Advanced biology最新文献

Mosquitoes remain a significant global health concern due to their role in transmitting deadly diseases including malaria, dengue, and yellow fever. Recent advances in genetic modification technologies have enabled researchers to better study disease transmission and is an emerging approach for vector control. However, a major bottleneck is the need for continuous rearing of each new strain, an intensive process requiring substantial manual effort and space with inherent risks of cross-contamination, genetic drift, and catastrophic loss. Cryopreservation offers a potential solution, where strains could be stored indefinitely and revived on an as-needed basis. Here, we report a cryopreservation protocol that results in the recovery of viable Anopheles gambiae larvae. After thawing, 82% of larvae showed signs of viability, including wriggling and mouth brush movements. Approximately 15% further exhibited coordinated swimming behavior. Although post-thaw survival was limited to 24 h, this study provides the first evidence that mosquito larvae can survive cryopreservation, representing a key milestone toward long-term storage of mosquito lines.

Aging is closely linked to epigenetic remodeling, with DNA methylation (DNAm) emerging as a robust biomarker for estimating epigenetic age (EA) and quantifying senescence. Dysregulation of aging-associated DNAm has been implicated in diverse pathologies, including acute myeloid leukemia (AML). However, the effect of these epigenetic alterations in diseases and the underlying mechanism remains largely uncharacterized. Using causality-enriched epigenetic clocks, we identified that adaptive DNAm dynamics are sensitive to short-term therapeutic intervention in treating AML and may exhibit adaptive effects linked to better health outcomes. Subsequently, integrative genomic analysis showed significant associations between epigenetic aging and recurrent AML driver mutated genes, particularly DNMT3A and IDH2. The elevated adaptive aging associates with improved overall survival in cytogenetically normal AML harboring these mutations, highlighting its prognostic value in specific genomic contexts. Mechanistic analysis demonstrated that differentially methylated CpG sites in mutated gene-specific AML subtypes are enriched at polycomb repressive complex 2 (PRC2) targets. These findings link mutation-specific epigenetic aging, PRC2-mediated methylation dynamics, and AML pathogenesis, offering insights into how aging-related epigenetic dysregulation fosters malignant transformation. This study shows that AdaptAge can help reveal AML‑related DNAm dynamics when combined with genetic stratification, suggesting a path toward future biomarker development.

One important step for evaluating and selecting a drug is toxicity studies, which are responsible for eliminating molecules that are considered promising for treating a certain disease based on their effectiveness in clinical studies, but are unsafe to go to the pharmaceutical market. We proposed an evaluation of dacarbazine as a positive control in toxicity effects in the context of macro- and micro effects represented by tissue and cell responses. A resazurin assay is used to evaluate cytotoxicity in cells (melanoma cells A375, Sk-Mel-103, and 1205Lu; immortalized skin cells HaCat and 3T3), and hematoxylin/eosin staining and TUNEL staining are used in skin explants. There is no toxicity demonstrated in the immortalized cells at the studied concentrations, whereas in the melanoma cells, A375 is the most sensitive to dacarbazine, with a high toxicity at all concentrations over 72 h (p < 0.05), Sk-Mel-103 showed toxicity effects only at 200 µg/mL, and 1205Lu showed no evidence of toxicity. Histological data showed that the entire skin structure of the explants is preserved, and no apoptotic cells are observed. Thus, we can conclude that cell lines behave differently when exposed to a drug, in this case Dacarbazine proved to be a good control for toxicity tests.

T. vaginalis is a protozoan parasite responsible for the most common non-viral sexually transmitted infection worldwide. Effective therapeutic evaluation is essential, particularly with rising concerns over drug resistance. In this study, we developed a microfluidic culture platform integrated with an AI-based imaging algorithm to quantify parasite attachment dynamics and assess drug efficacy. The platform enabled controlled exposure of T. vaginalis to human cancer cell lines (HeLa and BFTC905) under single and combined drug gradients of metronidazole and paromomycin. Real-time imaging and spatial color-coded map analysis revealed that metronidazole significantly reduced parasite attachment in a dose-dependent manner. Furthermore, combination therapy exhibited superior inhibitory effects compared to single-drug treatments, suggesting potential synergistic interactions. The platform demonstrated robust and reproducible results across different cell types, highlighting its value for high-throughput anti-parasitic screening. These findings support the application of combination regimens in managing T. vaginalis infections and establish the microfluidic-AI system as a promising tool for drug evaluation and therapeutic development.

Biomarkers are essential in drug development and diagnostics, aiding patient selection and disease monitoring. The lack of age-specific protein references complicates tracking patterns related to chronic disease or treatment. This exploratory, proof-of-concept study explores age-related changes in the serum proteome across the full human lifespan. Using proximity extension assays (Olink), we measured the Immuno-oncology panel in serum from 264 healthy individuals, another panel in a subgroup of 109, all without significant disease at blood draw, aged 0 days to 88 years. Cluster analysis of the Immuno-oncology panel revealed two clusters: cluster 1 included samples from children ≤11 days, cluster 2 encompassing samples with an age range from 2 months till 88 years old. Weighted correlation network analysis identified five protein modules, with four showing enrichment in specific pathways. The Organ-Damage panel showed similar age-related protein variations. Finally, we identified four protein patterns over age: constant, increasing, decreasing, or U-shaped and defined age-specific normal expression ranges. Altogether, our findings suggest that healthy aging across the entire lifespan involves alterations in protein expressions and distinct protein profiles exist in newborns, children, adults and older adults. We provide valuable reference data for the different protein patterns observed across the entire lifespan.

Mitochondrial metabolism plays a central role in organismal physiology and aging. In Caenorhabditis elegans, FAHD-1 (oxaloacetate decarboxylase) and PYC-1 (pyruvate carboxylase) catalyze opposing reactions that influence oxaloacetate homeostasis within the tricarboxylic acid cycle. To dissect their functional interplay, we analyzed single- and double-knockout strains generated by CRISPR/Cas9 alongside the classical allele. Fahd-1 mutants exhibit impaired mitochondrial respiration, reduced motility, and early egg-laying onset, whereas pyc-1 mutants display increased locomotion and enhanced metabolic flexibility. Paradoxically, although each single mutantion extended lifespan, combining them restored wild-type lifespan and partially normalized respiratory function, suggesting a compensatory interaction. These findings establish FAHD-1 and PYC-1 as antagonistic mitochondrial enzymes whose balance governs locomotion, reproduction, and lifespan in C. elegans, providing a conceptual framework for conserved links between mitochondrial metabolism and aging.