Contribution of Nuclear Fragmentation to Dose and RBE in Carbon-Ion Radiotherapy.

Variable relative biological effectiveness (RBE) of carbon radiotherapy may be calculated using several models, including the microdosimetric kinetic model (MKM), stochastic MKM (SMKM), repair-misrepair-fixation (RMF) model, and local effect model I (LEM), which have not been thoroughly compared. In this work, we compared how these four models handle carbon beam fragmentation, providing insight into where model differences arise. Monoenergetic and spread-out Bragg peak carbon beams incident on a water phantom were simulated using Monte Carlo.

Herpesvirus Infections After Chimeric Antigen Receptor T-Cell Therapy and Bispecific Antibodies: A Review.

In this narrative review, we explore the burden and risk factors of various herpesvirus infections in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies (BsAb) for the treatment of hematologic malignancies. Antiviral prophylaxis for herpes simplex/varicella zoster viruses became part of the standard of care in this patient population. Breakthrough infections may rarely occur, and the optimal duration of prophylaxis as well as the timing of recombinant zoster immunization remain to be explored.

Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance.

The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which led the WHO to declare this mpox outbreak a public health emergency of international concern. The FDA-approved small molecule antiviral tecovirimat (TPOXX) is recommended to treat mpox cases with severe symptoms, but the limited efficacy of TPOXX and the emergence of TPOXX resistant MPXV variants has challenged this medical practice of care and highlighted the urgent need for alternative therapeutic strategies. In this study we have used vaccinia virus (VACV) as a surrogate of MPXV to assess the antiviral efficacy of combination therapy of TPOXX together with mycophenolate mofetil (MMF), an FDA-approved immunosuppressive agent that we have shown to inhibit VACV and MPXV, or the N-myristoyltransferase (NMT) inhibitor IMP-1088.

A Comprehensive Review of the Development and Therapeutic Use of Antivirals in Flavivirus Infection.

Flaviviruses are a diverse group of viruses primarily transmitted through hematophagous insects like mosquitoes and ticks. Significant expansion in the geographic range, prevalence, and vectors of flavivirus over the last 50 years has led to a dramatic increase in infections that can manifest as hemorrhagic fever or encephalitis, leading to prolonged morbidity and mortality. Millions of infections every year pose a serious threat to worldwide public health, encouraging scientists to develop a better understanding of the pathophysiology and immune evasion mechanisms of these viruses for vaccine development and antiviral therapy.

eEF-2K Deficiency Boosts the Virus-Specific Effector CD8 T Cell Responses During Viral Infection.

In this study, we revealed a critical role of eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, in regulating T cells during vaccinia virus (VACV) infection. We found that eEF-2K-deficient (eEF-2K⁻/⁻) mice exhibited a significantly higher proportion of VACV-specific effector CD8 T cells without compromising the development of VACV-specific memory CD8 T cells. RNA sequencing demonstrated that eEF-2K⁻/⁻ VACV-specific effector CD8 T cells had enhanced functionality, which improves their capacity to combat viral infection during the effector phase.

Metabolite Profiling and Association Analysis of Leaf Tipburn in Heat-Tolerant Bunching Onion Varieties.

The bunching onion is an important leafy vegetable, prized for its distinctive flavor and color. It is consumed year-round in Japan, where a stable supply is essential. However, in recent years, the challenges posed by climate change and global warming have resulted in adverse effects on bunching onions, including stunted growth, discoloration, and the development of leaf tipburn, threatening both crop quality and yield.

Dietary Interventions, Supplements, and Plant-Derived Compounds for Adjunct Vitiligo Management: A Review of the Literature.

Vitiligo is a chronic autoimmune pigmentation disorder shaped by a complex interplay of genetic predispositions and environmental triggers. While conventional therapies-phototherapy, corticosteroids, and immunosuppressants-can be effective, their benefits are often partial and temporary, with recurrence common once treatment stops. As such, there is increasing interest in exploring complementary approaches that may offer a more sustainable impact.

Improving Cooking Skills, Lifestyle Behaviors, and Clinical Outcomes for Adults at Risk for Cardiometabolic Disease: Protocol for a Randomized Teaching Kitchen Multisite Trial (TK-MT).

