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Self-vibrating systems obtaining energy from their surroundings to sustain motion can offer great potential in micro-robots, biomedicine, radar systems, and amusement equipment owing to their adaptability, efficiency, and sustainability. However, there is a growing need for simpler, faster-responding, and easier-to-control systems. In the study, we theoretically present an advanced light-actuated liquid crystal elastomer (LCE) fiber–mass system which can initiate self-sliding motion along a rigid circular track under constant light exposure. Based on an LCE dynamic model and the theorem of angular momentum, the equations for dynamic control of the system are deduced to investigate the dynamic behavior of self-sliding. Numerical analyses show that the theoretical LCE fiber–mass system operates in two distinct states: a static state and a self-sliding state. The impact of various dimensionless variables on the self-sliding amplitude and frequency is further investigated, specifically considering variables like light intensity, initial tangential velocity, the angle of the non-illuminated zone, and the inherent properties of the LCE material. For every increment of π/180 in the amplitude, the elastic coefficient increases by 0.25% and the angle of the non-illuminated zone by 1.63%, while the light intensity contributes to a 20.88% increase. Our findings reveal that, under constant light exposure, the mass element exhibits a robust self-sliding response, indicating its potential for use in energy harvesting and other applications that require sustained periodic motion. Additionally, this system can be extended to other non-circular curved tracks, highlighting its adaptability and versatility. [ABSTRACT FROM AUTHOR]

Deep neural networks (DNNs) have emerged as a prominent model in medical image segmentation, achieving remarkable advancements in clinical practice. Despite the promising results reported in the literature, the effectiveness of DNNs necessitates substantial quantities of high-quality annotated training data. During experiments, we observe a significant decline in the performance of DNNs on the test set when there exists disruption in the labels of the training dataset, revealing inherent limitations in the robustness of DNNs. In this paper, we find that the neural memory ordinary differential equation (nmODE), a recently proposed model based on ordinary differential equations (ODEs), not only addresses the robustness limitation but also enhances performance when trained by the clean training dataset. However, it is acknowledged that the ODE-based model tends to be less computationally efficient compared to the conventional discrete models due to the multiple function evaluations required by the ODE solver. Recognizing the efficiency limitation of the ODE-based model, we propose a novel approach called the nmODE-based knowledge distillation (nmODE-KD). The proposed method aims to transfer knowledge from the continuous nmODE to a discrete layer, simultaneously enhancing the model's robustness and efficiency. The core concept of nmODE-KD revolves around enforcing the discrete layer to mimic the continuous nmODE by minimizing the KL divergence between them. Experimental results on 18 organs-at-risk segmentation tasks demonstrate that nmODE-KD exhibits improved robustness compared to ODE-based models while also mitigating the efficiency limitation. [ABSTRACT FROM AUTHOR]

The association between vascular calcification (VC) and kidney stone is still inconclusive. Therefore, we conducted a meta-analysis to estimate the risk of kidney stone disease in subjects with VC. To identify publications from related clinical studies, we performed a search on PubMed, Web of Science, Embase, and Cochrane Library databases from their inceptions until 1 September 2022. According to obvious heterogeneity, a random-effects model was used to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Subgroup analysis was conducted trying to dissect the effects of VC in different segments and population regions in predicting kidney stone risk. Seven articles were included with a total number of 69,135 patients, of which 10,052 have vascular calcifications and 4728 have kidney stones. There was a significantly higher risk of kidney stone disease in participants with VC versus control (OR = 1.54, 95% CI: 1.13–2.10). Sensitivity analysis confirmed the stability of the results. VC can be separated into abdominal, coronary, carotid, and splenic aortic calcification while pooled analysis of abdominal aorta calcification did not indicate a significant higher kidney stone risk. An obvious higher risk of kidney stone was observed in Asian VC patients (OR = 1.68, 95% CI: 1.07–2.61). Combined evidence of observational studies suggested patients with VC may be associated with an increased risk of kidney stone disease. Despite the predictive value was relatively low, it is still worth noting that patients with VC are under the threat of kidney stone disease. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) accounts for 15–20% of all invasive breast cancer subtypes. Owing to its clinical characteristics, such as the lack of effective therapeutic targets, high invasiveness, and high recurrence rate, TNBC is difficult to treat and has a poor prognosis. Currently, with the accumulation of large amounts of medical data and the development of computing technology, artificial intelligence (AI), particularly machine learning, has been applied to various aspects of TNBC research, including early screening, diagnosis, identification of molecular subtypes, personalised treatment, and prediction of prognosis and treatment response. In this review, we discussed the general principles of artificial intelligence, summarised its main applications in the diagnosis and treatment of TNBC, and provided new ideas and theoretical basis for the clinical diagnosis and treatment of TNBC. [ABSTRACT FROM AUTHOR]

Object detection of overhead transmission lines is a solution for promoting inspection efficiency for power companies. However, aerial images contain many complex backgrounds and small objects, and traditional algorithms are incompetent in the identification of details of power transmission lines accurately. To address this problem, this paper develops an object detection method based on optimized You Only Look Once v5-small (YOLOv5s). This method is designed to be engineering-friendly, with the objective of maximal detection accuracy and computation simplicity. Firstly, to improve the detecting accuracy of small objects, a larger scale detection layer and jump connections are added to the network. Secondly, a self-attention mechanism is adopted to merge the feature relationships between spatial and channel dimensions, which could suppress the interference of complex backgrounds and boost the salience of objects. In addition, a small object enhanced Complete Intersection over Union (CIoU) is put forward as the loss function of the bounding box regression. This loss function could increase the derived loss for small objects automatically, thereby improving the detection of small objects. Furthermore, based on the scaling factors of batch-normalization layers, a pruning method is adopted to reduce the parameters and achieve a lightweight method. Finally, case studies are fulfilled by comparing the proposed method with classic YOLOv5s, which demonstrate that the detection accuracy is increased by 4%, the model size is reduced by 58%, and the detection speed is raised by 3.3%. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has revolutionized cancer treatment, but most patients are refractory to immunotherapy or acquire resistance, with the underlying mechanisms remaining to be explored. Methods: We characterized the transcriptomes of ~92,000 single cells from 3 pre-treatment and 12 post-treatment patients with non-small cell lung cancer (NSCLC) who received neoadjuvant PD-1 blockade combined with chemotherapy. The 12 post-treatment samples were categorized into two groups based on pathologic response: major pathologic response (MPR; n = 4) and non-MPR (NMPR; n = 8). Results: Distinct therapy-induced cancer cell transcriptomes were associated with clinical response. Cancer cells from MPR patients exhibited a signature of activated antigen presentation via major histocompatibility complex class II (MHC-II). Further, the transcriptional signatures of FCRL4+FCRL5+ memory B cells and CD16+CX3CR1+ monocytes were enriched in MPR patients and are predictors of immunotherapy response. Cancer cells from NMPR patients exhibited overexpression of estrogen metabolism enzymes and elevated serum estradiol. In all patients, therapy promoted expansion and activation of cytotoxic T cells and CD16+ NK cells, reduction of immunosuppressive Tregs, and activation of memory CD8+T cells into an effector phenotype. Tissue-resident macrophages were expanded after therapy, and tumor-associated macrophages (TAMs) were remodeled into a neutral instead of an anti-tumor phenotype. We revealed the heterogeneity of neutrophils during immunotherapy and identified an aged CCL3+ neutrophil subset was decreased in MPR patients. The aged CCL3+ neutrophils were predicted to interact with SPP1+ TAMs through a positive feedback loop to contribute to a poor therapy response. Conclusions: Neoadjuvant PD-1 blockade combined with chemotherapy led to distinct NSCLC tumor microenvironment transcriptomes that correlated with therapy response. Although limited by a small patient sample size subjected to combination therapy, this study provides novel biomarkers to predict therapy response and suggests potential strategies to overcome immunotherapy resistance. [ABSTRACT FROM AUTHOR]

