Search Results (639)

Robotic-assisted bronchoscopy (RAB) represents a significant technological advance, providing superior precision, enhanced visualization, and increased maneuverability relative to conventional bronchoscopic methods. This review provides an overview of current research evaluating RAB’s diagnostic performance and exploring future prospects. Recent literature demonstrates advantages in navigating difficult-to-reach lung lesions with improved safety profiles compared to transthoracic approaches. Incorporating advanced imaging technologies has enhanced real-time decision-making during procedures, and artificial intelligence applications are emerging. RAB has been rapidly adopted at many high-volume centers based on favorable navigational success and safety data. As the field matures, ongoing prospective studies will further define its role in improving patient outcomes, cost-effectiveness, and optimal integration with lung cancer screening programs. RAB faces ongoing challenges including substantial capital costs, training requirements, and need for standardized protocols. Therapeutic applications show promise and are under active investigation. Full article

Background/Objectives: Alzheimer’s disease (AD) is defined by amyloid-β plaques and tau neurofibrillary tangles and is typically associated with progressive cognitive decline. However, a substantial subset of individuals remains cognitively intact despite intermediate-to-high AD pathology, a phenomenon termed cognitive resilience. This review aims to synthesize genetic variants and biological pathways associated with preserved cognition in the presence of AD neuropathology. Methods: We performed a narrative thematic synthesis of human genetic studies (GWAS, sequencing, biomarker-informed cohorts) and extreme resilience case reports. Variants were prioritized by replication, mechanistic plausibility, and relevance to clinicopathologic dissociation, and were organized by shared biological pathways. When applicable, cognitive resilience was operationalized using residual-based approaches modeling cognitive performance after adjustment for neuropathological burden, age, sex, and education or cognitive reserve proxies reported by each cohort. Results: Recurrent resilience-associated variants include APOE ε2, APOE3-Christchurch, RELN-COLBOS, ATP8B1, RAB10, PLCG2, PICALM, CLU, FN1, and synapse-linked markers such as NPTX2. These variants converge on lipid metabolism, synaptic function and neuroplasticity, tau regulation and proteostasis, immune and inflammatory signaling, vascular/BBB resilience, and RNA regulation. Conclusions: Genetic determinants of cognitive resilience highlight mechanisms that preserve neural integrity independent of pathological load. Targeting resilience pathways may enable precision therapies designed to maintain cognitive function in AD. Full article

Bovine Viral Diarrhea Virus (BVDV) poses a significant threat to the global cattle industry, causing substantial economic losses. Long non-coding RNAs (lncRNAs) play crucial regulatory roles in various biological processes, including viral infections. However, the specific lncRNAs influencing BVDV replication remain poorly characterized. This study identified lncSMIM14 as a key host factor upregulated during BVDV infection in MDBK cells. Functional analyses demonstrated that lncSMIM14 overexpression significantly enhanced BVDV replication, evidenced by increased viral mRNA levels, progeny virus titers, cytopathic effects, and dsRNA abundance, while its knockdown exerted the opposite effect. Mechanistically, we revealed that lncSMIM14 specifically targets and positively regulates the expression of the endocytosis-related GTPase Rab3a. Importantly, Rab3a itself was shown to be essential for efficient BVDV replication, as its overexpression promoted viral replication, and its knockdown inhibited it. Furthermore, Rab3a co-localized with key endocytic regulators Rab5a and Rab7a, and both lncSMIM14 overexpression and Rab3a overexpression promoted the formation of endocytic vesicles, particularly post-BVDV infection. Our findings unveil a novel mechanism wherein BVDV exploits the host lncRNA lncSMIM14 to hijack Rab3a-mediated endocytosis, facilitating its own replication. This study identifies the lncSMIM14-Rab3a axis as a critical host pathway subverted by BVDV, providing new potential targets for antiviral intervention. Full article

MYB transcription factors (TFs) are crucial for plant growth, development, and response to abiotic stress. However, their exact functions in abiotic stress responses in rapeseed remain largely unexplored. In this study, we identified and characterized BnaMYB73, a member of the R2R3-MYB subfamily, and investigated its role in abiotic stress tolerance. The transcription level of BnaMYB73 was significantly upregulated in response to salt and osmotic stress. Transgenic Arabidopsis thaliana lines expressing BnaMYB73 displayed significantly enhanced tolerance to salt and osmotic stress, while showing no phenotypic differences in growth compared with wild-type (WT) plants under normal conditions. Physiological analyses revealed that the BnaMYB73-expressing plants accumulated higher proline levels, exhibited elevated superoxide dismutase (SOD) and peroxidase (POD) activities, and reduced malondialdehyde (MDA) content under stress conditions. Moreover, the BnaMYB73-expressing plants significantly upregulated key stress-responsive genes, including AtRD29B, AtDREB2A, AtRAB18, AtP5CS1, AtSOS1 and AtCAT1. Collectively, these findings establish BnaMYB73 functions as a stress-responsive transcription factor that enhances abiotic stress tolerance and provide a promising target for breeding stress-resilient rapeseed cultivars. Full article

