NKS1/ELMO4 is an integral protein of a pectin synthesis protein complex and maintains Golgi morphology and cell adhesion in Arabidopsis.

Adjacent plant cells are connected by specialized cell wall regions, called middle lamellae, which influence critical agricultural characteristics, including fruit ripening and organ abscission. Middle lamellae are enriched in pectin polysaccharides, specifically homogalacturonan (HG). Here, we identify a plant-specific Arabidopsis DUF1068 protein, called NKS1/ELMO4, that is required for middle lamellae integrity and cell adhesion. NKS1 localizes to the Golgi apparatus and loss of NKS1 results in changes to Golgi structure and function. The nks1 mutants also display HG deficient phenotypes, including reduced seedling growth, changes to cell wall composition, and tissue integrity defects. These phenotypes are comparable to qua1 and qua2 mutants, which are defective in HG biosynthesis. Notably, genetic interactions indicate that NKS1 and the QUAs work in a common pathway. Protein interaction analyses and modeling corroborate that they work together in a stable protein complex with other pectin-related proteins. We propose that NKS1 is an integral part of a large pectin synthesis protein complex and that proper function of this complex is important to support Golgi structure and function.

Long-term super-resolution inner mitochondrial membrane imaging with a lipid probe.

The inner mitochondrial membrane (IMM) generates power to drive cell function, and its dynamics control mitochondrial health and cellular homeostasis. Here, we describe the cell-permeant, lipid-like small molecule MAO-N3 and use it to assemble high-density environmentally sensitive (HIDE) probes that selectively label and image the IMM in live cells and multiple cell states. MAO-N3 pairs with strain-promoted azide-alkyne click chemistry-reactive fluorophores to support HIDE imaging using confocal, structured illumination, single-molecule localization and stimulated emission depletion microscopy, all with significantly improved resistance to photobleaching. These probes generate images with excellent spatial and temporal resolution, require no genetic manipulations, are non-toxic in model cell lines and primary cardiomyocytes (even under conditions that amplify the effects of mitochondrial toxins) and can visualize mitochondrial dynamics for 12.5 h. This probe will enable comprehensive studies of IMM dynamics with high temporal and spatial resolution.

Activation of the alternative complement pathway modulates inflammation in thoracic aortic aneurysm/dissection.

Thoracic aortic aneurysm/dissection (TAAD) is a lethal vascular disease, and several pathological factors participate in aortic medial degeneration. We previously discovered that the complement C3a-C3aR axis in smooth muscle cells promotes the development of thoracic aortic dissection (TAD) through regulation of matrix metalloproteinase 2. However, discerning the specific complement pathway that is activated and elucidating how inflammation of the aortic wall is initiated remain unknown. We ascertained that the plasma levels of C3a and C5a were significantly elevated in patients with TAD and that the levels of C3a, C4a, and C5a were higher in acute TAD than in chronic TAD. We also confirmed the activation of the complement in a TAD mouse model. Subsequently, knocking out Cfb (Cfb) or C4 in mice with TAD revealed that the alternative pathway and Cfb played a significant role in the TAD process. Activation of the alternative pathway led to generation of the anaphylatoxins C3a and C5a, and knocking out their receptors reduced the recruitment of inflammatory cells to the aortic wall. Moreover, we used serum from wild-type mice or recombinant mice Cfb as an exogenous source of Cfb to treat Cfb KO mice and observed that it exacerbated the onset and rupture of TAD. Finally, we knocked out Cfb in the FBN1C1041G/+ Marfan-syndrome mice and showed that the occurrence of TAA was reduced. In summary, the alternative complement pathway promoted the development of TAAD by recruiting infiltrating inflammatory cells. Targeting the alternative pathway may thus constitute a strategy for preventing the development of TAAD.NEW & NOTEWORTHY The alternative complement pathway promoted the development of TAAD by recruiting infiltrating inflammatory cells. Targeting the alternative pathway may thus constitute a strategy for preventing the development of TAAD.

2D Film-Like Magnetic SERS Tag with Enhanced Capture and Detection Abilities for Immunochromatographic Diagnosis of Multiple Bacteria.

Here, a multiplex surface-enhanced Raman scattering (SERS)-immunochromatography (ICA) platform is presented using a graphene oxide (GO)-based film-like magnetic tag (GFe-DAu-D/M) that effectively captures and detects multiple bacteria in complex specimens. The 2D GFe-DAu-D/M tag with universal bacterial capture ability is fabricated through the layer-by-layer assembly of one layer of small Fe3O4 nanoparticles (NPs) and two layers of 30 nm AuNPs with a 0.5 nm built-in nanogap on monolayer GO nanosheets followed by co-modification with 4-mercaptophenylboronic acid (MPBA) and 5,5'-dithiobis-(2-nitrobenzoic acid).The GFe-DAu-D/M enabled the rapid enrichment of multiple bacteria by MPBA and quantitative analysis of target bacteria on test lines by specific antibodies, thus achieving multiple signal amplification of magnetic enrichment effect and multilayer dense hotspots and eliminating matrix interference in real-world applications. The developed technology can directly and simultaneously diagnose three major pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella typhimurium) with detection limits down to the level of 10 cells mL-1. The good performance of the proposed method in the detection of real urinary tract infection specimens is also demonstrated, suggesting the great potential of the GFe-DAu-D/M-ICA platform for the highly sensitive monitoring of bacterial infections or contamination.

