (mRNA and DNA vaccines), adenovirus-vectored vaccines, and protein-based subunit vaccines have been designed and developed to prevent or reduce COVID-19 infection, hospitalization, and mortality rates. In this focused review, at first, the most commonly reported clinical presentations of COVID-19 during these four years have been summarized. In addition, different therapeutic regimens and their latest status in COVID-19 management have been listed. Furthermore, the "long COVID" and related signs, symptoms, and complications have been mentioned. At the end, the effectiveness of available COVID-19 vaccines with different platforms against early SARS-CoV-2 variants and currently circulating variants of interest (VOI) and the necessity of booster vaccine shots have been summarized and discussed in more detail. [ABSTRACT FROM AUTHOR]

MRI-related anxiety in healthy participants is often characterized by a dominant breathing frequency at around 0.32Hz (19 breaths per minute, bpm) at the beginning but in a few cases also at the end of scanning. Breathing waves at 19bpm are also observed in patients with anxiety independently of the scanned body part. In patients with medically intractable epilepsy and intracranial electroencephalography (iEEG), spontaneous breathing through the nose varied between 0.24 and 0.37Hz (~19bpm). Remarkable is the similarity of the observed breathing rates at around 0.32Hz during different types of anxiety states (e.g., epilepsy, cancer, claustrophobia) with the preferred breathing frequency of 0.32Hz (19bpm), which is predicted by the binary hierarchy model of Klimesch. This elevated breathing frequency most likely reflects an emotional processing state, in which energy demands are minimized due to a harmonic coupling ratio with other brain-body oscillations. [ABSTRACT FROM AUTHOR]

The fibroblast activation protein inhibitor (FAPI), which has the ability to recognize and adhere to fibroblast activation protein-α (FAPα) within tumor tissue, enables precise targeting of tumor locations. Consequently, it is imperative to explore its diverse applications in imaging techniques, particularly in the realm of fluorescence imaging probes, which play a pivotal role in the precise localization of tumor sites. In this study, we have successfully conjugated FITC with FAPI, greatly enhancing its capacity for targeted tumor imaging. The efficacy of FITC-FAPI hinges on the highly specific interaction between the enzyme and its inhibitor. Notably, the residence time of the fluorescent probe within tumor tissue is significantly prolonged compared to the surrounding healthy tissue, resulting in a substantial enhancement of the targeted imaging effect on the tumor. Upon excitation by a 488-nanometer laser, the probe emits a robust fluorescent signal, showcasing its potential in the field of tumor diagnosis. This innovative tool holds promise of aiding healthcare professionals in more accurate tumor detection and diagnosis, and providing robust support for personalized tumor treatments. [ABSTRACT FROM AUTHOR]

Hematopoiesis is a finely orchestrated process, whereby hematopoietic stem cells give rise to all mature blood cells. Crucially, they maintain the ability to selfrenew and/or differentiate to replenish downstream progeny. This process starts at an embryonic stage and continues throughout the human lifespan. Blood cancers such as leukemia occur when normal hematopoiesis is disrupted, leading to uncontrolled proliferation and a block in differentiation of progenitors of a particular lineage (myeloid or lymphoid). Although normal stem cell programs are crucial for tissue homeostasis, these can be co-opted in many cancers, including leukemia. Myeloid or lymphoid leukemias often display stem cell-like properties that not only allow proliferation and survival of leukemic blasts but also enable them to escape treatments currently employed to treat patients. In addition, some leukemias, especially in children, have a fetal stem cell profile, which may reflect the developmental origins of the disease. Aberrant fetal stem cell programs necessary for leukemia maintenance are particularly attractive therapeutic targets. Understanding how hijacked stem cell programs lead to aberrant gene expression in place and time, and drive the biology of leukemia, will help us develop the best treatment strategies for patients. [ABSTRACT FROM AUTHOR]

Glaucoma is a group of optic neuropathies and the world's leading cause of irreversible blindness. Normal-tension glaucoma (NTG) is a subtype of glaucoma that is characterized by a typical pattern of peripheral retinal loss, in which the patient's intraocular pressure (IOP) is considered within the normal range (<21 mmHg). Currently, the only targetable risk factor for glaucoma is lowering IOP, and patients with NTG continue to experience visual field loss after IOP-lowering treatments. This demonstrates the need for a better understanding of the pathogenesis of NTG and underlying mechanisms leading to neurodegeneration. Recent studies have found significant connections between NTG and cerebral manifestations, suggesting NTG as a neurodegenerative disease beyond the eye. Gaining a better understanding of NTG can potentially provide new Alzheimer's Disease diagnostics capabilities. This review identifies the epidemiology, current biomarkers, altered fluid dynamics, and cerebral and ocular manifestations to examine connections and discrepancies between the mechanisms of NTG and Alzheimer's Disease. [ABSTRACT FROM AUTHOR]

