Molecular composition limits the reaction kinetics of riverine dissolved organic matter decomposition.

The bioavailability and degradation of riverine dissolved organic matter (DOM) play crucial roles in greenhouse gas emissions; however, studies on the kinetic decomposition of fluvial DOM remain scarce. In this study, the decomposition kinetics of dissolved organic carbon (DOC) were characterized using the reactivity continuum model through 28-day bio-incubation experiments with water samples from the Yangtze River. The relationship between DOM composition and decomposition kinetics was analyzed using optical and molecular characterization combined with apparent decay coefficients. Our results revealed that DOM compounds rich in nitrogen and sulfur were predominantly removed, exhibiting a transition from an unsaturated to a saturated state following microbial degradation. These heteroatomic compounds, which constituted 75.61 % of the DOM compounds positively correlated with the decay coefficient k0, underwent preferential degradation in the early stages of bio-incubation due to their higher bioavailability. Additionally, we observed that S-containing fractions with high molecular weight values (MW > 400 Da) may be associated with larger reactivity grades. This study underscored the complex interplay between DOM composition and its kinetic decomposition in river ecosystems, providing further support for the significance of molecular composition in large river DOM as crucial factors affecting decomposition.

Trametinib boosts palbociclib's efficacy in breast cancer via autophagy inhibition.

Breast cancer, a predominant global health issue, requires ongoing exploration of new therapeutic strategies. Palbociclib (PAL), a well-known cyclin-dependent kinase (CDK) inhibitor, plays a critical role in breast cancer treatment. While its efficacy is recognized, the interplay between PAL and cellular autophagy, particularly in the context of the RAF/MEK/ERK signaling pathway, remains insufficiently explored. This study investigates PAL's inhibitory effects on breast cancer using both in vitro (MCF7 and MDA-MB-468 cells) and in vivo (tumor-bearing nude mice) models. Aimed at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib (TRA), an MEK inhibitor, our research seeks to address the challenge of PAL-induced drug resistance. Our findings reveal that PAL significantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A cells. However, PAL also induces protective autophagy, potentially leading to drug resistance via the RAF/MEK/ERK pathway activation. Introducing TRA effectively neutralized this autophagy, enhancing PAL's anti-tumor efficacy. A combination of PAL and TRA synergistically reduced cell viability and proliferation, and in vivo studies showed notable tumor size reduction. In conclusion, the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance, offering a new horizon in breast cancer treatment.

Identification and functional analyses of CD4-1+ cells in grass carp (Ctenopharyngodon idella).

In mammals, CD4 is found to be expressed on T cells and innate immune cells, however, teleost cells bearing CD4 have not been well identified and characterized. In this study, we identified two different CD4-1+ cell subsets in grass carp (Ctenopharyngodon idella): CD4-1+ lymphocytes (Lym) and CD4-1+ myeloid cells (Mye), both of which had the highest proportions in the head kidney. The mRNA expression analysis showed that CD4-1, CD4-2, TCRß, CD3γ/δ, and LCK1 are highly expressed in CD4-1+ Lym and also expressed in CD4-1+ Mye. Furthermore, we found that CD4-1+ Lym have a Lym morphology and highly express T-cell cytokines, suggesting that they are CD4+ T cells equivalent to mammalian Th cells. On the other hand, CD4-1+ Mye were found to have a morphology of macrophage and highly express macrophage marker gene MCSFR, indicating that they are macrophages. In addition, functional analysis revealed that CD4-1+ Mye possess phagocytic ability and great antigen-processing ability. Taken together, our study sheds further light on the composition and function of CD4+ cells in teleost fish.

Synergistic effects of the combination of trametinib and alpelisib in anaplastic thyroid cancer with BRAF and PI3KCA co-mutations.

Background: Anaplastic thyroid cancer (ATC), a rare and aggressive malignancy with a poor prognosis, has shown promise with the approved dabrafenib/trametinib combination for BRAFV600E mutation. Co-occurring PI3KCA mutations, identified as negative prognostic factors in lung cancer with BRAFV600E mutation, emphasize the need to target both pathways. Exploring trametinib and alpelisib combination becomes crucial for ATC. Methods: A patient-derived xenograft (PDX) and primary cell line were obtained from an ATC patient with BRAF and PI3KCA co-mutation. Individual testing of targeted therapies against BRAF, MEK, and PI3KCA was followed by a combination treatment. Synergistic effects were evaluated using the combination index. Immunoblotting assessed the efficacy, with validation performed using a PDX model. Results: In this study, the ATC0802 cell line and PDX were established from a refractory ATC patient. NGS revealed BRAF and PI3KCA co-mutations pre- and post-dabrafenib/trametinib treatment. Trametinib/alpelisib combination showed synergy, suppressing both pERK and pAKT levels, unlike monotherapies or BRAF knockdown. The combination induced apoptosis and, in the PDX model, demonstrated superior tumor growth inhibition compared to monotherapies. Conclusions: The combination of trametinib and alpelisib showed promise as a strategy for treating ATC with co-mutations in BRAF and PI3KCA, both in vitro and in vivo. This combination offers insights into overcoming resistance to BRAF-targeted treatments in ATC with mutations in BRAF and PI3KCA.

Athermal panoramic annular lens design with a thermal analysis method.

An athermal 360∘×(30∘-100∘) and F/3.5 panoramic annular lens (PAL) system is designed. Through the optical mechanical thermal analysis results based on finite element analysis (FEA), it is expected that the system will have excellent performance under extreme temperature fluctuations. Simulation shows that the system is thermally insensitive in the temperature range from -40∘ C to 60°C, consistently providing great imaging capability with the modulation transfer function (MTF) value at 133 lp/mm greater than 0.3. The proposed design and analysis workflow contains an evaluation of thermal optical performance with a higher accuracy, thus having significance in future athermal optical design. We expect the designed PAL system to have a broad application prospect in the field of outdoor applications, including automatic navigation of vehicles and all-weather surveillance systems.