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We discuss here physics and evolution of globular proteins with a focus on the basic units of their structure and function, closed loops and elementary functional loops. A starting point of the journey here is a prebiotic evolution, in which short linear peptides and corresponding RNA duplexes with traits determined by demands to survive and to move on in the harshness of the Origin of Life emerged first. Next, we follow the fate of ring-like peptides, which apparently were the "Dayhoff fragments" that passed through abiogenic transition, formed first functional domains followed by their inclusion in multidomain structures, formation of complexes, assemblies, and molecular machines in later stages. I argue that physics, specifically polymer nature of protein chains, not only served as a determinant of the basic units of proteins-closed loops but also could play a decisive role in determining the size of another important structural unit-domain-based on the polymer nature of nucleic acids that governed the optimal ring closure size of DNA molecules. The protein closed loops served as scaffold for carrying elementary functions-descendants of ancient ring-like peptides, combinations of which provided the modern protein function universe. Another alliance between physics and evolution discussed here is the allosteric regulation of protein function, which is based on the structural dynamics underlying the allosteric signal transduction and its regulatory role. While the physics drive the structure-based conserved patterns of allosteric signalling determined by the folds, the evolution brings in a sequence diversity, allowing to alternate the allosteric communication and to make it archetypal for distinct functional (super)families using the same fold as the structural platform. Considering only few above aspects, I show that important lessons from the hand-in-hand walk of physics and evolution already helped to achieve the current state-of-the-art in understanding of protein structure and function. I conclude, however, that there is still even more to learn from Nature about long and remaining mainly mysterious 3.5 billion years endeavor.
Programmed death-ligand 1 (PD-L1) expression is routinely used to guide immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC), yet clinical benefit remains heterogeneous even among PD-L1-high tumors. Liquid biopsy based on cell-free DNA (cfDNA) enables minimally invasive, real-time monitoring of tumor evolution. We report four cases of metastatic lung adenocarcinoma treated with atezolizumab, integrating longitudinal whole-exome sequencing (WES) of cfDNA with radiological assessment. Four patients with PD-L1-positive (≥60%) metastatic NSCLC received atezolizumab monotherapy. Serial cfDNA samples (1-3 per patient) were analyzed by high-depth WES. Distinct molecular trajectories paralleled divergent clinical outcomes. One patient achieved a complete molecular response, characterized by progressive clearance of KRAS, ATM, and NF1 mutant clones, which was concordant with radiological remission. A second patient showed an initial molecular response, followed by clonal rebound of TP53, NF1, and NOTCH2 mutant populations and the emergence of PTEN and KIF1A variants, suggesting clinical progression. Two patients exhibited primary resistance despite high PD-L1 expression, with persistent or expanding clones and early subclonal diversification; in one case, new EGFR and BRAF alterations emerged under treatment pressure. Notably, switching to platinum-based chemotherapy in a non-responder induced a measurable molecular response, highlighting discordance between PD-L1 status and immunotherapy efficacy. Longitudinal cfDNA WES captured dynamic clonal remodeling under immunotherapy and anticipated radiological outcomes. These findings underscore the clinical necessity of integrating dynamic molecular monitoring by liquid biopsy to overcome the limitations of static PD-L1 assessment, refine therapeutic stratification, and identify early resistance mechanisms in advanced NSCLC.
