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Purpose: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function. Methods: We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Mouse body composition was assessed using dual-energy X-ray absorptiometry. Mouse lung function was measured using flexiVent. Results: Contrary to prior publications, the KO was not neonatal lethal. KO mice had lower body weight and shorter tibial length than wild-type (WT) mice. Their body composition revealed lower soft weight, fat weight, and bone mineral content. Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways. Conclusion: Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function. [ABSTRACT FROM AUTHOR]

Ferroptosis is an important pathological mechanism of chronic heart failure (CHF). This study aimed to investigate the protective mechanism of Astragaloside IV (AS-IV) on CHF rats by integrating bioinformatics and ferroptosis. CHF-related targets and ferroptosis-related targets were collected. After the intersection, the common targets were obtained. The PPI network of the common targets was constructed, and topological analysis of the network was carried out. The target with the highest topological parameter values was selected as the key target. The key target p53 was obtained through bioinformatics analysis, and its molecular docking model with AS-IV was obtained, as well as molecular dynamics simulation analysis. The rat models of CHF after myocardial infarction were established by ligation of left coronary artery and treated with AS-IV for 4 weeks. AS-IV treatment significantly improved cardiac function in CHF rats, improved cardiomyocyte morphology and myocardial fibrosis, reduced mitochondrial damage, decreased myocardial MDA and Fe2+ content, increased GSH content, inhibited the expression of p53 and p-p53, and up-regulated the expression of SLC7A11 and GPX4. In conclusion, AS-IV improved cardiac function in CHF rats, presumably by regulating p53/SLC7A11/GPX4 signaling pathway and inhibiting myocardial ferroptosis. [ABSTRACT FROM AUTHOR]

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Interfacial compatibilization of polylactide/ethylene-methyl acrylate-glycidyl methacrylate random terpolymer (PLA/EG-MA) incompatible blends is crucial for fabricating super-tough PLA materials. To regulate and control the interfacial reaction and adhesion between PLA and EG-MA, 1-carboxymethyl-3-methylimidazole bromide salt (ILs) was selected as an interfacial compatibilizer and controller for PLA/EG-MA blends. Morphologies, crystallization, and relaxation behaviors of the blends were systematically investigated. The results proved that the reaction between the end groups of PLA and the epoxy groups of EG-MA could be catalyzed by carboxyl-functionalized ILs. The phase morphology structure of blends changed from sea-island to co-continuous structure with the increase of ILs. Notably, the impact strength and elongation at break of the PLA/EG-MA/2ILs blend reached 67 kJ/m2 and 284%, respectively, which is a 71 and 22 fold increase caused by the formation of interfacial crosslinking. Vigorous interfacial adhesion obviously increased the crystallinity and induced co-continuous morphology, which triggered massive shear yielding. Super-tough PLA blends were easily fabricated owing to the interfacial catalytic crosslinking of carboxyl-functionalized ILs. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the most common malignancies and a leading cause of death in men. Owing to its excellent anti-tumor effects, androgen deprivation therapy (ADT) is widely used in the treatment of prostate cancer. However, its use is controversial because of its potential for inducing cognitive decline. In this review, we summarized the findings of preclinical and clinical studies investigating the effects of ADT on cognitive function in prostate cancer. We discussed the methods used to assess cognitive function in these studies, elucidated the mechanisms through which ADT affects cognitive function, and highlighted recent advancements in cognitive assessment methods. The findings of this review serve as a valuable reference for examining the relationship between ADT and cognitive function in future studies. Besides, the findings may help clinicians understand the advantages and disadvantages of ADT and optimize the treatment plan so as to minimize the adverse effects of ADT. [ABSTRACT FROM AUTHOR]

Ganoderma lucidum (GL) is a prominent medicinal mushroom in traditional Chinese medicine, known for its potent antitumor properties. This study aimed to illustrate the efficacy of GL extracts (GLE) on treating endometrial cancer (EC) and explore the underlying mechanisms via network pharmacology and experimental validation. Network pharmacological analysis was conducted to explore the therapeutic efficacy and mechanisms of GL on EC. In vitro experimental validation was performed on human endometrial cancer cell lines HEC-1-A and KLE. Network pharmacology revealed that key targets of GL against EC were primarily associated with the Rap1 signaling pathway. In in vitro experiments, GLE or GGTI-298 (a GTPase inhibitor) treatment inhibited cell proliferation and migration, promoted cell apoptosis, increased caspase-3 level, and arrested cell cycle in G1 phase in HEC-1-A and KLE cells. GLE increased the protein expression of Rap1-GTP, p-AKT, and p-ERK2 in HEC-1-A and KLE cells. Moreover, GGTI-298 enhanced the effects of GLE on suppressing the malignant progression of EC cells and on activating Rap1 signaling pathway. GLE inhibited the malignant progression of EC cells probably via activating the Rap1 signaling pathway. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the existence and uniqueness of the S-asymptotically ω -periodic mild solutions to a class of multi-term time-fractional measure differential equations with nonlocal conditions in an ordered Banach spaces. Firstly, we look for suitable concept of S-asymptotically ω -periodic mild solution to our concern problem, by means of Laplace transform and (β , γ k) -resolvent family { S β , γ k (t) } t ≥ 0 . Secondly, we construct monotone iterative method in the presence of the lower and upper solutions to the delayed fractional measure differential equations, and obtain the existence of maximal and minimal S-asymptotically ω -periodic mild solutions for the mentioned system. Finally, as the application of abstract results, an example is given to illustrate our main results. [ABSTRACT FROM AUTHOR]

Background: Medication burden and complexity have been longstanding problems in chronically ill patients. However, more data are needed on the extent and impact of medication burden and complexity in the transfusion-dependent thalassaemia population. Aim: The aim of this study was to determine the characteristics of medication complexity and polypharmacy and determine their relationship with drug-related problems (DRP) and control of iron overload in transfusion-dependent thalassaemia patients. Method: Data were derived from a cross-sectional observational study on characteristics of DRPs conducted at a Malaysian tertiary hospital. The medication regimen complexity index (MRCI) was determined using a validated tool, and polypharmacy was defined as the chronic use of five or more medications. The receiver operating characteristic curve analysis was used to determine the optimal cut-off value for MRCI, and logistic regression analysis was conducted. Results: The study enrolled 200 adult patients. The MRCI cut-off point was proposed to be 17.5 (Area Under Curve = 0.722; sensitivity of 73.3% and specificity of 62.0%). Approximately 73% and 64.5% of the patients had polypharmacy and high MRCI, respectively. Findings indicated that DRP was a full mediator in the association between MRCI and iron overload. Conclusion: Transfusion-dependent thalassaemia patients have high MRCI and suboptimal control of iron overload conditions in the presence of DRPs. Thus, future interventions should consider MRCI and DRP as factors in serum iron control. [ABSTRACT FROM AUTHOR]

