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Retraction Note: Real-time congestion control using cascaded LSTM deep neural networks for deregulated power markets
Nanomaterial-induced mitochondrial biogenesis enhances intercellular mitochondrial transfer efficiency
Intercellular mitochondrial transfer, the spontaneous exchange of mitochondria between cells, is a recently described phenomenon crucial for cellular repair, regeneration, and disease management. Enhancing this natural process holds promise for developing novel therapies targeting diseases associated with mitochondrial dysfunction. Here, we introduce a nanomaterial-based approach employing molybdenum disulfide (MoS 2 ) nanoflowers with atomic-scale vacancies to stimulate mitochondrial biogenesis in cells to make them mitochondrial biofactories. Upon cellular uptake, these nanoflowers result in a two-fold increase in mitochondrial mass and enhancing mitochondrial transfer to recipient cells by several-fold. This enhanced efficiency of transfer significantly improves mitochondrial respiratory capacity and adenosine triphosphate production in recipient cells under physiological conditions. In cellular models of mitochondrial and cellular damage, MoS 2 enhanced mitochondrial transfer achieved remarkable restoration of cell function. This proof-of-concept study demonstrates that nanomaterial-boosted intercellular mitochondrial transfer can enhance cell survivability and function under diseased conditions, offering a promising strategy for treating mitochondrial dysfunction-related diseases.
Downregulation of Akt induces proximal tubule epithelial cell apoptosis via FOXO and BIM pathway in proteinuric States
Roles of transposable elements and DNA methylation in the formation of CpG islands and CpG-depleted regulatory elements
The origins of CpG islands (CGIs) are not known. They are relatively short GC-rich regions of DNA with a higher-than-expected occurrence of CpG dinucleotides compared to most of the genome. They constitute less than 1% of the human genome but harbor approximately 40% of all transcription start sites (TSSs). CGIs are usually modulated by histone modifications in somatic cells or, in a minority of cases, permanently silenced by CpG methylation. Those that do not have TSSs are called “orphan CGIs”. Here, we show that CGIs containing TSSs almost never contain any of three major classes of transposable elements (TEs) and orphan CGIs rarely do. We hypothesize that CGIs persist across evolutionary time due to counterselection against TE insertion in the germ line. The 99% of the vertebrate genome, which is not CG rich, contains 60% of TSSs and putative enhancers. We postulate that conversion of an ancestral CpG-rich genome into the current CpG-depleted version present in vertebrates may also have allowed reversible DNA methylation to function in complex and dynamic gene control circuits. Therefore, we propose an evolutionary model in which vertebrate TEs are indirectly responsible for the existence of CGIs, and the formation of regulatory elements such as TSSs and enhancers that can potentially utilize dynamic DNA methylation for gene control.
Experimental evaluation of alterations in crude oil properties induced by hydrochloric acid, reservoir rock powder, and surfactants
Glycan recognition by collectin-11 drives SARS-CoV-2 infectivity and membrane injury of respiratory epithelial cells
SARS-CoV-2 respiratory-tract infection affects both vaccinated and unvaccinated persons suggesting factors besides adaptive immunity are operative. We investigated the role of collectin-11 (CL-11), an epithelial-secreted carbohydrate-binding lectin that drives innate immunity and eliminates pathogens by complement activation. SARS-CoV-2, despite binding CL-11 to activate complement, was resistant to lysis. Remarkably, opsonization by CL-11 enhanced virus production by infected respiratory epithelial cells independently of complement. Furthermore, infected cells expressing SARS-CoV-2 spike protein displayed enhanced vulnerability to CL-11 binding and membrane attack by complement. The mechanism of enhanced infectivity was ablated in the presence of L-fucose, which occupied the extended carbohydrate-binding cleft of CL-11 in a crystallographic analysis of complexes between L-fucose and CL-11. Our study suggests pathogenicity of SARS-CoV-2 is related to complement-resistance together with enhanced infectivity and injury of respiratory epithelial cells mediated by locally released CL-11.
