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Heart disease diagnosis and categorization from ECG signals using hybrid Fuzzy-CNN machine optimized by meta-heuristic algorithms
Trajectory tracking control of parafoil systems via soft actor-critic with benchmark task set generation
Abstract Parafoil systems are increasingly deployed in military and civilian missions that require high-precision trajectory tracking. However, conventional controllers based on linear strategies and limited decision information often fail to cope with task complexity, and existing reinforcement learning studies rarely consider the systematic construction of training task sets, thereby limiting generalization. To address these issues, this paper proposes a Benchmark Task Set Generation (BTSG) algorithm that builds high-quality task sets with diverse and balanced complexity for robust controller training and comprehensive evaluation, formulates the trajectory tracking problem as a Markov decision process with a 46-dimensional observation space and a dense reward structure to enrich decision-support information and improve learning efficiency, and develops a BTSG-SAC framework that integrates BTSG with Soft Actor-Critic (SAC) for controller training. Simulation results show that BTSG-SAC markedly outperforms PID and PPO controllers on the generated benchmark task set, reducing distance deviation by 50.7% and 33.2% under noise-free conditions; under sensor noise, BTSG-SAC attains a 98% success rate, whereas PPO reaches 77% and PID fails to achieve successful tracking. Overall, this paper extends the application of reinforcement learning to parafoil control and offers generalizable methodologies for future autonomous control research.
Human-mediated admixture shapes high genetic diversity and the invasion dynamics of Lupinus nootkatensis in Iceland
Abstract The invasion of the Nootka lupin ( Lupinus nootkatensis ) in Iceland presents a fascinating scenario: an introduced species on an isolated island that retains exceptionally high genetic diversity. Using inter-simple sequence repeat (ISSR) markers, we analysed the population structure of this widespread coloniser to understand the mechanisms behind its success. Contrary to expectations of a founder effect, our results reveal substantial polymorphism (100% at the dataset level) and high gene diversity, indicating that high propagule pressure from repeated, large-scale introductions has effectively countered genetic bottlenecks. Spatial analyses (PCoA, AMOVA) demonstrated a highly admixed structure where genetic clustering explains twice as much variance as geographical regions (12.3% vs. 5.9%). Importantly, a Mantel test confirmed a remarkably weak isolation-by-distance signal (explaining around 6% of the variance), aligning directly with the AMOVA results. This structural concordance shows that human-mediated transport—particularly from Reykjavík, the demographic hub—has completely overridden natural spatial gradients. We conclude that historical land reclamation efforts have acted as massive hyper-vectors, mixing diverse lineages to form a highly resilient, interconnected metapopulation. Therefore, effective management should shift from broad-scale eradication to targeted biosecurity measures that limit further human-facilitated mixing of these distinct genetic lineages.
Interfacial dipolar interactions drive giant second-harmonic generation in 2D organic–inorganic heterostructures
Holocene transition from climate-driven to human-dominated wetland dynamics in Sinchang-dong, South Korea
Macrophage-derived fibronectin suppresses antitumor immunity via tissue stiffening and immunosuppressive cell induction in cancer mouse models
Abstract Both tumor-associated macrophage (TAM) and tumor stiffness may support immunosuppression and limit immunotherapy response, particularly in non-small cell lung cancer (NSCLC). TAMs influence extracellular matrix (ECM) remodeling, but whether they also affect tumor stiffness, or are regulated by mechanical signals in turn, remains to be investigated. Here, we use single-cell transcriptomics of primary NSCLC samples to show that TAMs are associated with an immunosuppressive niche and are also a major source of the ECM component fibronectin (FN1). Mechanistically, macrophage-specific FN1 deficiency induces pro-inflammatory macrophages in a subcutaneous tumor mouse model, reduces ECM stiffness, increases lymphocyte infiltration into tumors, strengthens antitumor immunity, and enhances immune checkpoint blockade efficacy. Within TAMs, FN1-mediated cytoskeleton assembly and autophagy induction impair macrophage glycolysis by inhibiting the RAC1-mTOR axis, thereby limiting the antitumor activity of macrophages. Collectively, these findings highlight macrophage-derived FN1 as a mechanical cue for aggravating immunosuppression and as an intervention target to supplement immunotherapy in NSCLC.