In this paper, we study the asymptotic properties for the drift parameter estimators in the fractional Ornstein-Uhlenbeck process with periodic mean function and long range dependence. The Cremér-type moderate deviations, as well as the moderation deviation principle with explicit rate function can be obtained. [ABSTRACT FROM AUTHOR]

Data-driven garment animation is a current topic of interest in the computer graphics industry. Existing approaches generally establish the mapping between a single human pose or a temporal pose sequence, and garment deformation, but it is difficult to quickly generate diverse clothed human animations. We address this problem with a method to automatically synthesize dressed human animations with temporal consistency from a specified human motion label. At the heart of our method is a two-stage strategy. Specifically, we first learn a latent space encoding the sequence-level distribution of human motions utilizing a transformer-based conditional variational autoencoder (Transformer-CVAE). Then a garment simulator synthesizes dynamic garment shapes using a transformer encoder–decoder architecture. Since the learned latent space comes from varied human motions, our method can generate a variety of styles of motions given a specific motion label. By means of a novel beginning of sequence (BOS) learning strategy and a self-supervised refinement procedure, our garment simulator is capable of efficiently synthesizing garment deformation sequences corresponding to the generated human motions while maintaining temporal and spatial consistency. We verify our ideas experimentally. This is the first generative model that directly dresses human animation. [ABSTRACT FROM AUTHOR]

Purpose: PD-1 targeted immunotherapy has imparted a survival benefit to advanced head and neck squamous cell carcinoma (HNSCC), but less than 20% patients produce a durable response to this therapy. Here we aimed to investigate the potential biomarkers for predicting the clinical outcome and resistance to PD-1 targeted immunotherapy in HNSCC patients, and to examine the involvement of FAP+ cancer-associated fibroblasts (CAFs). Methods: Bioinformatics methods were applied to analyze multiple datasets and explore the role of PD-1 and FAP in HNSCC. Immunohistochemistry was used to detect the expression of FAP protein. Fap gene knockout mice (Fap−/−) and L929 cells with different levels of Fap overexpression (L929-Fap-Low/High) were established to demonstrate the role of FAP+ CAFs in tumor development and immune checkpoint blockade (ICB) resistance. Results: The expression level of PD-1 gene was positively correlated with better overall survival and therapeutic response to PD-1 blockade in HNSCC, but not all tumors with high expression of both PD-1 and PD-L1 were responsive. Moreover, FAP gene was overexpressed in pan-cancer tissues, and could serve as a prognostic biomarker for several cancers, including HNSCC. However, FAP protein was undetectable in mouse MTCQ1 tumors and barely expressed in human HNSCC tumors. Furthermore, FAP+ CAFs did not promote tumor growth or enhance the resistance to PD-1 inhibitor treatment. Conclusion: Although FAP+ CAFs have attracted increasing attention for their role in cancer, the feasibility and efficacy of FAP-targeting therapies for HNSCC remain doubtful. [ABSTRACT FROM AUTHOR]

Background: Data on the long-term oncological outcomes of patients who undergo conversion surgery (CS) in gastric cancer (GC) patients with peritoneal metastasis (PM) are limited. Methods: GC patients with PM who received intraperitoneal (ip) and systemic chemotherapy between April 2015 and January 2021 were enrolled. Multivariate analysis was performed to identify risk factors associated with survival. Clinicopathological and survival outcomes were compared between those with CS and those without CS (NCS). The paclitaxel (PTX) plus tegafur–gimeracil–oteracil potassium capsules (S-1) (PS) + ip PTX and oxaliplatin plus S-1 (SOX) + ip PTX groups were matched in a 1:1 ratio using propensity score matching. Oncological and survival data were collected and analyzed. Results: A total of 540 patients who received ip chemotherapy via subcutaneous port and systemic chemotherapy were analyzed and 268 patients were enrolled, including 113 who underwent CS and 155 who did not. Overall survival (OS) were 27.0 months and 11.8 months in the CS and NCS groups (P < 0.0001), respectively. R0 resection was an independent prognostic factor for patients who underwent CS. The OS of patients with or without ovariectomy was 21.3 or 12.0 months (P < 0.0001). No difference of clinicopathological and survival outcomes was found between the PS + ip PTX and SOX + ip PTX groups. Conclusion: Conversion therapy is safe and adverse events were manageable. CS improves the survival of GC patients with PM after ip and systemic chemotherapy. R0 is an important prognostic factor. Furthermore, outcomes are comparable between the PS + ip PTX and SOX + ip PTX groups. [ABSTRACT FROM AUTHOR]

Baccaurea ramiflora Lour., an evergreen tree of the Baccaurea genus of the Phyllanthaceae family, is primarily distributed in South Asia, Southeast Asia, and southern China, including southern Yunnan Province. It is a wild or semi-cultivated tree species with ornamental, edible, and medicinal value, exhibiting significant development potential. In this study, we present the whole-genome sequencing of B. ramiflora, employing a combination of PacBio SMRT and Illumina HiSeq 2500 sequencing techniques. The assembled genome size was 975.8 Mb, with a contig N50 of 509.33 kb and the longest contig measuring 7.74 Mb. The genome comprises approximately 73.47% highly repetitive sequences, of which 52.1% are long terminal repeat–retrotransposon sequences. A total of 29,172 protein-coding genes were predicted, of which 25,980 (89.06%) have been annotated, Additionally, 3452 non-coding RNAs were identified. Comparative genomic analysis revealed a close relationship between B. ramiflora and the Euphorbiaceae family, with both being sister groups that diverged approximately 59.9 million years ago. During the evolutionary process, B. ramiflora exhibited positive selection in 278 candidate genes. Synonymous substitution rate and collinearity analysis demonstrated that B. ramiflora underwent a single ancient genome-wide triploidization event, without recent genome-wide duplication events. This high-quality B. ramiflora genome provides a valuable resource for basic research and tree improvement programs focusing on the Phyllanthaceae family. [ABSTRACT FROM AUTHOR]

