Artiles
Open Access
Editorial
30 December 2025Immune Escape Mechanisms in Non-Small Cell Lung Cancer: From Biological Complexity to Actionable Targets
Despite significant progress in immune checkpoint inhibitors (ICIs) and targeted therapies, non-small cell lung cancer (NSCLC) continues to be associated with high rates of primary and acquired resistance. Although PD-1/PD-L1 blockade has revolutionized treatment, its clinical development has largely followed a one-size-fits-all approach, relying on limited biomarkers such as PD-L1 expression or tumor mutational burden. It is now increasingly clear that immune escape in NSCLC is orchestrated by a multifaceted, multilayered network of both tumor-intrinsic alterations and TME (tumor microenvironment)–driven mechanisms. The challenge has been to understand and to therapeutically exploit these immune escape pathways and this knowledge is now needed so that rather than embark on empirical combinations we can advance to rational, immune-informed targeted therapies.
Open Access
Review
30 December 2025Advances in Hydrology of Irrigation Districts in Cold Regions
Given the extreme complexity of systems, the strategic importance of water resources, and the high ecological vulnerability in cold-region irrigation districts (CRIDs), research on the hydrological processes in these areas represents not only an interdisciplinary scientific endeavor, but also a critical practical challenge with direct implications for food security, water security, ecological safety, and sustainable regional development in high-altitude and high-latitude regions. The evolution of this field has progressed from early phenomenon identification to mechanistic analysis and, more recently, to multi-process and multi-scale simulation frameworks. This paper provides a systematic review of hydrological processes in CRIDs. It first examines fundamental components such as precipitation, evaporation, snowmelt, and groundwater recharge, highlighting their distinct behaviors under the combined influence of freeze–thaw cycles and irrigation practices, and further discusses the interactions and coupling mechanisms among these processes. Irrigation not only alters soil moisture distribution and freeze–thaw dynamics but also, together with freeze–thaw processes, shapes the transient hydrological dynamics characteristics of water and energy transfer, thereby influencing system stability and agricultural productivity. Hydrological modeling has advanced from simplified empirical approaches to mechanistic frameworks that integrate multiple processes and scales, yet challenges remain in the representation of nonlinear freeze–thaw, the integration of irrigation management, and cross-scale consistency. Moreover, cold-region irrigation districts exhibit heightened sensitivity to extreme events, such as rapid snowmelt, severe droughts or heavy rainfall. Future research should deepen the integration of freeze–thaw mechanisms with crop models, advance multi-scale coupled simulations, enhance long-term monitoring and scenario analysis, and systematically incorporate water–carbon balance and ecological effects into hydrological assessments. These efforts will support sustainable management and precision regulation of water resources in cold-region irrigation districts.
Open Access
Article
30 December 2025Genetic Diversity Among Populations of Bighead Carp (Hypophthalmichthys nobilis) Upstream and Midstream Yangtze River by Microsatellite DNA Analysis
Bighead carp (Hypophthalmichthys nobilis) has an essential role in freshwater fisheries worldwide, especially in China, yet its germplasm resources in the upstream Yangtze River have been scarcely studied. We used nine polymorphic microsatellite markers to assess genetic diversity and differentiation in seven bighead carp populations from the upper-middle Yangtze River. In five populations from the upstream and two populations from the midstream of the Yangtze River, a total of 101 alleles were detected, with the mean value of alleles per population varying from 5.3 to 8.4. Moderate genetic diversity of seven populations was detected with the values of Ho, He and PIC ranging from 0.598 to 0.683, 0.647 to 0.703 and 0.591 to 0.639, respectively. Weak population differentiations (Fst = 0.0000–0.0478) were observed, which indicated that bighead carp populations up and down the Three Gorges Dam (TGD) could be regarded as a group. Structure and clustering analysis consistently supported that the bighead carp samples examined in this study were clustered as one group, except a population from Dongting Lake (DTL), the second largest lake of China, in the midstream of the Yangtze River. This study provided evidence of moderate genetic diversity and weak differentiation among bighead carp populations from upstream and midstream regions of the Yangtze River, suggesting that the TGD has not yet had a significant influence on population genetic structure. These results are valuable for conservation genetics and sustainable utilization of bighead carp resources in the Yangtze River.