Background: Limited data are currently available on protozoan parasites of the genus Sarcocystis that infect their avian hosts within the order Anseriformes (waterfowl). To date, no Sarcocystis species has been recorded in ducks in China. Methods: Leg muscles were sampled from 26 domestic ducks (Anas platyrhynchos) in China in 2021. Morphological characteristics of sarcocysts detected in the muscle tissue were described using light microscopy (LM) and transmission electron microscopy (TEM). Genomic DNA was extracted from single sarcocysts obtained from different ducks, and three genetic markers, 18S ribosomal DNA (18S rDNA), 28S ribosomal DNA (28S rDNA) and mitochondrial (mt) cytochrome oxidase subunit 1 (cox1), were amplified and cloned for sequence analyses. Results: Sarcocysts were observed by LM in only three of the 28 samples (10.7%). These sarcocysts had a thick cyst wall with numerous brush-like villar protrusions (vps) of 3.8–4.3 μm in length (n = 30) on the cyst surface. TEM observation showed that the sarcocysts had lanceolated vps. Each vps narrowed in the stalk and contained a bundle of microtubules that extended into the ground substance. Comparisons of the new sequences with those deposited in GenBank showed that the most similar sequences were those of Sarcocystishalieti in the great cormorant Phalacrocorax carbo and European starling Sturnus vulgaris, and Sarcocystis calchasi in the domestic pigeon (Columba livia) at the 18S rDNA (99.1% identity); Sarcocystiswenzeli from the domestic chicken Gallus gallus at the 28S rDNA (95.9–96.0% identity); and Sarcocystis speeri from the opossum at the mtcox1 (98.2% identity). The new 18S rDNA, 28S rDNA and mitochondrial cox1 sequences shared up to 99.0%, 95.6% and 97.7% identity, respectively, with those of Sarcocystis spp. obtained from Anseriformes avian hosts. Phylogenetic analysis inferred from the sequences of the three genetic markers placed the organism within a group of Sarcocystis spp. obtained from avian or carnivorous intermediate hosts and avian, marsupial or carnivorous definitive hosts. Based on the morphological observation and molecular analyses, the organism found in the Chinese domestic ducks was regarded as a new species and named Sarcocystis platyrhynchosi n. sp. Conclusions: Based on morphology and sequence analyses, the microcysts diagnosed in the domestic ducks examined in this study were named as a new species. This is the first record of Sarcocystis spp. from waterfowl in China. Sarcocysts of similar morphology occur frequently in different Anseriformes birds, and the relationships among these species need to be further clarified in future studies using more molecular markers. [ABSTRACT FROM AUTHOR]

When various urban functions are integrated into one location, they form a mixture of functions. The emerging big data promote an alternative way to identify mixed functions. However, current methods are largely unable to extract deep features in these data, resulting in low accuracy. In this study, we focused on recognizing mixed urban functions from the perspective of human activities, which are essential indicators of functional areas in a city. We proposed a framework to comprehensively extract deep features of human activities in big data, including activity dynamics, mobility interactions, and activity semantics, through representation learning methods. Then, integrating these features, we employed fuzzy clustering to identify the mixture of urban functions. We conducted a case study using taxi flow and social media data in Beijing, China, in which five urban functions and their correlations with land use were recognized. The mixture degree of urban functions in each location was revealed, which had a negative correlation with taxi trip distance. The results confirmed the advantages of our method in understanding mixed urban functions by employing various representation learning methods to comprehensively depict human activities. This study has important implications for urban planners in understanding urban systems and developing better strategies. [ABSTRACT FROM AUTHOR]

Background. Hypoxia is one of the driving forces of cancer progression, recurrence, and metastasis. However, the association between the tumor hypoxic tumor microenvironment and the tumor mutation burden (TMB) is poorly understood in gastrointestinal cancer. Methods. Approximately 2,000 samples from colorectal cancer (CRC) and stomach adenocarcinoma (STAD) patients were obtained from the gene expression omnibus database and the cancer genome Atlas databases and were clustered and subtyped by nonnegative matrix factorization. Significant differentially expressed genes that were possibly related to survival differences between the hypoxic and normoxic groups were subjected to multivariate Cox regression. Results. Gastrointestinal cancer patients with CRC and STAD were further divided into two subgroups, namely, the hypoxia group and the normoxia group, and hypoxia was correlated with unfavorable outcomes. Notably, hypoxic tumors had lower TMB but significantly higher levels of immune and stromal infiltration. A signature of HEYL and NRP1 selected by LASSO classified gastrointestinal cancer patients into either a low or high-risk group, allowing for the combination of TMB status with markers of hypoxia in future clinical applications. Conclusions. Hypoxia is an independent prognostic factor and a strong immune infiltration indicator in gastrointestinal tumors of different organs, especially for cancers with low TMB. [ABSTRACT FROM AUTHOR]

Background: So called cell-free fetal DNA (cffDNA) in the maternal plasma, which is derived from placenta, is widely used to screen fetal aneuploidies, including trisomy 21, 18, 13 and sex chromosomes. Here we reported a case of trisomy 8 mosaicism (T8M), which was initially identified via cffDNA screening in noninvasive prenatal testing (NIPT). Methods: A 35-year-old woman received cffDNA screening at 17th week of gestation. Amniocentesis was performed subsequently, and karyotyping, single-nucleotide polymorphism array (SNP-array) and BACs-on-Beads™ (BoBs™) were used to determine fetal chromosome content. Interphase fluorescence in situ hybridization (FISH) was applied to determine the copy number of chromosome 8. Results: An enhanced risk for fetal trisomy 8 was identified by cffDNA screening in the studied pregnant woman. After amniocentesis trisomy 8 was found in 1 of 73 metaphases. SNP-array on DNA derived from cultured amniocytes and neonatal cord blood cells suggested the presence of T8M. Interphase FISH on native neonatal cord blood cells confirmed T8M with a percentage of 10%. The Bobs™ fluorescence data also suggested that 8q23-8q24 was amplified. Conclusions: The current study shows that NIPT is suited to provide hints on rare autosomal trisomies, which have to be further validated and confirmed by other approaches. [ABSTRACT FROM AUTHOR]

Hemostasis of deep irregular wounds is a severe problem in clinical practice. The development of rapid-acting hemostatic agents for deep and irregular wound is urgently needed. Here, sodium alginate/carboxycellulose/polydopamine (SA/CNF/PDA) microspheres was prepared by reverse emulsification and crosslinking with Ca2+, and SA/CNF/PDA composite hemostatic microspheres with porous structure were obtained by freeze-drying. SA/CNF/PDA composite hemostatic microspheres exhibited excellent porosity and water absorption which could rapidly absorb blood on the wound surface. Moreover, SA/CNF/PDA composite microspheres demonstrated remarkable hemostatic capabilities both in vitro and in vivo. It exhibited strong hemostatic performance in models of mouse tail-break and liver damage. Especially in liver injury model, it was completely hemostatic in 95 s, and blood loss (19.3 mg). The hemostatic efficacy of the SA/CNF/PDA composite microspheres was amplified through the stimulation of both exogenous and endogenous coagulation pathways. Therefore, SA/CNF/PDA composite hemostatic microspheres are suitable for rapid hemostasis of deep irregular wounds which are potential rapid hemostatic material for surgical application. • SA/CNF/PDA hemostatic microsphere was obtained by reverse emulsification and freeze-drying. • SA/CNF/PDA microsphere stopped bleeding within 95 s in liver injury model. • The activation of exogenous and endogenous coagulation pathways were activated. [ABSTRACT FROM AUTHOR]