Background/objectives: This protocol describes a study to investigate the feasibility and preliminary efficacy of a novel Teaching Kitchen Multisite Trial (TK-MT) for adults with cardiometabolic abnormalities. The TK-MT protocol describes a hybrid lifestyle intervention combining in-person and virtual instruction in culinary skills, nutrition education, movement, and mindfulness with community support and behavior change strategies. This 18-month-long randomized controlled trial aims to evaluate the feasibility of implementing a 12-month, 24 class program, assess preliminary study efficacy, and identify barriers and facilitators to implementation.

Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults.

Vitamin C is an antioxidant and is essential for immune function and infection resistance. Supplementation is necessary when a sufficient amount of vitamin C is not obtained through the diet. Alternative formulations of vitamin C may enhance its bioavailability and retention over traditional ascorbic acid.

Mapping the Drivers of Multisectoral Nutrition Governance and Its Link to Nutrition Outcomes in Kenya: A Qualitative Inquiry.

Background: Malnutrition remains a significant public health issue in Kenya. Multisectoral Nutrition Governance (MNG) is increasingly being acknowledged as a catalyst for enhancing nutrition programming and outcomes. Effective MNG establishes policies, systems, and mechanisms that enable coordinated, adequately funded, and sustainable nutrition actions across sectors; however, its understanding and progress assessment remain inadequate.

Neuroprotective Actions of Cannabinoids in the Bovine Isolated Retina: Role of Hydrogen Sulfide.

Both hydrogen sulfide and endocannabinoids can protect the neural retina from toxic insults under in vitro and in vivo conditions. The aim of the present study was two-fold: (a) to examine the neuroprotective action of cannabinoids [methanandamide and 2-arachidonyl glycerol (2-AG)] against hydrogen peroxide (HO)-induced oxidative damage in the isolated bovine retina and (b) to evaluate the role of endogenously biosynthesized hydrogen sulfide (HS) in the inhibitory actions of cannabinoids on the oxidative stress in the bovine retina. Isolated neural retinas from cows were exposed to oxidative damage using HO (100 µM) for 10 min.

Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies.

Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of a wide range of brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) cause neuroinflammation, alter brain function, and accelerate disease development. Despite progress in understanding these pathways, effective medicines targeting brain inflammation are still limited.

Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance.

Recent developments in single-cell multi-omics technologies have provided the ability to identify diverse cell types and decipher key components of the tumor microenvironment (TME), leading to important advancements toward a much deeper understanding of how tumor microenvironment heterogeneity contributes to cancer progression and therapeutic resistance. These technologies are able to integrate data from molecular genomic, transcriptomic, proteomics, and metabolomics studies of cells at a single-cell resolution scale that give rise to the full cellular and molecular complexity in the TME. Understanding the complex and sometimes reciprocal relationships among cancer cells, CAFs, immune cells, and ECs has led to novel insights into their immense heterogeneity in functions, which can have important consequences on tumor behavior.

Exploring Zinc C295 as a Dual HIV-1 Integrase Inhibitor: From Strand Transfer to 3'-Processing Suppression.

: The global AIDS pandemic highlights the urgent need for novel antiretroviral therapies (ART). In our previous work, Zinc C295 was identified as a potent HIV-1 integrase strand transfer (ST) inhibitor. This study explores its potential to also inhibit 3'-processing (3'P), thereby establishing its dual-targeting capability.

Pathogen Detection and Resistome Analysis in Healthy Shelter Dogs Using Whole Metagenome Sequencing.

According to the Humane Society, 25 to 40 percent of pet dogs in the United States are adopted from animal shelters. Shelter dogs can harbor bacterial, viral, fungal, and protozoal pathogens, posing risks to canine and human health. These bacterial pathogens may also carry antibiotic resistance genes (ARGs), serving as a reservoir for antimicrobial resistance (AMR) transmission.

Flaviviruses-Induced Neurological Sequelae.

Flaviviruses, a group of single-stranded RNA viruses spread by mosquitoes or ticks, include several significant neurotropic viruses, such as West Nile virus (WNV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and Zika virus (ZIKV). These viruses can cause a range of neurological diseases during acute infection, from mild, flu-like symptoms to severe and fatal encephalitis. A total of 20-50% of patients who recovered from acute flavivirus infections experienced long-term cognitive issues.