Background/Objectives: CEU-938, an innovative antimicrotubule prodrug bioactivated by cytochrome P450 1A1 (CYP1A1), represents a promising targeted alternative for cancer cells overexpressing this enzyme. To optimize its clinical utility and minimize off-target effects in breast cancer (BC) patients, this study aims to identify predictive biomarkers of CEU-938 efficacy. Methods: The antiproliferative activity of CEU-938 was assessed across a panel of 39 human breast cancer and non-tumorigenic cell lines. Differential expression analyses were subsequently performed to distinguish CEU-938-responsive from non-responsive cell lines using a threshold of 1000 nM. Candidate biomarkers identified through this approach were then validated by RT-qPCR and Western blot analyses. Results: CEU-938 demonstrated marked and selective antiproliferative activity across molecular subtypes of human breast cancer, with efficacy observed in approximately 40% of triple-negative breast cancer (TNBC), 70% of estrogen receptor-positive (ER⁺), and 80% of human epidermal growth factor receptor 2-positive (HER2⁺) breast cancer cell lines, while sparing non-tumorigenic human breast cells (MCF 10A, MCF-12A, 184B5). Differential expression analysis identified five candidate biomarkers associated with CEU-938 responsiveness, namely, FOXA1 (log2-fold change (LFC) = 3.1), RAB25 (LFC = 3.8), RHOV (LFC = 2.9), PRKCH (LFC = 1.6), and HDAC9 (LFC = −1.7). Among these, FOXA1 and RAB25 robustly validated by RT-qPCR and Western blot analyses, showing strong inverse correlations with CEU-938 sensitivity (Spearman correlation coefficients of −0.82 and −0.61, respectively, at the protein level). The predictive value of FOXA1 and RAB25 was further confirmed by Western blot analyses in two independent breast cell line models, the non-responsive MCF-12A and the responsive MDA-kb2. Conclusions: Collectively, these findings identify FOXA1 and RAB25 as robust predictive biomarkers of response to CEU-938. Notably, FOXA1 and RAB25 are strongly implicated in breast cancer biology, and FOXA1 has been directly linked to the aryl hydrocarbon receptor (AHR), the main regulator of CYP1A1. These results position CEU-938 as a strong precision-therapy candidate that combines target selectivity, a favorable toxicity profile, and biomarker-enabled patient stratification, with potential clinical benefit in ER⁺ and HER2⁺ enriched tumors, as well as a subset of TNBC. Full article

Mutations in leucine-rich repeat kinase 2 (LRRK2) are among the most common genetic causes of Parkinson’s disease (PD), yet substantial heterogeneity exists among pathogenic variants. How mutations in distinct functional domains of LRRK2 differentially perturb cellular homeostasis remains incompletely understood. Here, we compared two pathogenic LRRK2 mutations—G2019S in the kinase domain and I1371V in the GTPase domain—across multiple cellular models, including SH-SY5Y and U87 cells, and healthy human iPSC-derived floor plate cells. We demonstrate that the I1371V mutation induces markedly more severe cellular dysfunction than G2019S. I1371V-expressing cells exhibited elevated LRRK2 autophosphorylation at S1292 and robust hyperphosphorylation of Rab8A and Rab10, indicating enhanced downstream signaling. These alterations impaired sterol trafficking, leading to selective depletion of membrane cholesterol without changes in total cellular cholesterol. Consequently, I1371V cells displayed increased membrane fluidity, disrupted microdomain organization, altered membrane topology, reduced caveolin-1 expression, and impaired dopamine transporter surface expression and dopamine uptake. Lipidomic profiling further revealed a broad disruption of lipid homeostasis, including reductions in cholesteryl esters, sterols, sphingolipids, and glycerophospholipids, whereas G2019S cells showed comparatively modest changes. Pharmacological intervention revealed mutation-specific responses, with the non-selective LRRK2 modulator GW5074 outperforming the kinase-selective inhibitor MLi-2 in restoring Rab8A phosphorylation, membrane integrity, and dopaminergic function. Collectively, these findings identify membrane lipid dysregulation as a central cell biological mechanism in LRRK2-associated PD and underscore the importance of variant-specific therapeutic strategies. Full article

