Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Targeting EPHB2/ABL1 restores antitumor immunity in preclinical models of ependymoma.

Ependymoma (EPN) is a common form of brain tumor in children, often resistant to available cytotoxic therapies. Molecular profiling studies have led to a better understanding of EPN subtypes and revealed a critical role of oncogenes ZFTA-RELA fusion and EPHB2 in supratentorial ependymoma (ST-EPN). However, the immune system's role in tumor progression and response to therapy remains poorly understood.

Recommendations for reporting and evaluating proton therapy beyond dose and constant relative biological effectiveness.

Background And Purpose: In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used to convert proton dose into an equivalent photon dose. However, RBE varies with tissue type, fraction dose, and beam quality parameters beyond dose such as linear energy transfer (LET) raising concerns about increased local effectiveness and potential toxicity.

CMTM4 promotes the motility of colon cancer cells under radiation and is associated with an unfavorable neoadjuvant chemoradiotherapy response and patient survival in rectal cancer.

Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer (LARC). Pathological complete regression is closely linked to disease outcomes. However, biomarkers predicting nCRT response and patient survival are lacking for LARC.

Radiomics model based on computed tomography images for prediction of radiation-induced optic neuropathy following radiotherapy of brain and head and neck tumors.

Purpose: We aimed to build a machine learning-based model to predict radiation-induced optic neuropathy in patients who had treated head and neck cancers with radiotherapy.

Materials And Methods: To measure radiation-induced optic neuropathy, the visual evoked potential values were obtained in both case and control groups and compared. Radiomics features were extracted from the area segmented which included the right and left optic nerves and chiasm.

Engineering of acyl ligase domain in non-ribosomal peptide synthetases to change fatty acid moieties of lipopeptides.

Cyclic lipopeptides (CLPs) produced by the genus Bacillus are amphiphiles composed of hydrophilic amino acid and hydrophobic fatty acid moieties and are biosynthesised by non-ribosomal peptide synthetases (NRPSs). CLPs are produced as a mixture of homologues with different fatty acid moieties, whose length affects CLP activity. Iturin family lipopeptides are a family of CLPs comprising cyclic heptapeptides and β-amino fatty acids and have antimicrobial activity.

Myeloablative conditioning in cord blood transplantation for acute myeloid leukemia patients is efficacious only until age 55.

Umbilical cord blood transplantation (CBT) is accepted as an effective treatment for acute myeloid leukemia (AML), and reduced-intensity conditioning (RIC), rather than myeloablative conditioning (MAC) regimens allowed elderly patients to be treated safely. However, appropriate intensities of conditioning regimens are still unclear, especially for middle-aged patients. To compare outcomes after RIC and MAC regimens, we analyzed AML patients aged 16 years or older in the Japanese registry database, who underwent single cord unit CBT between 2010-2019.

GnIH secreted by green light exposure, regulates bone mass through the activation of Gpr147.

Reproductive hormones associated with the hypothalamic-pituitary-gonadal (HPG) axis are closely linked to bone homeostasis. In this study, we demonstrate that Gonadotropin inhibitory hormone (GnIH, one of the key reproductive hormones upstream of the HPG axis) plays an indispensable role in regulating bone homeostasis and maintaining bone mass. We find that deficiency of GnIH or its receptor Gpr147 leads to a significant reduction in bone mineral density (BMD) in mice primarily by enhancement of osteoclast activation in vivo and in vitro.

Declining precipitation frequency may drive earlier leaf senescence by intensifying drought stress and enhancing drought acclimation.

Precipitation is an important factor influencing the date of foliar senescence, which in turn affects carbon uptake of terrestrial ecosystems. However, the temporal patterns of precipitation frequency and its impact on foliar senescence date remain largely unknown. Using both long-term carbon flux data and satellite observations across the Northern Hemisphere, we show that, after excluding impacts from of temperature, radiation and total precipitation by partial correlation analysis, declining precipitation frequency may drive earlier foliar senescence date from 1982 to 2022.

Computed Tomography-Based Radiomics and Genomics Analyses for Survival Prediction of Stage III Unresectable Non-Small Cell Lung Cancer Treated With Definitive Chemoradiotherapy and Immunotherapy.

The standard therapy for locally unresectable advanced non-small cell lung cancer (NSCLC) is comprised of chemoradiotherapy (CRT) before immunotherapy (IO) consolidation. However, how to predict treatment outcomes and recognize patients that will benefit from IO remain unclear. This study aimed to identify prognostic biomarkers by integrating computed tomography (CT)-based radiomics and genomics.

The molecular mechanism of transforming red light signal to (E)-β-caryophyllene biosynthesis in Arabidopsis.

It is known that red light irradiation enhances the biosynthesis of (E)-β-caryophyllene in plants. However, the underlying mechanism connecting red light to (E)-β-caryophyllene biosynthesis remains elusive. This study reveals a molecular cascade involving the phyB-PIF4-MYC2 module, which regulates (E)-β-caryophyllene biosynthesis in response to the red light signal in Arabidopsis thaliana.

BRAT1 - a new therapeutic target for glioblastoma.

Glioblastoma (GBM), the most malignant primary brain tumor in adults, has poor prognosis irrespective of therapeutic advances due to its radio-resistance and infiltrative growth into brain tissue. The present study assessed functions and putative druggability of BRCA1-associated ATM activator 1 (BRAT1) as a crucial factor driving key aspects of GBM, including enhanced DNA damage response and tumor migration. By a stable depletion of BRAT1 in GBM and glioma stem-like (GSC) cell lines, we observed a delay in DNA double-strand break repair and increased sensitivity to radiation treatment, corroborated by in vitro and in vivo studies demonstrating impaired tumor growth and invasion.

