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This document presents the initial scientific case for upgrading the Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab (JLab) to 22 GeV. It is the result of a community effort, incorporating insights from a series of workshops conducted between March 2022 and April 2023. With a track record of over 25 years in delivering the world's most intense and precise multi-GeV electron beams, CEBAF's potential for a higher energy upgrade presents a unique opportunity for an innovative nuclear physics program, which seamlessly integrates a rich historical background with a promising future. The proposed physics program encompass a diverse range of investigations centered around the nonperturbative dynamics inherent in hadron structure and the exploration of strongly interacting systems. It builds upon the exceptional capabilities of CEBAF in high-luminosity operations, the availability of existing or planned Hall equipment, and recent advancements in accelerator technology. The proposed program cover various scientific topics, including Hadron Spectroscopy, Partonic Structure and Spin, Hadronization and Transverse Momentum, Spatial Structure, Mechanical Properties, Form Factors and Emergent Hadron Mass, Hadron-Quark Transition, and Nuclear Dynamics at Extreme Conditions, as well as QCD Confinement and Fundamental Symmetries. Each topic highlights the key measurements achievable at a 22 GeV CEBAF accelerator. Furthermore, this document outlines the significant physics outcomes and unique aspects of these programs that distinguish them from other existing or planned facilities. In conclusion, this document provides an exciting rationale for the energy upgrade of CEBAF to 22 GeV, outlining the transformative scientific potential that lies within reach, and the remarkable opportunities it offers for advancing our understanding of hadron physics and related fundamental phenomena.

Here, the purpose of this document is to outline the developing scientific case for pursuing an energy upgrade to 22 GeV of the Continuous Electron Beam Accelerator Facility (CEBAF) at the Thomas Jefferson National Accelerator Facility (TJNAF, or JLab). This document was developed with input from a series of workshops held in the period between March 2022 and April 2023 that were organized by the JLab user community and staff with guidance from JLab management (see Sec. 10). The scientific case for the 22 GeV energy upgrade leverages existing or already planned Hall equipment and world-wide uniqueness of CEBAF high-luminosity operations.

The growing global importance of antimicrobial resistance (AMR) in public health has prompted the creation of innovative approaches to combating the issue. In this study, the promising potential of bimetallic nanoparticles (BMNPs) was investigated as a novel weapon against AMR. This research begins by elaborating on the gravity of the AMR problem, outlining its scope in terms of the effects on healthcare systems, and stressing the urgent need for novel solutions. Because of their unusual features and wide range of potential uses, bimetallic nanoparticles (BMNPs), which are tiny particles consisting of two different metal elements, have attracted a lot of interest in numerous fields. This review article provides a comprehensive analysis of the composition, structural characteristics, and several synthesis processes employed in the production of BMNPs. Additionally, it delves into the unique properties and synergistic effects that set BMNPs apart from other materials. This review also focuses on the various antimicrobial activities shown by bimetallic nanoparticles, such as the rupturing of microbial cell membranes, the production of reactive oxygen species (ROS), and the regulation of biofilm formation. An extensive review of in vitro studies confirms the remarkable antibacterial activity of BMNPs against a variety of pathogens and sheds light on the dose-response relationship. The efficacy and safety of BMNPs in practical applications are assessed in this study. It also delves into the synergistic effects of BMNPs with traditional antimicrobial drugs and their ability to overcome multidrug resistance, providing mechanistic insight into these phenomena. Wound healing, infection prevention, and antimicrobial coatings on medical equipment are only some of the clinical applications of BMNPs that are examined, along with the difficulties and possible rewards of clinical translation. This review covers nanoparticle-based antibacterial regulation and emerging uses. The essay concludes with prospects for hybrid systems, site-specific targeting, and nanoparticle-mediated gene and drug delivery. In summary, bimetallic nanoparticles have surfaced as a potential solution, offering the public a more promising and healthier future.

Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types-dense granules, α-granules, and lysosomes-although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways. Both are formed from the trans-Golgi network and early endosomes and mature in multivesicular bodies, but the formation of dense granules requires trafficking machinery different from that of α-granules. Following formation in the megakaryocyte body, both granule types are transported through and mature in long proplatelet extensions prior to the release of nascent platelets into the bloodstream. Granules remain stored in circulating platelets until platelet activation triggers the exocytosis of their contents. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, located on both the granules and target membranes, provide the mechanical energy that enables membrane fusion during both granulogenesis and exocytosis. The function of these core fusion engines is controlled by SNARE regulators, which direct the site, timing, and extent to which these SNAREs interact and consequently the resulting membrane fusion. In this review, we assess new developments in the study of platelet granules, from their generation to their exocytosis.

Foster parents are the largest group providing care for children in the foster care system. In the course of caring for children who have experienced significant trauma, loss, and uncertainty, foster parents face significant stressors unique to their position. Stress among foster parents can negatively impact the quality of their parenting and, subsequently, the children in their care. However, relatively little is known about those factors which impact foster parent well-being within the context of this stressful role. This study aims to address this gap by examining the relationship between parenting stress and well-being in foster parents, and the potential moderating effect of social support in this relationship. The study utilized a cross-sectional design and web-based survey methodology with a sample of licensed foster parents (both non-relative and relative caregivers) from one county in the midwestern United States. Multiple linear regression analysis indicated that parenting stress is significantly, negatively related to foster parent well-being. Further, social support functions as a moderator, or buffer, in this relationship. Foster parents who indicated higher levels of social support reported being less negatively impacted by parenting stress. While qualitative research has suggested the importance of social support in foster family resilience, this study offers the first known quantitative findings among licensed foster parents on the protective function of social support in the context of parenting stress. These findings have implications for this population and the professionals and systems they encounter, including improved foster parent training and assessment, toward the greater goal of an improved child welfare system for the children within it.

Breast cancer is the most common malignancy in women of the Western world. Doxorubicin (DOX) continues to be used extensively to treat early-stage or node-positive breast cancer, human epidermal growth factor receptor-2 (HER2)-positive breast cancer, and metastatic disease. We have previously demonstrated in a mouse model that sulforaphane (SFN), an isothiocyanate isolated from cruciferous vegetables, protects the heart from DOX-induced toxicity and damage. However, the effects of SFN on the chemotherapeutic efficacy of DOX in breast cancer are not known. Present studies were designed to investigate whether SFN alters the effects of DOX on breast cancer regression while also acting as a cardioprotective agent. Studies on rat neonatal cardiomyocytes and multiple rat and human breast cancer cell lines revealed that SFN protects cardiac cells but not cancer cells from DOX toxicity. Results of studies in a rat orthotopic breast cancer model indicated that SFN enhanced the efficacy of DOX in regression of tumor growth, and that the DOX dosage required to treat the tumor could be reduced when SFN was administered concomitantly. Additionally, SFN enhanced mitochondrial respiration in the hearts of DOX-treated rats and reduced cardiac oxidative stress caused by DOX, as evidenced by the inhibition of lipid peroxidation, the activation of NF-E2-related factor 2 (Nrf2) and associated antioxidant enzymes. These studies indicate that SFN not only acts synergistically with DOX in cancer regression, but also protects the heart from DOX toxicity through Nrf2 activation and protection of mitochondrial integrity and functions.