Regeneration is an essential pathway for the continuity of tree populations and a critical ecological process for the maintenance and restoration of natural forest ecosystems. Seed regeneration and sprout regeneration represent two strategies shaped by long-term evolution, reflecting adaptive trade-offs in response to resource limitations and environmental disturbances. In the context of global change, such trade-off is undergoing profound alteration. Based on regeneration niche theory, we reviewed the biological foundations and ecological significance of seed regeneration (colonization niche) and sprout regeneration (persistence niche) in tree species, with a focus on the mechanisms of global climate change, shifting in disturbance regimes, and habitat fragmentation that influence these two regeneration strategies. There are deficiencies in current research regarding the systematic analysis of the formation and evolution mechanisms of different tree species' preference for regeneration, the physiological and molecular mechanisms of shoot occurrence, the methodological challenges in multi-dimensional quantification of regeneration niches and their responses to global change, the need for further research on the response of forest tree regeneration strategies under global change, and the insufficient integration of the regeneration niche theory and forest management practices. Future efforts should be made to strengthen the molecular ecological and systems biological basis for the evolution of forest tree regeneration trade-off strategies under global change, to quantify the conversion thresholds of tree seedling regeneration and shoot regeneration, to construct a multi-dimensional research framework for forest tree regeneration niches, to strengthen the research on the response mechanisms of main forest tree species' regeneration strategies under global change, and to promote the deep integration of forest tree regeneration trade-off theory and forest management practices. These efforts would provide scientific basis for the sustainable management and ecological restoration of forests. 森林天然更新是森林生态系统维持与恢复的关键生态过程,也是林木种群延续的重要途径。种子更新与萌蘖更新作为林木在长期进化中形成的两种策略,体现了其对资源限制与干扰环境的适应性权衡。在全球变化背景下,这一权衡关系正发生深刻变化。本文基于更新生态位理论,梳理了林木种子更新(定居生态位)与萌蘖更新(驻留生态位)的生物学基础与生态学意义,探讨了全球气候变化、干扰格局改变及生境破碎化对两类更新策略的影响机制。现有研究主要存在的问题:缺乏对不同造林树种更新偏好的形成与进化机制成因的系统解析,萌蘖发生的生理与分子机制研究薄弱,更新生态位的多维度量化及其对全球变化的动态响应面临方法学挑战,林木更新策略对全球变化的响应研究有待深化,更新生态位理论与森林经营实践的结合尚显不足。今后应加强解析全球变化背景下林木更新权衡策略进化的分子生态学与系统生物学基础、量化林木种子更新与萌蘖更新的转化阈值、构建林木更新生态位的多维研究框架、强化全球变化背景下主要造林树种更新策略的响应机制研究,推动林木更新权衡理论与森林经营实践的深度融合,为森林可持续经营与生态恢复提供科学依据。.
The origin of life through prebiotic chemistry and molecular evolution processes is a significant and unresolved issue in science. A key part of this process is how simple molecules, such as amino acids, transition into functional polymers, like peptides, which can store information and facilitate reactions. During this transition, wet-dry cycles and the interaction with ionizing radiation are essential mechanisms for increasing molecular complexity. This process involves the repeated hydration and dehydration of organic compounds, promoting the formation of peptide bonds that connect amino acids into longer chains. On a faster-spinning ancient Earth, these cycles might have been more relevant for the shorter days. In this scenario, a faster rotation rate affected the climate, tidal forces, and evaporation rates. The transition from simple amino acids to functional peptides remains a central question in understanding the complexation of molecules that led to life's origins. This work investigates how hydration-dehydration cycles impact solid-state gamma irradiated (40 kGy) DL-glutamic acid oligomerization. Infrared spectroscopy analysis confirms the presence of the characteristic amide I and II bands (approximately 1700 -1500 cm⁻¹), indicating an apparent change in peptide bond formation in gamma-irradiated samples. DSC and TGA thermal analysis reveal a contrasting difference in the thermograms from the control and gamma-irradiated samples. Thermal analyses demonstrate enhanced thermal stability in irradiated samples, agreeing with HyperChem computer simulations. The increase in stability in the oligomerization process. These findings support the model where cosmic ionizing radiation synergized with more frequent wet-dry cycles to promote prebiotic peptide synthesis. Our preliminary results substantiate the possibility that dry-wet cycles and ionizing irradiation on ancient Earth might have had planetary conditions to drive the molecular evolution towards abiotic synthesis of peptides.
