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1.
Biophys J ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961622

ABSTRACT

The angular optical trap (AOT) is a powerful instrument for measuring the torsional and rotational properties of a biological molecule. Thus far, AOT studies of DNA torsional mechanics have been carried out using a high numerical aperture oil-immersion objective, which permits strong trapping but inevitably introduces spherical aberrations due to the glass-aqueous interface. However, the impact of these aberrations on torque measurements is not fully understood experimentally, partly due to a lack of theoretical guidance. Here, we present a numerical platform based on the finite element method to calculate forces and torques on a trapped quartz cylinder. We have also developed a new experimental method to accurately determine the shift in the trapping position due to the spherical aberrations by using a DNA molecule as a distance ruler. We found that the calculated and measured focal shift ratios are in good agreement. We further determined how the angular trap stiffness depends on the trap height and the cylinder displacement from the trap center and found full agreement between predictions and measurements. As a further verification of the methodology, we showed that DNA torsional properties, which are intrinsic to DNA, could be determined robustly under different trap heights and cylinder displacements. Thus, this work has laid both a theoretical and experimental framework that can be readily extended to investigate the trapping forces and torques exerted on particles with arbitrary shapes and optical properties.

2.
Phytochemistry ; 226: 114209, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38972439

ABSTRACT

Seven undescribed benzoate glycosides (1-7) and five known ones (8-12) were isolated from the rhizomes of Gentiana scabra Bge. Their structures were characterized by comprehensive NMR and MS spectroscopic data analysis. The lipid-lowering effects of these compounds were evaluated by measuring the triglyceride (TG) contents and intracellular lipid droplets (LDs) in oleic acid (OA)-treated HepG2 cells. The results showed that compounds 1, 5, 7, and 11 significantly reduced the TG content at 20 µM, and the Bodipy staining displayed that OA enhanced the levels of LDs in the cell, while these compounds reversed the lipid accumulation caused by OA. These findings provide a basis for further development and utilization of G. scabra as a natural source of potential lipid-lowering agents.

3.
Clin Exp Med ; 24(1): 117, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833019

ABSTRACT

To carry out an in-depth analysis of the scientific research on autoimmunity, we performed the first bibliometric analysis focusing on publications in journals dedicated to autoimmunity (JDTA) indexed by science citation index during the period 2004-2023. Using bibliometric analysis, we quantitatively and qualitatively analyzed the country, institution, author, reference and keywords information of publications in JDTA, so as to understand the quantity, publication pattern and publication characteristics of these publications. The co-occurrence networks, clustering map and timeline map were created by CiteSpace and VOSviewer software to visualize the results. The CiteSpace was also used to analyze the strongest citation burst of keywords, which could describe the frequency, intensity and time period of high-frequency keywords, and indicate the research hotspots in the field. A total of 5 710 publications were analyzed, and their annual distribution number was basically stable from 2004 to 2023, fluctuating around 300. The United States and Italy led the way in terms of the number of publications, followed by France and China. For international cooperation, the developed countries represented by the United States cooperate more closely, but the cooperation was localized, reflecting that there was no unified model of autoimmunity among countries. UDICE-French Research Universities had the greatest number of publications. Subsequently, the number of publications decreased slowly with the ranking, and the gradient was not large. Eric Gershwin and Yehuda Shoenfeld stood out among the authors. They had an excellent academic reputation and great influence in the field of autoimmunity. The results of keyword analysis showed that JDTA publications mainly studied a variety of autoimmune diseases, especially SLE and RA. At the same time, JDTA publications also paid special attention to the research of cell function, autoantibody expression, animal experiments, disease activity, pathogenesis and treatment. This study is the first to analyze the publications in JDTA from multiple indicators by bibliometrics, thus providing new insights into the research hotspots and development trends in the field of autoimmunity.