Connection of pre-competition anxiety with gut microbiota and metabolites in wrestlers with varying sports performances based on brain-gut axis theory.

OBJECTIVE: The purpose of this study is to investigate the connection of pre-competition anxiety with gut microbiota and metabolites in wrestlers with different sports performances. METHODS: One week prior to a national competition, 12 wrestlers completed anxiety questionnaires. Faecal and urine samples were collected for the analysis of gut microbiota and metabolites through the high-throughput sequencing of the 16 S rRNA gene in conjunction with untargeted metabolomics technology. The subjects were divided into two groups, namely, achievement (CP) and no-achievement (CnP) wrestlers, on the basis of whether or not their performances placed them in the top 16 at the competition. The relationship amongst the variations in gut microbiota, metabolites, and anxiety indicators was analyzed. RESULTS: (1) The CP group exhibited significantly higher levels of "state self-confidence," "self-confidence," and "somatic state anxiety" than the CnP group. Conversely, the CP group displayed lower levels of "individual failure anxiety" and "sports competition anxiety" than the CnP group. (2) The gut microbiota in the CP group was more diverse and abundant than that in the CnP group. Pre-competition anxiety was linked to Oscillospiraceae UCG_005, Paraprevotella, Ruminococcaceae and TM7x. (3) The functions of differential metabolites in faeces and urine of the CP/CnP group were mainly enriched in caffeine metabolism, lipopolysaccharide biosynthesis and VEGF and mTOR signaling pathways. Common differential metabolites in feces and urine were significantly associated with multiple anxiety indicators. CONCLUSIONS: Wrestlers with different sports performance have different pre-competition anxiety states, gut microbiota distribution and abundance and differential metabolites in faeces and urine. A certain correlation exists between these psychological and physiological indicators.

AUXIN RESPONSE FACTORS 6 and 17 control the flag leaf angle in rice by regulating secondary cell wall biosynthesis of lamina joints.

Flag leaf angle impacts the photosynthetic capacity of densely grown plants and is thus an important agronomic breeding trait for crop architecture and yield. The hormone auxin plays a key role in regulating this trait, yet the underlying molecular and cellular mechanisms remain unclear. Here, we report that two rice (Oryza sativa) auxin response factors (ARFs), OsARF6 and OsARF17, which are highly expressed in lamina joint tissues, control flag leaf angle in response to auxin. Loss-of-function double osarf6 osarf17 mutants displayed reduced secondary cell wall levels of lamina joint sclerenchymatous cells (Scs), resulting in an exaggerated flag leaf angle and decreased grain yield under dense planting conditions. Mechanical measurements indicated that the mutant lamina joint tissues were too weak to support the weight of the flag leaf blade, resembling the phenotype of the rice increased leaf angle1 (ila1) mutant. We demonstrate that OsARF6 and OsARF17 directly bind to the ILA1 promoter independently and synergistically to activate its expression. In addition, auxin-induced ILA1 expression was dependent on OsARF6 and OsARF17. Collectively, our study reveals a mechanism that integrates auxin signaling with the secondary cell wall composition to determine flag leaf angle, providing breeding targets in rice, and potentially other cereals, for this key trait.

Experimental study on monitoring microwave ablation efficacy by real-time shear wave elastography in ex vivo porcine brain.

Objective: Glioma constitutes the most common primary malignant tumor in the central nervous system. In recent years, microwave ablation (MWA) was expected to be applied in the minimally invasive treatment of brain tumors. This study aims to evaluate the feasibility and accuracy of microwave ablation in ex vivo brain tissue by Shear Wave Elastography (SWE) to explore the application value of real-time SWE in monitoring the process of MWA of brain tissue.Methods: Thirty ex vivo brain tissues were treated with different microwave power and ablation duration. The morphologic and microscopic changes of MWA tissues were observed, and the diameter of the ablation areas was measured. In this experiment, SWE is used to quantitatively evaluate brain tissue's degree of thermal injury immediately after ablation.Results: This study It is found that the ablation range measured by SWE after ablation is in good consistency with the pathological range [ICCSWEL1-L1 = 0.975(95% CI:0.959 - 0.985), ICCSWEL2-L2 = 0.887(95% CI:0.779 - 0.938)]. At the same time, the SWE value after ablation is significantly higher than before (mean ± SD,9.88 ± 2.64 kPa vs.23.6 ± 13.75 kPa; p < 0.001). In this study, the SWE value of tissues in different pathological states was further analyzed by the ROC curve (AUC = 0.86), and the threshold for distinguishing normal tissue from tissue after ablation was 13.7 kPa. The accuracy of evaluating ablation tissue using SWE can reach 84.72%, providing data support for real-time quantitative observation of the ablation range.Conclusion: In conclusion the accurate visualization and real-time evaluation of the organizational change range of the MWA process can be realized by real-time SWE.