The diagnosis of leukemic T-cell malignancies is often challenging, due to overlapping features with reactive T-cells and limitations of currently available T-cell clonality assays. Recently developed therapeutic antibodies specific for the mutually exclusive T-cell receptor constant β chain (TRBC)1 and TRBC2 isoforms provide a unique opportunity to assess for TRBC-restriction as a surrogate of clonality in the flow cytometric analysis of T-cell neoplasms. To demonstrate the diagnostic utility of this approach, we studied 164 clinical specimens with (60) or without (104) T-cell neoplasia, in addition to 39 blood samples from healthy donors. Dual TRBC1 and TRBC2 expression was studied within a comprehensive T-cell panel, in a fashion similar to the routine evaluation of kappa and lambda immunoglobulin light chains for the detection of clonal B-cells. Polytypic TRBC expression was demonstrated on total, CD4+ and CD8+ T-cells from all healthy donors; and by intracellular staining on benign T-cell precursors. All neoplastic T-cells were TRBC-restricted, except for 8 cases (13%) lacking TRBC expression. T-cell clones of uncertain significance were identified in 17 samples without T-cell malignancy (13%) and accounted for smaller subsets than neoplastic clones (median: 4.7 vs. 69% of lymphocytes, p < 0.0001). Single staining for TRBC1 produced spurious TRBC1-dim subsets in 24 clinical specimens (15%), all of which resolved with dual TRBC1/2 staining. Assessment of TRBC restriction by flow cytometry provides a rapid diagnostic method to detect clonal T-cells, and to accurately determine the targetable TRBC isoform expressed by T-cell malignancies. [ABSTRACT FROM AUTHOR]

Ketogenic diet (KD) alleviates refractory epilepsy and reduces seizures in children. However, the metabolic/cell biologic mechanisms by which the KD exerts its antiepileptic efficacy remain elusive. Herein, we report that KD-produced β-hydroxybutyric acid (BHB) augments brain gamma-aminobutyric acid (GABA) and the GABA/glutamate ratio to inhibit epilepsy. The KD ameliorated pentetrazol-induced epilepsy in mice. Mechanistically, KD-produced BHB, but not other ketone bodies, inhibited HDAC1/HDAC2, increased H3K27 acetylation, and transcriptionally upregulated SIRT4 and glutamate decarboxylase 1 (GAD1). BHB-induced SIRT4 de-carbamylated and inactivated glutamate dehydrogenase to preserve glutamate for GABA synthesis, and GAD1 upregulation increased mouse brain GABA/glutamate ratio to inhibit neuron excitation. BHB administration in mice inhibited epilepsy induced by pentetrazol. BHB-mediated relief of epilepsy required high GABA level and GABA/glutamate ratio. These results identified BHB as the major antiepileptic metabolite of the KD and suggested that BHB may serve as an alternative and less toxic antiepileptic agent than KD. [ABSTRACT FROM AUTHOR]

To observe the expression changes of P2 protein in cochlear spiral ganglion cells before and after noise injury, and to explore the relationship between the changes of purinergic receptors in spiral ganglion cells and noise-induced hearing loss, so that the signal transduction of purinergic receptors can be used to treat SNHL The target point provides a theoretical basis. The experimental animals were randomly divided into normal and experimental groups. The experimental group was given 120 dB white noise continuous exposure for 10 days and 3 h a day. The auditory brainstem response was measured before and after the noise exposure. After the noise exposure, the two groups of animals were collected. Do immunofluorescence staining, western blot, fluorescence real-time quantitative PCR to observe the expression of P2 protein. The average hearing threshold of the animals in the experimental group increased to 38.75 ± 6.44 dB SPL after 7 days of noise exposure, and the high-frequency hearing loss was lower and severe; the average hearing threshold increased to 54.38 ± 6.80 dB SPL after 10 days of noise exposure, and the hearing loss at 4 k Hz was relatively high. Light; Frozen sections of cochlear spiral ganglion cells and staining of isolated spiral ganglion cells found that P2X2, P2X3, P2X4, P2X7, P2Y2, and P2Y4 proteins were all expressed in cochlear spiral ganglion cells before noise exposure. Among them, P2X3 expression increased and P2X4, the down-regulation of P2Y2 expression was statistically significant (P < 0.05); Western blot and real-time quantitative PCR detection results showed that the expression of P2X3 was significantly increased after noise exposure than before noise exposure (P < 0.05), and P2X4 and P2Y2 were expressed after noise exposure The amount was significantly lower than before noise exposure (P < 0.05). (Figure. 4). After noise exposure, the expression of P2 protein is upregulated or downregulated. By affecting the Ca2+ cycle, the transmission of sound signals to the auditory center is blocked, which provides a theoretical basis for the signal transduction of purinergic receptors to become a target for the treatment of SNHL. [ABSTRACT FROM AUTHOR]

Abstract The approval of bedaquiline has placed energy metabolism in the limelight as an attractive target space for tuberculosis antibiotic development. While bedaquiline inhibits the mycobacterial F1F0 ATP synthase, small molecules targeting other components of the oxidative phosphorylation pathway have been identified. Of particular interest is Telacebec (Q203), a phase 2 drug candidate inhibitor of the cytochrome bcc:aa3 terminal oxidase. A functional redundancy between the cytochrome bcc:aa3 and the cytochrome bd oxidase protects M. tuberculosis from Q203‐induced death, highlighting the attractiveness of the bd‐type terminal oxidase for drug development. Here, we employed a facile whole‐cell screen approach to identify the cytochrome bd inhibitor ND‐011992. Although ND‐011992 is ineffective on its own, it inhibits respiration and ATP homeostasis in combination with Q203. The drug combination was bactericidal against replicating and antibiotic‐tolerant, non‐replicating mycobacteria, and increased efficacy relative to that of a single drug in a mouse model. These findings suggest that a cytochrome bd oxidase inhibitor will add value to a drug combination targeting oxidative phosphorylation for tuberculosis treatment.

The given text is a study published in the Blood Cancer Journal that explores the phenomenon of lineage switch in leukemia, where cells change from one lineage to another. The study includes 33 cases of acute leukemia that underwent lineage switch and provides valuable insights into the clinicopathological features and genetic drivers of this event. The findings suggest that certain risk factors, such as specific genetic abnormalities and the presence of a previous chronic myeloid malignancy, may increase the likelihood of lineage switch. The study emphasizes the importance of early detection and potential benefits of early allogeneic stem cell transplant in these cases, while also highlighting the need for further research to develop preventive and therapeutic strategies. [Extracted from the article]

