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Cancer immunotherapy based on the engineering of chimeric antigen receptors (CAR) on T cells has emerged as one of the most promising new therapies for patients with B‐cell malignancies. Preclinical assessments of essential CAR T cell functions such as trafficking and cytotoxicity are critical for accelerating the development of highly effective therapeutic candidates. However, current tools for evaluating CAR‐T functions lack sufficient precision. Here, a micropatterned tumor array (MiTA) is described that enables detailed and dynamic characterization of CAR T cell trafficking toward tumor‐cell islands and subsequent killing of tumor cells. It is shown that CAR T cells often merge into large clusters that envelop and kill the tumor cells with high efficiency. Significant differences are also measured between CAR T cells from different donors and between various CAR T cell constructs. Overall, the assay allows for multifaceted, dynamic, high‐content evaluation of CAR T trafficking, clustering, and killing and could eventually become a useful tool for immune‐oncology research and preclinical assessments of cell‐based immunotherapies. A micropatterned tumor array enables multifaceted and dynamic characterization of antitumor activity of CAR T cells. The assay demonstrates that CAR T cells migrate and merge into clusters that envelop the tumor islands and eliminate the tumor cells. It reveals significant differences in antitumor function between CAR T cells from different donors and between different CAR T cell constructs.

Autophagy is a highly conserved physiological process that maintains cellular homeostasis by recycling cellular contents. Selective autophagy is based on the specificity of cargo recognition and has been implicated in various human diseases, including neurodegenerative diseases and cancer. Selective autophagy receptors and modulators play key roles in this process. Identifying these receptors and modulators and their roles is critical for understanding the machinery and physiological function of selective autophagy and providing therapeutic value for diseases. Using modern researching tools and novel screening technologies, an increasing number of selective autophagy receptors and modulators have been identified. A variety of Strategies and approaches, including protein-protein interactions (PPIs)-based identification and genome-wide screening, have been used to identify selective autophagy receptors and modulators. Understanding the strengths and challenges of these approaches not only promotes the discovery of even more such receptors and modulators but also provides a useful reference for the identification of regulatory proteins or genes involved in other cellular mechanisms. In this review, we summarize the functions, disease association, and identification strategies of selective autophagy receptors and modulators.

Background Aptamers refer to the artificially synthesized nucleic acid sequences (DNA/RNA) that can bind to a wide range of targets with high affinity and specificity, which are generally generated from systematic evolution of ligands by exponential enrichment (SELEX). As a novel method of aptamers screening, whole-cell-SELEX (WC-SELEX) has gained more and more attention in many fields such as biomedicine, analytical chemistry, and molecular diagnostics due to its ability to screen multiple potential aptamers without knowing the detailed structural information of target molecules. Methods and Results In recent years, with the deepening of research on application of aptamers, the traditional WC-SELEX cannot meet the practical application because of long experimental period, complicated operation process and low specificity, etc. Therefore, the development of more efficient methods for screening aptamer is always on the road. This paper summarizes the current research status of WC-SELEX for bacteria, parasites and animal cells, and reviews the latest advances of WC-SELEX techniques that are dependent on novel instruments, materials and microelectronics, including fluorescence-activated cell sorting-assisted SELEX, three-dimensional assisted WC-SELEX, and microfluidic chip system-assisted WC-SELEX. In addition, the application of aptamers targeting cells was discussed. Conclusion Taken together, this review is aimed at providing a reference for WC-SELEX selection and application of aptamer targeting cells.

New mobile platforms such as vehicles, drones, aircraft, and satellites have emerged to help identify and reduce fugitive methane emissions from the oil and gas sector. When deployed as part of leak detection and repair (LDAR) programs, most of these technologies use multi-visit LDAR (MVL), which consists of four steps: (a) rapidly screen all facilities, (b) triage by emission rate, (c) follow-up with close-range methods at the highest-emitting sites, and (d) conduct repairs. The proposed value of MVL is to identify large leaks soon after they arise. Whether MVL offers an improvement over traditional single-visit LDAR (SVL), which relies on undirected close-range surveys, remains poorly understood. We use the Leak Detection and Repair Simulator (LDAR-Sim) to examine the performance and cost-effectiveness of MVL relative to SVL. Results suggest that facility-scale MVL programs can achieve fugitive emission reductions equivalent to SVL, but that improved cost-effectiveness is not guaranteed. Under a best-case scenario, we find that screening must cost < USD 100 per site for MVL to achieve 30% cost reductions relative to SVL. In scenarios with non-target vented emissions and screening quantification uncertainty, triaging errors force excessive close-range follow-up to achieve emissions reduction equivalence. The viability of MVL as a cost-effective alternative to SVL for reducing fugitive methane emissions hinges on accurate triaging after the screening phase.

This paper proposes decarbonization pathways for Thailand based on a review of the status of renewable and fossil energies, technology evaluation and scenario studies. Results show that renewable electricity generation needs to grow at a 7.1% average annual growth rate (AAGR) between now and 2050 for the power sector to achieve net-zero by 2050. This would require it to reach 400 TWh, exceeding its technical potential. We propose a more achievable scenario of between 5% and 6% AAGR wherein renewable electricity will grow from 51 TWh to 217–291 TWh between 2020 and 2050. Gas-powered electricity will grow from 127 TWh to 185–111 TWh, requiring carbon capture and storage (CCS) to mitigate 75–45 Mtpa CO2 by 2050. For the transport sector, electric vehicles have the highest decarbonization potential, but they would add 45 TWh of electricity demand by 2050. For the industry sector, installing CCS in existing plants has the highest decarbonization potential. Overall, CCS is a key decarbonization technology and its large-scale implementation will be needed for Thailand to achieve net-zero by 2050.