The root of the tree of life remains a controversial issue in the study of the origins and evolution of early life on Earth, and so is the origin and evolution of early biochemistry. Here, we describe the methodological procedures of reconstructing global phylogenies of early life based on RNA secondary structure, with the rooting of phylogenies developed and improved to ultimately gain insights into the deep evolution of ancient molecules. As an example, we explore the evolution of the transfer RNA (tRNA) molecules using statistical characters describing their structure. An evolutionary model of molecular accretion of tRNA modeled at the atomic level illustrates the experimental exercise.
Synaptic vesicle proteins, including the synaptophysin, synaptogyrins, and synaptic vesicle glycoprotein 2 family are fundamental for neurotransmitter release and synaptic function, influencing numerous physiological processes. Although these proteins hold promise as therapeutic targets, their study has remained complicated due to their location within the cell membrane. To tackle this, we performed comparative analyses on these proteins and their water-soluble variants, which were designed using the QTY code. This approach involves systematically replacing hydrophobic amino acids L (leucine), V/I (valine/isoleucine), and F (phenylalanine) with hydrophilic amino acids Q (glutamine), T (threonine), and Y (tyrosine). The water-soluble QTY variants generated in our study, despite having significant differences in their transmembrane sequences up to 55%, maintained structural similarity, with RMSD values below 1.9 Å. We performed 100 ns molecular dynamics simulations to evaluate the structural stability and conformational dynamics of native and QTY variants. The analysis revealed that QTY substitutions preserved overall fold integrity while inducing localized flexibility, with lipid interactions contributing nonlinear effects that modulate residue-specific dynamics and evolutionary constraints. Our study further identified 155 single nucleotide variants (SNVs) in human genomic databases, and we examined their phenotypic and topological properties. By integrating evolutionary statistics, we provided insights into the substitutional dynamics of hydrophilic and hydrophobic alpha-helices. Notably, we found a strong evolutionary relationship between threonine and valine frequencies in homologous sequences. This coupling persists despite the high mutational barrier requiring a double-nucleotide change, suggesting a functional evolutionary necessity. Our data suggest that QTY variants of synaptic vesicle proteins could be valuable for research in structural biology, evolutionary studies, and medicine, potentially leading to innovative therapeutic strategies for a range of conditions.
Substitution rate estimates are central to evolutionary biology, underpinning divergence-time inference and a wide range of macroevolutionary analyses. Mitochondrial DNA (mtDNA) rates are widely used for this purpose, yet they are often derived from a limited set of genes, closely related taxa, or a small number of model organisms. Here, we use nearly complete mitogenomes from 27 pleurodontan species (Squamata: Pleurodonta) to estimate substitution rates across the mitochondrial genome, explicitly evaluating the effects of data partitioning, calibration strategies, and model specification. Bayesian analyses revealed pronounced heterogeneity in substitution rates among codon positions and between coding and non-coding regions. Estimated rates ranged from approximately 0.004 to 0.02 substitutions per site per million years, consistent with previous lineage-specific estimates. Commonly used rates closely matched those estimated for third codon positions and for analyses based on combined partitions, suggesting that widely adopted values may primarily reflect signals from faster-evolving sites or aggregated partitioning schemes. Calibrated analyses generally yielded lower substitution rate estimates with reduced variance relative to non-calibrated analyses. However, substantial overlap in 95% highest posterior density intervals indicates limited evidence for systematic differences between these approaches, suggesting that much of the relative rate structure is already captured by the molecular data under a partitioned relaxed-clock framework. Comparisons between alternative partitioning strategies further showed that, although data-driven schemes recover broad patterns of rate variation, they may do so at the cost of reduced parameter resolution, particularly in the absence of calibration. Together, these results highlight that substitution rate estimates are sensitive to partitioning and modeling choices, and that model complexity should be evaluated in terms of parameter resolution and data informativeness rather than parameter count alone. By providing partition-specific rate estimates across the mitogenome, this study offers a robust empirical framework for improving molecular dating and evolutionary inference in squamates and other non-model systems.