Structural biology efforts using cryogenic electron microscopy are frequently stifled by specimens adopting "preferred orientations" on grids, leading to anisotropic map resolution and impeding structure determination. Tilting the specimen stage during data collection is a generalizable solution but has historically led to substantial resolution attenuation. Here, we develop updated data collection and image processing workflows and demonstrate, using multiple specimens, that resolution attenuation is negligible or significantly reduced across tilt angles. Reconstructions with and without the stage tilted as high as 60° are virtually indistinguishable. These strategies allowed the reconstruction to 3 Å resolution of a bacterial RNA polymerase with preferred orientation, containing an unnatural nucleotide for studying novel base pair recognition. Furthermore, we present a quantitative framework that allows cryo-EM practitioners to define an optimal tilt angle during data acquisition. These results reinforce the utility of employing stage tilt for data collection and provide quantitative metrics to obtain isotropic maps. Here, the authors quantify the effect of cryo-EM data acquisition with stage-tilt on the global resolution of reconstructions and present a tool for predicting an optimal stage-tilt angle to ameliorate the effects of preferred specimen orientation. [ABSTRACT FROM AUTHOR]

Severe trauma could induce sepsis due to the loss of control of the infection, which may eventually lead to death. Accurate and timely diagnosis of sepsis with severe trauma remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis. We compared the diagnostic characteristics of routinely used biomarkers of sepsis alone and in combination, trying to define a biomarker panel to predict sepsis in severe patients. This prospective observational study included patients with severe trauma (Injury severity score, ISS = 16 or more) in the emergency intensive care unit (EICU) at a university hospital. Blood samples were collected and plasma levels of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. A total of 100 patients were eligible for analysis. Of these, 52 were diagnosed with sepsis. CRP yielded the highest discriminative value followed by PCT. In multiple logistic regression, SAA, CRP, and PCT were found to be independent predictors of sepsis. Bioscore which was composed of SAA, CRP, and PCT was shown to be far superior to that of each individual biomarker taken individually. Therefore, compared with single markers, the biomarker panel of PCT, CRP, and SAA was more predictive of sepsis in severe polytrauma patients. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the performances of the various estimated glomerular filtration rate (eGFR) equations of the Chronic Kidney Disease Epidemiology Collaboration, the Berlin Initiative Study (BIS), and the Full Age Spectrum (FAS) in older Chinese. Methods: This study enrolled Chinese adults aged ≥ 65 years who underwent GFR measurements (via 99Tcm-DTPA renal dynamic imaging) in our hospital from 2011 to 2022. Using the measured glomerular filtration rate (mGFR) as the reference, we derived the bias, precision, accuracy, and consistency of each equation. Results: We enrolled 519 participants, comprising 155 with mGFR ≥ 60 mL/min/1.73 m2 and 364 with mGFR < 60 mL/min/1.73 m2. In the total patients, the BIS equation based on creatinine and cystatin C (BIScr-cys) exhibited the lowest bias [median (95% confidence interval): 1.61 (0.77–2.18)], highest precision [interquartile range 11.82 (10.32–13.70)], highest accuracy (P30: 81.12%), and best consistency (95% limit of agreement: 101.5 mL/min/1.73 m2). In the mGFR ≥ 60 mL/min/1.73 m2 subgroup, the BIScr-cys and FAS equation based on creatinine and cystatin C (FAScr-cys) performed better than the other equations; in the mGFR < 60 mL/min/1.73 m2 subgroup, all equations exhibited relatively large deviations from the mGFR. Of all eight equations, the BIScr-cys performed the best. Conclusions: Although no equation was fully accurate in the mGFR < 60 mL/min/1.73 m2 subgroup, the BIScr-cys (of the eight equations) assessed the eGFRs of the entire population best. A new equation is urgently required for older Chinese and even East Asians, especially those with moderate-to-severe renal insufficiency. [ABSTRACT FROM AUTHOR]

Increased circulating amino acid levels have been linked to insulin resistance and development of type 2 diabetes (T2D), but the underlying mechanism remains largely unknown. Herein, we show that tryptophan modifies insulin receptor (IR) to attenuate insulin signaling and impair glucose uptake. Mice fed with tryptophan-rich chow developed insulin resistance. Excessive tryptophan promoted tryptophanyl-tRNA synthetase (WARS) to tryptophanylate lysine 1209 of IR (W-K1209), which induced insulin resistance by inhibiting the insulin-stimulated phosphorylation of IR, AKT, and AS160. SIRT1, but not other sirtuins, detryptophanylated IRW−K1209 to increase the insulin sensitivity. Collectively, we unveiled the mechanisms of how tryptophan impaired insulin signaling, and our data suggested that WARS might be a target to attenuate insulin resistance in T2D patients. [ABSTRACT FROM AUTHOR]

This paper aims to use the unified bubble dynamics equation to investigate bubble behavior in complex scenarios involving hybrid free surface/wall boundaries and interactions between multiple bubbles. The effect of singularity movement on the unified equation's form is analyzed after deriving the bubble pulsation equation using a moving point source and a dipole, followed by discussions on the effect of migration compressibility-related terms on the bubble dynamics. In addition, the present study accounts for the impact of hybrid boundaries, including crossed and parallel boundaries, by introducing a finite number of mirror bubbles for the former and an infinite number of mirror bubbles for the latter. Spark bubble experiments and numerical simulation are conducted to validate the present theory. The application of the unified equation in multi-bubble interactions is exemplified by computing a spherical bubble array containing more than 100 uniformly distributed cavitation bubbles under different boundary conditions. The bubble cluster-induced pressure peak can reach nearly two times or even higher than that of an individual bubble, highlighting the damage potential caused by cavitation bubble clusters. [ABSTRACT FROM AUTHOR]

While originally designed for natural language processing tasks, the self-attention mechanism has recently taken various computer vision areas by storm. However, the 2D nature of images brings three challenges for applying self-attention in computer vision: (1) treating images as 1D sequences neglects their 2D structures; (2) the quadratic complexity is too expensive for high-resolution images; (3) it only captures spatial adaptability but ignores channel adaptability. In this paper, we propose a novel linear attention named large kernel attention (LKA) to enable self-adaptive and long-range correlations in self-attention while avoiding its shortcomings. Furthermore, we present a neural network based on LKA, namely Visual Attention Network (VAN). While extremely simple, VAN achieves comparable results with similar size convolutional neural networks (CNNs) and vision transformers (ViTs) in various tasks, including image classification, object detection, semantic segmentation, panoptic segmentation, pose estimation, etc. For example, VAN-B6 achieves 87.8% accuracy on ImageNet benchmark, and sets new state-of-the-art performance (58.2 PQ) for panoptic segmentation. Besides, VAN-B2 surpasses Swin-T 4 mIoU (50.1 vs. 46.1) for semantic segmentation on ADE20K benchmark, 2.6 AP (48.8 vs. 46.2) for object detection on COCO dataset. It provides a novel method and a simple yet strong baseline for the community. The code is available at https://github.com/Visual-Attention-Network. [ABSTRACT FROM AUTHOR]