Open Access
Article
30 December 2025Fabrication, Properties of Dense CA6 Refractory and Its Reaction Behavior with Titanium Aluminum Alloy
The key objective in the production of titanium-aluminum alloys by vacuum induction melting technology is to develop crucible materials with excellent thermal stability and thermal shock resistance. In this work, a dense CA6 (calcium hexaluminate) refractory material was successfully prepared by a two-step sintering method using industrial Al2O3 and CaCO3 as raw materials. The properties of CA6 refractory and its refaction behavior with Ti6Al4V alloy were investigated, by setting Al2O3 and CA6-Al2O3 materials as control groups. The CA6 refractory showed the highest flexural strength and medium thermal shock resistance. By comparing the reaction behavior of different crucibles with Ti6Al4V alloy, the pure CA6 crucible showed the best resistance to alloy corrosion. It was almost not eroded after melting (only ~100 μm of penetration was observed), and the alloy was the least polluted. Based on the excellent chemical stability and thermal shock resistance of CA6, it could be a potential titanium aluminum alloy smelting material.
Open Access
Article
29 December 2025Vertical Axis Tidal Turbine Behaviour under Sheared Flow Effects
Tidal turbines are often subjected to complex flow conditions that can affect their power output and the risk of failure. In this article, an experimental study on a vertical axis tidal turbine with twin counter-rotating rotors is carried out at 1/20 scale, submitted to a sheared turbulent (ST) flow and a sheared weakly turbulent (SWT) flow. The performance and wake development comparison indicates that the turbine behaves differently depending on the shear rate considered. A 7% decrease in performance is observed at the turbine’s nominal operating point between uniform and ST conditions. The asymmetry of the flow along the vertical axis is reflected in the angular and frequency distributions of the rotor torque, indicating a production asymmetry between the lower and the upper rotors. Analysis of wake development reveals that transport terms constitute the main mechanism of wake dissipation. In the case of SWT and uniform flow, vertical advection largely dominates the other terms, whereas in ST flow, transverse advection is initially predominant. This results in a higher average wake height and a lower average wake width in the ST case compared to the other flow conditions, and a faster wake recovery.
Open Access
Review
29 December 2025Consanguineous Marriage in Global Perspective: Anthropological Roots, Genetic Risks, Contemporary Relevance, and the Way Forward
Consanguineous marriage—defined as unions between biologically related individuals, typically first or second cousins—has been a culturally embedded practice across diverse societies for millennia. Drawing on publicly available sources, the study seeks to review both regional and global perspectives of consanguineous marriage across time and space. Rooted in anthropological traditions of kinship and alliance, these unions historically served functions such as preserving lineage, consolidating property, ensuring social trust, and reinforcing group identity. Anthropological scholarship, from Morgan’s kinship classifications to Lévi-Strauss’s alliance theory, situates cousin marriage as a structured and rational social strategy rather than a random or anomalous choice. Contemporary practices, however, are shaped by complex intersections of tradition, religion, gender, and modernity. While biomedical research consistently associates consanguinity with increased risks of congenital disorders, pregnancy wastage, and mental health conditions, many communities continue to view it as beneficial for kin solidarity, economic security, and marital stability. Global prevalence remains heterogeneous: highly normative in South Asia, the Middle East, and North Africa, declining in parts of India and North Africa, and largely absent in Western societies except among diasporas. Recent transformations—including urbanization, women’s education, migration, digital matchmaking, and premarital genetic screening—have shifted perceptions, particularly among youth. Ethnographic accounts highlight tensions between generational expectations and individual autonomy, revealing ambivalence and negotiation rather than outright rejection. This review underscores consanguinity as a dynamic institution at the intersection of anthropology, genetics, religion, and public health. Rather than framing it solely as a biomedical risk or a cultural relic, it should be understood as a multifaceted practice continually redefined in response to social, economic, and political change.