Background: Data on the genus Sarcocystis in insectivores are limited. The Asian gray shrew Crocidura attenuata is one of the most common species of the insectivore family Soricidae in South Asia and Southeast Asia. To our knowledge, species of Sarcocystis have never been recorded previously in this host. Methods: Tissues were obtained from 42 Asian gray shrews caught in 2017 and 2018 in China. Sarcocysts were observed using light microscopy (LM) and transmission electron microscopy (TEM). To describe the parasite life cycle, muscle tissues of the host infected with sarcocysts were force-fed to two beauty rat snakes Elaphe taeniura. Individual sarcocysts from different Asian gray shrews, and oocysts/sporocysts isolated from the small intestines and feces of the experimental snakes, were selected for DNA extraction, and seven genetic markers, namely, two nuclear loci [18S ribosomal DNA (18S rDNA) and internal transcribed spacer region 1 (ITS1)], three mitochondrial genes [cytochrome oxidase subunit 1 (cox1), cox3 and cytochrome b], and two apicoplast genes (RNA polymerase beta subunit and caseinolytic protease C), were amplified, sequenced and analyzed. Results: Sarcocysts were found in 17 of the 42 (40.5%) Asian gray shrews. Under LM, the microscopic sarcocysts showed saw- or tooth-like protrusions measuring 3.3–4.5 μm. Ultrastructurally, the sarcocyst wall contained numerous lancet- or leaf-like villous protrusions, similar to those described for type 9h of the common cyst wall classification. The experimental beauty rat snakes shed oocysts/sporocysts measuring 11.9–16.7 × 9.2–10.6 μm with a prepatent period of 10–11 days. Comparison of the newly obtained sequences with those previously deposited in GenBank revealed that those of 18S rDNA and cox1 were most similar to those of Sarcocystis scandentiborneensis recorded in the tree shrews Tupaia minor and Tupaiatana (i.e., 97.6–98.3% and 100% identity, respectively). Phylogenetic analysis based on 18S rDNA or ITS1 sequences placed this parasite close to Sarcocystis spp. that utilize small animals as intermediate hosts and snakes as the known or presumed definitive host. On the basis of morphological and molecular characteristics and host specificity, the parasite was proposed as a new species, named Sarcocystis attenuati. Conclusions: Sarcocysts were recorded in Asian gray shrews, to our knowledge for the first time. Based on morphological and molecular characterization, a new species of parasite is proposed: Sarcocystisattenuati. According to the LM and TEM results, S. attenuati sarcocysts are distinct from those of Sarcocystis spp. in other insectivores and those of S. scandentiborneensis in tree shrews. The 18S rDNA or cox1 sequences of Sarcocystis attenuati shared high similarity with those of Sarcocystisscandentiborneensis, Sarcocystis zuoi, Sarcocystis cf. zuoi in the Malayan field rat, and Sarcocystis sp. in the greater white-toothed shrew. Therefore, we suggest that more research on the relationships of these closely related taxa should be undertaken in the future. [ABSTRACT FROM AUTHOR]

Despite dramatic responses to immune checkpoint inhibitors (ICIs) in patients with colon cancer (CC) harboring deficient mismatch repair (dMMR), more than half of these patients ultimately progress and experience primary or secondary drug resistance. There is no useful biomarker that is currently validated to accurately predict this resistance or stratify patients who may benefit from ICI-based immunotherapy. As hypoxic and acidic tumor microenvironment would greatly impair tumor-suppressing functions of tumor-infiltrating lymphocytes (TILs), we sought to explore distinct immunological phenotypes by analysis of the intratumoral hypoxia state using a well-established gene signature. Based on the Gene Expression Omnibus (GEO) (n = 88) and The Cancer Genome Atlas (TCGA) (n = 49) databases of patients with CC, we found that dMMR CC patients could be separated into normoxia subgroup (NS) and hypoxia subgroup (HS) with different levels of expression of hypoxia-related genes (lower in NS group and higher in HS group) using NMF package. Tumoral parenchyma in the HS group had a relatively lower level of immune cell infiltration, particularly CD8+ T cells and M1 macrophages than the NS group, and coincided with higher expression of immune checkpoint molecules and C-X-C motif chemokines, which might be associated with ICI resistance and prognosis. Furthermore, three genes, namely, MT1E, MT2A, and MAFF, were identified to be differentially expressed between NS and HS groups in both GEO and TCGA cohorts. Based on these genes, a prognostic model with stable and valuable predicting ability has been built for clinical application. In conclusion, the varying tumor-immune microenvironment (TIME) classified by hypoxia-related genes might be closely associated with different therapeutic responses of ICIs and prognosis of dMMR CC patients. [ABSTRACT FROM AUTHOR]

Transcatheter mitral valve replacement is increasingly being used as a treatment for high-risk patients who have native mitral valve disease; however, no comprehensive studies on its effectiveness have been reported. We therefore searched the literature for reports on patients with native mitral valve disease who underwent transcatheter access treatment. We found 40 reports, published from September 2013 through April 2017, that described the cases of 66 patients (mean age, 71 ± 12 yr; 30 women; 30 patients with mitral stenosis, 34 with mitral regurgitation, and 2 mixed) who underwent transcatheter mitral valve replacement. We documented their baseline clinical characteristics, comorbidities, diagnostic imaging results, procedural details, and postprocedural results. Access was transapical in 41 patients and transseptal in 25. The 30-day survival rate was 82.5%. The technical success rate (83.3% overall) was slightly but not significantly better in patients who had mitral regurgitation than in those who had mitral stenosis. Transapical access procedures resulted in fewer valve-in-valve implantations than did transseptal access procedures (P=0.026). These current results indicate that transcatheter mitral valve replacement is feasible in treating native mitral disease. The slightly higher technical success rate in patients who had mitral regurgitation suggests that a valve with a specific anchoring system is needed when treating mitral stenosis. Our findings indicate that transapical access is more reliable than transseptal access and that securely anchoring the valve is still challenging in transseptal access. [ABSTRACT FROM AUTHOR]

Background: A number of studies have reported hyperprogressive disease (HPD) in non-small cell lung cancer (NSCLC) after treatment with immune checkpoint inhibitor (ICI). This study aimed to summarize the incidence and survival outcome of HPD in NSCLC and identify the clinicopathological features associated with HPD based on available eligible studies.Methods: Four databases (Medline/PubMed, Embase, Web of Science, and Cochrane Library) were searched for eligible studies on HPD published before January 23, 2020, to evaluate the incidence, outcome, and clinical features of HPD. Statistical analyses were performed using STATA 15.0. All meta-analyses were performed based on the random-effects model.Results: This study included 6 studies involving 1389 patients. The incidence of HPD ranged from 8.02 to 30.43%. Compared with patients with non-HPD, those with HPD were associated with worse overall survival. We identified that Eastern Cooperative Oncology Group > 1, Royal Marsden Hospital score ≥ 2, serum lactate dehydrogenase > upper limit of normal, the number of metastasis sites > 2, and liver metastasis were associated with the risk of HPD.Conclusions: This study summarized the clinical features of HPD in NSCLC patients. The meta-analysis showed that five pre-treatment clinicopathological features might be associated with HPD, which may help in selecting patients for ICIs. [ABSTRACT FROM AUTHOR]

The Jurassic sequence in the northern Qaidam Basin can be represented by the lower coal‐bearing swamp‐lacustrine sediments unit and the upper reddish clastic deposits suite, which recorded dramatic transition of deposit environment changes. Whole‐rock geochemical data of this succession in Dameigou profile were used to reconstruct the provenance and chemical weathering history. Based on the major element discrimination diagrams, trace element ratios and chondritenormalized REE patterns, most sediments were derived from a similar source area with felsic‐intermediate rocks as dominant contributors. Multiple geochemical parameters and index displayed good correlation, via vertical variations sequence, Jurassic chemical weathering history of northern Qaidam Basin was established, and four stages were recognized from the profile. Phases I and III experienced intense chemical weathering, while Phases II and IV are characterized by mild to moderate chemical weathering. Based on this, long‐term Jurassic climatic evolution of the Qaidam Basin was reconstructed. Early‐middle period of Early Jurassic and middle period of Middle Jurassic developed warm and humid climate. On the contrary, late Early Jurassic‐early Middle Jurassic and late Middle Jurassic‐Late Jurassic was deposited under relatively semiarid to arid climatic conditions. [ABSTRACT FROM AUTHOR]