Integrating Remote Sensing and Soil Features for Enhanced Machine Learning-Based Corn Yield Prediction in the Southern US.

Efficient and reliable corn ( L.) yield prediction is important for varietal selection by plant breeders and management decision-making by growers. Unlike prior studies that focus mainly on county-level or controlled laboratory-scale areas, this study targets a production-scale area, better representing real-world agricultural conditions and offering more practical relevance for farmers.

Conjugation of Short-Chain Fatty Acids to Bicyclic-Amines for Analysis by Liquid Chromatography Tandem Mass Spectroscopy.

Conjugation of short-chain fatty acids (SDFAs) to amines containing ring structures allows for better measurement by liquid chromatography tandem mass spectroscopy (LC-MS/MS). However, collision-induced dissociation (CID) results in breaking the conjugate back to the original SCFA and amine. We therefore set out to find an amine that would remain on the SCFA after CID and create a unique daughter for selectivity of measurement.

Hydrogen-Bonded Di(hydroperoxy)alkane Adducts of the Type CyP=O·(HOO)CHR (R = Alkyl).

Five representatives of a novel type of di(hydroperoxy)alkane adducts of phosphine oxides have been synthesized and fully characterized, including their solubility in organic solvents. The phosphine oxide CyPO () has been used in combination with the corresponding aldehydes to create the adducts CyPO·(HOO)CHCH (), CyPO·(HOO)CHCHCH (), CyPO·(HOO)CH(CH)CH (), CyPO·(HOO)CH(CH)CH (), and CyPO·(HOO)CH(CH)CH (). All adducts crystallize easily and contain the peroxide and phosphine oxide hydrogen-bonded in 1:1 ratios.

Genetic Algorithm-Enhanced Direct Method in Protein Crystallography.

Direct methods based on iterative projection algorithms can determine protein crystal structures directly from X-ray diffraction data without prior structural information. However, traditional direct methods often converge to local minima during electron density iteration, leading to reconstruction failure. Here, we present an enhanced direct method incorporating genetic algorithms for electron density modification in real space.

Modeling, Design, and Laboratory Testing of a Passive Friction Seismic Metamaterial Base Isolator (PFSMBI).

This paper focuses on the theoretical and analytical modeling of a novel seismic isolator termed the Passive Friction Mechanical Metamaterial Seismic Isolator (PFSMBI) system, which is designed for seismic hazard mitigation in multi-story buildings. The PFSMBI system consists of a lattice structure composed of a series of identical small cells interconnected by layers made of viscoelastic materials. The main function of the lattice is to shift the fundamental natural frequency of the building away from the dominant frequency of earthquake excitations by creating low-frequency bandgaps (FBGs) below 20 Hz.

Assessing Corrosion Effects on the Electrical Performance of Wearable Photovoltaic Cells: A Comparative Analysis of Current Consistency and Resistance.

Wearable photovoltaic (PV) cells offer a sustainable and lightweight solution for energy-harvesting applications, including safety gear and protective textiles. Despite their growing adoption, the application of PV cells in marine environments is limited due to the corrosive conditions that can degrade performance. This study evaluates the impact of corrosion on commercially sourced PV cells by analyzing maximum current and electrical resistance.

A Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy.

To identify the differences between aged and young human hematopoiesis, we performed a direct comparison of aged and young human hematopoietic stem and progenitor cells (HSPCs). Alterations in transcriptome profiles upon aging between humans and mice were then compared. Human specimens consist of CD34+ cells from bone marrow, and mouse specimens of hematopoietic stem cells (HSCs; Lin- Kit+ Sca1+ CD150+).

Targeting Bacterial Cell Division with Benzodioxane-Benzamide FtsZ Inhibitors as a Novel Strategy to Fight Gram-Positive Ovococcal Pathogens.

The widespread emergence of antimicrobial resistance (AMR) is a serious threat to global public health and among Gram-positive cocci, constitutes a priority in the list of AMR-threatening pathogens. To counteract this fundamental problem, the bacterial cell division cycle and the crucial proteins involved in this process emerged as novel attractive targets. FtsZ is an essential cell division protein, and FtsZ inhibitors, especially the benzamide derivatives, have been exploited in the last decade.