Introduction: Lung cancer is a leading cause of cancer-related deaths globally, with approximately 1.5 million new peripheral pulmonary lesions (PPLs) detected annually in the United States. Robotic-assisted bronchoscopy (RAB) has emerged as a promising technology, with two platforms initially approved, the Monarch platform (Auris Health Inc, Redwood City, CA, USA) and the Ion Endoluminal System (Intuitive Surgical, Sunnyvale, CA, USA), offering improved stability and distal airway visualization. As RAB adoption increases, there is a critical need for comparative effectiveness data of these systems to guide clinical decision-making and institutional investments. This study aims to compare the diagnostic yield and safety profiles of the Ion and Monarch RAB platforms after introduction at a single institution. Methods: We conducted a retrospective chart review of patients undergoing RAB in the first six months following the introduction of each platform. Demographic and radiographic data were collected. Diagnostic yield was defined as obtaining a malignant or specific benign diagnosis from bronchoscopy. Results: The study included 56 Ion and 36 Monarch procedures. Diagnostic yield was similar between Ion (75%) and Monarch (72%) groups (p = 0.8), with an adjusted odds ratio 0.89 (95% CI 0.30–2.72). Complications were low, with one pneumothorax occurring in each group. Conclusions: Early adoption and use of both RAB platforms suggests comparable diagnostic yields and safety profiles in our limited sample size. Larger studies including standardized anesthesia protocol and systematic use of real-time imaging are needed for further evaluation and comparative analysis. Full article

In Mammalia, the COP9 signalosome (CSN) is associated with cullin-RING ubiquitin ligases (CRLs). This study focuses on the variants CSNCSN7A and CSNCSN7B, which form complexes with CRL3 and CRL4A, respectively. Although some research has been conducted on the assembly of the complexes, little is known about their breakdown. Here, we show that entire CSNCSN7A-CRL3 and CSNCSN7B-CRL4A complexes are degraded via autophagy. CSN-CRL complexes are degraded in the absence of serum via bulk autophagy and in the presence of the specific inhibitor of CSN, CSN5i-3, via selective macroautophagy. Surprisingly, the self-ubiquitylation of cullins in the CRLs was identified as a specific signal for selective macroautophagy. The self-ubiquitylation of cullins takes place in the presence of CSN5i-3, and CSN-CRL complexes are expelled from the nucleus to be degraded in the cytosol. Selective macroautophagy can be blocked by chloroquine, a specific inhibitor of autophagy. Interestingly, the process can also be inhibited by MLN4924, a neddylation inhibitor. Confocal fluorescence microscopy illustrates the interaction of CSN subunits with ATG8, as well as with RAB7, both in HeLa and in LiSa-2 cells. Confocal fluorescence microscopy produces images that suggest the localization of CSN-CRL particles in autophagosomes. Our data place CSN-CRL in the category of large complexes that are degraded through autophagy. Full article

The plant cuticle is a hydrophobic layer covering the cell wall that protects cells from pathogen invasion and water loss. In this study, we analyzed the cuticles of transgenic Arabidopsis thaliana plants overexpressing the vesicular trafficking small GTPase RabA2b. The RabA2b-overexpressing plants exhibited distinctive structural and chemical modifications in their cuticles, including enhanced hair-like wax crystals and increased accumulation of phenolic compounds such as ferulic acid and coumaric acid, which contribute to cutin cross-linking and reinforcement of the cuticle matrix. These chemical and structural changes were associated with improved barrier function and increased drought resistance. Our findings suggest the involvement of RabA2b in affecting the plant cell’s exterior by altering the cuticle composition and architecture, thereby improving plant tolerance to water deficit. Full article

Myosin XI-K plays an important role in cell expansion and polarized growth, acting as a motor protein that drives organelle trafficking and cytoplasmic streaming. To elucidate the molecular mechanisms of myosin XI-K’s role in the polarized growth of cotton fiber, we investigated the interactions between GhXI-K and Rab GTPases in cotton (Gossypium hirsutum). Protein docking analyses based on AlphaFold3 predicted that GhXI-K interacted with eight Rab GTPases. A total of 37 interaction residues were identified in GhXI-K, of which 5 crucial contact residues were located in the globular tail domain (GTD) and 2 were located in the motor domain. Key interaction residues in the Rab GTPases were also found to be located in conserved regions: switch-I and switch-II. Yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assays confirmed the predictions and showed that these interactions occur primarily in the GTD and the motor domain. Our findings reveal that GhXI-K interacts with Rab GTPases through both the motor and tail domains, suggesting a synergistic mechanism that facilitates polarized vesicle trafficking in cotton fiber cells. Full article