The future renewable-based power system will have an increased need for balancing power. Prosumers, having both generation and consumption capabilities, are expected to provide balancing power to the grid, if their flexibility can be appropriately managed. Meanwhile, undesirable line congestions and voltage violations may arise in the distribution network, when flexible resources respond to external control or price signals on a large scale. Hence, the development of an effective framework to coordinate flexibility at the distribution system level is of utmost importance. Such a framework should allow for an optimal provision of prosumer balancing power services within the boundaries of local network security constraints. In this study, a balancing market participation framework is proposed, adopting the concept of network-constrained transactive energy, to facilitate the interactions between the transmission system operator and aggregators who manage prosumer energy profiles. This framework retains user privacy and complies with the current market setup, where flexible energy is traded on the spot and balancing markets; however, it is ensured that the resulting energy profiles do not cause problems in the distribution network. [ABSTRACT FROM AUTHOR]

• Equilibrium position of the non-isothermal particle deviates from the centerline of the channel. • Dependence of the equilibrium position of the particle on Gr is not monotonic. • Equilibrium position of the particle is closer to the centerline of the channel with Re increasing. The migration of a neutrally buoyant particle in a shear flow with thermal convection is studied with the lattice Boltzmann method. Due to the effect of thermal convection, the equilibrium position of the particle is different qualitatively from the isothermal case. The dependence of the equilibrium position of the particle on the Grashof number is not monotonic, and four driving forces, which affect the migration of the particle, are investigated. Since the migration of the particle is affected by both forced convection and thermal convection, with the Reynolds number increasing, forced convection becomes stronger, which weakens the effect of thermal convection, as a result, the equilibrium position of the particle is closer to the isothermal case. [ABSTRACT FROM AUTHOR]

Programmed death ligand 1 (PD-L1) exosomes are important biomarkers of immune activation in the initial stages of treatment and can predict clinical responses to PD-1 blockade in various cancer patients. However, traditional PD-L1 exosome bioassays face challenges such as high interface fouling in complex detection environments, limited detection specificity, and poor clinical serum applicability. Inspired by the multi-branched structure of trees, a biomimetic tree-like multifunctional antifouling peptide (TMAP)-assisted electrochemical sensor was developed for high-sensitivity exosomes detection. Multivalent interaction of TMAP significantly enhances the binding affinity of PD-L1 exosomes, thanks to the designed branch antifouling sequence, TMAPs antifouling performance is further improved. The addition of Zr4+ forms coordination bonds with the exosome's lipid bilayer phosphate groups to achieve highly selective and stable binding without interference from protein activity. The specific coordination between AgNCs and Zr4+ contributes to a dramatic change in the electrochemical signals, and lowing detection limit. The designed electrochemical sensor exhibited excellent selectivity and a wide dynamic response within the PD-L1 exosome concentration range from 78 to 7.8 × 107 particles/mL. Overall, the multivalent binding ability of TMAP and the signal amplification characteristics of AgNCs have a certain driving role in achieving clinical detection of exosomes. [ABSTRACT FROM AUTHOR]

The epigenome may be an important interface between exposure to environmental contaminants and adverse outcome on human health. Many environmental pollutants deregulate gene expression and promote diseases by modulating the epigenome. Adverse epigenetic responses have been widely used for risk assessment of chemical substances. Various pollutants, including trace elements and persistent organic pollutants, have been detected frequently in the environment. Epigenetic toxicity of environmental matrices including water, air, soil, and food cannot be ignored. This review provides a comprehensive overview of epigenetic effects of pollutants and environmental matrices. We start with an overview of the mechanisms of epigenetic regulation and the effects of several types of environmental pollutants (trace elements, persistent organic pollutants, endocrine disrupting chemicals, and volatile organic pollutants) on epigenetic modulation. We then discuss the epigenetic responses to environmental water, air, and soil based on in vivo and in vitro assays. Finally, we discuss recommendations to promote the incorporation of epigenotoxicity into contamination screening and health risk assessment. Image 1097 • Integrate review of epigenetic profiles of environmental exposure. • Epigenetic markers as linkage between pollutants exposure and adverse outcomes. • Progress of epigenetic modulations as risk assessment indicators on various matrices. • Epigenetic responses incorporated into epigenotoxicant screening and risk assessment. [ABSTRACT FROM AUTHOR]

Retinopathy of Prematurity (ROP) is a retinal vasproliferative disorder disease principally observed in infants born prematurely with low birth weight. ROP is an important cause of childhood blindness. Although automatic or semi-automatic diagnosis of ROP has been conducted, most previous studies have focused on “plus” disease, which is indicated by abnormalities of retinal vasculature. Few studies have reported methods for identifying the “stage” of the ROP disease. Deep neural networks have achieved impressive results in many computer vision and medical image analysis problems, raising expectations that it might be a promising tool in the automatic diagnosis of ROP. In this paper, convolutional neural networks with a novel architecture are proposed to recognize the existence and severity of ROP disease per-examination. The severity of ROP is divided into mild and severe cases according to the disease progression. The proposed architecture consists of two sub-networks connected by a feature aggregate operator. The first sub-network is designed to extract high-level features from images of the fundus. These features from different images in an examination are fused by the aggregate operator, then used as the input for the second sub-network to predict its class. A large data set imaged by RetCam 3 is used to train and evaluate the model. The high classification accuracy in the experiment demonstrates the effectiveness of the proposed architecture for recognizing the ROP disease. [ABSTRACT FROM AUTHOR]

This paper applies a robust optimization technique for coordinating reserve allocations in multiple-cell based power systems. The linear decision rules (LDR)-based policies were implemented to achieve the reserve robustness, and consist of a nominal power schedule with a series of linear modifications. The LDR method can effectively adapt the participation factors of reserve providers to respond to system imbalance signals. The policies considered the covariance of historic system imbalance signals to reduce the overall reserve cost. When applying this method to the cell-based power system for a certain horizon, the influence of different time resolutions on policy-making is also investigated, which presents guidance for its practical application. The main results illustrate that: (a) the LDR-based method shows better performance, by producing smaller reserve costs compared to the costs given by a reference method; and (b) the cost index decreases with increased time intervals, however, longer intervals might result in insufficient reserves, due to low time resolution. On the other hand, shorter time intervals require heavy computational time. Thus, it is important to choose a proper time interval in real time operation to make a trade off. [ABSTRACT FROM AUTHOR]

A two-dimensional study of mass transfer from a circular composite particle settling in a vertical channel is conducted with the lattice Boltzmann method. The particle is composed of two materials, one insoluble while the other soluble in the ambient fluid. In the problem, mass transfer, particle motion and fluid flow are closely coupled, where the concentration at the particle surface and particle properties vary with mass transfer. It is observed that mass transfer follows a Schmidt number independent scaling law of [ t / ( t ν Sc ) ] - 1.5 ( t is the physical time, t ν is the momentum diffusion time scale and Sc is the Schmidt number), which is quite different from the pure diffusion of a stationary particle, ∼ ( t / t α ) - 0.5 ( t α is the mass diffusion time scale). An analysis of the concentration and flow pattern around the particle suggests that the scaling law for a settling particle is related to both diffusion distance and convection distance, while it is only relevant to the diffusion distance in the case of a stationary particle. For a settling particle, mass transfer is enhanced by two mechanisms due to convection, i.e., the concentration around the particle surface transported to the downstream of the particle by the fluid flow and the interface of mass transfer stretched with the particle motion, which are absent in the case of a stationary particle. Thus, the rate of mass transfer in the case of a settling particle is much higher than that for a stationary particle. [ABSTRACT FROM AUTHOR]