Explanatory frameworks for mental disorders influence stigmatisation and clinical attitudes. Mechanistic biological explanations often yield negative effects on prognostic optimism and empathy. Evolutionary framings might reduce stigma, but this has rarely been tested empirically. To experimentally test whether a brief educational intervention presenting an evolutionary explanation of anxiety, compared with a genetic explanation, would influence clinicians' attitudes in directions consistent with anti-stigma goals. In this pre-registered, multi-site, cluster-randomised trial, 171 practising mental health clinicians across the UK and Ireland were randomised by session to receive a 30 min educational presentation on either evolutionary or genetic explanations for anxiety. Pre- and post-session questionnaires assessed clinicians' optimism regarding patient recovery, perceived efficacy of psychosocial interventions, expected patient willingness to share diagnosis and seek help and perceived usefulness of the information. Data were analysed using Bayesian cumulative ordinal regression models. In line with pre-registered hypotheses, clinicians rated evolutionary explanations as substantially more useful for patients (odds ratio 5.05, 95% credible interval [2.46, 10.28], latent standard deviation shift 1.07) and for clinicians (odds ratio 3.10, 95% credible interval [1.62, 5.81], latent standard deviation shift 0.76) compared with genetic explanations. Evolutionary explanations also resulted in higher anticipated public willingness to seek psychiatric help (odds ratio 1.79, 95% credible interval [0.93, 3.35]) and share a diagnosis (odds ratio 1.62, 95% credible interval [0.88, 2.97]); optimism about patient recovery (odds ratio 1.58, 95% credible interval [0.71, 3.46]); perceived effectiveness of psychosocial interventions (odds ratio 1.62, 95% credible interval [0.84, 3.10]); and belief in the functional usefulness of negative emotions (β = 0.25 s.d., 95% credible interval [0.01, 0.49]). These effects were driven by both positive pre-post effects of evolutionary education and negative pre-post effects of genetic education compared with pre-education baseline. Exploratory analysis showed further anti-stigma effects. Framing anxiety through an evolutionary lens substantially improved clinicians' attitudes on various measures of stigmatisation compared with genetic explanations, and was rated as highly useful for both clinicians and patients.
Systems of oligonucleotide chemical replicator molecules provide some of the finest, empirically realizable models of prebiotic evolution. Yet, a full understanding of their eco-evolutionary implications is hampered by conflicting assumptions, modeling strategies, and therefore predictions in the literature. Here we construct a model of these systems that accounts for the reversible association of templates and copies, ultimately leading to self-inhibition and sub-exponential growth. We show that, contrary to predictions from simplified model descriptions, there are well-defined limits on the attainable diversity of different replicator species. We also demonstrate that increasing the overall concentration of the system increases diversity, but counterintuitively, an analogous increase in the available resource concentration has the opposite effect. Most notably, if an exponentially-growing replicator is also present in the system, it absorbs any increase in the total replicator concentration, while the concentrations of the sub-exponential replicators remain unchanged. In the context of prebiotic evolution, this means that in high-concentration local environments, an exponential replicator can reach disproportionately high concentrations even if its copying rate is lower than that of the sub-exponential replicators. In a variable environment, this can lead to the eventual stochastic extinction of its competitors, with the exponentially growing species taking over the community.