Substandard and falsified medicines threaten global health and require reliable data and screening technologies to combat their spread. This study examined the quality of 241 samples containing azithromycin, cefixime, esomeprazole and losartan collected from licenced private vendors in the Saptari (121 samples; convenience sampling) and Kathmandu (120 samples; randomised sampling) districts of Nepal. Nearly 10% (24 samples; 95% CI 6.5–14.5) of samples failed pharmacopoeial quality analysis and were classified as ‘substandard’ or ‘probably substandard’. No falsified medicines were identified. Small-scale dissolution acceptance criteria were applied to all 20 three-unit combinations of 213 samples tested in the first stage of the United States Pharmacopoeia dissolution test. Approximately 1% of these results were false positives when compared with the final United States Pharmacopoeia dissolution test results, suggesting the test’s usefulness in encouraging dissolution testing in resource-limited contexts. In the narrow sense of presence/absence, two portable Raman spectrometers reliably detected azithromycin, cefixime and losartan in most samples based on effective methods for detecting falsified medicines; however, none of the substandard samples were identified. The findings suggest that falsified medicines are less prevalent in Nepal and the surrounding region than suggested by regional concerns about Nepal and global concerns about low- and middle-income countries. Nevertheless, the Nepalese government should continue to ensure the quality of all distributed medicines.

The lysosomal cation channel TMEM175 is a Parkinson’s disease-related protein and a promising drug target. Unlike whole-cell automated patch-clamp (APC), lysosomal patch-clamp (LPC) facilitates physiological conditions, but is not yet suitable for high-throughput screening (HTS) applications. Here, we apply solid supported membrane-based electrophysiology (SSME), which enables both direct access to lysosomes and high-throughput electrophysiological recordings. In SSME, ion translocation mediated by TMEM175 is stimulated using a concentration gradient at a resting potential of 0 mV. The concentration-dependent K+ response exhibited an I/c curve with two distinct slopes, indicating the existence of two conducting states. We measured H+ fluxes with a permeability ratio of PH/PK = 48,500, which matches literature findings from patch-clamp studies, validating the SSME approach. Additionally, TMEM175 displayed a high pH dependence. Decreasing cytosolic pH inhibited both K+ and H+ conductivity of TMEM175. Conversely, lysosomal pH and pH gradients did not have major effects on TMEM175. Finally, we developed HTS assays for drug screening and evaluated tool compounds (4-AP, Zn as inhibitors; DCPIB, arachidonic acid, SC-79 as enhancers) using SSME and APC. Additionally, we recorded EC50 data for eight blinded TMEM175 enhancers and compared the results across all three assay technologies, including LPC, discussing their advantages and disadvantages.

In this work, high-throughput screening technology is applied to four-member refractory multi-principal element alloys (RMPEAs) films with high W content. The exploration of refractory metals such as W is strictly limited by the high melting temperature in this work; a multi-gradient deposition method was introduced to overcome this obstacle. By adjusting the power and distance from the target to the sample, component Zr11Mo11Ta25W53 with the best hardening performance was successfully obtained. The uniformity of the material library was analyzed from the perspectives of phase structure and micromorphology. With the help of Hume-Rothery theory and XRD analysis, it is shown that the film has a stable bcc structure. It is believed that film uniformity, nanoscale size, preferential orientation, surface roughness, and solution mechanism are the pivotal factors to improve hardness performance, especially for high W components. The hardness and modulus of elasticity can reach 20 GPa and 300 GPa, respectively, and the H/Er and H3/Er2 values are 0.067 and 0.065, showing the best wear resistance in many samples.

In the era of climate change and rapid urbanisation, communities and infrastructures need to be planned and designed in a way that promotes sustainable living. The provision of clean and affordable energy is a key to this aim. This paper proposes a technology assessment approach that is based on the triple bottom line (environmental, social and economic) sustainability framework. This approach can be employed in the technology screening that is involved in the early stages of the energy master planning process and can be applied to different community typologies in various locations and climates. The developed approach is demonstrated through a new urban renewal project case study in Fishermans Bend, Melbourne, in which a set of technological options were screened according to the project’s goals. The connection between the energy master plan and local and global sustainable development goals is discussed and policy interventions are proposed. The results show that the proposed approach could effectively enable the evaluation of the technological sustainability performance of the community by demonstrating the design trade-offs and the implementation of the sustainability objectives during the energy master planning process. Moreover, the proposed approach could provide guidance for effective policy making. It was found that government energy policies, regulations and incentives play a vital role in the feasibility of an energy master plan. Lastly, the proposed approach could facilitate the achievement of local and international targets, such as the UN SDGs, by 2050.

The aim of this study is to analyze the relationship between the incidence of breast cancer and income per capita across countries. Data on breast cancer incidence in 52 countries were obtained from GLOBOCAN, along with economic indicators of gross domestic product per capita from the World Bank. Number of computed tomography scanners and magnetic resonance imaging (from World Health Organization) were used as a surrogate for technology and access to screening for cancer diagnosis. Statistical analyses for correlation and regression were performed, along with an analysis of variance (ANOVA). A strong positive association between breast cancer incidence and gross domestic product per capita, Pearson’s r  = 65.4 %, controlling latitude, density of computed tomography scanners and magnetic resonance imaging was found in countries of temperate zones. The estimated relationship suggests that 1 % higher gross domestic product per capita, within the temperate zones (latitudes), increases the expected age-standardized breast cancer incidence by about 35.6 % ( p  < 0.001). ANOVA confirms these vital results. While some have argued that latitude and seasonality may affect breast cancer incidence, these findings suggest that wealthier nations may have a higher incidence of breast cancer independent of geographic location and screening technology.