• An ultralight MoS 2 QDs-NRGO composites modified separator is designed for Li-S batteries. • The synergistic inhibitory effect of MoS 2 QDs-NRGO can effectively inhibit LiPSs shuttle. • Under high sulfur loading, the inhomogeneous deposition of Li 2 S in the separator will blocked the lithium-ion diffusion. • An appropriate thickness of the modified coating layer can mitigate the capacity decline under high sulfur loading. Although functionalized separators have been proved to effectively mitigate the shuttle of lithium polysulfides (LiPSs), the capacity degradation of lithium-sulfur (Li-S) batteries with functionalized separators under high sulfur loading still hasn't been detailed investigated totally. Herein, the synergistic inhibition effect of ultralight MoS 2 quantum dots decorated nitrogen doped reduction of graphene oxides composites (MoS 2 QDs-NRGO) modified separator on polysulfides shuttling is achieved. The Li-S batteries with this functional separator exhibit an impressive drop in cycle performance under high sulfur loading that the capacity retention at 71.5 % under sulfur loading of 2 mg cm−2, and only 53.1 % under 6 mg cm−2. Through the in-situ/ex-situ Raman spectroscopy investigation, kinetics analysis and electrochemical performance test, we discover that the inhomogeneous deposition of Li 2 S is seriously on the separator modified layer under high sulfur loading, which blocks the lithium-ion diffusion kinetics in the separator and increases the reaction between Li 2 S and lithium anode, leading to the fast capacity fading of Li-S batteries. Afterward, we find an appropriate area-loading of the modified layer can effectively mitigate the deposition of the Li 2 S, thereby improving the cycling stability of Li-S batteries under the high sulfur loading. [ABSTRACT FROM AUTHOR]

The migration of a neutrally buoyant particle in a Poiseuille flow with thermal convection is investigated with the double-population lattice Boltzmann method. Compared with the isothermal case, the migration of the particle is notably affected by thermal convection. Five competing mechanisms are responsible for the lateral migration of the particle, i.e., wall repulsion due to lubrication, inertial lift related to shear slip, a lift due to particle rotation, a lift due to the curvature of the undisturbed velocity profile and a lift induced by thermal convection. Within the parameter range examined ( Gr < 2000 , Re c < 200 ), a critical Grashof number Gr c is identified, beyond which the equilibrium position is insensitive to the initial position. Furthermore, a power law dependence of the critical Grashof number Gr c on the channel Reynolds number Re c is discovered. In addition, with the channel Reynolds number Re c increasing, the forced flow relative to the particle is becoming stronger, leading to a declining effect of thermal convection. [ABSTRACT FROM AUTHOR]

Owing to the increasing penetration of single‐phase small generation units and electric vehicles connected to distribution grids, system operators are facing challenges related to local unbalanced voltage rise or drop issues, which may lead to a violation of the allowed voltage band. To address this problem, distribution transformers with on‐load tapping capability are under development. This study presents model and experimental validation of a 35 kVA three‐phase power distribution transformer with independent on‐load tap‐changer control capability on each phase. With the purpose of investigating and evaluating its effectiveness under different operative conditions, appropriate scenarios are defined and tested considering both balanced and unbalanced situations, also in case of reverse power flow. The experimental setup is built starting from an analysis of a Danish distribution network, in order to reproduce the main feature of an unbalanced grid. The experimental activities are recreated in by carrying out dynamics simulation studies, aiming at validating the implemented models of both the transformer as well as the other grid components. Phase–neutral voltages' deviations are limited, proving the effectiveness of the phase‐independent tap operations. Furthermore, minor deviations of the results from simulations and experiments confirm that all the system components have been properly modelled. [ABSTRACT FROM AUTHOR]

The design and implementation of management policies for plug-in electric vehicles (PEVs) need to be supported by a holistic understanding of the functional processes, their complex interactions, and their response to various changes. Models developed to represent different functional processes and systems are seen as useful tools to support the related studies for different stakeholders in a tangible way. This paper presents an overview of modeling approaches applied to support aggregation-based management and integration of PEVs from the perspective of fleet operators and grid operators, respectively. We start by explaining a structured modeling approach, i.e., a flexible combination of process models and system models, applied to different management and integration studies. A state-of-the-art overview of modeling approaches applied to represent several key processes, such as charging management, and key systems, such as the PEV fleet, is then presented, along with a detailed description of different approaches. Finally, we discuss several considerations that need to be well understood during the modeling process in order to assist modelers and model users in the appropriate decisions of using existing, or developing their own, solutions for further applications. [ABSTRACT FROM AUTHOR]

Whey protein isolate (WPI) interacts with cinnamaldehyde (CA) to form conjugates with superior functional properties, which are affected by the conjugate structures formed by different food processing techniques, especially heating treatment. Initially, we compared three preparation methods of conjugates, including heating WPI before interacting with CA [(HWPI)/CA)], heating the resulting conjugates without heating WPI initially [H-(WPI/CA)], and the normal conjugates without any heating process (WPI/CA). Subsequently, these conjugates were used to stabilize emulsions for the encapsulation and delivery of β-carotene. Both the aforementioned heating methods increased the interaction and enhanced the conjugates' surface hydrophobicity. Synchronous fluorescence suggested that heating expanded the protein structure and exposed hydrophobic groups, while higher CA concentration had a shielding effect on this process. Moreover, H-(WPI/CA) conjugates reduced the interfacial tension to 4.38 mN/m, resulting in the best emulsification, which effectively stabilized emulsions and protected β-carotene from the influence of temperature. H-(WPI/CA) conjugates helped to maintain the retention rate at more than 70% within 28 days and improved β-carotene bioaccessibility during digestion. This knowledge provides insights into investigating the relationship between conjugates preparation methods and their properties, and is of great significance for developing a novel multifunctional food ingredient system based on protein modification. • Heating treatment could enhance the interaction between WPI and CA. • WPI/CA conjugate after heating treatment had better stability effect on emulsion. • H-(WPI/CA) conjugate had the best protective effect on β-carotene. • H-(WPI/CA) conjugate emulsion had the highest bioaccessibility of β-carotene. [ABSTRACT FROM AUTHOR]

Geochemical characteristics of the Middle Permian mudstones from the Longge Formation in the Jiaomuri area, central uplift zone of Qiangtang Basin have been analysed to constrain their provenance, tectonic setting, depositional redox condition and palaeoclimate. Based on the geochemical parameters like CIA, PIA, ICV values and Th/U, K/Rb ratios indicate that the source rocks were affected by low degree weathering conditions. The U/Th, V/Cr, Ni/Co, V/Sc ratios and Uau, C-values of samples suggest that the mudstones were formed in an oxic environment, with arid palaeoclimate. Bulk-rock geochemistry analysis indicates that they are mainly arkose and subarkose, derived from dominantly andesitic rocks, probably a mixing of felsic and mafic provenance. The CIA, PIA and ICV values of these samples suggest that the Longge mudstones are compositionally immature and related to moderate weathering. The tectonic discrimination diagrams, as well as critical trace and REE characteristic parameters imply an oceanic arc or continental arc setting for the depositional basin of mudstones from the Longge Formation, probably back-arc basin. This study supports an occurrence of archipelagic oceanic basins in the Jiaomuri area in the Middle Permian, which provides evidence for the research of the Longmu Co-Shuanghu-Lancangjiang Suture. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Various tumor cells overexpress programmed death ligand 1 (PD-L1), a main immune checkpoint protein (ICP) embedded in the tumor cells membrane, to evade immune recognition through the interaction between PD-L1 and its receptor programmed death 1 (PD-1) which is from T-cells for maintaining immune tolerance. So inhibitors targeting the PD-1 or PD-L1 can block the PD-1/PD-L1 signaling pathway to restore the recognition activity of the immune system to tumor cells, which also have been utilized as a novel approach to improve the clinical therapeutic effect for cancer patients. Since not all cancer patients can respond to these inhibitors effectively, previous diagnosis of PD-L1 is significant to target the right treatments for cancer patients. This review pays attention to the PD-L1 detection and recent progress in the measurement of PD-L1 concentration, including various detection methods based on optical sensors as well as electrochemical assays. Apart from above those, we also focus on the prospects of PD-L1 detection in precision medicine. • A critical review of the detection for programmed death ligand 1 is presented. • Both current methods and emerging approaches are included. • The significance of accurate measurement of PD-L1 concentration for precision medicine is highlighted. • Challenges and future outlooks of detection for programmed death ligand 1 are presented. [ABSTRACT FROM AUTHOR]

