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As the most powerful antigen-presenting cell type, dendritic cells (DCs) can induce potent antigen-specific immune responses in vivo, hence becoming optimal cell population for vaccination purposes. DCs can be derived ex vivo in quantity and manipulated extensively to be endowed with adequate immune-stimulating capacity. After pulsing with cancer antigens in various ways, the matured DCs are administrated back into the patient. DCs home to lymphoid organs to present antigens to and activate specific lymphocytes that react to a given cancer. Ex vivo pulsed DC vaccines have been vigorously investigated for decades, registering encouraging results in relevant immunotherapeutic clinical trials, while facing some solid challenges. With more details in DC biology understood, new theory proposed, and novel technology introduced (featuring recently emerged mRNA vaccine technology), it is becoming increasingly likely that ex vivo pulsed DC vaccine will fulfill its potential in cancer immunotherapy.

BackgroundThe ecotoxicological risk posed by metals and their mixtures in sediments depends on their bioavailability. Many methods for evaluating the bioavailability of metals in sediments/soils are time-consuming and expensive, and frequently result in equivocal outcomes. The diffusive gradients in thin films (DGT) technique is a good measure of bioavailability for metals that can avoid the above drawbacks. Therefore, more effective approaches to this method should be developed that focus on metal bioavailability. No studies have been conducted using DGT to assess metal mixtures to aquatic biota in sediments. This study is therefore the first attempt to assess sediment toxicity of metals and their mixtures to aquatic biota based on the DGT technique. The intertidal zone of the Pearl River Estuary is selected as a case study.ResultsThe bioavailable (DGT-labile) concentrations of metals range as follows (μg/L): Cd, 0.34–3.62; Pb, 1.35–1.92; Ni, 0.67–92.83; Cu, 0.74–10.30; Zn, 28.60–296.94; Co, 0.03–58.85; Fe, 7.23–4539.36; and Mn, 19.40–6626.83. The risk quotient (RQ), which is the ratio between the measured metal concentrations in the environment (MEC) and the predicted no-effect concentration (PNEC), is conducted to evaluate the single metal risk. The RQ based on summing up the MEC/PNEC ratios (RQMEC/PNEC) and the RQ based on sum of toxic units (RQSTU) are used to assess risk of metal mixture. TheRQ values of Cd, Pb, Ni, Cu, Zn, Fe, and Mn significantly exceed 1, indicating that the adverse effects of the metals are not negligible. Regarding the toxicity of metal mixtures, the values of RQMEC/PNEC and RQSTU are both between 62.45 and 743.48, revealing that the possible risk has already occurred in the study area.ConclusionsThe two methods of RQMEC/PNEC and RQSTU based on DGT-labile metal concentrations are effective and suitable to estimate the toxicity of metal mixtures in sediments.

As a popular research direction in the field of intelligent transportation, various scholars have widely concerned themselves with traffic sign detection However, there are still some key issues that need to be further solved in order to thoroughly apply related technologies to real scenarios, such as the feature extraction scheme of traffic sign images, the optimal selection of detection methods, and the objective limitations of detection tasks. For the purpose of overcoming these difficulties, this paper proposes a lightweight real-time traffic sign detection integration framework based on YOLO by combining deep learning methods. The framework optimizes the latency concern by reducing the computational overhead of the network, and facilitates information transfer and sharing at diverse levels. While improving the detection efficiency, it ensures a certain degree of generalization and robustness, and enhances the detection performance of traffic signs in objective environments, such as scale and illumination changes. The proposed model is tested and evaluated on real road scene datasets and compared with the current mainstream advanced detection models to verify its effectiveness. In addition, this paper successfully finds a reasonable balance between detection performance and deployment difficulty by effectively reducing the computational cost, which provides a possibility for realistic deployment on edge devices with limited hardware conditions, such as mobile devices and embedded devices. More importantly, the related theories have certain application potential in technology industries such as artificial intelligence or autonomous driving.

Gut microbial transformations of flavonoids, an enormous class of polyphenolic compounds abundant in plant-based diets, are closely associated with human health. However, the enzymes that initiate the gut microbial metabolism of flavones and flavonols, the two most abundant groups of flavonoids, as well as their underlying molecular mechanisms of action remain unclear. Here, we discovered a flavone reductase (FLR) from the gut bacterium, Flavonifractor plautii ATCC 49531 (originally assigned as Clostridium orbiscindens DSM 6740), which specifically catalyses the hydrogenation of the C2–C3 double bond of flavones/flavonols and initiates their metabolism as a key step. Crystal structure analysis revealed the molecular basis for the distinct catalytic property of FLR. Notably, FLR and its widespread homologues represent a class of ene-reductases that has not been previously identified. Genetic and biochemical analyses further indicated the importance of FLR in gut microbial consumption of dietary and medicinal flavonoids, providing broader insight into gut microbial xenobiotic transformations and possible guidance for personalized nutrition and medicine. Flavonoids are abundant polyphenols in plants but it is not well understood how their metabolism is initiated by microbes in the human gut. Here, the authors identify and characterise an ene-reductase from the gut bacterium, Flavonifractor plautii ATCC 49531 that catalyses the hydrogenation of the C2–C3 double bond of flavones and flavonols and present its crystal structure.