Subject(s)
Autoimmunity , Bibliometrics , Periodicals as Topic , Humans , Biomedical Research/trends , United States , France , China , Italy
4.
Physiol Mol Biol Plants ; 30(5): 851-866, 2024 May.
Article in English | MEDLINE | ID: mdl-38846461

ABSTRACT

Leucine-rich repeat receptor-like kinases (LRR-RLKs) represent the largest subgroup of receptor-like kinases (RLKs) in plants. While some LRR-RLK members play a role in regulating various plant growth processes related to morphogenesis, disease resistance, and stress response, the functions of most LRR-RLK genes remain unclear. In this study, we identified 397 LRR-RLK genes from the genome of Camellia sinensis and categorized them into 16 subfamilies. Approximately 62% of CsLRR-RLK genes are situated in regions resulting from segmental duplications, suggesting that the expansion of CsLRR-RLK genes is due to segmental duplications. Analysis of gene expression patterns revealed differential expression of CsLRR-RLK genes across different tissues and in response to stress. Furthermore, we demonstrated that CssEMS1 localizes to the cell membrane and can complement Arabidopsis ems1 mutant. This study is the initial in-depth evolutionary examination of LRR-RLKs in tea and provides a basis for future investigations into their functionality. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01458-1.

5.
bioRxiv ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38853956

ABSTRACT

The angular optical trap (AOT) is a powerful instrument for measuring the torsional and rotational properties of a biological molecule. Thus far, AOT studies of DNA torsional mechanics have been carried out using a high numerical aperture oil-immersion objective, which permits strong trapping, but inevitably introduces spherical aberrations due to the glass-aqueous interface. However, the impact of these aberrations on torque measurements is not fully understood experimentally, partly due to a lack of theoretical guidance. Here, we present a numerical platform based on the finite element method to calculate forces and torques on a trapped quartz cylinder. We have also developed a new experimental method to accurately determine the shift in the trapping position due to the spherical aberrations by using a DNA molecule as a distance ruler. We found that the calculated and measured focal shift ratios are in good agreement. We further determined how the angular trap stiffness depends on the trap height and the cylinder displacement from the trap center and found full agreement between predictions and measurements. As further verification of the methodology, we showed that DNA torsional properties, which are intrinsic to DNA, could be determined robustly under different trap heights and cylinder displacements. Thus, this work has laid both a theoretical and experimental framework that can be readily extended to investigate the trapping forces and torques exerted on particles with arbitrary shapes and optical properties. SIGNIFICANCE: We developed a simulation platform based on the finite element method for force and torque calculation for particles in an angular optical trap (AOT), with considerations of tightly focused Gaussian beam, spherical aberrations, and optically anisotropic particles. Experimental measurements of focal shift ratio, force, and torque under multiple conditions were in good agreement with predictions from the simulations. We also demonstrated that intrinsic DNA torsional properties can be robustly measured under different AOT measurement conditions, strongly validating our simulations and calibrations. Our platform can facilitate trapping particle design for single-molecule assays using the AOT.

6.
Article in English | MEDLINE | ID: mdl-38796735

ABSTRACT

OBJECTIVE: This study aims to evaluate the accuracy of ChatGPT in answering allergic rhinitis (AR) and chronic rhinosinusitis (CRS) related questions. STUDY DESIGN: This is a cross-sectional study. SETTING: Each question was inputted as a separate, independent prompt. METHODS: Responses to AR (n = 189) and CRS (n = 242) related questions, generated by GPT-3.5 and GPT-4, were independently graded for accuracy by 2 senior rhinology professors, with disagreements adjudicated by a third reviewer. RESULTS: Overall, ChatGPT demonstrated a satisfactory performance, accurately answering over 80% of questions across all categories. Specifically, GPT-4.0's accuracy in responding to AR-related questions significantly exceeded that of GPT-3.5, but distinction not evident in CRS-related questions. Patient-originated questions had a significantly higher accuracy compared to doctor-originated questions when utilizing GPT-4.0 to respond to AR-related questions. This discrepancy was not observed with GPT-3.5 or in the context of CRS-related questions. Across different types of content, ChatGPT excelled in covering basic knowledge, prevention, and emotion for AR and CRS. However, it experienced challenges when addressing questions about recent advancements, a trend consistent across both GPT-3.5 and GPT-4.0 iterations. Importantly, the accuracy of responses remained unaffected when questions were posed in Chinese. CONCLUSION: Our findings suggest ChatGPT's capability to convey accurate information for AR and CRS patients, and offer insights into its performance across various domains, guiding its utilization and improvement.