Electric vehicles (EVs) are widely regarded as valuable assets in the smart grid as distributed energy resources in addition to their primary transportation function. However, connecting EVs to the distribution network and recharging the EV batteries without any control may overload the transformers and cables during peak hours when the penetration of EVs is relatively high. In this study, a two level hierarchical control method for integrating EVs into the distribution network is proposed to coordinate the self-interests and operational constraints of two actors, the EV owner and Distribution system operator (DSO), facilitated by the introduction of the fleet operator (FO) and the grid capacity market operator (CMO). Unlike the typical hierarchical control system where the upper level controller commands the low level unit to execute the actions, in this study, market based control are applied both in the upper and low level of the hierarchical system. Specifically, in the upper level of the hierarchy, distribution system operator uses market based control to coordinate the fleet operator׳s power schedule. In the low level of the hierarchy, the fleet operator use market based control to allocate the charging power to the individual EVs, by using market based control, the proposed method considers the flexibility of EVs through the presence of the response-weighting factor to the shadow price sent out by the FO. Furthermore, to fully demonstrate the coordination behavior of the proposed control strategy, we built a multi-agent system (MAS) that is based on the co-simulation environment of JACK, Matlab and Simulink. A use case of the MAS and the results of running the system are presented to intuitively illustrate the effectiveness of the proposed solutions. [ABSTRACT FROM AUTHOR]

• Melatonin (Mel) was synthesized from serotonin in granulosa cells. • E2 inhibited the expression of Mel receptors and Mel synthesis through ERA and ERB. • We firstly describe the mechanisms of E2 regulation Mel in follicle. • The effect of E2 regulated Mel deserves further study in follicular development. Melatonin, an important regulator of mammalian reproduction, is mainly produced in the pineal gland, and granulosa cells (GCs), the main mammalian ovarian secretory cells, synthesize melatonin and express melatonin receptors (MRs) MT1 and MT2. However, studies on melatonin regulation in GCs are lacking in sheep. In this study, we explored the effects of β-estradiol (E2) on melatonin production and MR expression in GCs. We cultured sheep GCs to analyze the expression of the melatonin rate-limiting enzymes AANAT and HIOMT and the effects of E2 on AANAT, HIOMT, and MR expression and melatonin synthesis. To determine whether estrogen receptors (ERs) mediated E2 action on melatonin secretion and MR expression, we assessed ERA and ERB expression in GCs and observed whether ER antagonists counterbalanced the effects of E2. GCs expressed AANAT and HIOMT mRNA, indicating that they transformed exogenous serotonin into melatonin. E2 inhibited melatonin production by downregulating AANAT, HIOMT, and MRs. GCs expressed ERA and ERB; ERA/ERB inhibitors abolished E2-mediated inhibition of melatonin secretion and MR expression. PHTPP upregulated melatonin secretion and MT1 expression in E2-treated GCs, but did not significantly affect AANAT and MT2 expression. In conclusion, melatonin secretion in GCs was inhibited by E2 through an ERA- and ERB-mediated process. [ABSTRACT FROM AUTHOR]

Since it is low in cost and low in toxicity and has good biodegradability, gas-liquid-foam three-phase flow has been widely used in industrial fire protection. Due to the different characteristics of gas, liquid, and foam, liquid precipitation is liable to occur under static conditions, resulting in unstable performance of the mixture. To improve fire extinguishing efficiency, it is of great significance to study the separation process of gas-liquid-foam. In the present study, the effects of the surface tension (range from 0.04 to 0.07) and initial liquid volume fraction (range from 0.2 to 0.5) on the gas-liquid-foam separation process are investigated with the numerical tool Fluent. The liquid volume fraction is mainly influenced by two inverse effects: (a) the transformation of liquid into foam, and (b) the liquid drainage and bursting of foam. In the separation process, the volume fraction of small foam decreases monotonically while the volume fraction of medium and large foam increases slightly. Since the volume fraction of small foam is much greater than medium and large foam and its bursting process is dominant, the liquid volume fraction presents a monotonic increasing trend. The volume of the separated liquid increases almost linearly with time at various surface tensions and initial volume fractions, and the increase rate is about 0.004. In the range of the surface tension examined, the separation process is insensitive to the surface tension, resulting in almost the same drainage time. On the other hand, the separation process depends on the initial liquid volume fraction non-monotonically; namely, when the initial volume fraction is small, with the increase of the initial volume fraction, the liquid is more easily separated from the mixture, and when the initial volume fraction is over a critical value (about 0.4), the separation process is decelerated. [ABSTRACT FROM AUTHOR]

This research focused on the inhibition effect and mechanism of a selective depressant PBTCA (2-phosphonobutane-1,2,4-tricarboxylic acid) on flotation separation of magnesite from calcite. The inhibition effect of PBTCA was investigated through micro-flotation tests, and the results showed that PBTCA presented selective inhibition effect on calcite in sodium oleate (NaOL) system. The inhibition mechanism of PBTCA was analyzed by contact angle measurements, zeta potential analysis and X-ray photoelectron spectroscopy (XPS) analysis. The results of contact angle measurements indicated that PBTCA could increase the hydrophilicity of calcite surface while magnesite surface still maintained hydrophobicity with PBTCA and NaOL. Zeta potential measurements results indicated that the adsorption of PBTCA on calcite surface was stronger than magnesite, and NaOL could further adsorb on magnesite surface even PBTCA existed. Furthermore, XPS results confirmed the stronger adsorption between PBTCA and calcite, which could be attributed to the interaction between phosphonyl (–PO 3 H 2) structure of PBTCA and calcium ions on calcite surface. [Display omitted] • PBTCA was firstly used as a depressant in magnesite/calcite flotation. • PBTCA could selectively inhibit calcite but not magnesite. • The inhibition mechanism of PBTCA was studied. • The stronger interaction of –PO 3 H 2 and Ca2+ was the main cause of inhibition. [ABSTRACT FROM AUTHOR]

Noble metal nanoparticles could provide a significant gain in sensitivity of surface plasmon resonance (SPR) sensor by electromagnetic field coupling between the localized plasmon resonance of nanoparticles and gold film. A facile and cost-effective SPR sensor based on magnetic field-aligned Fe 3 O 4 -coated silver magnetoplasmonic nanoparticles (Ag@MNPs) nanochain (M-Ag@MNPs) was proposed to improve the sensitivity of the sensor, which gave access to detect clinical targets at low concentration. Optimization experiments proved that 80 ng mL−1 M-Ag@MNPs-based SPR sensor showed high refractive index sensitivity and increased detection accuracy and quality factor when comparing with those of bare gold. Sialic acid binding Ig like lectins-15 (Siglec-15) was used as proof of concept to verify the sensitivity enhancement performance of M-Ag@MNPs in the actual detection process. SPR angle shifts of M-Ag@MNPs/gold sensor were significantly higher than those of traditional gold sensor under the same concentration of Siglec-15, which was consistent with previous performance analysis. Also, the detection limit of M-Ag@MNPs/gold sensor was calculated to be 1.36 pg mL−1. All these results had proved that aligning M-Ag@MNPs onto the gold chip could improve the performance of the SPR sensor and achieve sensitive detection of small amounts of clinical biomarkers. • A novel and facile biosensor based on M-Ag@MNPs was fabricated to detect Siglec-15 with low detection limit. • M-Ag@MNPs with enhanced electrochemical activities and SPR sensitivity was utilized. • The M-Ag@MNPs-based sensor provide a significant gain in RI S due to enhanced LSPR and high refractive index of Ag@MNPs. [ABSTRACT FROM AUTHOR]