Clinical features, treatment modalities, and survival rates of pediatric central nervous system tumors: A retrospective analysis from a single center (2000-2020).

Pediatric central nervous system (CNS) tumors represent 20-25% of childhood malignancies, with 35-40 new cases annually in Slovakia. Despite treatment advances, high mortality and poor quality of life in a lot of cases persist. This study assesses the clinical features, treatment modalities, and survival rates of pediatric CNS tumor patients in the single largest center in Slovakia.

Extracellular vesicle-mediated VEGF-A mRNA delivery rescues ischaemic injury with low immunogenicity.

Background And Aims: Lackluster results from recently completed gene therapy clinical trials of VEGF-A delivered by viral vectors have heightened the need to develop alternative delivery strategies. This study aims to demonstrate the pre-clinical efficacy and safety of extracellular vesicles (EVs) loaded with VEGF-A mRNA for the treatment of ischaemic vascular disease.

Methods: After encapsulation of full-length VEGF-A mRNA into fibroblast-derived EVs via cellular nanoporation (CNP), collected VEGF-A EVs were delivered into mouse models of ischaemic injury.

The interplay between RNA m6A modification and radiation biology of cancerous and non-cancerous tissues: a narrative review.

The diverse radiation types in medical treatments and the natural environment elicit complex biological effects on both cancerous and non-cancerous tissues. Radiation therapy (RT) induces oncological responses, from molecular to phenotypic alterations, while simultaneously exerting toxic effects on healthy tissue. N-methyladenosine (mA), a prevalent modification on coding and non-coding RNAs, is a key epigenetic mark established by a set of evolutionarily conserved enzymes.

An orally available P1'-5-fluorinated M inhibitor blocks SARS-CoV-2 replication without booster and exhibits high genetic barrier.

We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (M) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2 and SARS-CoV-2 than two M inhibitors: nirmatrelvir and ensitrelvir. Notably, the administration of ritonavir-boosted nirmatrelvir and ensitrelvir causes drug-drug interactions warranting cautions due to their CYP3A4 inhibition, thereby limiting their clinical utility. When orally administered, TKB272 blocked SARS-CoV-2 replication without ritonavir in B6.

High Intelectin-1 Expression Associated with Aggressive Tumor Behavior and Worse Survival in Rectal Cancer.

Background: Multimodal treatment involving preoperative chemoradiotherapy (CRT) followed by surgery is the current standard of care for rectal cancer. Despite advancements, the risk of recurrence, metastasis, and decreased survival remains high. This study aims to evaluate potential biomarkers to stratify prognosis in patients with rectal cancer undergoing preoperative CRT and surgery.

Assessing Metabolic Ageing via DNA Methylation Surrogate Markers: A Multicohort Study in Britain, Ireland and the USA.

Metabolomics and epigenomics have been used to develop 'ageing clocks' that assess biological age and identify 'accelerated ageing'. While metabolites are subject to short-term variation, DNA methylation (DNAm) may capture longer-term metabolic changes. We aimed to develop a hybrid DNAm-metabolic clock using DNAm as metabolite surrogates ('DNAm-metabolites') for age prediction.

IBI310 plus sintilimab vs. placebo plus sintilimab in recurrent/metastatic cervical cancer: A double-blind, randomized controlled trial.

Background: It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC).

Methods: In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3 weeks for 12 weeks, followed by sintilimab alone.

Interplay of Light, Melatonin, and Circadian Genes in Skin Pigmentation Regulation.

Circadian regulation of skin pigmentation is essential for thermoregulation, ultraviolet (UV) protection, and synchronization of skin cell renewal. This regulation involves both cell-autonomous photic responses and non-cell-autonomous hormonal control, particularly through melatonin produced in a light-sensitive manner. Photosensitive opsins, cryptochromes, and melatonin regulate circadian rhythms in skin pigment cells.

Functional variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with increased risk of colorectal cancer.

Background: Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.

Methods: Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk.

Rapid radiation of a plant lineage sheds light on the assembly of dry valley biomes.

Southwest China is characterized by high plateaus, large mountain systems, and deeply incised dry valleys formed by major rivers and their tributaries. Despite the considerable attention given to alpine plant radiations in this region, the timing and mode of diversification of the numerous dry valley plant lineages remain unknown. To address this knowledge gap, we investigated the macroevolution of Isodon (Lamiaceae), a lineage commonly distributed in the dry valleys in southwest China and wetter areas of Asia and Africa.

Recurrent glioblastoma in national guidelines on the diagnosis and treatment of gliomas: A matter of European practice variation.

Introduction: The optimal treatment for recurrent glioblastoma patients remains not well-defined in international guidelines. On top of that, the availability of national guidelines is uncharted.

Research Question: This study aimed to investigate the availability of national guidelines on the diagnosis and treatment of adult glioma throughout Europe, specifically focusing on recurrent glioblastoma.

Solar-based technologies for removing potentially toxic metals from water sources: a review.

Technological advances have led to a proportional increase in the deposition of contaminants across various environmental compartments, including water sources. Heavy metals, also known as potentially toxic metals, are of particular concern due to their significant harmful impacts on environmental and human health. Among the available methods for mitigating the threat of these metals in water, solar radiation-based technologies stand out for their cleanliness, cost-effectiveness, and efficiency in removing or reducing the toxicity of heavy metals.

Improving timing resolution of BGO for TOF-PET: a comparative analysis with and without deep learning.

Background: The renewed interest in BGO scintillators for TOF-PET is driven by the improved Cherenkov photon detection with new blue-sensitive SiPMs. However, the slower scintillation light from BGO causes significant time walk with leading edge discrimination (LED), which degrades the coincidence time resolution (CTR). To address this, a time walk correction (TWC) can be done by using the rise time measured with a second threshold.