With the rapid development of object detection technology for unmanned aerial vehicles (UAVs), it is convenient to collect data from UAV aerial photographs. They have a wide range of applications in several fields, such as monitoring, geological exploration, precision agriculture, and disaster early warning. In recent years, many methods based on artificial intelligence have been proposed for UAV object detection, and deep learning is a key area in this field. Significant progress has been achieved in the area of deep-learning-based UAV object detection. Thus, this paper presents a review of recent research on deep-learning-based UAV object detection. This survey provides an overview of the development of UAVs and summarizes the deep-learning-based methods in object detection for UAVs. In addition, the key issues in UAV object detection are analyzed, such as small object detection, object detection under complex backgrounds, object rotation, scale change, and category imbalance problems. Then, some representative solutions based on deep learning for these issues are summarized. Finally, future research directions in the field of UAV object detection are discussed.

During February 2023, the quasi‐4‐day wave (Q4DW) with westward zonal wavenumber 2 (W2) reached its largest amplitude of ∼400 m in the Southern Hemisphere (SH) geopotential height observations since 2004, which occurred simultaneously with an Arctic major sudden stratospheric warming (SSW) with an elevated stratopause (ES). However, the Q4DW‐W2 perturbations in the Northern Hemisphere (NH) were unexpectedly suppressed despite the unstable Arctic stratosphere and mesosphere during the 2023 ES‐SSW. Diagnostic analysis shows that the westward winds at ∼54°N–70°N in the upper stratosphere of ∼‐79 m/s during the 2023 ES‐SSW were the strongest during boreal winters over the past two decades, which benefited from the onset of a preceding minor SSW at the end of January. The strongest westward wind generated a wave geometry configuration of full reflection for Q4DW‐W2 in the NH, while the Q4DW‐W2 enhancement in the SH was induced by the in‐situ amplification of the surviving seeding perturbations. Plain Language Summary Among the planetary waves with a period of about 4 days, the eastward quasi‐4‐day wave (Q4DW) excited by the double‐jet structure in the Southern Hemisphere is the most famous one, while another Q4DW with westward zonal wavenumber 2 (W2) belonging to the normal modes of the Earth's atmosphere has attracted little attention. During the February 2023 sudden stratospheric warming (SSW) with an elevated stratopause (ES), the exceptional enhancement and suppression of Q4DW‐W2 were captured in the Southern Hemisphere and Northern Hemisphere, respectively. Such global structure is first observed and abnormal among traveling planetary waves during SSW since they usually have a peak region in the unstable winter hemisphere. We found that the rare sequence of stratospheric disturbances in the 44‐year historical record that a minor SSW followed by an ES‐SSW led to the excessively strong westward wind during the 2023 ES‐SSW, which resulted in a wave geometry configuration of full reflection for Q4DW‐W2 in the Northern Hemisphere. Our current results well establish the relationship between a new global structure of traveling planetary waves during SSW and the rare sequence of stratospheric disturbances. This will deepen the understanding of the less studied Q4DW‐W2 and the Earth's whole atmospheric coupling during SSW. Key Points The anomalous burst and suppression of quasi‐4‐day wave (Q4DW) with westward zonal wavenumber 2 (W2) were observed in the Southern Hemisphere and Northern Hemisphere (NH) respectively during the February 2023 major sudden stratospheric warming (SSW) with elevated stratopause (ES) The rare sequence of SSWs in January and February 2023 led to the strongest westward wind during boreal winters over the past two decades The strongest westward wind during the 2023 ES‐SSW created a wave geometry configuration of full reflection weakening the Q4DW‐W2 in the NH

Testicular endothelial cells have been found to play an important role in spermatogenesis and fertility, but their mechanism is obscure. Exosomes released by various cells are recognized as cell-cell communication mediators during the initiation and progression of many diseases. Therefore, the current study aimed to investigate the protein and miRNA components of human testicular endothelial cell-derived exosomes (HTEC-Exos) and to explore their potential effects on spermatogenesis. In this study, HTEC-Exos were first isolated by the ultracentrifugation method, and then identified by nanoparticle tracking analysis, transmission electron microscopy (TEM), and western blotting. The characteristics of HTEC-Exos were examined by liquid chromatography-mass spectrometry and microRNA (miRNA) chip analysis. Bioinformatics analysis was performed to explore the potential role of the exosomal content on spermatogenesis. A total of 945 proteins were identified, 11 of which were closely related to spermatogenesis. A total of 2578 miRNAs were identified. Among them, 30 miRNAs demonstrated potential associations with male reproductive disorders, such as azoospermia, and spermatogenesis disorders. In particular, 11 out of these 30 miRNAs have been proven to be involved in spermatogenesis based on available evidence. This study provides a global view of the proteins and miRNAs from HTEC-Exos, suggesting that HTEC-Exos may function as potential effectors during the process of spermatogenesis.