Glioblastoma multiforme (GBM) is characterized by aggressive growth, extensive vascularization, high metabolic malleability, and a striking capacity for therapy resistance. Current treatments involve surgical resection and concomitant radiation therapy and chemotherapy, prolonging survival times marginally due to the therapy resistance that is built up by the tumor cells. A growing body of research has identified exosomes as critical enablers of therapy resistance. These nanoscale vesicles enable GBM cells to disseminate oncogenic proteins, nucleic acids, and lipids that collectively promote angiogenesis, maintain autophagy under metabolic pressure, and suppress apoptosis. As interest grows in targeting tumor communication networks, exosome-based therapeutic strategies have emerged as promising avenues for improving therapeutic outcomes in GBM. This review integrates current insights into two complementary therapeutic strategies: inhibiting exosome biogenesis and secretion, and engineering exosomes as precision vehicles for the delivery of anti-tumor molecular cargo. Key molecular regulators of exosome formation—including the endosomal sorting complex required for transport (ESCRT) machinery, tumor susceptibility gene 101 (TSG101) protein, ceramide-driven pathways, and Rab GTPases—govern the sorting and release of factors that enhance GBM survival. Targeting these pathways through pharmacological or genetic means has shown promise in suppressing angiogenic signaling, disrupting autophagic flux via modulation of autophagy-related gene (ATG) proteins, and sensitizing tumor cells to apoptosis by destabilizing mitochondria and associated survival networks. In parallel, advances in exosome engineering—encompassing siRNA loading, miRNA enrichment, and small-molecule drug packaging—offer new routes for delivering therapeutic agents across the blood–brain barrier with high cellular specificity. Engineered exosomes carrying anti-angiogenic, autophagy-inhibiting, or pro-apoptotic molecules can reprogram the tumor microenvironment and activate both the intrinsic mitochondrial and extrinsic ligand-mediated apoptotic pathways. Collectively, current evidence underscores the potential of strategically modulating endogenous exosome biogenesis and harnessing exogenous engineered therapeutic exosomes to interrupt the angiogenic and autophagic circuits that underpin therapy resistance, ultimately leading to the induction of apoptotic cell death in GBM. Full article

Cancer patients are highly vulnerable to severe COVID-19, requiring models that capture tumor–virus interactions. We investigated tumor- and variant-specific effects of SARS-CoV-2 Gamma and Delta infections using patient-derived organoids (PDOs) from metastatic breast, lung, and colorectal cancers. Viral infection was quantified by Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) 24 h post-infection, and morphological changes and immune mediators were profiled. Genomic analysis using whole-exome sequencing was performed to identify contributing host-related gene alterations. The Delta variant produced consistently higher viral loads in lung and breast PDOs, while colorectal PDOs showed variable susceptibility. Infection led to reduced area and perimeter and increased circularity across all tumor types. Immune profiling revealed distinct responses: Gamma decreased Interferon alpha (IFNα) in lung PDOs and increased E-selectin in colorectal PDOs. Delta broadly reduced inflammatory mediators in lung [10 kDa interferon gamma-induced protein (IP-10) and Intercellular adhesion molecule 1 (ICAM-1)] and breast [Interleukin-6 (IL-6), Interleukin-13 (IL-13), and Interleukin-17A (IL-17A)] PDOs, while increasing Macrophage inflammatory protein 1-beta (MIP-1β) in colorectal PDOs. Host gene variants involved in trafficking (FYCO1 and RAB7A) and immune signaling (FOXA2, SFTPD, STAT3, and TET2) were associated with differential infection profiles. These findings show that SARS-CoV-2 induces variant- and tumor-specific morphological and immunological changes in cancer PDOs, highlighting the potential of this model to unravel host–virus interactions and identify genetic factors that shape infection outcomes in cancer. Full article