Clinical significance of gut microbiota-derived metabolite trimethylamine N-oxide in patients with systemic lupus erythematosus
Abstract Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, is associated with cardiovascular disease (CVD) via pro-inflammatory and pro-atherogenic mechanisms. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a significantly increased risk of CVD, however, the role of TMAO in SLE remains unclear. This study aimed to assess the clinical significance of TMAO in patients with SLE, including analyses of precursor metabolites and gut microbiome. A total of 207 participants were enrolled, including 157 patients with SLE and 50 healthy controls. Serum TMAO levels were measured using ELISA, fecal precursor metabolites including trimethylamine (TMA) were quantified by 1 H-NMR spectroscopy, and gut microbiota composition was assessed using 16S rRNA sequencing. SLE patients with CVD had significantly higher TMAO levels than HC ( P = 0.028) and SLE patients without CVD ( P = 0.004). Serum TMAO ( P = 0.025) and fecal TMA ( P = 0.032) levels were positively correlated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index. Serum TMAO was negatively correlated with steroid dose ( P = 0.038). Distinct gut microbiota compositions were observed between SLE patients with and without CVD. TMAO is associated with cardiovascular disease and cumulative organ damage in SLE, potentially mediated by gut microbiome alterations and modulated by steroid therapy.
Mapping neuro-vascular unit communications reveals distinct angiogenic programs across developing mouse brain regions
Research on multi-stage deep learning based intelligent diagnosis of skin diseases and skin medicine diagnosis community construction concept
The current Ebola outbreak is a public health emergency of international concern
Dynamic multi-strategy Grey Wolf optimizer and its applications
Structural basis of signal peptide recognition by the signal peptidase complex
Abstract The signal peptidase complex (SPC) is responsible for cleaving signal peptides (SPs) from approximately 10% of the human proteome. SPs are characterized by a tripartite structure, consisting of an N-terminal n-region, a central helical h-region and a C-terminal c-region, each defined by rather general chemical properties rather than strict sequence conservation. Despite their sequence diversity, SPC recognizes and processes SPs with exquisite specificity. Here, we present a 2.6 Å cryo-EM map of the human SPC-A, one of two SPC paralogs, bound to a model SP. The c-region binds to a hydrophobic binding groove near the active site, a narrow gate marks the transition from c- to h-region, and the h-region localizes in a transmembrane (TM) window. Substrate engagement stabilizes N- and C-terminal helices of Sec11A, which frame the SP and are unresolved in the apo structure. Molecular dynamics (MD) simulations confirm a stable hydrogen-bonding network at the c-region and indicate dynamic interactions within a thinned lipid environment at the TM window. AlphaFold modeling supports this binding mode across physiological SPs. Collectively, our structural and computational analyses explain how the SPC achieves its specificity by combining the selectivity of the luminal binding groove and of the transmembrane window.
Acute effects of caffeine withdrawal on headache among regular caffeinated coffee drinkers
Abstract Headaches are among the most common neurological disorders, often leading to significant disability and reduced quality of life 1,2 . However, much remains unknown about the triggers that precipitate headaches 3 . Coffee is one of the most widely consumed beverages worldwide, and coffee withdrawal is thought to be associated with headache 4,5 . However, research linking caffeine withdrawal to headache in healthy adult populations is largely limited to observational studies prone to confounding or single snapshot assessments prone to recall bias 6–8 . While small, near-term randomized trials have been conducted, these generally are done in artificial study-based settings (rather than among ambulatory individuals) and fail to capture repeated events that best represent real-life circumstances 9,10 . We sought to leverage a prospective, randomized, case-crossover trial to assess acute relationships between caffeine withdrawal and headaches among healthy individuals 11 . Here, we show that among regular caffeinated coffee consumers, caffeine avoidance likely contributes to headaches. When headaches are present, caffeine avoidance was also associated with increased headache severity. These results suggest that headache, commonly experienced by a substantial proportion of the population, may often occur as a consequence of caffeinated coffee withdrawal. Together, these findings may inform behaviors and recommendations regarding coffee consumption and minimizing headache burden on a day-to-day basis.