Synthesizing garment dynamics according to body motions is a vital technique in computer graphics. Physics-based simulation depends on an accurate model of the law of kinetics of cloth, which is time-consuming, hard to implement, and complex to control. Existing data-driven approaches either lack temporal consistency, or fail to handle garments that are different from body topology. In this paper, we present a motion-inspired real-time garment synthesis workflow that enables high-level control of garment shape. Given a sequence of body motions, our workflow is able to generate corresponding garment dynamics with both spatial and temporal coherence. To that end, we develop a transformerbased garment synthesis network to learn the mapping from body motions to garment dynamics. Frame-level attention is employed to capture the dependency of garments and body motions. Moreover, a post-processing procedure is further taken to perform penetration removal and auto-texturing. Then, textured clothing animation that is collision-free and temporally-consistent is generated. We quantitatively and qualitatively evaluated our proposed workflow from different aspects. Extensive experiments demonstrate that our network is able to deliver clothing dynamics which retain the wrinkles from the physics-based simulation, while running 1 000 times faster. Besides, our workflow achieved superior synthesis performance compared with alternative approaches. To stimulate further research in this direction, our code will be publicly available soon. [ABSTRACT FROM AUTHOR]

PPARα corepressor NCoR1 is a key regulator of fatty acid β-oxidation and ketogenesis. However, its regulatory mechanism is largely unknown. Here, we report that oncoprotein p21-activated kinase 4 (PAK4) is an NCoR1 kinase. Specifically, PAK4 phosphorylates NCoR1 at T1619/T2124, resulting in an increase in its nuclear localization and interaction with PPARα, thereby repressing the transcriptional activity of PPARα. We observe impaired ketogenesis and increases in PAK4 protein and NCoR1 phosphorylation levels in liver tissues of high fat diet-fed mice, NAFLD patients, and hepatocellular carcinoma patients. Forced overexpression of PAK4 in mice represses ketogenesis and thereby increases hepatic fat accumulation, whereas genetic ablation or pharmacological inhibition of PAK4 exhibites an opposite phenotype. Interestingly, PAK4 protein levels are significantly suppressed by fasting, largely through either cAMP/PKA- or Sirt1-mediated ubiquitination and proteasome degradation. In this way, our findings provide evidence for a PAK4-NCoR1/PPARα signaling pathway that regulates fatty acid β-oxidation and ketogenesis. PPARα corepressor NCoR1 is a key regulator of fatty acid β-oxidation and ketogenesis. Here, the authors demonstrate that p21-activated kinase 4 phosphorylates NCoR1 at T1619/T2124, resulting in PPARα transrepression and ketone body reduction. [ABSTRACT FROM AUTHOR]

Studies have confirmed that hepatic iron overload is one of the important factors causing liver damage in the metabolic syndrome (MS). As a special form of autophagy, ferritinophagy is involved in the regulation of iron metabolism. Our previous studies have shown that chronic intermittent hypobaric hypoxia (CIHH) can improve the iron metabolism disorder. The aim of this study was to investigate how CIHH improves liver damage through ferritinophagy in MS rats. Male Sprague–Dawley rats aged 8–10 weeks were randomly divided into four groups: control (CON), CIHH (exposed to hypoxia at a simulated altitude of 5000 m for 28 days, 6 h daily), MS model (induced by a 16-week high-fat diet and 10% fructose water feeding), and MS + CIHH (exposed to CIHH after a 16-week MS inducement) groups. Liver index, liver function, iron content, tissue morphology, oxidative stress, ferritinophagy, ferroptosis, and iron metabolism-related protein expression were measured, and the ferritinophagy flux in the liver was further analyzed. Compared with CON rats, MS rats had an increased liver index, damaged liver tissue and function, increased iron content and iron deposition, disrupted iron metabolism, significantly increased oxidative stress indicators in the liver, significantly upregulated expression of ferroptosis-related proteins, and downregulated expression of nuclear receptor coactivator 4 (NCOA4) and ferritinophagy flux. After CIHH treatment, the degree of liver damage and various abnormal indicators in MS rats were significantly improved. CIHH may improve liver damage by promoting NCOA4-mediated ferritinophagy, reducing iron overload and oxidative stress, and thereby alleviating ferroptosis in MS rats. [ABSTRACT FROM AUTHOR]

Deep neural networks have greatly facilitated the applications of semantic segmentation. However, most of the existing neural networks bring massive calculations with lots of model parameters for achieving a higher precision, which is unaffordable for resource-constrained edge devices. To achieve an appropriate trade-off between computing efficiency and segmentation accuracy, we proposed an effective lightweight attention-guided network (ELANet) for real-time semantic segmentation based on an asymmetrical encoder–decoder framework in this work. In the encoding phase, we combined atrous convolution and depth-wise convolution to design two types of effective context guidance blocks to learn contextual semantic information. A refined feature fusion module with a dual attention-guided fusion (DAF) unit was developed in the decoder to exploit different levels of features. Without any pretraining, we estimated the performance of multi-attention ELANet with extensive experiments on the Cityscapes dataset with an input resolution of 512 × 1024, resulting in 75.4% mIoU and 83 FPS inference speed with only 0.76 M parameters and 10.34 GFLOPs on a single 3090 GPU. The code is publicly available at https://github.com/DGS666/ELANet. [ABSTRACT FROM AUTHOR]

Land subsidence is a geohazard phenomenon caused by the lowering of land elevation due to the compression of the sinking land soil body, thus creating an excessive constraint on the safe construction and sustainable development of cities. The use of accurate and efficient means for land subsidence prediction is of remarkable importance for preventing land subsidence and ensuring urban safety. Although the current time-series prediction method can accomplish relatively high accuracy, the predicted settlement points are independent of each other, and the existence of spatial dependence in the data itself is lost. In order to unlock this problem, a spatial convolutional long short-term memory neural network (ConvLSTM) based on the spatio-temporal prediction method for land subsidence is constructed. To this end, a cloud platform is employed to obtain a long time series deformation dataset from May 2017 to November 2021 in the understudied area. A convolutional structure to extract spatial features is utilized in the proposed model, and an LSTM structure is linked to the model for time-series prediction to achieve unified modeling of temporal and spatial correlation, thereby rationally predicting the land subsidence progress trend and distribution. The experimental results reveal that the prediction results of the ConvLSTM model are more accurate than those of the LSTM in about 62% of the understudied area, and the overall mean absolute error (MAE) is reduced by about 7%. The achieved results exhibit better prediction in the subsidence center region, and the spatial distribution characteristics of the subsidence data are effectively captured. The present prediction results are more consistent with the distribution of real subsidence and could provide more accurate and reasonable scientific references for subsidence prevention and control in the Beijing-Tianjin-Hebei region. [ABSTRACT FROM AUTHOR]