Background: Destruxin A (DA) is a microbial insecticide with potent bioactivity against Spodoptera litura larvae. A previous proteomic analysis of S. litura (SL-1) cells exposed to DA showed the abnormal expression of wing disc-like protein of S. litura (SLAWD). To further understand the effect of DA on SLAWD expression, a functional study was carried out. Principal Findings: The SLAWD gene (SLAWD) was cloned and an open reading frame of 537 bp encoding a polypeptide of 178 amino acids was detected. Real-time fluorescence quantitative PCR (qRT-PCR) suggested that SLAWD is expressed in all developmental stages of S. litura, but expression was highest during the pupal and adult stages. RNAi knockdown of SLAWD expression in 6th-stage larvae was achieved by the microinjection of a specific double-stranded RNA (dsRNA). The results showed a significant decrease in SLAWD mRNA expression levels between the prepupal and adult stages. Interestingly, SLAWD expression was similarly down-regulated by treating 6th-stage larvae with DA. Growth- and development-related statistics confirmed the observed abnormalities in S. litura development after either RNAi or DA treatment. Conclusions: SLAWD appears to have a biosynthetic function in the pupal and adult stages of S. litura. The toxic effect of DA on S. litura development is due the negative effect of DA on SLAWD gene expression. [ABSTRACT FROM AUTHOR]

How is the characteristic shape of an organelle generated? Recent work has provided insight into how the tubular network of the endoplasmic reticulum (ER) is formed. The tubules themselves are shaped by the reticulons and DP1/Yop1p, whereas their fusion into a network is brought about by membrane-bound GTPases that include the atlastins, Sey1p, and RHD3. [Copyright &y& Elsevier]

Summary: The endoplasmic reticulum (ER) consists of tubules that are shaped by the reticulons and DP1/Yop1p, but how the tubules form an interconnected network is unknown. Here, we show that mammalian atlastins, which are dynamin-like, integral membrane GTPases, interact with the tubule-shaping proteins. The atlastins localize to the tubular ER and are required for proper network formation in vivo and in vitro. Depletion of the atlastins or overexpression of dominant-negative forms inhibits tubule interconnections. The Sey1p GTPase in S. cerevisiae is likely a functional ortholog of the atlastins; it shares the same signature motifs and membrane topology and interacts genetically and physically with the tubule-shaping proteins. Cells simultaneously lacking Sey1p and a tubule-shaping protein have ER morphology defects. These results indicate that formation of the tubular ER network depends on conserved dynamin-like GTPases. Since atlastin-1 mutations cause a common form of hereditary spastic paraplegia, we suggest ER-shaping defects as a neuropathogenic mechanism. [ABSTRACT FROM AUTHOR]

Programmed death ligand 1 (PD-L1) immune checkpoint has been regarded as a new target for predicting cancer immunotherapy. As a transmembrane protein, PD-L1 has very low blood concentration and is likely to deplete their native activity when separated from the membrane environment due to significant hydrophobic domains, which make it difficult to measure sensitively. The reported PD-L1 aptamers and antibodies are both extracellular region binding molecules with the overlapping binding sites, which seriously limit with the construction of biosensor. Specific intracellular binding peptide (SIBP) as a unique PD-L1 intracellular region homing probe molecule is utilized for specifically capture targets. A simple and sensitive surface plasmon resonance (SPR) sandwich assay was constructed to detect serum soluble PD-L1 (sPD-L1) based on the unique and strong binding ability of SIBP to the intracellular region of sPD-L1. The designed SPR sensor showed great selectivity and wide dynamic response range of sPD-L1 concentration from 10 ng/mL to 2000 ng/mL. The limit of detection was calculated to be 1.749 ng/mL (S/N = 3). Owing to the SIBP's strong and specific binding ability with sPD-L1, the sensitive sensor can successfully detect sPD-L1 in serum samples, paving the way for the development of efficient test tools for clinical diagnosis and analysis. • A serum sensor was constructed based on the PD-L1 specific intracellular binding peptide (SIBP) which was proposed. • SIBP eliminates the steric interference of most PD-L1 immune binding molecules during sandwich sensor assembly. • The SPR sensor based on SIBP's robust binding force has excellent clinical detection capability. [ABSTRACT FROM AUTHOR]

Summary: Grb14, a member of the Grb7 adaptor protein family, possesses a pleckstrin homology (PH) domain, a C-terminal Src homology-2 (SH2) domain, and an intervening stretch of ∼45 residues known as the BPS region, which is unique to this adaptor family. Previous studies have demonstrated that Grb14 is a tissue-specific negative regulator of insulin receptor signaling and that inhibition is mediated by the BPS region. We have determined the crystal structure of the Grb14 BPS region in complex with the tyrosine kinase domain of the insulin receptor. The structure reveals that the N-terminal portion of the BPS region binds as a pseudosubstrate inhibitor in the substrate peptide binding groove of the kinase. Together with the crystal structure of the SH2 domain, we present a model for the interaction of Grb14 with the insulin receptor, which indicates how Grb14 functions as a selective protein inhibitor of insulin signaling. [Copyright &y& Elsevier]

The adaptor protein APS is a substrate of the insulin receptor and couples receptor activation with phosphorylation of Cbl to facilitate glucose uptake. The interaction with the activated insulin receptor is mediated by the Src homology 2 (SH2) domain of APS. Here, we present the crystal structure of the APS SH2 domain in complex with the phosphorylated tyrosine kinase domain of the insulin receptor. The structure reveals a novel dimeric configuration of the APS SH2 domain, wherein the C-terminal half of each protomer is structurally divergent from conventional, monomeric SH2 domains. The APS SH2 dimer engages two kinase molecules, with pTyr-1158 of the kinase activation loop bound in the canonical phosphotyrosine binding pocket of the SH2 domain and a second phosphotyrosine, pTyr-1162, coordinated by two lysine residues in β strand D. This structure provides a molecular visualization of one of the initial downstream recruitment events following insulin activation of its dimeric receptor. [Copyright &y& Elsevier]

• Progesterone (P4) is secreted in sheep epididymis. • P4 moderately inhibits dihydrotestosterone secretion through its nuclear receptor. • P4 is involved in sperm maturation and functionality in sheep. Progesterone (P4) is an anti-androgen compound whose role in sperm maturation and functionality remains unclear in sheep. Here, we aimed to investigate the regulation mechanism of P4 on the epididymal secretion of dihydrotestosterone (DHT). To this end, we performed enzyme-linked immunosorbent assays, immunohistochemical staining, western blotting, and quantitative real-time polymerase chain reaction to detect P4 concentration as well as StAR, P450scc, and 3β-HSD expression in sheep epididymis. Besides, cauda epithelial cells were cultured at different concentrations of P4 (10-9–10-5 g ml−1) as well as with or without the P4 receptor (PGR) inhibitor RU486 (10-7 M) or the PI3K-AKT inhibitor LY294006 (10-7 M) to explore the effect of P4 on DHT secretion and the underlying regulatory mechanism. The results showed that the caput, corpus, and cauda of sheep epididymis could synthesize P4 but had different synthesis ability. The PGR expression levels were the highest in the cauda, followed by the corpus. In vitro cell culture showed that P4 inhibition of DHT secretion and 5α-reductase 1 and 2 expression in epididymal epithelial cells could be moderately mitigated by RU486 but not by LY294002. Our results indicated that the paracrine and autocrine P4 could affect the secretion of DHT in epididymal cells through PGR. Overall, this study provides new data regarding the involvement of P4 in sperm maturation and functionality in sheep. [ABSTRACT FROM AUTHOR]