7.
J Biomed Res ; : 1-10, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38808554

ABSTRACT

Pericytes are located in the stromal membrane of the capillary outer wall and contain endothelial cells (ECs). They are pivotal in regulating blood flow, enhancing vascular stability, and maintaining the integrity of the blood-retina barrier (BRB)/blood-brain barrier (BBB). The pluripotency of pericytes allows them to differentiate into various cell types, highlighting their significance in vascular disease pathogenesis, as demonstrated by previous studies. This potential enables pericytes to be a potential biomarker for the diagnosis and a target for treatment of vascular disorders. The retina, an essential part of the eyeball, is an extension of cerebral tissue with a transparent refractive medium. It offers a unique window for assessing systemic microvascular lesions. Routine fundus examination is necessary for patients with diabetes and hypertension. Manifestations, such as retinal artery tortuosity, dilation, stenosis, and abnormal arteriovenous anastomosis, serve as typical hallmarks of retinal vasculopathy. Therefore, studies of ocular vascular diseases significantly facilitate the exploration of systemic vascular diseases.

8.
Toxicol Appl Pharmacol ; 486: 116950, 2024 May.
Article in English | MEDLINE | ID: mdl-38701902

ABSTRACT

Antidepressant duloxetine has been shown protective effect on indomethacin-induced gastric ulcer, which was escorted by inflammation in the gastric mucosa. Cytokines are the principal mediators of inflammation. Thus, by screening the differential expression of cytokines in the gastric mucosa using cytokine array at 3 h after indomethacin exposure, when the gastric ulcer began to format, we found that indomethacin increased cytokines which promoted inflammation responses, whereas duloxetine decreased pro-inflammatory cytokines increased by indomethacin and increased RANTES expression. RANTES was consistently increased by pretreated with both 5 mg/kg and 20 mg/kg duloxetine at 3 h and 6 h after indomethacin exposure in male rats. Selective blockade of RANTES-CCR5 axis by a functional antagonist Met-RANTES or a CCR5 antagonist maraviroc suppressed the protection of duloxetine. Considering the pharmacologic action of duloxetine on reuptake of monoamine neurotransmitters, we examined the serotonin (5-HT), norepinephrine and dopamine contents in the blood and discovered 20 mg/kg duloxetine increased 5-HT levels in platelet-poor plasma, while treatment with 5-HT promoted expression of RANTES in the gastric mucosa and alleviated the indomethacin-induced gastric injury. Furthermore, duloxetine activated PI3K-AKT-VEGF signaling pathway, which was regulated by RANTES-CCR5, and selective inhibitor of VEGF receptor axitinib blocked the prophylactic effect of duloxetine. Furthermore, duloxetine also protected gastric mucosa from indomethacin in female rats, and RANTES was increased by duloxetine after 6 h after indomethacin exposure too. Together, our results identified the role of cytokines, particularly RANTES, and the underlying mechanisms in gastroprotective effect of duloxetine against indomethacin, which advanced our understanding in inflammatory modulation by monoamine-based antidepressants.


Subject(s)
Chemokine CCL5 , Duloxetine Hydrochloride , Gastric Mucosa , Indomethacin , Proto-Oncogene Proteins c-akt , Rats, Sprague-Dawley , Serotonin , Signal Transduction , Stomach Ulcer , Vascular Endothelial Growth Factor A , Animals , Duloxetine Hydrochloride/pharmacology , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Gastric Mucosa/metabolism , Male , Indomethacin/toxicity , Proto-Oncogene Proteins c-akt/metabolism , Chemokine CCL5/metabolism , Signal Transduction/drug effects , Rats , Vascular Endothelial Growth Factor A/metabolism , Stomach Ulcer/chemically induced , Stomach Ulcer/prevention & control , Stomach Ulcer/pathology , Stomach Ulcer/metabolism , Serotonin/metabolism , Phosphatidylinositol 3-Kinases/metabolism
9.
Sensors (Basel) ; 24(8)2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38676176

