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ObjectiveTriple-negative breast cancer (TNBC) is a heterogeneous disease with poor prognosis. Circulating tumor cells (CTCs) are a promising predictor for breast cancer prognoses but their reliability regarding progression-free survival (PFS) is controversial. We aim to verify their predictive value in TNBC.MethodsIn present prospective cohort study, we used the Pep@MNPs method to enumerate CTCs in baseline blood samples from 75 patients with TNBC (taken at inclusion in this study) and analyzed correlations between CTC numbers and outcomes and other clinical parameters.ResultsMedian PFS was 6.0 (range: 1.0-25.0) months for the entire cohort, in whom we found no correlations between baseline CTC status and initial tumor stage (P=0.167), tumor grade (P=0.783) or histological type (P=0.084). However, among those getting first-line treatment, baseline CTC status was positively correlated with ratio of peripheral natural killer (NK) cells (P=0.032), presence of lung metastasis (P=0.034) and number of visceral metastatic site (P=0.037). Baseline CTC status was predictive for PFS in first-line TNBC (P=0.033), but not for the cohort as a whole (P=0.118). This prognostic limitation of CTC could be ameliorated by combining CTC and NK cell enumeration (P=0.049).ConclusionsBaseline CTC status was predictive of lung metastasis, peripheral NK cell ratio and PFS in TNBC patients undergoing first-line treatment. We have developed a combined CTC-NK enumeration strategy that allows us to predict PFS in TNBC without any preconditions.

Isoprene dominates global non-methane volatile organic compound emissions, and impacts tropospheric chemistry by influencing oxidants and aerosols. Isoprene emission rates vary over several orders of magnitude for different plants, and characterizing this immense biological chemodiversity is a challenge for estimating isoprene emission from tropical forests. Here we present the isoprene emission estimates from aircraft eddy covariance measurements over the Amazonian forest. We report isoprene emission rates that are three times higher than satellite top-down estimates and 35% higher than model predictions. The results reveal strong correlations between observed isoprene emission rates and terrain elevations, which are confirmed by similar correlations between satellite-derived isoprene emissions and terrain elevations. We propose that the elevational gradient in the Amazonian forest isoprene emission capacity is determined by plant species distributions and can substantially explain isoprene emission variability in tropical forests, and use a model to demonstrate the resulting impacts on regional air quality.

Although possessing well‐defined nanostructures and excellent multi‐electron redox properties, polyoxometalate clusters have poor intrinsic electrical conductivity and are prone to aggregation due to large surface energy, which makes them difficult to be fully utilized when applying as electrode materials for lithium‐ion batteries. In this paper, monodisperse K7MnV13O38 (MnV13) clusters are achieved by rationally utilizing nano‐sized high conductive carbon dots (CDs) as stabilizers. Benefiting from the fully exposed redox sites of MnV13 clusters (high utilization rate) and sufficient interfaces with carbon dots (extra interfacial energy storage), the optimized MnV13/10CDs anode delivers a high discharge capacity up to 1348 mAh g−1 at a current density of 0.1 A g−1 and exhibits superb rate/cycling capabilities. Density functional theory (DFT) calculations verify that ionic archway channels are formed between MnV13 and CDs, eliminating the bandgap and greatly improving the electron/ion conductivity of MnV13 and CDs. This paper paves a brand‐new way for synthesis of monodisperse clusters and maximization of extra interfacial energy storage. [ABSTRACT FROM AUTHOR]

Aerodynamic contour dimensional accuracy is very important for the stable and safe flight of aerospace vehicles. Nevertheless, due to the influence of various factors such as material properties, machining and manufacturing deviations, and assembly and installation deviations, key structural geometric dimensions are frequently exceeded. Therefore, this paper investigates a data-driven combined vector loop method (VLM)–Skin Model Shapes (SMS) method to realize aerospace vehicle structural geometric accuracy analysis; assembly optimization targeting contour deviation is also achieved. Tests are carried out on a typical aerospace vehicle's underconstrained structural workpieces to validate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Line planning and timetabling play important roles in the design of urban rail transportation services. Due to the complexity of the integrated optimization of entire transportation plans, previous studies have generally considered line planning and timetabling design independently, which cannot ensure the global optimality of transportation services. In this study, the integrated design problem of line planning and timetabling was characterized as an equilibrium space–time network design problem and solved with a bi-objective nonlinear integer programming model. The model, in which train overtaking and passenger path choice behavior were considered, adjusted the network topology and link attributes (time and capacity) of the travel space–time network by optimizing the train service frequency, operation zone, stopping pattern, train formation, and train order to minimize the system life cycle cost and total passenger travel time perception. An algorithm was constructed using the non-dominated sorting genetic algorithm II combined with the self-adaptive gradient projection algorithm to solve the model. A real-world case was considered to evaluate the effectiveness of the proposed model and algorithm. The results showed that the model not only performed well in the trade-off between system cost and passenger travel efficiency, but it could also reduce the imbalance of train and station loads. Pareto front analysis of the model with different parameters showed that more types of trains did not correlate with a better performance, some line-planning strategies had a combination effect, and multi-strategy line planning was more suitable for scenarios with a high imbalance in the temporal and spatial distributions of passenger flow. [ABSTRACT FROM AUTHOR]

