TCA cycle-derived oncometabolites in cancer and the immune microenvironment.

Oncometabolites are aberrant metabolic byproducts that arise from mutations in enzymes of the tricarboxylic acid (TCA) cycle or related metabolic pathways and play central roles in tumor progression and immune evasion. Among these, 2-hydroxyglutarate (2-HG), succinate, and fumarate are the most well-characterized, acting as competitive inhibitors of α-ketoglutarate-dependent dioxygenases to alter DNA and histone methylation, cellular differentiation, and hypoxia signaling. More recently, itaconate, an immunometabolite predominantly produced by activated macrophages, has been recognized for its dual roles in modulating inflammation and tumor immunity.

Caffeine mitigates ROS accumulation and attenuates motor neuron degeneration in the wobbler mouse model of amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by oxidative stress and progressive motor neuron degeneration. This study evaluates the potential neuroprotective effects of caffeine in the Wobbler mouse, an established model of ALS.

Methods: Wobbler mice received caffeine supplementation (60 mg/kg/day) via drinking water, and key parameters, including muscle strength, NAD metabolism, oxidative stress, and motor neuron morphology, were assessed at critical disease stages.

A novel fluorescent aptasensor using magnetic silica nanospheres and Ag@MOF nanocomposites for extraction and detection of Salmonella Typhimurium in eggs.

Salmonella Typhimurium (S. Typhimurium) is one of the most common food-borne diseases, highlighted as the top food-borne bacterial pathogen in the world with a low infectious dose (1 CFU) and high mortality rate. It is commonly associated with numerous foods such as dairy products, protein sources (multiple types of meat, poultry, and eggs), and bakery products.

Slowing down the clock on ovarian aging-does the ovary hold the secret to the fountain of youth?

In the past century, the human Lifespan has doubled. However, this is not equivalent to Healthspan which refers to the number of years spent healthy and free from disease. Women have an additional level of complexity on the path to optimal healthspan where health resilience dramatically decreases following menopause and this is due to their ovaries aging by midlife.

Detection of Wolbachia in Natural Populations of Ceratitis capitata (Wiedemann) (Diptera: Tephritidae) Infesting Argan Fruits in Morocco.

The argan tree (Argania spinosa L. Skeels), native to the sub-Saharan region of Morocco, is an endangered agroforestry species renowned for producing one of the world's most expensive and sought-after oils. However, this valuable resource is threatened by the Mediterranean fruit fly (Ceratitis capitata (Wied.

Factors Associated with Loneliness Among Older Adults Who Experienced Homelessness: Results from the HOPE HOME Study.

Background: Older homeless-experienced adults are at higher risk of loneliness than general older adults. Loneliness is associated with multiple adverse health and mental health outcomes. Less is known about factors contributing to loneliness among older adults who experience homelessness.

MRI-based radiomics signatures for predicting the efficacy of targeted therapy with lenvatinib in hepatocellular carcinoma: a retrospective cohort study.

Purpose: Targeted therapy with lenvatinib is a preferred option for advanced hepatocellular carcinoma, however, predicting its efficacy remains challenging. This study aimed to build a nomogram integrating clinicoradiological indicators and radiomics features to predict the response to lenvatinib in patients with hepatocellular carcinoma.

Methods: This study included 211 patients with hepatocellular carcinoma from two centers, who were allocated into the training (107 patients), internal test (46 patients) and external test set(58 patients).

Genetic and epigenetic analysis of plasma glial fibrillary acidic protein (GFAP) levels in PTSD.

Glial fibrillary acidic protein (GFAP) is an astrocytic marker that can be assessed in blood using single molecule array technology. Recent studies suggest that individuals with posttraumatic stress disorder (PTSD) have suppressed circulating levels of this CNS biomarker. This study examined the hypothesis that PTSD and plasma GFAP levels share common genetic and epigenetic pathways.

Probing the Kitaev honeycomb model on a neutral-atom quantum computer.

Quantum simulations of many-body systems are among the most promising applications of quantum computers. In particular, models based on strongly correlated fermions are central to our understanding of quantum chemistry and materials problems, and can lead to exotic, topological phases of matter. However, owing to the non-local nature of fermions, such models are challenging to simulate with qubit devices.

Redox-driven mineral and organic associations in Jezero Crater, Mars.

The Perseverance rover has explored and sampled igneous and sedimentary rocks within Jezero Crater to characterize early Martian geological processes and habitability and search for potential biosignatures. Upon entering Neretva Vallis, on Jezero Crater's western edge, Perseverance investigated distinctive mudstone and conglomerate outcrops of the Bright Angel formation. Here we report a detailed geological, petrographic and geochemical survey of these rocks and show that organic-carbon-bearing mudstones in the Bright Angel formation contain submillimetre-scale nodules and millimetre-scale reaction fronts enriched in ferrous iron phosphate and sulfide minerals, likely vivianite and greigite, respectively.

Health disparities in neurology.

Health disparities are preventable differences in health between different populations, and they are endemic throughout medicine owing to social, economic and environmental disadvantages. Neurology is no exception, and health disparities for systematically marginalized groups are present in the prevention, diagnosis, treatment and outcomes of all neurological disorders. The aetiology of these disparities is complex and multifactorial, reflecting the interplay of structural, institutional and individual-level factors.