ABSTRACT

In the field of robotic automation, achieving high position accuracy in robotic vision systems (RVSs) is a pivotal challenge that directly impacts the efficiency and effectiveness of industrial applications. This study introduces a comprehensive modeling approach that integrates kinematic and joint compliance factors to significantly enhance the position accuracy of a system. In the first place, we develop a unified kinematic model that effectively reduces the complexity and error accumulation associated with the calibration of robotic systems. At the heart of our approach is the formulation of a joint compliance model that meticulously accounts for the intricacies of the joint connector, the external load, and the self-weight of robotic links. By employing a novel 3D rotary laser sensor for precise error measurement and model calibration, our method offers a streamlined and efficient solution for the accurate integration of vision systems into robotic operations. The efficacy of our proposed models is validated through experiments conducted on a FANUC LR Mate 200iD robot, showcasing notable improvements in the position accuracy of robotic vision system. Our findings contribute a framework for the calibration and error compensation of RVS, holding significant potential for advancements in automated tasks requiring high precision.

10.
Front Cell Neurosci ; 18: 1292969, 2024.
Article in English | MEDLINE | ID: mdl-38628398

ABSTRACT

During the development of neural circuits, axons are guided by a variety of molecular cues to navigate through the brain and establish precise connections with correct partners at the right time and place. Many axon guidance cues have been identified and they play pleiotropic roles in not only axon guidance but also axon fasciculation, axon pruning, and synaptogenesis as well as cell migration, angiogenesis, and bone formation. In search of receptors for Sema3E in axon guidance, we unexpectedly found that Plexin B3 is highly expressed in retinal ganglion cells of zebrafish embryos when retinal axons are crossing the midline to form the chiasm. Plexin B3 has been characterized to be related to neurodevelopmental disorders. However, the investigation of its pathological mechanisms is hampered by the lack of appropriate animal model. We provide evidence that Plexin B3 is critical for axon guidance in vivo. Plexin B3 might function as a receptor for Sema3E while Neuropilin1 could be a co-receptor. The intracellular domain of Plexin B3 is required for Semaphorin signaling transduction. Our data suggest that zebrafish could be an ideal animal model for investigating the role and mechanisms of Sema3E and Plexin B3 in vivo.

11.
BMC Genomics ; 25(1): 350, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38589807

ABSTRACT

BACKGROUND: In Eukaryotes, inositol polyphosphates (InsPs) represent a large family of secondary messengers and play crucial roes in various cellular processes. InsPs are synthesized through a series of pohophorylation reactions catalyzed by various InsP kinases in a sequential manner. Inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase/IP3K), one member of InsP kinase, plays important regulation roles in InsPs metabolism by specifically phosphorylating inositol 1,4,5-trisphosphate (IP3) to inositol 1,3,4,5-tetrakisphosphate (IP4) in animal cells. IP3Ks were widespread in fungi, plants and animals. However, its evolutionary history and patterns have not been examined systematically. RESULTS: A total of 104 and 31 IP3K orthologues were identified across 57 plant genomes and 13 animal genomes, respectively. Phylogenetic analyses indicate that IP3K originated in the common ancestor before the divergence of fungi, plants and animals. In most plants and animals, IP3K maintained low-copy numbers suggesting functional conservation during plant and animal evolution. In Brassicaceae and vertebrate, IP3K underwent one and two duplication events, respectively, resulting in multiple gene copies. Whole-genome duplication (WGD) was the main mechanism for IP3K duplications, and the IP3K duplicates have experienced functional divergence. Finally, a hypothetical evolutionary model for the IP3K proteins is proposed based on phylogenetic theory. CONCLUSION: Our study reveals the evolutionary history of IP3K proteins and guides the future functions of animal, plant, and fungal IP3K proteins.