Objectives: The assessment of mindfulness has relied predominantly on self-report questionnaires, indicating a need for alternative methods based on objective data. The Breath-Counting Task (BCT) has been proposed as a viable candidate by several mindfulness researchers, but has been subject to relatively little scientific scrutiny. Method: We conducted a mega-analysis using combined data from five separate studies, using multiple linear regression models to examine the relationship between BCT performance and self-reported mindfulness after controlling for age and gender. We examined associations with trait mindfulness as indexed by the Five Facet Mindfulness Questionnaire (FFMQ) and Mindful Attention Awareness Scale (MAAS). Results: Accuracy on the BCT correlated only with a combined dataset of z-scores derived from FFMQ-Acting with Awareness and MAAS. We also examined associations with two different types of task errors: miscounts (uncaught errors) and resets (self-caught errors). While reset rates correlated with FFMQ-Acting with Awareness, miscount rates did not correlate with any mindfulness measure. Conclusions: Our analyses provide confirmatory evidence that BCT performance is related to the attentional aspects of trait mindfulness and not its attitudinal aspects – however the relevant correlations are fairly small. In seeking an objective measure of mindful attention, the weak association observed with BCT resets and the lack thereof with BCT accuracy suggests more promise in paradigms based on self-monitoring lapses of attention, while sustained attention tasks such as the present BCT may be of limited application among individuals new to meditation due to their lack of prior practice. [ABSTRACT FROM AUTHOR]

Background: Regarding trochanteric hip fractures, one type of posterior coronal fragments was described as the "banana-shaped fragment", while the impact of the banana-shaped fragment on mechanical stability has not been further studied. The current study investigated the association between the banana-shaped fragment and mechanical complications after surgery. Methods: This retrospective cohort study included 273 patients treated by proximal femoral nail antirotation (PFNA) in the full analysis. The age, the sex, the fracture side, the follow-up time, the American Society of Anesthesiologists classification, the operators, the fracture classification, the tip-apex distance, the blade positions, the reduction quality and the bone mineral density were analyzed in relation to mechanical complications, through univariate and multivariate approaches. Results: Mechanical complications happened in 33 patients. The banana-shaped fragment (adjusted odds ratio 5.240, 95% CI 2.172 to 12.641; p < 0.001), the tip-apex distance and the reduction quality showed significant association with mechanical complications in both univariate and multivariate analysis. Moreover, for 118 patients with the banana-shaped fragment, we found that the use of wire cerclage couldn't significantly lower the rates of mechanical complications (p = 0.648). Conclusions: The banana-shaped fragment had a negative impact on mechanical stability of trochanteric hip fractures treated by PFNA. In the perioperative period, the BSF should be carefully evaluated, and its specific handling deserves further study. [ABSTRACT FROM AUTHOR]

Grasp detection is a visual recognition task where the robot makes use of its sensors to detect graspable objects in its environment. Despite the steady progress in robotic grasping, it is still difficult to achieve both real-time and high accuracy grasping detection. In this paper, we propose a real-time robotic grasp detection method, which can accurately predict potential grasp for parallel-plate robotic grippers using RGB images. Our work employs an end-to-end convolutional neural network which consists of a feature descriptor and a grasp detector. And for the first time, we add an attention mechanism to the grasp detection task, which enables the network to focus on grasp regions rather than background. Specifically, we present an angular label smoothing strategy in our grasp detection method to enhance the fault tolerance of the network. We quantitatively and qualitatively evaluate our grasp detection method from different aspects on the public Cornell dataset and Jacquard dataset. Extensive experiments demonstrate that our grasp detection method achieves superior performance to the state-of-the-art methods. In particular, our grasp detection method ranked first on both the Cornell dataset and the Jacquard dataset, giving rise to the accuracy of 98.9% and 95.6%, respectively at real-time calculation speed. [ABSTRACT FROM AUTHOR]

Immunity-related GTPase family M (IRGM), located on human chromosome 5q33.1, encodes a protein that promotes autophagy and suppresses the innate immune response. The minor allele of rs13361189 (−4299T>C), a single nucleotide polymorphism in the IRGM promoter, has been associated with several diseases, including Crohn's disease and tuberculosis. Although patterns of linkage disequilibrium and minor allele frequency for this polymorphism differ dramatically between subjects of European and African descent, studies of rs13361189 have predominantly been conducted in Europeans and the mechanism of association is poorly understood. We recruited a cohort of 68 individuals (30 White, 34 African American, 4 other race) with varying rs13361189 genotypes and assessed a panel of immune response measures including whole blood cytokine induction following ex vivo stimulation with Toll-like Receptor ligands. Minor allele carriers were found to have increased serum immunoglobulin M, C-reactive protein, and circulating CD8+ T cells. No differences in whole blood cytokines were observed between minor allele carriers and non-carriers in the overall study population; however, minor allele status was associated with increased induction of a subset of cytokines among African American subjects, and decreased induction among White subjects. These findings underline the importance of broad racial inclusion in genetic studies of immunity. [ABSTRACT FROM AUTHOR]

The films of Co1−xMnxFe2O4 (x = 0 − 0.4) were prepared on the substrates of Pt (111)/Ti/SiO2/Si by the sol-gel method. The effect of mole fraction of doping Mn ions on the microstructure, ferromagnetism and optic properties was investigated. The results show that, when x is less than 0.4, Mn ions have dissolved into the crystal lattices of CoFe2O4 without forming secondary phases. The surfaces of the films of Co1−xMnxFe2O4 possess polygonal and dense structures. The results of Raman show that Co2+ migrates from octahedral interstice to tetrahedral interstice when x is greater than 0.2. The results of XPS indicate that, in the Co0.8Mn0.2Fe2O4 film, Fe ions exist in the form of Fe2+ and Fe3+ and Mn ions exist in the form of Mn2+ and Mn3+. The results also show that, with increasing mole fraction of Mn ions, the values of saturation magnetization increase firstly, then decrease. When x is equal to 0.2, there is the maximum value of saturation magnetization (443.12 emu·cm−3). [ABSTRACT FROM AUTHOR]