Open Access
Review
29 December 2025Porous Framework Materials for C1 Biotransformation
The bioconversion of C1 compounds (CO2, methane, methanol, etc.) constitutes a crucial pathway for green biomanufacturing. However, the process efficiency is constrained by several challenges, including the difficult capture of gaseous substrates, instability of biocatalysts, and the high cost as well as operational complexity of cofactor regeneration. Porous framework materials offer promising solutions due to their high specific surface area, tunable pore structures, and ease of functionalization. This review provides a systematic and forward-looking analysis that moves beyond the conventional view of porous frameworks as simple immobilization matrices. We distinctly highlight their emerging multifunctional and integrative roles in C1 bioconversion, emphasizing several novel strategic contributions: (1) Serving as intelligent immobilization carriers that not only enhance biocatalyst stability and recyclability but also concurrently enable efficient C1 substrate enrichment and localized concentration; (2) Facilitating synergistic energy conversion by interfacing with photocatalysis or electrocatalysis to enable in-situ and sustainable cofactor regeneration, thereby addressing a key economic bottleneck; (3) Actively regulating microbial metabolism and community dynamics through tailored material-microbe interactions, optimizing carbon flux and system resilience; and (4) Mimicking natural enzymes to create robust and tunable biomimetic catalysts for C1 conversion under non-physiological conditions. Remaining challenges, such as mass transfer limitations, the scalability of material synthesis, and the integration of hybrid systems, are analyzed through the lens of these advanced functionalities. We conclude that the synergistic and rational integration of synthetic biology-designed biocatalysts with engineered multifunctional frameworks represents a paradigm shift, paving the way for efficient, stable, and high-value utilization of C1 resources.
Open Access
Commentary
29 December 2025Breath and Life: Emerging Nanotechnologies for Cystic Fibrosis Therapy
The treatment of cystic fibrosis (CF) remains challenging due to formidable biological barriers in the lungs, including thick mucus and resilient biofilms that severely limit the efficacy of conventional therapies. Nanotechnology, engineered to overcome these barriers, is emerging as a transformative approach for CF therapy. This opinion highlighted the most recent and advanced nanotechnologies, categorizing them into four strategic frontiers: (1) nanocarriers that achieve mucus penetration through surface modifications; (2) nanoplatforms for efficient delivery of genetic therapeutics; (3) nanocarriers for antimicrobial delivery to cure infections associated with CF; and (4) combinatorial nanomedicines for synchronized delivery of multiple drugs. We concluded that, with the help of these nanotechnologies, therapies for CF will now undergo a paradigm shift, moving CF from a fatal disease to a treatable and potentially curable one. Although the clinical transition is challenging, it holds immense promise for revolutionizing CF management.
Open Access
Article
26 December 2025Leveraging Productivity Analysis for Smallholders’ Sustainable Development: Dairy Efficiency in Central Madagascar’s Crop-Livestock Family Farms
Milk production in developing African countries is a viable path for smallholders’ sustainable development. Supporting interventions should be shaped by evidence from comprehensive, context-specific analyses. Using survey data, this study contributes to the development-oriented literature on dairy productivity in African smallholder systems by conducting the first stochastic frontier analysis in the Malagasy context. Focusing on milk producers in central Madagascar’s crop-livestock family farms, a stochastic frontier production function with inefficiency effects is developed. The fitted frontier comprises the number of cows, annual purchased feed expenditure, farmer’s labor, and total household assets owned. Distance from the frontier is explained by the use of improved breeds, integration in the regional milk zone, farmer years of experience, the presence of off-farm income, and the number of oxen owned. Technical efficiency ranged from 4.6% to 90.8% around a mean of 55.5%. Results revealed how, in this context, cows are embedded in diversified family farming systems where resources are allocated across production activities and household needs. The study’s multidisciplinary stochastic frontier analysis provides a more complete picture to guide research and policy for smallholders’ sustainable rural development.
Open Access
Article
26 December 2025A Multiplex Flow Cytometric Approach to Define Molecularly Distinct Extracellular Vesicle Subsets
Extracellular vesicles (EVs) are molecularly very heterogeneous, and their characterization at the single-particle level is technically challenging. Existing approaches, such as nanoparticle tracking analysis, fluorescence microscopy, and nano-flow cytometry, provide important insights but often lack the flexibility to detect multiple molecular markers simultaneously. Here, we describe an optimized workflow for multiparametric EV phenotyping using a spectral flow cytometry instrument with enhanced small particle detection capacity. EVs were isolated from murine melanoma and melanocyte cell lines via size-exclusion chromatography and labeled with a fluorogenic membrane probe that enables robust, single EV detection. In this study, we systematically optimized staining conditions, EV concentrations, and fluorophore combinations for a 5-color antibody panel on single EVs. We show that single-particle flow cytometry can reliably detect and resolve multiple EV surface markers simultaneously. Data analysis by unsupervised clustering further enabled unbiased identification of distinct EV subsets, providing a practical approach for EV phenotyping in both research and clinical contexts.