Symbioses are widespread in nature and have been the source of much evolutionary innovation. While some types of symbioses evolved multiple times, others are extremely rare. Only two purple photosymbioses between heterotrophic eukaryotes and intracellular purple bacteria have been documented. What factors prevent the more frequent establishment of purple photosymbioses? To shed light on this question, we investigated the evolutionary history of the purple-green ciliate Pseudoblepharisma tenue (Spirostomidae) using a phylogenetic and comparative approach and newly discovered species. We sampled about 30 new isolates of spirostomid ciliates from Germany and South Korea, inferred a comprehensive and robust phylogeny based on >200 proteins, and resolved the sister relationship between Pseudoblepharisma and Spirostomum. Furthermore, we characterized P. tenue's sister species, here renamed Pseudoblepharisma chlorelligerum, and revealed that it constitutes a quadripartite symbiosis between a ciliate, a green alga, and two non-photosynthetic bacteria. This oxygenic photosymbiosis is presumed to be supplemented with amino acids by its bacterial symbionts. In addition, we discovered three colorless, non-photosymbiotic Pseudoblepharisma species, which branch as sister to the photosymbiotic P. tenue and P. chlorelligerum. Our phylogenetic and comparative genomic analyses suggest that the green algal symbionts of P. tenue predated the acquisition of purple bacterial symbionts, and that the ancestor of the extant Pseudoblepharisma species was non-photosymbiotic and facultatively anaerobic. These data allowed us to hypothesize on the evolutionary steps that led to the origin of P. tenue and thus bring us closer to explaining the conditions that led to the evolutionary emergence of a unique purple-green symbiosis.
The error catastrophe refers to the proliferation of nonfunctional molecules in conditions where molecular replication has low accuracy, which is likely to correspond to conditions present at the Origin of Life. This error catastrophe can be avoided thanks to transient compartmentalization, provided that the compartments are sufficiently tight to prevent molecular leakage. Typically, transient compartmentalization models assume that the content of the compartments is completely pooled periodically, resulting in the complete loss of the compositional memory of the compartment. Furthermore, previous models that include the possibility of ecological interactions between molecular parasites and replicators within compartments generally do not study the effect of transient compartmentalization on their coevolution. To address both issues, we develop a framework that accounts for the coevolution of molecular replicators and parasites, along with specific compartmentalization dynamics that are transient yet partial, allowing compositional memory to accumulate from one round of compartmentalization to the next. We benchmark our model with a serial dilution experiment that displays complex oscillatory dynamics among four well-characterized RNA replicators. We also perform experiments to quantify the level of mixing in compartments when stronger stirring tends to homogenize their composition. We then model stirring-induced mixing and show how stirring alters the dynamics of compartmentalized replicators. We conclude that compositional memory arising from transient compartmentalization plays a major role in the dynamics of early molecular systems.
The mechanisms underlying how adrenocortical carcinoma (ACC) progresses into a metastatic and lethal disease remain poorly understood. To address this, we performed comprehensive genomic analyses to delineate the evolutionary trajectory of advanced ACC. Fresh frozen tumour samples (n = 29) were obtained from nine patients, all of whom had matched primary and relapse specimens, including recurrent (n = 4) and metastatic (n = 11) lesions. In four patients, multiple primary and metastatic samples were available, enabling detailed evolutionary comparisons. All tumours underwent whole-genome sequencing, RNA sequencing, and DNA methylation profiling. Our analyses revealed that seven of nine patients exhibited global loss of heterozygosity (LOH) often followed by whole-genome doubling, resulting in copy-neutral LOH. SNP-based analyses indicated that these alterations occurred as a single catastrophic event that was conserved across all matched samples within each patient, suggesting that this event constitutes a truncal feature of the evolutionary tree. These results support a model in which chromosomal aneuploidy is important in ACC tumourigenesis, potentially distinguishing carcinomas from benign adrenal adenomas. This may explain the rarity of adenoma-to-carcinoma transformation and suggest a diagnostic and therapeutic relevance of chromosomal instability in ACC.