This machine learning (ML)-based phishing detection employs statistical models and algorithms to assess and recognize phishing attacks. These algorithms can learn patterns and features that distinguish between phishing and nonphishing attacks once they are trained on vast amounts of data from both types of cases. Phishing detection systems can quickly evaluate considerable data, identify possible phishing attempts, and warn users of potential dangers. ML-based phishing detection systems have the potential to continuously improve their accuracy over time through ongoing feature refinement, iterative model evaluation, and algorithm optimization. In contrast to conventional techniques, these systems offer a more effective and efficient approach to identifying and mitigating phishing attacks. This research critically analyzes existing literature on phishing detection, aiming to identify all proposed features and determine the critical ones necessary for accurate and fast phishing attack detection. By eliminating unnecessary overhead, this research enhances our understanding of feature eliminator methods and their role in improving ML-based phishing detection. The findings would contribute to the development of more robust cybersecurity measures to combat phishing attacks, as well as advance the field's knowledge and application of ML in detecting and mitigating such threats. The study highlights the importance of feature selection and optimization in achieving accurate and efficient phishing detection, ultimately strengthening the overall security posture of organizations and individuals against phishing attacks. [ABSTRACT FROM AUTHOR]

Hematopoiesis is a tightly regulated process that produces all adult blood cells and immune cells from multipotent hematopoietic stem cells (HSCs). HSCs usually remain quiescent, and in the presence of external stimuli like infection or inflammation, they undergo division and differentiation as a compensatory mechanism. Normal hematopoiesis is impacted by systemic inflammation, which causes HSCs to transition from quiescence to emergency myelopoiesis. At the molecular level, inflammatory cytokine signaling molecules such as tumor necrosis factor (TNF), interferons, interleukins, and toll-like receptors can all cause HSCs to multiply directly. These cytokines actively encourage HSC activation, proliferation, and differentiation during inflammation, which results in the generation and activation of immune cells required to combat acute injury. The bone marrow niche provides numerous soluble and stromal cell signals, which are essential for maintaining normal homeostasis and output of the bone marrow cells. Inflammatory signals also impact this bone marrow microenvironment called the HSC niche to regulate the inflammatory-induced hematopoiesis. Continuous pro-inflammatory cytokine and chemokine activation can have detrimental effects on the hematopoietic system, which can lead to cancer development, HSC depletion, and bone marrow failure. Reactive oxygen species (ROS), which damage DNA and ultimately lead to the transformation of HSCs into cancerous cells, are produced due to chronic inflammation. The biological elements of the HSC niche produce pro-inflammatory cytokines that cause clonal growth and the development of leukemic stem cells (LSCs) in hematological malignancies. The processes underlying how inflammation affects hematological malignancies are still not fully understood. In this review, we emphasize the effects of inflammation on normal hematopoiesis, the part it plays in the development and progression of hematological malignancies, and potential therapeutic applications for targeting these pathways for therapy in hematological malignancies. [ABSTRACT FROM AUTHOR]

Photosystem II (PSII) uses light energy to split water into protons, electrons, and oxygen, ultimately sustaining heterotrophic life on Earth. The major light harvesting complex in plants (LHCII) is packed with chlorophylls and carotenoids and is the main supplier of excitation energy to PSII reaction centers. The protein scaffold acts as a programmed solvent for the pigments in LHCII, tuning their orientations while at the same time impeding concentration quenching to ensure efficient storage of excitation energy by chlorophylls. However, under stress, the very fuel of PSII, solar photons, can damage its delicate inner components and hamper photosynthesis. In a crucial regulatory strategy in plants, LHCII evolved a flexible design that allows it to switch between light-harvesting and dissipative conformations, thereby safely releasing the excess energy that is absorbed into heat. Several mechanisms have been proposed to explain chlorophyll de-excitation pathways in LHCII, such as chlorophyll–chlorophyll charge transfer states, resonance energy transfer from chlorophylls to a carotenoid S1 state, and chlorophyll–carotenoid reductive energy transfer. This Perspective critically assesses the listed proposals, addressing both the physical mechanism of quenching and the nature of the quenching pigment. These hypotheses are then discussed in the context of state-of-the-art biochemical, physiological, and genetic knowledge to scrutinize their likeliness to occur in the native thylakoid membranes. [ABSTRACT FROM AUTHOR]

The low adsorption capacity of metal–organic frameworks (MOFs) limits their practical application in high-arsenic wastewater for adsorption owing to their insufficient active sites and suboptimal pore structure. Accordingly, we employed a one-pot hydrothermal method to synthesise mixed-metal La/Zr-MOFs with complex pore structures. Notably, the material possesses both La-BDC and Zr-BDC morphology features and integrates the advantages of monometallic MOFs through a framework symbiotic structure. This complex pore structure promotes the migration and diffusion of arsenic ions in the pore channels, improving the adsorption kinetics. Moreover, mixed-metal functional centres can expose more active sites, which is conducive to enhancing adsorption capacity. Experiments showed that mixed-metal La/Zr-BDC-4 rapidly reached adsorption equilibrium in 60 min, corresponding to a maximum adsorption amount of 694 mg g−1. Batch adsorption experiments and X-ray photoelectron and Fourier-transform infrared spectroscopy analyses revealed that mixed-metal La/Zr-BDC-4 arsenates tend to form internal complexes with each other, suggesting that As(V) adsorption is an exothermic and spontaneous chemisorption process. After four adsorption–desorption cycles, the material maintained an arsenic removal rate of 85%, exhibiting its potential application in wastewater treatment. Therefore, the mixed-metal La/Zr-BDC-4 MOF is a promising material for wastewater treatment. [ABSTRACT FROM AUTHOR]