Formic acid (FA) has emerged as a promising one-carbon feedstock for biorefinery. However, developing efficient microbial hosts for economically competitive FA utilization remains a grand challenge. Here, we discover that the bacterium Vibrio natriegens has exceptional FA tolerance and metabolic capacity natively. This bacterium is remodeled by rewiring the serine cycle and the TCA cycle, resulting in a non-native closed loop (S-TCA) which as a powerful metabolic sink, in combination with laboratory evolution, enables rapid emergence of synthetic strains with significantly improved FA-utilizing ability. Further introduction of a foreign indigoidine-forming pathway into the synthetic V. natriegens strain leads to the production of 29.0 g · L −1 indigoidine and consumption of 165.3 g · L −1 formate within 72 h, achieving a formate consumption rate of 2.3 g · L −1  · h −1 . This work provides an important microbial chassis as well as design rules to develop industrially viable microorganisms for FA biorefinery. Formic acid (FA) is a promising CO2-equivalent feedstock for onecarbon biorefinery, but microbial host that can efficiently utilize FA is unavailable. Here, the authors engineer a non-native closed loop in Vibrio natriegens and demonstrate its application in promoting FA utilization.

During the 2023/2024 austral summer, the quasi‐two‐day (QTDW) with westward zonal wavenumber 3 (W3) abnormally reached its maximum amplitude at the December solstice (22 December 2023) for the first time in 20 years of Aura Microwave Limb Sounder observations, while the strongest event during austral summer usually occurs ∼2–6 weeks after the December solstice (on average January 21). Diagnostic analysis reveals that the westward winds in the Southern (summer) Hemisphere were anomalously strong (maximum of ∼90 m/s) during December 2023, which significantly shortened the e‐folding time of QTDW‐W3, and additionally generated the QTDW‐W3 critical layers at the tropical summer stratopause from December 7. These two factors contributed to the earliest amplification of QTDW‐W3. In essence, the cold equatorial stratosphere triggered the exceptionally strong westward winds in the Southern Hemisphere via thermal wind balance, which was related to the enhanced upward middle‐atmosphere Hadley circulation during a prolonged Arctic stratopause warming event. Plain Language Summary As one of the prominent dynamic features in the Earth's summer middle and upper atmosphere, the quasi‐two‐day wave (QTDW) with westward zonal wavenumber 3 (W3) has significant influences on the global zonal‐mean circulation and temperature. Long‐term satellite and ground‐based observations have shown that the QTDW‐W3 is stably amplified twice yearly after the solstice, namely January/February in the Southern Hemisphere and July/August in the Northern Hemisphere. Such climatological features are very sensitive to the spatial distribution of the zonal‐mean zonal wind in the summer stratosphere and mesosphere. This study focuses on the unusual amplification of QTDW‐W3 just at the December solstice during the recent austral summer of 2023/2024, which has been never observed in the past 20 years of Aura Microwave Limb Sounder observations. Further analysis indicates that this earliest amplification of QTDW‐W3 was induced by a persistent and dramatic stratopause warming event in the Arctic (winter) stratosphere during December 2023, which caused the westward winds in the Southern (summer) Hemisphere to be anomalously strong via secondary Rossby wave‐induced interhemispheric coupling process. The current results first reveal that stratopause warming also has great potential to alter the global middle and upper atmospheric dynamics like the famous sudden stratospheric warming. Key Points The quasi‐two‐day wave (QTDW) with s=3$s=3$(W3) was maximized at the December solstice for the first time during the 2023/2024 austral summer The burst window for QTDW‐W3 appeared 2 weeks earlier than usual due to the anomalously strong summer westward winds in December 2023 The prolonged winter stratopause warming in December 2023 greatly enhanced the summer westward winds by cooling the equatorial stratosphere

Introduction: The normalized implementation of the centralized volume-based procurement policy for pharmaceuticals is a concerted push for supply-side structural reform of the pharmaceutical industry in China. The impact of the centralized drug procurement policy on pharmaceutical companies' transition from imitation to innovation is investigated to test whether a positive effect occurs in the innovation landscape of the pharmaceutical market. Methods: The double difference method and a series of robustness tests were used based on data from a sample of listed pharmaceutical companies in Shanghai and Shenzhen A-shares between 2015 and 2021. Results: The study found that the centralized drug procurement policy significantly contributed to the increased intensity of innovation input in the Chinese pharmaceutical industry. In terms of regional and firm nature heterogeneity, it was found that firms in the seven provinces belonging to the three economic regions had a better increase in innovation input intensity than other regions. Firms of state-owned nature had a better increase in innovation input intensity than private companies. The mechanism test found a partial mediating effect of nearly 10% for the cost of sales rate on the innovation input intensity of listed companies and a negative mediating effect on corporate operating profit. Discussion: Further research found that the effect of centralized drug procurement policy on the improvement of innovation quality of listed pharmaceutical companies was evident. The innovation development of Chinese pharmaceutical companies no longer focused on the accumulation of innovation quantity.