Transposable elements (TEs) are dynamic DNA sequences that play a significant role in shaping genome structure and function in eukaryotic species. Advances in next-generation sequencing technologies have enhanced our understanding of the abundance and diversity of transposable element families. Transcriptionally active TEs contribute to intra-species genetic variability and facilitate adaptation to environmental stressors, such as heat, drought, and salinity, by inducing mutations, modulating gene expression, and promoting genome rearrangements. Recent studies highlight the important role of horizontal transfer and vertical transmission mechanisms in the evolution of Class I and Class II TE families. The Opie and Ji families of LTR elements serve as examples of conserved TEs that contribute to the expansion of the maize genome. In contrast to RIRE1, which remains relatively stable, Tos17 is largely inactive under normal conditions but can be activated under stress, such as tissue culture, thereby contributing to genome dynamics. This review explores key examples of horizontal transfer and vertical transmission of TEs in plant species, along with their structural features, evolutionary trajectories, and divergence patterns.
The transition from marine to freshwater environments represents a remarkable evolutionary shift in cetaceans, yet the genomic underpinnings of this adaptation remain poorly understood. This study investigates the genomic signatures of freshwater adaptation in riverine cetaceans through comparative evolutionary analyses of six species: Inia geoffrensis, Lipotes vexillifer, Platanista gangetica, Platanista minor, Neophocaena asiaeorientalis asiaeorientalis, and Sotalia fluviatilis. By integrating positive selection analysis, gene family dynamics, and evolutionary rate convergence, we identified key molecular adaptations associated with freshwater colonization. The analysis revealed that five of the six species exhibited positive selection in the NSMAF and CTRL genes, suggesting widespread selective pressures related to inflammatory responses and digestive adaptations, respectively. Functional enrichment analyses revealed adaptive signatures in hematopoiesis, osmoregulation, skeletal development, and immune responses, reflecting the physiological challenges of freshwater environments. Gene family evolution analyses using CAFE identified dynamic patterns of expansions and contractions in immune-related genes, transcriptional regulation, and cell adhesion pathways across riverine lineages. Relative evolutionary rate (RER) analysis using RERconverge identified 95 genes showing convergent rate shifts associated with freshwater adaptation, including genes involved in cellular nitrogen compound responses and transcriptional regulation. Despite positively selected genes overlap was limited and did not follow simple clade-wide patterns, our results demonstrate that freshwater adaptation in cetaceans involves putative convergent evolution of fundamental biological systems, including immune responses, metabolic regulation, and morphological development. These findings provide new insights into the molecular mechanisms underlying speciation in aquatic mammals and highlight critical biological pathways that have enabled the successful colonization of freshwater ecosystems by multiple independent cetacean lineages.
Ibaraki virus (IBAV), a strain of epizootic hemorrhagic disease virus serotype 2 (EHDV-2), remains poorly characterized genetically, particularly in South Korea. Here, we present a comprehensive genomic characterization of a South Korean IBAV isolate. Whole-genome phylogenetic analysis, selective pressure assessment, and structural protein prediction were performed to investigate its evolutionary features and antigenic potential. Phylogenetic analysis revealed that the isolate clustered most closely with Japanese isolates of EHDV-2, indicating regional genetic continuity. Codon-based models showed that purifying selection predominated across most genomic segments, reflecting strong functional constraints on core and non-structural proteins. Positive selection was detected at a few sites in VP6, suggesting minor adaptive changes. By contrast, VP2 and VP5, the major antigenic outer capsid proteins, displayed minimal divergence, an unusual finding for proteins involved in immune recognition. Structural modeling further showed that VP6 substitutions induced structural distortions, whereas VP2 changes had little impact. These findings suggest that IBAV is presently genetically stable yet emphasize the importance of sustained genomic surveillance to prepare for possible future variations.