Aiming at the requirement of autonomous navigation capability of the underwater unmanned vehicle (UUV), a novel bionic method for underwater navigation based on polarization pattern within Snell's window is proposed. Inspired by creatures, polarization navigation is a satellite-free navigation scheme and has great potential to be used in the water. However, because of the complex underwater environment, whether UUV polarization navigation can be realized is doubtful. To illustrate the feasibility of underwater polarization navigation, we firstly establish the model of underwater polarization patterns to prove the stability and predictability of the underwater polarization pattern within Snell's window. Then, we carry out static and dynamic experiments of underwater heading determination based on developed polarization information detection equipment. Finally, we obtain underwater polarization patterns and conduct the tracking experiment at different water depths. The experimental results of the underwater polarization patterns are consistent with the simulation, which proves the correctness of the proposed model. At the water depth of 5 m, the average angle and position error of the tracking experiment are 14.3508° and 4.0812 m, respectively. It is illustrated that underwater polarization navigation is realizable and the precision can meet the real-time navigation requirements of UUV. This study promotes the improvement of underwater navigation ability and the development of marine equipment. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to determine whether the integrity of the entry portal of head-neck implant is related to postoperative mechanical complications. Methods: We retrospectively reviewed consecutive patients with pertrochanteric fractures in our hospital treated from January 1, 2018, to September 1, 2021. Based on the integrity of the entry portal for head-neck implants on the femoral lateral wall, patients were divided into two groups, including the ruptured entry portal (REP) group and the intact entry portal (IEP) group. After 4:1 propensity score-matched analyses were used to balance the baseline of the two groups, a total of 55 patients were extracted from the original participants, including 11 patients in the REP group and 44 matched patients in the IEP group. The anterior to posterior cortex width on the mid-level of the lesser trochanter was measured and defined as the residual lateral wall width (RLWW). Results: Compared with the IEP group, the REP group was correlated with postoperative mechanical complications (OR = 12.00, 95% CI 1.837–78.369, P = 0.002) and hip-thigh pain (OR = 26.67, 95% CI 4.98–142.86). RLWW ≤ 18.55 mm indicated a high likelihood (tau-y = 0.583, P = 0.000) of becoming the REP type postoperatively and being more likely to suffer from mechanical complications (OR = 30.67, 95% CI 3.91–240.70, P = 0.000) and hip-thigh pain (OR = 14.64, 95% CI 2.36–90.85, P = 0.001). Conclusion: Rupture of entry portal is a high-risk factor for mechanical complications in intertrochanteric fractures. RLWW ≤ 18.55 mm is a reliable predictor of the postoperative REP type. [ABSTRACT FROM AUTHOR]

Astragalus adsurgens (A. adsurgens), which is considered a forage in China, grows widely in Eurasia and North America. However, Alternaria gansuense (A. gansuense) (synonym: Embellisia astragali) systematically infects A. adsurgens, producing swainsonine (SW), which poisons domesticated animals. In this study, we hypothesized that the A. gansuense SW-producing fungus is morphologically and molecularly related to the locoweed endophyte, Alternaria oxytropis (A. oxytropis), which systematically grows in host plants. Therefore, pure cultures of the fungi from diseased plants or endophytic interactions were collected from fields and assayed for SW via high-performance liquid chromatography linked to mass spectroscopy (HPLC–MS). The production of SW was also detected in A. adsurgens, A. oxytropis and diseased plants by assaying for the presence of the β-ketoacyl synthase (KS) gene, which is required for SW synthesis. Diseased A. adsurgens and pure cultures of A. gansuense have SW and the healthy-looking A. adsurgens plants also contained SW, probably because they were infected with A. gansuense. Therefore, A. adsurgens-infected A. gansuense are not safe for livestock consumption. [ABSTRACT FROM AUTHOR]

In situ special-shaped microfibrillar composites, employing polyolefin elastomer (POE) as matrix and poly(lactic acid)/polyamide 6 (PLA/PA6) masterbatch as dispersed phase, were successfully prepared by using multistage stretching extrusion technology. The special-shaped microfibrils liking "gourd skewers" or "trepang" can be readily tuned by changing the weight ratio of PLA to PA6 in the POE/(PLA/PA6) composites. It was found that the morphological evolution of special shaped structure microfibril were mainly ascribed to the phase separation and viscosity difference between PLA and PA6 during stretching extrusion process. Owing to the large specific surface area and the "hang nail" effect of special-shaped microfibrils, the excellent elongation at break(867%) and tensile strength (20.1 MPa) can be achieved for the POE/(PLA/PA6) composites (PLA/PA6 = 12.5/12.5), which were 1.2 and 2 times higher than those of pure POE respectively. Dynamic rheology studies showed that the viscoelasticity of POE/(PLA/PA6) composites can be improved significantly compared to pure POE. This work provided a facile and cost-effective way to fabricate special shaped microfibrillar composites to improved strength and toughness simultaneously. [ABSTRACT FROM AUTHOR]

Proteomics technology reveals the marker proteins, potential pathogenesis, and intervention targets after noise-induced hearing loss. To study the differences in cochlea protein expression before and after noise exposure using proteomics to reveal the pathological mechanism of noise-induced hearing loss (NIHL). A guinea pig NIHL model was established to test the ABR thresholds before and after noise exposure. The proteomics technology was used to study the mechanism of differential protein expression in the cochlea by noise stimulation. The average hearing threshold of guinea pigs on the first day after noise exposure was 57.00 ± 6.78 dB Sound pressure level (SPL); the average hearing threshold on the seventh day after noise exposure was 45.83 ± 6.07 dB SPL. The proteomics technology identified 3122 different inner ear proteins, of which six proteins related to the hearing were down-regulation: Tenascin C, Collagen Type XI alpha two chains, Collagen Type II alpha one chain, Thrombospondin 2, Collagen Type XI alpha one chain and Ribosomal protein L38, and are enriched in protein absorption, focal adhesion, and extracellular matrix receptor pathways. Impulse noise can affect the expression of differential proteins through focal adhesion pathways. This data can provide an experimental basis for the research on the prevention and treatment of NIHL. [ABSTRACT FROM AUTHOR]