Mechanical computing has garnered significant interest as a supplement to traditional electronic computing, which often grapples with issues like high power consumption, security vulnerabilities, and susceptibility to extreme environmental conditions such as intense heat and radiation. Yet, most research in mechanical computing has been limited to the ad hoc design of simple logic gates and has not fully achieved the implementation of simple arithmetic computation within an electricity‐free framework. Additionally, progress in environmentally adaptive computing, crucial for decentralized intelligence, has also been slow. New ground is broken with the development of a mechanical transistor that synergizes a Kirigami thermomechanical sensor and a bistable actuator, enabling in‐memory computing for combinational and sequential logic. The design stands out by employing modular construction, symmetry breaking, and nonlinear materials, crafting logic gates, and memory units that respond to environmental stimuli through thermal delay. These transistors integrate design and material intelligence to establish nonvolatile memories, essential for logic‐in‐memory, and align thermal transport with mechanical deformation for environmental responsiveness. The mechanical transistor heralds a new age in mechanical computing, proving to be as versatile and vital as the electronic transistor has been in the era of modern computing. [ABSTRACT FROM AUTHOR]

The process of degrading unwanted or damaged mitochondria by autophagy, called mitophagy, is essential for mitochondrial quality control together with mitochondrial apoptosis. In mammalian cells, pan-Bcl-2 family members including conical Bcl-2 members and non-conical ones are involved in and govern the two processes. We have illustrated recently the BH3 receptor Hsp70 interacts with Bim to mediate both apoptosis and mitophagy. However, whether similar pathways exist in lower eukaryotes where conical Bcl-2 members are absent remained unclear. Here, a specific inhibitor of the Hsp70-Bim PPI, S1g-10 and its analogs were used as chemical tools to explore the role of yeast Bxi1/Ybh3 in regulating mitophagy and apoptosis. Using Om45-GFP processing assay, we illustrated that yeast Ybh3 mediates a ubiquitin-related mitophagy pathway in both yeast and mammalian cells through association with Hsp70, which is in the same manner with Bim. Moreover, by using Bax/Bak double knockout MEF cells, Ybh3 was identified to induce apoptosis through forming oligomerization to trigger mitochondrial outer membrane permeabilization (MOMP) like Bax. We not only illustrated a conserved ubiquitin-related mitophagy pathway in yeast but also revealed the multi-function of Ybh3 which combines the function of BH3-only protein and multi-domain Bax protein as one. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) have significant clinical value in early tumor detection, dynamic monitoring and immunotherapy. CTC detection stands out as a leading non-invasive approach for tumor diagnostics and therapeutics. However, the high heterogeneity of CTCs and the occurrence of epithelial-mesenchymal transition (EMT) during metastasis pose challenges to methods relying on EpCAM-positive enrichment. To address these limitations, a method based on negative enrichment of CTCs using specific leukocyte targets has been developed. In this study, aiming to overcome the low purity associated with immunomagnetic beads targeting solely the leukocyte common antigen CD45, we introduced CD66b-modified immunomagnetic beads. CD66b, a specific target for neutrophils with abundant residues, was chosen as a complementary approach. The process involved initial collection of nucleated cells from whole blood samples using density gradient centrifugation. Subsequently, magnetically labeled leukocytes were removed by magnetic field, enabling the capture of CTCs with higher sensitivity and purity while retaining their activity. Finally, we selected 20 clinical blood samples from patients with various cancers to validate the effectiveness of this strategy, providing a new generalized tool for the clinical detection of CTCs. [ABSTRACT FROM AUTHOR]