Nup98 is a key component of the nuclear pore complex that plays essential roles in nucleocytoplasmic transport and gene regulation. To investigate the evolutionary diversification of Nup98 in ciliates, homologous sequences were collected from genomic and transcriptomic databases representing major ciliate lineages. Most species possessed multiple Nup98 paralogs, indicating that gene duplication events have occurred repeatedly during ciliate evolution. Phylogenetic analyses based on the conserved Nucleoporin2 domain revealed that Nup98 proteins from each ciliate class tend to form distinct monophyletic groups, suggesting lineage-specific diversification patterns. These results are consistent with a scenario in which early ciliates possessed a limited number of Nup98 genes, followed by independent duplication and diversification events in multiple lineages. However, alternative evolutionary scenarios remain possible. Differences in repeat motif composition were observed among paralogs across lineages, although these patterns were not conserved across all ciliates. While such variation may suggest potential functional diversification, phylogenetic evidence alone does not demonstrate functional differences among paralogs. Overall, the present diversity of Nup98 genes in ciliates is best interpreted as the result of lineage-specific evolutionary processes. These findings provide a framework for understanding Nup98 evolution and generate testable hypotheses regarding its potential roles in the diversification of nuclear dualism.
BACKGROUND: This study aimed to analyze mortality trends, causes of death, and key prognostic factors among people living with HIV (PLWH) receiving antiretroviral therapy (ART) in Huangshi, Hubei Province, from 2003 to 2025, to inform the optimization of clinical management and public health policy. METHODS: A retrospective cohort analysis was conducted, collecting demographic characteristics, WHO clinical stage, CD4 counts, initial ART Regimen, and follow-up information. The primary outcome was all-cause mortality. First, a univariable Cox regression analysis was performed. The proportional hazards assumption was then tested using the Schoenfeld residual test. If time dependency was detected, a time-stratified Cox model was constructed. Kaplan-Meier (KM) survival curves were used for visual presentation of survival patterns across different groups. RESULTS​: After screening, 2,494 ART-treated PLWH were included, of whom 671 died. Mortality peaked in 2017 and 2022, followed by a subsequent decline. The leading causes of death were opportunistic infections and cardiovascular diseases. Univariate analysis indicated that age, sex, marital status, transmission route, presence of AIDS-related symptoms, WHO clinical stage, CD4 count, and initial ART regimen were associated with mortality risk. In the time-stratified Cox model, age, transmission route, AIDS-related symptoms, baseline CD4 count, recent CD4 count, and initial ART regimen were significantly associated with mortality risk (P < 0.05). KM survival curves demonstrated lower survival rates among older individuals, those infected via heterosexual transmission, patients with clinical symptoms, those with low CD4 levels, and NVP-based regimen groups. CONCLUSION: In the ART era, mortality among PLWH is influenced by multiple factors. Opportunistic infections remain the primary cause of death, while the rise in cardiovascular disease reflects the evolving chronic disease profile of HIV. Enhancing early diagnosis, immune monitoring, and opportunistic infection prevention, and integrating chronic disease management are pivotal for improving survival and quality of life.
In South Korea, studies on methicillin-resistant Staphylococcus aureus (MRSA) have predominantly focused on molecular typing, with ST5 and ST72 consistently identified as dominant lineages. However, data on the distribution of virulence factors and antimicrobial resistance genes among recent clinical MRSA isolates remain limited. This study aimed to characterize antimicrobial resistance determinants and virulence gene profiles in contemporary clinical MRSA isolates from South Korea. One hundred human-derived clinical MRSA isolates, collected between February 2024 and January 2025 from the Antibiotic Resistance Specialized Pathogen Resource Bank of Hallym University Sacred Heart Hospital (Anyang-si, Republic of Korea), were analyzed. The isolates were evaluated for antimicrobial susceptibility and molecular characterization including multilocus sequence typing (MLST), staphylococcal cassette chromosome mec typing, accessory gene regulator grouping, staphylococcal protein A typing, and profiling of virulence and antimicrobial resistance genes. Genetic relatedness among isolates was also assessed. The isolates demonstrated high resistance rates to penicillins, cephalosporins, fluoroquinolones, macrolides, lincosamides, and tetracyclines, whereas most remained susceptible to vancomycin, linezolid, nitrofurantoin, and trimethoprim-sulfamethoxazole. Amino acid substitutions in antimicrobial resistance-associated genes were identified in 74% of isolates, with the greatest diversity observed among ST5 strains. MLST analysis revealed that ST5 isolates harbored a broader spectrum of resistance determinants, while ST72 isolates exhibited a more limited resistance profile. PFGE identified three major clone clusters, each associated with distinct superantigen gene profile. Panton-Valentine leukocidin genes were detected exclusively in ST8 and ST22 isolates, whereas the arginine catabolic mobile element was found only in ST8 isolates. Contemporary MRSA isolates in South Korea tested in this study share a conserved core virulence repertoire but display lineage-specific differences in resistance and virulence determinants. These findings enhance comparative molecular characterization of MRSA in South Korea and underscore the need for continued surveillance to elucidate lineage evolution and transmission dynamics.