Therapeutic comparison of MitoTEMPO and rosmarinic acid as mitochondria targeted and non targeted antioxidants evaluated in rat sciatic nerve crush injury model
Lipid raft proteomics identify endothelial myosin-9 (MYH9) as a regulator of low-density lipoprotein transcytosis and atherosclerosis
Background: In early atherosclerosis, circulating Low-Density Lipoprotein (LDL) crosses the endothelium by transcytosis. This involves caveolar uptake of LDL by scavenger receptor BI (SR-BI) and activin-like kinase 1 (ALK1) and requires the protein caveolin-1 (Cav-1). We identified mediators of LDL transcytosis by isolating membrane microdomains enriched in caveolin-1 from human coronary endothelial cells (HCAECs) treated with LDL and performing mass spectrometry. One of the proteins identified was myosin-9 (MYH9). Methods: Total internal reflection fluorescence microscopy was conducted to measure LDL transcytosis by HCAECs. We measured LDL transcytosis in vivo in mice lacking endothelial MYH9 (EC- Myh9 −/− ). Atherosclerosis studies were also performed in EC- Myh9 −/− deleted of hepatic LDLR via (adeno-associated virus, AAV)-CRISPR. Additionally, we performed analysis of human transcriptomic data. Results: Gene ontology analysis in human aortic endothelial cells suggested a role for MYH9 in exocytosis. Both knockdown and pharmacologic inhibition of MYH9 inhibited LDL transcytosis. MYH9 depletion caused an accumulation of LDL-containing vesicles at the base of the cell; overexpression caused an increase in LDL exocytosis. EC- Myh9 −/− mice accumulated less LDL in the aortic arch after acute injection with LDL. To investigate the role of MYH9 in atherosclerosis, we deleted hepatic LDL in EC- Myh9 −/− mice using AAV-CRISPR and fed them a high-fat diet. The aortic arch and root of AAV-CRISPR; EC- Myh9 −/− mice exhibited smaller plaques. Human transcriptomic data showed greater messenger RNA (mRNA) levels of aortic MYH9 in atherosclerotic aortas compared to healthy controls. Conclusions: Lipid raft proteomics identified MYH9 as a regulator of LDL transcytosis. MYH9 is required for endothelial LDL exocytosis and contributes to early atherosclerosis.
The impact of very low birth weight on children’s oral health in adolescence
Improving outbreak forecasts through model augmentation
Accurate forecasts of disease outbreaks are critical for effective public health responses, management of healthcare surge capacity, and communication of public risk. There are a growing number of powerful forecasting methods that fall into two broad categories-empirical models that extrapolate from historical data, and mechanistic models based on fixed epidemiological assumptions. However, these methods often underperform precisely when reliable predictions are most urgently needed-during periods of rapid epidemic escalation. Here, we introduce epimodulation, a hybrid approach that integrates fundamental epidemiological principles into existing predictive models to enhance forecasting accuracy, especially around epidemic peaks. When applied to empirical and machine learning forecasting methods (Autoregressive Integrated Moving Average, Holt-Winters, gradient-boosting machines, Prophet, and spline models), epimodulation improved overall prediction accuracy by an average of 12.3% (range: 8.5 to 18.7%) for COVID-19 hospital admissions and by 32.9% (range: 24.2 to 43.7%) for influenza hospital admissions; accuracy during epidemic peaks improved even further, by an average of 27.9% and 43.8%, respectively. Epimodulation also substantially enhanced the performance of complex forecasting methods, including the COVID-19 Forecast Hub ensemble model, demonstrating its broad utility in improving forecast reliability at critical moments in disease outbreaks.
Aggregate index of systemic inflammation as a new prognostic marker in patients with coronary artery disease undergoing PCI
A Bayesian perspective on single-shot laser characterization
We introduce a Bayesian framework for measuring spatiotemporal couplings in ultraintense lasers that reconceptualizes what constitutes a “single-shot” measurement. Moving beyond traditional distinctions between single- and multishot devices, our approach provides rigorous criteria for determining when measurements can truly resolve individual laser shots rather than statistical averages. By contextualizing single measurements, this framework shows that single-shot capability is not an intrinsic device property but emerges from the relationship between measurement precision and predictability. Implementing this approach with a custom measurement device at the ATLAS-3000 petawatt laser, we provide quantitative uncertainty bounds on pulse front tilt and curvature. Notably, we observe that our Bayesian method reduces uncertainty by up to 60% compared to traditional approaches. Through this analysis, we reveal how the interplay between measurement precision and intrinsic system variability defines achievable resolution-insights that have direct implications for applications where precise control of laser–matter interaction is critical.
Impact of meditation on brain age derived from multimodal neuroimaging in experts and older adults from a randomized trial
Abstract Meditation is thought to promote healthy aging by improving mental health, preserving brain integrity and reducing Alzheimer’s disease risk. We examined the impact of long-term meditation expertise and an 18-month meditation training on brain aging in older adults using machine learning. We included 25 Older Expert Meditators (OldExpMed) with > 20 years of practice and 135 Cognitively Unimpaired Older Adults (CUOA) from the Age-Well randomized controlled trial. CUOA were randomized (1:1:1) into an 18-month meditation training, a non-native language training, and a no intervention group. Brain age was predicted using a machine learning model trained on gray and white matter volume and glucose metabolism data from ADNI and replicated with a second model. Brain Predicted Age Difference (BrainPAD) was computed as the gap between predicted and chronological age. We assessed meditation expertise effects on BrainPAD, its links with meditation hours, cognitive, and affective measures, and the impact of 18-month training. Compared to CUOA, OldExpMed exhibited significantly lower/more negative BrainPAD, linked to meditation hours, mental imagery, and prosocialness. No significant effect of 18-month training was observed. Results were consistent across the replication model. Long-term meditation is associated with younger brain age, but 18-month training has no effect, emphasizing the need for sustained practice to support healthy brain aging.