Subject(s)
Inositol 1,4,5-Trisphosphate , Phosphotransferases (Alcohol Group Acceptor) , Animals , Inositol 1,4,5-Trisphosphate/metabolism , Phosphotransferases (Alcohol Group Acceptor)/genetics , Phylogeny , Plants/genetics , Plants/metabolism , Evolution, Molecular
12.
Int Immunopharmacol ; 133: 112074, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38615383

ABSTRACT

The tumor microenvironment plays a vital role in glioblastoma growth and invasion. PD-1 and PD-L1 modulate the immunity in the brain tumor microenvironment. However, the underlying mechanisms remain unclear. In the present study, in vivo and in vitro experiments were conducted to reveal the effects of PD-1/PD-L1 on the crosstalk between microglia and glioma. Results showed that glioma cells secreted PD-L1 to the peritumoral areas, particularly microglia containing highly expressed PD-1. In the early stages of glioma, microglia mainly polarized into the pro-inflammatory subtype (M1). Subsequently, the secreted PD-L1 accumulated and bound to PD-1 on microglia, facilitating their polarization toward the microglial anti-inflammatory (M2) subtype primarily via the STAT3 signaling pathway. The role of PD-1/PD-L1 in M2 polarization of microglia was partially due to PD-1/PD-L1 depletion or application of BMS-1166, a novel inhibitor of PD-1/PD-L1. Consistently, co-culturing with microglia promoted glioma cell growth and invasion, and blocking PD-1/PD-L1 significantly suppressed these processes. Our findings reveal that the PD-1/PD-L1 axis engages in the microglial M2 polarization in the glioma microenvironment and promotes tumor growth and invasion.


Subject(s)
B7-H1 Antigen , Brain Neoplasms , Glioma , Microglia , Programmed Cell Death 1 Receptor , Animals , Humans , Male , Mice , B7-H1 Antigen/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/immunology , Cell Line, Tumor , Cell Proliferation/drug effects , Coculture Techniques , Glioma/metabolism , Glioma/pathology , Glioma/immunology , Microglia/metabolism , Microglia/immunology , Programmed Cell Death 1 Receptor/metabolism , Signal Transduction , STAT3 Transcription Factor/metabolism , Tumor Microenvironment/immunology
13.
PLoS One ; 19(3): e0300240, 2024.
Article in English | MEDLINE | ID: mdl-38547150

ABSTRACT

Recommender system has made great strides in two major research fields, rating prediction and Top-k recommendation. In essence, rating prediction is a regression task, which aims to predict users scores on other items, while Top-k is a classification task selecting the items that users have the most potential to interact with. Both characterize users and items, but the optimization of parameters varies widely for their respective tasks. Inspired by the idea of transfer learning, we consider extracting the information learned from rating prediction models for serving for Top-k tasks. To this end, we propose a universal transfer model for recommender systems. The transfer model consists of two sub-components: quadruple-based Bayesian Converter (BC) and Prediction-based Multi-Layer Perceptron (PMLP). As the main part, BC is responsible for transforming the feature vectors extracted from the rating prediction model. Meanwhile, PMLP extracts the prediction ratings, constructs the prediction rating matrix, and uses multi-layer perceptron to enhance the final performance. On four benchmark datasets, we use the information extracted from the singular value decomposition plus plus (SVD++) model to demonstrate the effectiveness of BC-PMLP, comparing to classical and state-of-the-art baselines. We also conduct extra experiments to verify the utility of BC, and performance within different parameter values.


Subject(s)
Algorithms , Neural Networks, Computer , Bayes Theorem , Machine Learning
14.
Chempluschem ; : e202400027, 2024 Feb 18.
Article in English | MEDLINE | ID: mdl-38369654

ABSTRACT

Membrane separation plays a crucial role in the current increasingly complex energy environment. Membranes prepared by metal-organic framework (MOF) materials usually possess unique advantages in common, such as uniform pore size, ultra-high porosity, enhanced selectivity and throughput, and excellent adsorption property, which have been contributed to the separation fields. In this comprehensive review, we summarize various designs and synthesized strategies of free-standing MOF and composite MOF-based membranes for water treatment. Special emphases are given not only on the effects of MOF on membrane performance, removal efficiencies, and elimination mechanisms, but also on the importance of MOF-based membranes for the applications of oily and micro-pollutant removal, adsorption, separation, and catalysis. The challenges and opportunities in the future for the industrial implementation of MOF-based membranes are also discussed.