Urban soil and water contamination by xenobiotics is an increasing hazard to ecosystem health and human well-being. Xenobiotics including synthetic chemicals and contaminants from industrial, agricultural, and urban activities are renowned for accumulating in the environment. As urbanization expands, the detrimental impacts of xenobiotics on ecosystems and public health will intensify, making it more necessary than ever to learn about and implement appropriate remediation methods. This review article is focused on diverse categories of xenobiotics, their health impacts, and a range of xenobiotic removal methods from urban soils and water sources. We also explored extensive literature based on established and novel technological and natural approaches, spanning the physical, chemical, and biological sciences. Physicochemical methods including soil cleaning, electrokinetics, and adsorption may decontaminate xenobiotic-contaminated sites. Bioremediation using bacteria and plants degrades and detoxifies several xenobiotics. Advanced oxidation methods can also degrade persistent water pollutants very effectively. Nanoremediation, phytoremediation, and microbial-assisted remediation are some of the emerging technologies that effectively remove persistent pollutants and preserve ecological balance. Nature-based solutions like artificial wetlands and biofiltration can lessen xenobiotic impacts and sustainably increase urban ecosystem services. These methods have been tested in several urban locations. We also explored the hybrid approaches for the removal of xenobiotics and secondary pollution. A combination of techniques may be effective for efficient cleanup thereby promoting sustainable cleanup solutions for urban expansion and safeguarding the environment and residents from emerging contaminants.

Extracellular vesicles (EVs) are lipid-bound nanocarriers released by various eukaryotic cells and found in diverse bodily fluids. EVs have transitioned from being considered cellular waste disposers to significant players in intercellular communication and signaling. These EVs carry signature cargos of infected cells and thus can be helpful as biomarkers or prognostic markers for infectious diseases. Viruses can manipulate the EV biogenesis machinery in their own dissemination. EVs released from virus-infected cells can carry immune modulatory molecules, thus contributing to disease progression. This comprehensive review collates the information on the impact of EVs on viral infection and disease progression.

Background A decline in skeletal muscle mass and function known as skeletal muscle sarcopenia is an inevitable consequence of aging. Sarcopenia is a major cause of decreased muscle strength, physical frailty and increased muscle fatigability, contributing significantly to an increased risk of physical disability and functional dependence among the elderly. There remains a significant need for a novel therapy that can improve sarcopenia and related problems in aging. Iron accumulation, especially catalytic iron (labile iron) through increased oxidative stress, could be one of the contributing factors to sarcopenia. Our study aimed to examine the effect of an iron chelator on age‐related sarcopenia in mice. Methods We investigated the effect of iron chelation (deferiprone, DFP) in sarcopenia, using mice with klotho deficiency (kl/kl), an established mouse model for aging. Four weeks old Klotho −/− male mice were treated with 25 mg/kg body weight of iron chelator deferiprone in drinking water for 8–14 weeks (n = 12/group, treated and untreated). At the end of the study, gastrocnemius, quadriceps and bicep muscles were dissected and used for western blot and immunohistochemistry analysis, histopathology and iron staining. Serum total iron, catalytic iron and cytokine ELISAs were performed with established methods. Results Treatment with DFP significantly reduced loss of muscle mass in gastrocnemius and quadriceps muscles (p < 0.0001). Total and catalytic iron content of serum and iron in muscles were significantly (both p < 0.0001) lower in the treated animals. The inhibitory factor of myogenesis, the myostatin protein in gastrocnemius muscles (p = 0.019) and serum (p = 0.003) were downregulated after 8 weeks of therapy accompanied by an increased in muscle contractile protein myosin heavy chain (~2.9 folds, p = 0.0004). Treatment decreased inflammation (serum IL6 and TNFα) (p < 0.0001, p = 0.005), respectively, and elevated insulin‐like growth factor levels (p = 0.472). This was associated with reduced DNA damage and reduced 8‐hydroxy 2 deoxyguanosine in muscle and HO‐1 protein (p < 0.001, p = 079), respectively. Significant weight loss (p < 0.001) and decreased water intake (p = 0.012) were observed in untreated mice compared to treatment group. Kaplan–Meier survival curves show the median life span of treated mice was 108 days as compared to 63 days for untreated mice (p = 0.0002). Conclusions In summary, our research findings indicate that deferiprone reduced age‐related sarcopenia in the muscles of Klotho−/− mice. Our finding suggests chelation of excess iron could be an effective therapy to counter sarcopenia. However, additional studies are needed to evaluate and determine the efficacy in humans.