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Cancer cachexia in STK11/LKB1-mutated non-small cell lung cancer is dependent on tumor-secreted GDF15
Abstract Cachexia is a wasting syndrome involving adipose, muscle, and body weight loss in cancer patients. Tumor loss-of-function mutations in STK11 / LKB1 , a regulator of AMP-activated protein kinase, induce cancer cachexia (CC) in preclinical models and are linked to weight loss in non-small cell lung cancer (NSCLC) patients. This study examines the role of the integrated stress response (ISR) cytokine growth differentiation factor 15 (GDF15) in regulating cachexia using patient-derived and engineered STK11/LKB1 -mutant NSCLC lines. Tumor cell-derived serum GDF15 levels are elevated in mice bearing these tumors. Treatment with a GDF15-neutralizing antibody or silencing GDF15 from tumor cells prevents adipose/muscle loss, strength decline, and weight reduction, identifying tumors cells as the GDF15 source. Restoring wild-type STK11/LKB1 in NSCLC lines with endogenous STK11/LKB1 loss reverses the ISR and reduces GDF15 expression rescuing the cachexia phenotype. Collectively, these findings implicate tumor-derived GDF15 as a key mediator and therapeutic target in STK11/LKB1 -mutant NSCLC-associated cachexia.
Leveraging metabolic similarity in a 1H NMR database of medicinal plants to advance pharmacognostic insights
Harmonic non-Hermitian skin effect
Reduced expression of BIRC2 and BIRC3 associated with longer survival in pediatric high-grade gliomas
Abstract Inhibitors of apoptosis proteins (IAPs), coded by BIRC genes, are cellular checkpoints that can regulate and inhibit pro-apoptotic caspase signaling. Overexpression of BIRC genes has been associated with cancer progression, multidrug resistance, poor prognosis, and shorter survival in several types of cancer. Using quantitative real-time polymerase chain reaction, we examined the expression of IAP family genes and their regulators: NAIP , BIRC2 , BIRC3 , XIAP , BIRC5 , BIRC6 , BIRC7 , CASP3 , CASP9 , DIABLO and XAF1 . We also evaluated the impact of clinical parameters (programmed death receptor 1 [PD1] expression, oligodendrocyte transcription factor 2 [Olig2] expression, Ki-67 antigen expression, tumor protein p53 expression in tumor cells, patient survival time, and progression-free survival) on gene expression levels. The expression of BIRC3 ( p = 0.049), NAIP ( p = 0.008), and XAF1 ( p = 0.032) was significantly higher in tumors negative for Ki67, whereas the remaining genes showed no significant correlation with Ki67 expression. In contrast, BIRC2 ( r =-0.478 p < 0.05) and BIRC3 ( r =-0.536 p < 0.05) expression levels were negatively correlated with overall survival. A similar negative association was observed between progression-free survival and the expression of BIRC2 ( r =–0.481, p < 0.05) and BIRC3 ( r =-0.540, p < 0.05). To our knowledge, this is the first study to comprehensively assess the relationship between the expression of IAP family genes and their regulators in a homogeneous group of patients diagnosed with pediatric high-grade gliomas (pHGGs). Our findings provide new insights into molecular mechanisms involved in the pathogenesis of pHGGs, however, these preliminary results require confirmation in larger and more detailed studies.
Twist engineering induced spin-orbit coupling for photosynthesis of ethane from carbon dioxide and water
Hydrodynamic response of an Antarctic glacial bay to cross-bay winds and its potential impact on primary production
Abstract Antarctic glacial bays are important, productive regions of the Southern Ocean. Certain glacial bays, including our research area, Admiralty Bay, are less favorable for phytoplankton growth due to wind-enhanced high energy levels, but they still host localized biological blooms. Westerly winds are predominant in Admiralty Bay; the strongest storms are from the east. These winds act perpendicular to the main axis of the bay. This study investigates the impact of cross-bay winds on the bay’s hydrodynamics and its potential effects on primary production. A hydrodynamic model, coupled with a Lagrangian model tracking potential iron sources, was run under seven wind scenarios. Results indicate that all winds reduce water column stratification, but energy increase rates and circulation pattern shifts vary with wind direction. Westerly winds restrict outflow and promote the formation of submesoscale eddies near inner inlet openings, concentrating water masses that are expected to be iron-rich, potentially stimulating phytoplankton growth. Conversely, easterly winds enhance outflow, flushing bay waters and likely negatively impacting productivity. Limited observational and satellite-derived biological data provide supportive evidence for the model-based hypothesis that the direction of cross-bay winds, rather than just their magnitude, significantly influences local productivity.