Mitochondria-associated condensates maintain mitochondrial homeostasis and promote lifespan.

Membraneless organelles assembled by liquid-liquid phase separation interact with diverse membranous organelles to regulate distinct cellular processes. It remains unknown how membraneless organelles are engaged in mitochondrial homeostasis. Here we demonstrate that mitochondria-associated translation organelles (MATOs) mediate local synthesis of proteins required for structural and functional maintenance of mitochondria.

A rapid imaging-based screen for induced-proximity degraders identifies a potent degrader of oncoprotein SKP2.

Targeted protein degraders hold potential as therapeutic agents to target conventionally 'undruggable' proteins. Here, we develop a high-throughput screen, DEath FUSion Escaper (DEFUSE), to identify small-molecule protein degraders. By conjugating the protein of interest to a fast-acting triggerable death protein, this approach translates target protein degradation into a cell survival phenotype to illustrate the presence of degraders.

Pleistocene terrestrial warming trend in East Asia linked to Antarctic ice sheets growth.

How terrestrial mean annual temperature (MAT) evolved throughout the past 2 million years (Myr) remains elusive, limiting our understanding of the patterns, mechanisms, and impacts of past temperature changes. Here we report a ~2-Myr terrestrial MAT record based on fossil microbial lipids preserved in the Heqing paleolake, East Asia. The increased amplitude and periodicity shift of glacial-interglacial changes in our record align with those in sea surface temperature (SST) records.

Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours.

Monocyte-derived macrophages (mo-macs) often drive immunosuppression in the tumour microenvironment (TME) and tumour-enhanced myelopoiesis in the bone marrow fuels these populations. Here we performed paired transcriptome and chromatin accessibility analysis over the continuum of myeloid progenitors, circulating monocytes and tumour-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. We show that lung tumours prime accessibility for Nfe2l2 (NRF2) in bone marrow myeloid progenitors as a cytoprotective response to oxidative stress, enhancing myelopoiesis while dampening interferon response and promoting immunosuppression.

Neuronal activity-dependent mechanisms of small cell lung cancer pathogenesis.

Neural activity is increasingly recognized as a crucial regulator of cancer growth. In the brain, neuronal activity robustly influences glioma growth through paracrine mechanisms and by electrochemical integration of malignant cells into neural circuitry via neuron-to-glioma synapses. Outside of the central nervous system, innervation of tumours such as prostate, head and neck, breast, pancreatic, and gastrointestinal cancers by peripheral nerves similarly regulates cancer progression.

Observing differential spin currents by resonant inelastic X-ray scattering.

Controlling spin currents, that is, the flow of spin angular momentum, in small magnetic devices, is the principal objective of spin electronics, a main contender for future energy-efficient information technologies. A pure spin current has never been measured directly because the associated electric stray fields and/or shifts in the non-equilibrium spin-dependent distribution functions are too small for conventional experimental detection methods optimized for charge transport. Here we report that resonant inelastic X-ray scattering (RIXS) can bridge this gap by measuring the spin current carried by magnons-the quanta of the spin wave excitations of the magnetic order-in the presence of temperature gradients across a magnetic insulator.

Stabilizing effect of amino acids on protein and colloidal dispersions.

Amino acids (AAs) have a long history of being used as stabilizers for biological media. For example, they are important components in biomedical formulations. The effect of AAs on biological systems is also starting to be appreciated.

ABCA7 variants impact phosphatidylcholine and mitochondria in neurons.

Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease, yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways.

Loss-of-function mutations in PLD4 lead to systemic lupus erythematosus.

Monogenic lupus offers valuable insights into the underlying mechanisms and therapeutic approaches for systemic lupus erythematosus (SLE). Here we report on five patients with SLE carrying recessive mutations in phospholipase D family member 4 (PLD4). Deleterious variants in PLD4 resulted in impaired single-stranded nucleic acid exonuclease activity in in vitro and ex vivo assays.

Nanotechnology for CAR T cells and tumour-infiltrating lymphocyte therapies.

Adoptive T-cell therapies, and particularly CAR T cells and tumour-infiltrating lymphocytes, have transformed cancer treatment by selectively targeting malignant cells. Despite their clinical success, these therapies face substantial challenges, including costly manufacturing processes and tumour-imposed barriers that limit efficacy. Advances in understanding the nanoscale mechanisms governing T-cell activation and the role of the tumour microenvironment in restricting T-cell responses have driven the development of nanotechnology-based strategies that integrate key chemical and physical cues.

Antiemetic drug fosaprepitant exerts anti-tumor effects against NSCLC by targeting FAK to inhibit AKT and JNK/c-Jun pathways.

Non-small cell lung cancer (NSCLC) is an aggressive malignancy with a poor prognosis. Abnormal expression of focal adhesion kinase (FAK) is closely linked to NSCLC progression, highlighting the need for effective FAK inhibitors in NSCLC treatment. In this study we conducted high-throughput virtual screening combined with cellular assays to identify potential FAK inhibitors for NSCLC treatment.