15.
Mol Plant ; 17(3): 409-422, 2024 03 04.
Article in English | MEDLINE | ID: mdl-38335958

ABSTRACT

Plant high-affinity K+ transporters (HKTs) mediate Na+ and K+ uptake, maintain Na+/K+ homeostasis, and therefore play crucial roles in plant salt tolerance. In this study, we present cryoelectron microscopy structures of HKTs from two classes, class I HKT1;1 from Arabidopsis thaliana (AtHKT1;1) and class II HKT2;1 from Triticum aestivum (TaHKT2;1), in both Na+- and K+-bound states at 2.6- to 3.0-Å resolutions. Both AtHKT1;1 and TaHKT2;1 function as homodimers. Each HKT subunit consists of four tandem domain units (D1-D4) with a repeated K+-channel-like M-P-M topology. In each subunit, D1-D4 assemble into an ion conduction pore with a pseudo-four-fold symmetry. Although both TaHKT2;1 and AtHKT1;1 have only one putative Na+ ion bound in the selectivity filter with a similar coordination pattern, the two HKTs display different K+ binding modes in the filter. TaHKT2;1 has three K+ ions bound in the selectivity filter, but AtHKT1;1 has only two K+ ions bound in the filter, which has a narrowed external entrance due to the presence of a Ser residue in the first filter motif. These structures, along with computational, mutational, and electrophysiological analyses, enable us to pinpoint key residues that are critical for the ion selectivity of HKTs. The findings provide new insights into the ion selectivity and ion transport mechanisms of plant HKTs and improve our understanding about how HKTs mediate plant salt tolerance and enhance crop growth.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Symporters , Arabidopsis Proteins/metabolism , Cryoelectron Microscopy , Arabidopsis/metabolism , Ion Transport , Ions/metabolism , Potassium/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism
16.
Adv Mater ; 36(23): e2313663, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38415854

ABSTRACT

2D <100>-oriented Dion-Jacobson or Ruddlesden-Popper perovskites are widely recognized as promising candidates for optoelectronic applications. However, the large interlayer spacing significantly hinders the carrier transport. <110>-oriented 2D perovskites naturally exhibit reduced interlayer spacings, but the tilting of metal halide octahedra is typically serious and leads to poor charge transport. Herein, a <110>-oriented 2D perovskite EPZPbBr4 (EPZ = 1-ethylpiperazine) with minimized tilting is designed through A-site stereo-hindrance engineering. The piperazine functional group enters the space enclosed by the three [PbBr6]4- octahedra, pushing Pb─Br─Pb closer to a straight line (maximum Pb─Br─Pb angle ≈180°), suppressing the tilting as well as electron-phonon coupling. Meanwhile, the ethyl group is located between layers and contributes an extremely reduced effective interlayer distance (2.22 Å), further facilitating the carrier transport. As a result, EPZPbBr4 simultaneously demonstrates high µτ product (1.8 × 10-3 cm2 V-1) and large resistivity (2.17 × 1010 Ω cm). The assembled X-ray detector achieves low dark current of 1.02 × 10-10 A cm-2 and high sensitivity of 1240 µC Gy-1 cm-2 under the same bias voltage. The realized specific detectivity (ratio of sensitivity to noise current density, 1.23 × 108 µC Gy-1 cm-1 A-1/2) is the highest among all reported perovskite X-ray detectors.