Crowdsourced biodiversity monitoring fills gaps in global plant trait mapping
Abstract Plant functional traits are fundamental to ecosystem dynamics and Earth system processes, but their global characterization is limited by available field surveys and trait measurements. Recent expansions in biodiversity data aggregation—including vegetation surveys, citizen science observations, and trait measurements—offer new opportunities to overcome these constraints. Here we demonstrate that combining these diverse data sources with high-resolution Earth observation data enables accurate modeling of key plant traits at up to 1 km 2 resolution. Our approach achieves correlations up to 0.63 (15 of 31 traits exceeding 0.50) and improved spatial transferability, effectively bridging gaps in under-sampled regions. By capturing a broad range of traits with high spatial coverage, these maps can enhance understanding of plant community properties and ecosystem functioning, while serving as tools for modeling global biogeochemical processes and informing conservation efforts. Our framework highlights the power of crowdsourced biodiversity data in addressing longstanding extrapolation challenges in global plant trait modeling, with continued advancements in data collection and remote sensing poised to further refine trait-based understanding of the biosphere.
Molten salt-assisted one-pot synthesis of Ag nanoparticles supported on clay minerals for enhanced antibacterial performance
Supercharging-enhanced nDIA-MS enables global profiling of drug-induced proteome solubility shifts
Quercetin alleviates incontinence-associated dermatitis via IKK/NF-κB pathway
On-surface synthesis platform for highly branched oligomers based on sequential C—C coupling and C—H activation of carbenes
Abstract On-surface synthesis is an emerging field for fabricating low-dimensional nanostructures. While carbenes are versatile reactive intermediates in solution-phase organic synthesis, they have rarely been explored in on-surface synthesis. Here, we demonstrate the versatility of carbenes in synthesizing highly branched zero-dimensional oligomers with distinct structures on a metal surface by combining bond-resolved scanning tunneling microscopy imaging, manipulation, X-ray photoelectron spectroscopy, surface infrared spectroscopy, and ab initio theoretical modeling. We synthesize highly symmetric branched oligomers through the C−C coupling of two carbene molecules to form a core of oligomers, followed by C−H activation of the core with up to four additional carbene molecules to create branches. Branched oligomers of lower symmetry are formed through cyclodehydrogenation of the highly symmetric oligomers. Our on-surface synthetic strategy based on C−H activation of carbene building blocks provides a platform for the design and synthesis of highly branched zero-dimensional oligomers with distinct structures.
Automated smart drip irrigation system in internet of things using adaptive residual hybrid network for precision farming
Evolutionary repurposing of a metabolic thiolase complex enables antibiotic biosynthesis
High reclassification rate of height-indexed left atrial volume in obese and overweight patients with cardiac pathologies in daily clinical practice
Abstract We sought to investigate the frequency of left atrial (LA) size reclassification in obese and overweight patients with heart disease, adjusting LA volume (LAvol) for height rather than BSA. Obesity is associated with cardiovascular diseases, heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation, among others. Indexing LAvol in obese patients by BSA may misclassify LAvol and the diagnosis of LA dilation. We consecutively studied 253 patients, mean age of 64.3 ± 15.1 years, 146 men (57.7%) with cardiac pathologies. LAvol was measured by the biplane Simpson’s rule. We compared LAvol indexed by BSA, height and height², prevalence and degree of LA dilation among normal weight (< 25 kg/m²), overweight (≥ 25 < 30 kg/m²) and obese (≥ 30 kg/m²) patients. There were 111 (44%) normal weight, 59 (23%) obese and 83 (33%) overweight patients. Overall, the frequency of LA dilation was 58%, 64.2% and 63.8%, indexed by BSA, height and height², respectively. In obese patients these figures were 46%, 65% and 66.6%. Twelve of 30 (40%) obese and 7 of 33 (21%) overweight patients were reclassified from non-dilated to dilated LA when indexed either by height or height². Half (50%) of obese patients were upgraded by one grade, and 37.5% by two grades. Obesity, BMI ≥ 27.5 kg/m² and atrial fibrillation were independent predictors of reclassification. Reclassification of LAvol indexed for height in obese or overweight patients with heart disease is very high. It seems appropriate to use LAvol indexed for height in these patients.
Global metagenomics reveals plastid diversity and unexplored algal lineages
The predictors of treatment adherence among hypertensive patients with cost-free access
Structural basis of pausing during transcription initiation in mycobacterium tuberculosis
Abstract In bacteria, RNA polymerase (RNAP) often pauses during the early stages of transcription initiation. The structural basis for these transient pauses remains unclear. Here, we present cryo-electron microscopy (cryo-EM) structures of the paused initiation complex (PIC) and initiation complex (IC) of Mycobacterium tuberculosis ( Mtb ), which include the RNAP core enzyme, the ECF σ factor σ E , transcription factor CarD, promoter DNA, and nascent RNA. Our structures with pre-melted scaffolds reveal an intermediate at the 6–7 nt stage compatible with a paused-like intermediate, associated with steric hindrance between the emerging RNA and the σ3.2 region. This clash triggers a swivel of the RNAP structural module and scrunching of the transcription bubble. We also observe positional rearrangement of the σ4 domain, suggesting a poised pre-escape state. In addition, complementary reconstructions with fully matched DNA scaffolds (N-IC and N-PIC) support the physiological relevance of the captured intermediates. Together, our results support the existence of a mechanistic checkpoint during transcription initiation and suggest an RNA-induced model how RNAP conformational dynamics regulate early transcription.