XND1-centered network regulates salt tolerance by integrating root xylem plasticity and Na <sup>+</sup> unloading in <i>Arabidopsis</i>
Soil salinization has emerged as a significant challenge for crop production worldwide. Xylem adjustments through plastic development and sodium unloading from root xylem, as mediated by sodium transporter HKT1, both play crucial roles in controlling sodium transport and salt tolerance in plants. Here, we report that XYLEM NAC DOMAIN 1 (XND1) of Arabidopsis contributes to the coordination of these two processes during salt stress responses. XND1 is predominantly accumulated in roots under salt exposure and confers plant salt tolerance, as demonstrated by analysis of overexpression and loss-of-function mutant lines. XND1 mediates discontinuous root protoxylem differentiation under salt stress, potentially limiting sodium transport. In addition, XND1 directly targets and activates the expression of HKT1 , thereby facilitating the removal of sodium from root xylem. We also show that MYBS2, a MYB transcription factor, interacts with XND1 to antagonistically regulate HKT1 , whereas VND-INTERACTING 2 (VNI2), a NAC transcription factor, activates XND1 in response to salt stress. Characterization of the XND1 ortholog of rice suggests a conserved regulatory role under salt stress. Collectively, our findings unveil an XND1-centered regulatory network that modulates salt stress response, through the integration of root xylem developmental plasticity and sodium unloading.
A comprehensive assessment of the applicability of semianalytical models of vortex characterization for gravitational water vortex hydropower plants
Transcriptional condensates encode a “golden mean” to optimize enhancer–promoter communication across genomic distances
Enhancers regulate gene expression by physically contacting their target promoters, yet these contacts often span large genomic distances. Phase-separated condensates (droplet-like clusters) of transcription factors (TFs) are thought to facilitate such long-range enhancer–promoter (E-P) communication, but the quantitative principles underlying this mechanism remain unclear. Here, we use polymer-based chromatin simulations to systematically vary the strength of TF clustering and the E-P genomic distance, examining their combined effects on E-P contact formation. We find that E-P contact frequency shows a nonmonotonic dependence on the degree of TF clustering: Contact frequency peaks at an intermediate TF abundance and TF–TF affinity, leading to a “golden mean” optimum. Two distinct regimes emerge: Under weak TF–TF attraction, contact probability increases with condensate size, whereas strong TF attraction produces a peaked response that declines at high condensation levels. These results indicate that TF condensate acts as a tunable “rheostat,” buffering E-P interactions against increasing genomic distances. However, excessive TF clustering leads to molecular crowding and competition that ultimately impair E-P communication. Our study, consistent with recent experiments, establishes a mechanistic framework at the molecular level, where balanced TF condensation enables robust long-range E-P communication, reconciling the stochastic nature of chromatin dynamics with the fidelity of gene regulation.
New characteristics of MiRNA and IsomiR interactions with mRNA
A cytoplasmic motif in HLA-E that drives clathrin-mediated endocytosis and VCP-associated postendocytic trafficking
Human Leukocyte Antigen E (HLA-E) is a nonclassical MHC class I molecule that exhibits dual immunological functions in regulating natural killer (NK) cells and T cells through unusual trafficking patterns. We previously reported that HLA-E surface expression is low and transient due to its cytoplasmic tail and dominant VL9 peptide, making it a dynamic indicator of cellular status for NK cell surveillance. Here, we identify a sequence motif in the HLA-E cytoplasmic tail that enables rapid internalization via clathrin-mediated endocytosis (CME) through interaction with the adaptor protein 2 (AP-2) complex. Following internalization, HLA-E is routed to endosomes, where the same cytoplasmic motif and peptide loading together facilitate its reappearance on the cell surface—a process influenced by valosin-containing protein (VCP). Our findings reveal previously unrecognized endosomal trafficking pathways and regulatory mechanisms that distinguish HLA-E from classical HLA class I molecules, with broad implications for understanding the immunoregulatory roles of HLA-E.
Nanotechnology Meets superbugs: biocompatible polymeric nanoparticles combat MDR Klebsiella pneumoniae via gene suppression and biofilm Inhibition
A yeast mating platform for multiplex screening of fungal GPCR–ligand interactions
Fungi are essential members across ecosystems, yet phytopathogenic fungi pose an increasing risk to crop yields. Despite their ecologic importance, cell–cell communication in fungi is underexplored, partly due to the lack of high-throughput techniques. Here, we developed a Yeast Mating Platform (YeMaP) to investigate the interaction between fungal G protein–coupled receptors (GPCRs) and pheromone peptides. We used YeMaP for high-throughput screening of 8,000 pheromone sequences and identified peptides with improved agonism or antagonism action. We found that these peptides can be applied in a native fungal system such as the plant pathogen Fusarium oxysporum , to control hyphal chemotropism and reduce plant root penetration. Additionally, we utilized YeMaP in a one-pot assay to investigate how abiotic factors influence the communication of multiple pheromone–GPCR combinations and found that the cell–cell communication mediated by the GPCR Ste2 from F. oxysporum signaled robustly across different abiotic factors, while other fungal GPCR–pheromone interactions were more sensitive to changes. Taken together, YeMaP accelerates the identification of fungal GPCR–peptide interactions by enabling one-pot assays, and serves as a model system for studying fungal cell–cell communication.