Background: The diversity of histologic composition reflects the inter- and intra-tumor heterogeneity of lung adenocarcinomas (LUADs) macroscopically. Insights into the oncological characteristics and tumor microenvironment (TME) of different histologic subtypes of LUAD at the single-cell level can help identify potential therapeutic vulnerabilities and combinational approaches to improve the survival of LUAD patients.Methods: Through comparative profiling of cell communities defined by scRNA-seq data, we characterized the TME of LUAD samples of distinct histologic subtypes, with relevant results further confirmed in multiple bulk transcriptomic, proteomic datasets and an independent immunohistochemical validation cohort.Results: We find that the hypoxic and acidic situation is the worst in the TME of solid LUADs compared to other histologic subtypes. Besides, the tumor metabolic preferences vary across histologic subtypes and may correspondingly impinge on the metabolism and function of immune cells. Remarkably, tumor cells from solid LUADs upregulate energy and substance metabolic activities, particularly the folate-mediated one-carbon metabolism and the key gene MTHFD2, which could serve as a potential therapeutic target. Additionally, ubiquitination modifications may also be involved in the progression of histologic patterns. Immunologically, solid LUADs are characterized by a predominance of exhausted T cells and immunosuppressive myeloid cells, where the hypoxic, acidified and nutrient-deprived TME has a non-negligible impact. Discrepancies in stromal cell function, evidenced by varying degrees of stromal remodeling and fibrosis, may also contribute to the specific immune phenotype of solid LUADs.Conclusions: Overall, our research proposes several potential entry points to improve the immunosuppressive TME of solid LUADs, thereby synergistically potentiating their immunotherapeutic efficacy, and may provide precise therapeutic strategies for LUAD patients of distinct histologic subtype constitution. [ABSTRACT FROM AUTHOR]

Background: Stool DNA (sDNA) tests and fecal immunochemical test (FIT) are used for the detection of colorectal cancer (CRC). Here we performed a novel evaluation using sDNA and FIT to assess their performance in CRC screening and monitoring in Hubei, China.Methods: Stool samples were collected from a high-risk population in Hubei, China (n = 359). sDNA tests and FIT were performed to test for KRAS mutations, NDRG4 and BMP3 methylation, and check hemoglobin levels. The methylation in BMP3 and NDRG4 genes was detected by TaqMan PCR method from human fecal samples. KRAS gene mutation in human fecal DNA was tested using TaqMan probe and amplification-refractory mutation system method. The colloid gold method was used for detection of hemoglobin in fecal samples. Finally, a novel evaluation by software was used to calculate the comprehensive value of the combined results for CRC detection and monitoring.Results: The sensitivity and specificity of the novel evaluation for early CRC (stage I and II), advanced adenoma (AA), and non-colon cancer neoplasm (NA) detection were 95.45% and 81.6%, 29.63% and 75.9%, and 23.08% and 75.17%, respectively. The receiver operating characteristic (ROC) curves of the combined value for the above diseases were 0.945 ± 0.015, 0.543 ± 0.055, and 0.547 ± 0.038, respectively. The levels of the novel evaluation were not significantly associated with the pathology and stage (P > 0.05). In 20 out of 22 CRC patients, the novel evaluation of sDNA and FIT had decreased below threshold (< 165) at after surgery.Discussion: The novel evaluation with sDNA test and FIT has increased sensitivity for screening of CRC and AA. The novel evaluation may have potential importance as an indicator of early CRC. Additionally, the dynamic changes of the comprehensive value after surgery were correlated with CRC treatment. [ABSTRACT FROM AUTHOR]

Underwater wet welding processes with minimal energy consumption and high efficiency is the future goal for researchers in the field. Al/CuO exothermic mixtures in consumables for land welding process can improve welding process stability and decrease the electrical dependence of the welding process. To confirm the beneficial effects of Al/CuO thermite and gain a better understanding of metallurgical properties of the thermite welds in underwater environment, this study investigated underwater wet self-shielded flux-cored arc welding (FCAW-S) of high-strength low-alloy steel with highly exothermic Al/CuO mixture. The effects of Al/CuO thermite on arc stability, weld metallurgical behavior and melting characteristics of flux-cored wire were clarified. The ratio of chemical heat in the flux to the heat required to melt welding wire increased from 4.7 % to 38.4 % with the addition of Al/CuO, potentially accelerating the melting of flux-cored wires. The arc stability with thermite addition was superior to that without the addition of thermite. The presence of copper as a result of metallurgical reactions had a substantial impact on metallurgical behavior of underwater wet welds. The ferrite weld was a non-equilibrium Cu supersaturated solid solution, which increased the microhardness and tensile strength of wet welds. The measured cooling time proved that the incorporation of Al/CuO had the capacity to reduce cooling rate. The incorporation of 50 wt% thermite yielded a 7.8 % increase in welding process efficiency compared to the base formulation. Current work provided an important direction for the development of a chemically self-heating flux-cored wire. [Display omitted] • High-strength low-alloy steel was welded using flux-cored wire with Al/CuO mixture. • The Al/CuO mixture changed metallurgical behavior of underwater wet welds. • The incorporation of Al/CuO had the capacity to reduce the cooling rate. • The Al/CuO addition to the flux-cored wire increased arc process efficiency. [ABSTRACT FROM AUTHOR]

The detection probability of underwater weak targets using active sonar is low, and inter-pulse coherent integration can improve the signal-to-noise ratio of echoes. When a target executes a maneuvering turn, complex range and Doppler frequency migrations occur during the coherent integration time that decrease the coherent integration gain. Most existing integration methods simplify the target motion to a finite-order polynomial model but fail to integrate a maneuvering turning target (MTT) due to model mismatch. Hence, this study proposes an underwater MTT integration method based on the modified Radon-Fourier transform. The proposed method constructs a theoretically accurate motion model for the MTT and a phase compensation function to compensate for the Doppler frequency migration. Furthermore, it yields a well-focused integration peak in the range-velocity and offset angle-turn rate dimensions and accurately estimates the target motion parameters. Moreover, the proposed method is suitable for targets with radial and oblique uniform motions. The effectiveness of the proposed method is demonstrated through simulations and a lake test. The proposed method demonstrates good integration performance, with an integration gain approximately 4–7 dB higher than that of traditional methods when using 30 integration pulses. [ABSTRACT FROM AUTHOR]

The northeastern periphery of the Qaidam Basin is a crucial region for comprehending the northeastward growth of the Tibetan Plateau, as it documents Late Cenozoic crustal deformation that elucidates the plateau's growth process. In this study, we reconstruct three stages of crustal deformation in the northeastern periphery of the Qaidam Basin during the Late Cenozoic based on interpretation of growth strata from five seismic profiles, structural mapping of the typical superimposed folds and detailed detrital zircon analysis within the study area. (1) During the Early Miocene to Late Miocene period (23–8.6 Ma), there was NW–SE extensional deformation in the northeast margin of the Qaidam Basin, which exerted control over the deposition of the Youshashan Formation. (2) The NW–SE shortening occurred during the Late Miocene period (8.6–8.1 Ma), subsequent to the deposition of the Youshashan Formation and preceding the deposition of the Shizigou Formation, resulting in a parallel unconformity between these two geological units. (3) The intense shortening of the NE–SW direction occurred during the Late Miocene and Pliocene epochs (8.1–2.5 Ma). The timing of this deformation aligns with the sedimentary age of the Shizigou Formation, suggesting that the initial deformation age may represent the onset of NE extrusion from the Tibetan Plateau towards the northeast margin of the Qaidam Basin. The present study not only delineates a Late Cenozoic structural dome resulting from two‐stage crustal shortening in the northeastern periphery of the Tibetan Plateau, but also provides a crucial evidence for reconstructing the Late Cenozoic intracontinental deformation process in this region. [ABSTRACT FROM AUTHOR]