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage loss, extracellular matrix degradation, chondrocyte apoptosis, and elevated inflammatory mediators. Chondrocytes respond to IL-1β and other inflammatory signals by secreting cytokines and activating transcriptional pathways that perpetuate inflammation. Because current therapies do not prevent OA progression, bioactive compounds with cytoprotective and immunomodulatory activity are of considerable interest. Lonomia obliqua bristle extract (LOCBE) and its recombinant proteins rLOPAP and rLOSAC exhibit cytoprotective, proliferative, and antioxidant effects in mammalian cells, as well as the ability to influence cytoskeletal dynamics. Given the importance of Rac-1, RhoA, Rab9, and β-catenin in chondrocyte function and cartilage homeostasis, we evaluated LOCBE, rLOPAP, and rLOSAC in human chondrocytes stimulated or not with IL-1β. LOCBE and rLOPAP induced IL-6 and IL-8 secretion, although at lower levels than IL-1β. LOCBE exerts a cytoprotective effect in IL-1β-treated chondrocytes and reduces β-catenin, RhoA, and Rab9 expression without affecting NF-κB p65 translocation. rLOPAP increased mitochondrial activity, cytokine secretion, Rab9 expression, and membrane-associated β-catenin, and under inflammatory conditions, enhanced Rac-1 levels. In contrast, rLOSAC did not induce inflammatory cytokines and decreased RhoA and Rac-1 expression while increasing membrane-associated β-catenin. These findings suggest that L. obliqua extract and its derived-proteins rLOPAP and rLOSAC modulate cytoskeletal regulatory pathways and inflammatory responses in chondrocytes, supporting their potential as therapeutic leads for targeting mechanisms relevant to OA progression. Full article

Although the clownfish, Amphiprion ocellaris (A. ocellaris), is a popular ornamental marine fish worldwide, the mechanisms underlying color pattern variation remain unclear. Given that the Platinum-type clownfish, nearly entirely white, has high economic value, understanding the biological mechanism that accounts for the difference between orange and white colors in A. ocellaris is crucial. To investigate these coloration differences, we performed RNA sequencing analysis and identified differentially expressed genes (DEGs) by comparing white and orange skin samples from three A. ocellaris individuals. A total of 76 DEGs were detected, including 56 downregulated and 20 upregulated genes. DEG sequences were annotated using Danio rerio and Stegastus partitus as reference species, selecting the best hit based on the lowest E-value. A protein–protein interaction (PPI) network and Gene Ontology biological process terms were additionally analyzed. Several DEGs previously reported to be associated with pigmentation, including hpdb, cldn11b, sfrp5, slc2a9, slc2a11b, si:ch211-256m1.8, fhl2, rab38, and ttc39b were identified. Based on the functions of these DEGs, it is inferred that leucophores and xanthophores contribute to both white and orange coloration by modulating related genes, including slc2a11b and slc2a9. Additionally, sfrp5, sost, and sp7 genes were identified to interact with each other in the PPI analysis, with sfrp5 and sost being associated with the Wnt signaling pathway, which contributes to melanocyte specification and osteoblast differentiation. Based on these findings, we propose sost and sp7 as candidate genes that might provide insights relevant to extreme white pigmentation phenotypes, such as those observed in Platinum-type clownfish. For a clearer understanding, further studies integrating quantitative genetics and functional analyses are required. Full article

This study aims to establish a method-integrative framework for emotion-oriented architectural image generation. The framework combines Stable Diffusion with targeted LoRA (Low-Rank Adaptation), a lightweight and parameter-efficient fine-tuning approach, together with ControlNet-based structural constraints, to examine how controllable design-element manipulations influence emotional responses. The methodology follows a closed-loop “generation–evaluation” workflow, with each LoRA module independently targeting a single design element. Guided by the relaxation–arousal emotional dimension, the framework is evaluated using subjective ratings and electroencephalogram (EEG) measures. Twenty-seven participants viewed six architectural space categories, each comprising four conditions (baseline, color, material, and form modification). EEG α/β power ratio (RAB) served as the primary neurophysiological marker of arousal. Statistical analysis indicated that LoRA-based modifications of design elements produced distinct emotional responses: color and material changes induced lower arousal, whereas changes in form elicited a bidirectional pattern involving relaxation and arousal. The right parietal P4 electrode site showed the most sensitive emotional response to design element changes, with consistent statistical significance. P4 is a human scalp EEG location associated with cortical activity related to visuospatial processing. Descriptive results suggested opposite directional effects with similar intensity trends; however, linear mixed-effects model (LMM) inference did not support significant group-level linear coupling, indicating individual variation. This study demonstrates the feasibility of emotion-guided architectural image generation, showing that controlled manipulation of color, material, and form can elicit measurable emotional responses in human brain activity. The findings provide a methodological basis for future multimodal, adaptive generative systems and offer a quantitative pathway for investigating the relationship between emotional states and architectural design elements. Full article