Emerging evidence has demonstrated that lung cancer patients with brain oligometastases (oligo-BMs) could benefit from local radical therapies. Despite rapid advancements in the treatment of oligometastatic disease, the molecular determinants governing the oligometastatic phenotype in the central nervous system remain elusive. We performed 1021-panel sequencing, transcriptome profiling, DNA methylation mapping, and multiplex immunohistochemistry on 20 paired primary lung adenocarcinoma and oligo-BMs specimens to delineate their evolutionary dynamics and microenvironmental characteristics. A pronounced intertumor heterogeneity was observed between primary tumors (PTs) and oligo-BMs, while intratumoral heterogeneity was conserved across lesions. Subclonal analysis and phylogenetic reconstruction demonstrated that oligo-BMs exhibited predominant polyclonal seeding patterns and parallel progression trajectories. Moreover, oligo-BMs displayed a more immunosuppressed microenvironment compared to PTs, characterized by attenuated immunogenic cell death signatures, downregulation of immune-activated pathways, and diminished infiltration of activated immune cells (including B cells, NK cells, and Th1 cells). The methylation levels at functional genomic regions were highly concordant between PTs and oligo-BMs. Notably, we identified NLGN1 as a potential regulator of oligo-BM, where the hypermethylation at its genebody regions was mechanistically associated with transcriptional upregulation. Clinical validation revealed that NLGN1 was specifically overexpressed in BMs compared to PTs and extracranial metastases, correlating with advanced pathological stages and poor prognosis. In vivo studies further confirmed NLGN1 promotes BM in mice. Our findings provide novel insights into the evolutionary trajectory, immune landscape and methylation pattern of oligo-BMs, potentially paving the way for the development of innovative therapeutic strategies for lung cancer patients with oligo-BMs.
The rapid evolution of technology has triggered profound cultural, social, and psychological changes, along with a constant demand for human adaptation to new challenges. Digital wellbeing (DW) refers to the individual's positive and healthy relationship with information and communication technology (ICT), characterized by feelings of comfort, support, safety, satisfaction, and low levels of stress during their interactions with ICT. However, DW can be threatened by ergonomic, organizational, and psychological issues, particularly in the workplace. Despite efforts to improve the objective conditions of user experience, the understanding of the role of psychological factors in HCI remains partially disregarded. This study aimed to validate a new multidimensional psychometric tool designed to assess the perceived quality of HCI in the workplace, the Work-Related Human Computer Interaction Questionnaire (wrHCI-Q). A sample of 1,198 employees of a large Italian banking group (52% females; age: 49.04 ± 8.7) underwent an online survey. Reliability, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA) were performed. The wrHCI-Q consisted of 35 items and a four-factor structure (technostress, self-efficacy, positive attitude, and HCI aversion), supported by the CFA indices. The wrHCI-Q is a new, valid, and reliable scale to catch some crucial human factors affecting the quality of HCI. It is expected to foster the understanding of the determinants of individual DWE and to shed light on the factors that undermine a healthy employee's interaction with ICT.