Background: The prognosis of advanced gastric cancer (GC) invading the gastric serosa remains poor, mainly owing to high incidence of peritoneal recurrence. Patients with peritoneal metastases are often treated with neoadjuvant intraperitoneal and systemic chemotherapies (NIPS). Good responders to NIPS often undergo conversion gastrectomy. This study aims to explore biomarkers predicting the occurrence of peritoneal metastasis (PM) and evaluating the efficacy of NIPS in GC patients. Methods: We collected six peritoneal lavage (PL) samples from two patients with PM, two without PM, and two with diminished PM after NIPS via intraperitoneal access ports. We equally isolated microRNAs from exosomes derived from PL samples for deep sequencing. Two microRNAs (hsa-let-7g-3p and hsa-miR-10395-3p) were identified, and their expression levels were examined in PL samples of 99 GC patients using qRT-PCR. Moreover, we performed in vivo and in vitro functional assays to investigate effects of these microRNAs on metastasis and chemoresistance of GC cells. Results: Exosomal microRNA expression profiling of six PL samples indicated that the microRNA signature in exosomes of PLs from patients with diminished PM was similar to that from patients without PM. Expression levels of hsa-let-7g-3p and hsa-miR-10395-3p were associated with PM. In vivo and in vitro functional assays confirmed that hsa-let-7g-3p and hsa-miR-10395-3p are involved in GC metastasis and chemoresistance. Conclusion: PL-derived exosomes in GC contain large amounts of microRNAs related to PM. Moreover, hsa-let-7g-3p and hsa-miR-10395-3p could be used as biomarkers predicting PM and NIPS efficacy and are involved in GC metastasis and chemoresistance. [ABSTRACT FROM AUTHOR]

Traditional Pb(Mg1/3Nb2/3)O3-PbTiO3 based relaxor ferroelectrics have attracted much attention. However, the relatively low Tm restricts their application in the high temperature range. In the present study, a novel (0.8-x)Bi(Mg1/2Ti1/2)O3-xPbTiO3-0.2PbZrO3 ((0.8-x)BMT-xPT-PZ) relaxor ferroelectric based on the high temperature BMT-PT piezoelectrics was designed. All samples exhibit pure perovskite structures and the phase structures show a gradual transition from relaxor rhombohedral (R) to normal tetragonal (T) phases via the morphotropic phase boundary (MPB) in the composition range x = 0.36–0.39. The dielectric relaxation behavior can be observed in all samples although a spontaneous normal-relaxor ferroelectric transformation is observed in the T phase region. The x = 0.38 sample exhibits the optimal overall electrical properties with the d33 value of 325 pC/N, the kp value of 0.38, the Tm value of 290 oC. The results indicate that the present studied ternary system has a good potential as high temperature relaxor ferroelectrics. [ABSTRACT FROM AUTHOR]

Graphdiyne (GDY) has attracted a lot of interest in electrochemical sensing application with the advantages of a large conjugation system, porous structure, and high structure defects. Herein, to further improve the sensing effect of GDY, conductive MWCNTs were chosen as the signal accelerator. To get a stable composite material, polydopamine (PDA) was employed as connecting bridge between GDY and MWCNTs-NH2, where DA was firstly polymerized onto GDY, followed by covalently linking MWCNTs-NH2 with PDA through Michael-type reaction. The formed GDY@PDA/MWCNTs-NH2 composite was then explored as an electrochemical sensor for benomyl (Ben) determination. GDY assists the adsorption and accumulation of Ben molecules to the sensing surface, while MWCNTs-NH2 can enhance the electrical conductivity and electrocatalytic activity, all of which contributing to the significantly improved performance. The proposed sensor displays an obvious oxidation peak at 0.72 V (vs. Hg|Hg2Cl2) and reveals a wide linear range from 0.007 to 10.0 µM and a low limit of detection (LOD) of 1.8 nM (S/N = 3) toward Ben detection. In addition, the sensor shows high stability, repeatability, reproducibility, and selectivity. The feasibility of this sensor was demonstrated by detecting Ben in apple and cucumber samples with a recovery of 94–106% and relative standard deviations (RSDs) less than 2.3% (n = 5). A sensitive electrochemical sensing platform was reported for benomyl (Ben) determination based on a highly stable GDY@PDA/MWCNTs-NH2 composite. [ABSTRACT FROM AUTHOR]

Apelin receptor (APJ) ligands elabela (ELA) and apelin have divergent distributions and function differently in vitro and in vivo. Whether differences exist in their capacity of recruitment of β-arrestins (ARRBs) to APJ remains unknown. The aim of the current study was to investigate the different effects of ELA and apelin on the interaction between APJ and ARRBs in live cells by NanoBiT®. NanoBiT® system is a new technology for studying protein–protein interaction in real-time in live cells, based on the emission of luminescence when two split components of NanoLuc luciferase, large Bit (LgBit) and small Bit (SmBit), complement each other to form an enzymatically active entity. We tagged the APJ and ARRBs with LgBit or SmBit and then evaluated their interactions in transiently transfected HEK293T cells, and determined the signal strength yielded as a result of the interaction. We also investigated the concentration-dependent response of the APJ-ARRB interaction in response to ELA and apelin. Finally, we assessed the effect of F13A, an APJ antagonist which is structurally very similar to apelin-13, on ELA- and apelin-mediated APJ-ARRB interactions. The NanoLuc® luciferase signal was highest in the pair of APJ-LgBit with SmBit-ARRB1 or SmBit-ARRB2. NanoLuc® luciferase signal increased in a concentration-dependent manner from 0.1 nM to 10 μM in response to ELA or apelin. Interestingly, ELA elicited weaker APJ-ARRB interaction signals than apelin. Pre-treatment with F13A potently reduced the APJ-ARRB interaction in response to both ELA and apelin. Our results demonstrated that both ELA and apelin promoted the interaction of APJ and ARRBs in a concentration-dependent manner, and ELA is less efficacious than apelin in inducing the recruitment of ARRBs to APJ, providing a biased functional aspect of ELA vs. apelin at the receptor signaling level. Additionally, ELA and apelin may share the same binding site(s) or pocket(s) at the APJ level. [ABSTRACT FROM AUTHOR]

Directed differentiation of human pluripotent stem cells (hPSCs) into functional ureteric and collecting duct (CD) epithelia is essential to kidney regenerative medicine. Here we describe highly efficient, serum-free differentiation of hPSCs into ureteric bud (UB) organoids and functional CD cells. The hPSCs are first induced into pronephric progenitor cells at 90% efficiency and then aggregated into spheres with a molecular signature similar to the nephric duct. In a three-dimensional matrix, the spheres form UB organoids that exhibit branching morphogenesis similar to the fetal UB and correct distal tip localization of RET expression. Organoid-derived cells incorporate into the UB tips of the progenitor niche in chimeric fetal kidney explant culture. At later stages, the UB organoids differentiate into CD organoids, which contain >95% CD cell types as estimated by single-cell RNA sequencing. The CD epithelia demonstrate renal electrophysiologic functions, with ENaC-mediated vectorial sodium transport by principal cells and V-type ATPase proton pump activity by FOXI1-induced intercalated cells. Kidney collecting duct cells with physiologic functions are generated from human pluripotent stem cells. [ABSTRACT FROM AUTHOR]

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