PATTY corrects open-chromatin bias for improved bulk and single-cell CUT&Tag profiling
Hypoxia, metastatic origin and HPV16 E6/E7 expression differentially shape the radiation response in head and neck squamous cell carcinoma cell lines
Abstract Hypoxia, a common feature of head and neck squamous cell carcinoma (HNSCC), significantly compromises radiotherapy efficacy by modulating DNA repair, cell‑cycle progression, and inflammatory signaling pathways. In addition, intrinsic tumor heterogeneity—including tumor origin and human papillomavirus (HPV) oncogene expression—further shapes therapeutic response. Despite these recognized factors, the integrated impact of oxygen tension, tumor origin, and viral oncogene expression on radiation response remains poorly defined. We examined the effects of hypoxia (1% O 2 ) and gamma-irradiation (6 Gy) on proliferation, cell-cycle progression, apoptosis, transcriptomic profiles, and cytokine secretion in three HNSCC cell lines: FaDu (primary origin), Detroit-562 (metastatic origin), and 2A3, an isogenic FaDu derivative stably expressing HPV-16 E6/E7 oncogenes. Hypoxia prolonged cell doubling time across all lines, independent of origin or E6/E7 expression, while irradiation induced features of an intermediate epithelial–mesenchymal transition phenotype. Compared with FaDu, 2A3 cells exhibited distinct transcriptional responses, reduced cytokine secretion (IL-8, Serpin E1), and altered cell-cycle regulation following irradiation. Detroit-562 cells secreted markedly higher cytokine levels and showed no increase in cleaved caspase-3 under hypoxia after irradiation. Our findings demonstrate that oxygen tension and biological factors—including metastatic origin and E6/E7 expression—modulate radiation response in HNSCC cell lines. These results highlight the need for biomarker-driven strategies that consider both hypoxic tumor microenvironment and key biological factors such as metastatic origin and HPV‑related E6/E7 oncogene expression.
A scalable Tn5-based method for genome-wide DNA methylation profiling in development and disease
Abstract DNA methylation is a key epigenetic modification involved in development and disease, including cancer, and serves as a biomarker for diagnosis. Current detection methods, such as bisulfite sequencing, provide base-pair resolution but require high sequencing depth and cost. Here, we developed C me CUT&Tag, a Tn5-based approach that uses methylation-binding domain fusion proteins to selectively target methylated DNA in chromatinized and isolated DNA. This enables adapter insertion into methylated regions, allowing low-depth sequencing for quantitative analysis or optional cytosine conversion for base-pair resolution. C me CUT&Tag enables genome-wide DNA methylation profiling with reduced input and sequencing requirements. We demonstrate its performance in characterizing DNA methylation across development and disease in human stem cells, organoids, zebrafish embryogenesis, and tumor biopsies. The method shows strong concordance with bisulfite sequencing and supports the classification of brain tumor samples into methylation subtypes. These features make C me CUT&Tag a scalable and cost-effective approach for epigenetic research and potential clinical applications.
Optimizing multi-label image annotation: a hybrid CNN-Transformer deep learning approach
Ancient DNA reveals a family ossuary and long-distance migration on the Pacific coast before the Inca Empire
Abstract This paper tracks long-distance migration on the Pacific coast that began no later than the thirteenth century AD. Genome-wide data for 21 sampled individuals from the lower and middle Chincha Valley of southern Peru show shared ancestry with groups 700 km to the north. A large-scale polity known as the Chincha Kingdom controlled the Chincha Valley from the thirteenth century until the fifteenth century, when it fell to the Inca Empire. The earliest migrants have unadmixed ancestry, whereas in subsequent generations, intermarriage resulted in admixtures from neighboring coastal areas. Relatives buried together in a family ossuary practiced consanguineous endogamy. We build a generation-scale Bayesian model informed by an aDNA-based family tree and individual calibration curves for estimated proportions of marine diet, addressing long-standing difficulties with temporal precision on the Pacific coast due to the marine reservoir effect and uncertainty inherent in estimating marine consumption based on δ 15 N. These data demonstrate population continuity from the thirteenth to fifteenth centuries, coinciding with persistent traditions of cranial modification and postmortem red pigment application. We reveal close-knit and far-reaching coastal interaction networks that shaped the sociopolitical landscape encountered by Inca emissaries before they integrated these communities into their empire.