17.
Sci Rep ; 14(1): 2913, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38316941

ABSTRACT

24/7 continuous recording of in-home daily trajectories is informative for health status assessment (e.g., monitoring Alzheimer's, dementia based on behavior patterns). Indoor device-free localization/tracking are ideal because no user efforts on wearing devices are needed. However, prior work mainly focused on improving the localization accuracy. They relied on well-calibrated sensor placements, which require hours of intensive manual setup and respective expertise, feasible only at small scale and by mostly researchers themselves. Scaling the deployments to tens or hundreds of real homes, however, would incur prohibitive manual efforts, and become infeasible for layman users. We present SCALING, a plug-and-play indoor trajectory monitoring system that layman users can easily set up by walking a one-minute loop trajectory after placing radar nodes on walls. It uses a self calibrating algorithm that estimates sensor locations through their distance measurements to the person walking the trajectory, a trivial effort without taxing layman users physically or cognitively. We evaluate SCALING via simulations and two testbeds (in lab and home configurations of sizes 3[Formula: see text]6 sq m and 4.5[Formula: see text]8.5 sq m). Experimental results demonstrate that SCALING outperformed the baseline using the approximate multidimensional scaling (MDS, the most relevant method in the context of self calibration) by 3.5 m/1.6 m in 80-percentile error of self calibration and tracking, respectively. Notably, only 1% degradation in performance has been observed with SCALING compared to the classical multilateration with known sensor locations (anchors), which costs hours of intensive calibrating effort. In addition, we conduct Monte Carlo experiments to numerically analyze the impact of sensor placements and develop practical guidelines for deployment in real life scenarios.

18.
Science ; 383(6685): eadj2609, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38305684

ABSTRACT

Insects rely on a family of seven transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities, such as sweet and bitter. We report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBDs, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBDs. Sugar binding to LBDs induces local conformational changes, which are subsequently transferred to the PD to cause channel opening. Our studies reveal a structural basis for sugar recognition and activation of GRs.


Subject(s)
Drosophila Proteins , Drosophila melanogaster , Sugars , Taste Perception , Taste , Animals , Taste/physiology , Taste Perception/physiology , Drosophila melanogaster/physiology , Drosophila Proteins/chemistry , Protein Conformation
19.
Heliyon ; 10(3): e25906, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38371980

ABSTRACT

Discogenic low back pain (DLBP) is a multifactorial disease and associated with intervertebral disc degeneration. Calcitonin gene-related protein (CGRP) plays a critical role in pain processing, while the role in DLBP remains unclear. This study aims to investigate the anti-nociceptive role and related mechanisms of CGRP in DLBP. Here we established the DLBP rat and validated the model using histology and radiography. Minocycline, a microglial inhibitor, and CGRP were intrathecally injected and the behavioral test was performed to determine hyperalgesia. Further, BV2 microglial cells and microglial activation agent lipopolysaccharide (LPS) were employed for the in vitro experiment. We observed obvious lumbar intervertebral disc degeneration and hyperalgesia at 12 weeks postoperation in DLBP group, with significantly activated microglia in the spinal cord. CGRP treatment significantly inhibited the upregulation of proinflammatory cytokines and NLRP3/caspase-1 expression induced by LPS in BV2 cells, whereas treatment with CGRP alone had little effect on BV2 cells. The intrathecal injection of CGRP into DLBP rats relieved mechanical and thermal hyperalgesia, reverted the microglial activation and decreased the expression of NLRP3/caspase-1, similar to the effects produced by minocycline. Our results provide evidence that microglial activation in the spinal cord play a key role in hyperalgesia in DLBP rats. CGRP alleviates DLBP induced hyperalgesia and inhibits microglial activation in the spinal cord. Regulation of CGRP and microglial activation may provide a new strategy for ameliorating DLBP.

20.
Gene ; 893: 147936, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38381507

ABSTRACT

Pollen intine serves as a protective layer situated between the pollen exine and the plasma membrane. It performs essential functions during pollen development, including maintaining the morphological structure of the pollen, preventing the loss of pollen contents, and facilitating pollen germination. The formation of the intine layer commences at the bicellular pollen stage. Pectin, cellulose, hemicellulose and structural proteins are the key constituents of the pollen intine. In Arabidopsis and rice, numerous regulatory factors associated with polysaccharide metabolism and material transport have been identified, which regulate intine development. In this review, we elucidate the developmental processes of the pollen wall and provide a concise summary of the research advancements in the development and genetic regulation of the pollen intine in Arabidopsis and rice. A comprehensive understanding of intine development and regulation is crucial for unraveling the genetic network underlying intine development in higher plants.


Subject(s)
Arabidopsis , Oryza , Oryza/genetics , Arabidopsis/genetics , Gene Regulatory Networks , Gene Expression Regulation , Pollen/genetics
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