Restored UBE2C expression in islets promotes ß-cell regeneration in mice by ubiquitinating PER1.

Insulin deficiency may be due to the reduced proliferation capacity of islet ß-cell, contributing to the onset of diabetes. It is therefore imperative to investigate the mechanism of the ß-cell regeneration in the islets. NKX6.1, one of the critical ß-cell transcription factors, is a pivotal element in ß-cell proliferation. The ubiquitin-binding enzyme 2C (UBE2C) was previously reported as one of the downstream molecules of NKX6.1 though the exact function and mechanism of UBE2C in ß-cell remain to be elucidated. Here, we determined a subpopulation of islet ß-cells highly expressing UBE2C, which proliferate actively. We also discovered that ß-cell compensatory proliferation was induced by UBE2C via the cell cycle renewal pathway in weaning and high-fat diet (HFD)-fed mice. Moreover, the reduction of ß-cell proliferation led to insulin deficiency in ßUbe2cKO mice and, therefore, developed type 2 diabetes. UBE2C was found to regulate PER1 degradation through the ubiquitin-proteasome pathway via its association with a ubiquitin ligase, CUL1. PER1 inhibition rescues UBE2C knockout-induced ß-cell growth inhibition both in vivo and in vitro. Notably, overexpression of UBE2C via lentiviral transduction in pancreatic islets was able to relaunch ß-cell proliferation in STZ-induced diabetic mice and therefore partially alleviated hyperglycaemia and glucose intolerance. This study indicates that UBE2C positively regulates ß-cell proliferation by promoting ubiquitination and degradation of the biological clock suppressor PER1. The beneficial effect of UBE2C on islet ß-cell regeneration suggests a promising application in treating diabetic patients with ß-cell deficiency.

Diagnostic feasibility of middle cerebral artery stenosis or occlusion evaluated by TCCS and CEUS: Repeatability, reproducibility, and diagnostic agreement with DSA.

AIM: This study aimed to evaluate the feasibility of transcranial color-coded sonography (TCCS) and contrast-enhanced ultrasound (CEUS) in assessing middle cerebral artery (MCA) stem stenosis or occlusion compared to digital subtraction angiography (DSA). METHODS: A total of 48 cases including 96 MCAs suspected stem stenosis or obstruction in the MCA were assessed by TCCS, CE-TCCS, and DSA. The diameters of the most severe stenosis (Ds), proximal normal artery (Dn), and diameter stenosis rate of MCA were measured using both the color doppler flow imaging (CDFI) modality of TCCS or CEUS and the CEUS imaging modality. The intraclass correlation coefficients (ICCs) and 95 % confidence intervals (CI) were evaluated, and a weighted Kappa value was used to evaluate the intra-observer agreement, inter-observer agreement, agreement between CDFI modality and DSA stenosis or occlusion, and agreement between CEUS imaging modality and DSA stenosis or occlusion. RESULTS: The ICC results indicated excellent repeatability and reproducibility (all ICCs > 0.75; weighted Kappa values >0.81). Compared with DSA, the weighted Kappa values and 95 % CIs of stenosis (the first measurement was taken by two observers) of CDFI modality and CEUS imaging modality were 0.175 (0.041, 0.308) and 0.779 (0.570, 0.988) for observers A and 0.181 (0.046, 0.316) and 0.779 (0.570, 0.988) for observers B respectively. CONCLUSION: This study indicates that inter- and intra-observer agreements were good for the direct method of measuring percentages of MCA stenosis by TCCS and CEUS. CEUS imaging modality is a new and reliable imaging modality approach to evaluate the MCAs stenosis and occlusion.

Single-cell RNA sequencing combined with single-cell proteomics identifies the metabolic adaptation of islet cell subpopulations to high-fat diet in mice.

AIMS/HYPOTHESIS: Islets have complex heterogeneity and subpopulations. Cell surface markers representing alpha, beta and delta cell subpopulations are urgently needed for investigations to explore the compositional changes of each subpopulation in obesity progress and diabetes onset, and the adaptation mechanism of islet metabolism induced by a high-fat diet (HFD). METHODS: Single-cell RNA sequencing (scRNA-seq) was applied to identify alpha, beta and delta cell subpopulation markers in an HFD-induced mouse model of glucose intolerance. Flow cytometry and immunostaining were used to sort and assess the proportion of each subpopulation. Single-cell proteomics was performed on sorted cells, and the functional status of each alpha, beta and delta cell subpopulation in glucose intolerance was deeply elucidated based on protein expression. RESULTS: A total of 33,999 cells were analysed by scRNA-seq and clustered into eight populations, including alpha, beta and delta cells. For alpha cells, scRNA-seq revealed that the Ace2low subpopulation had downregulated expression of genes related to alpha cell function and upregulated expression of genes associated with beta cell characteristics in comparison with the Ace2high subpopulation. The impaired function and increased fragility of ACE2low alpha cells exposure to HFD was further suggested by single-cell proteomics. As for beta cells, the CD81high subpopulation may indicate an immature signature of beta cells compared with the CD81low subpopulation, which had robust function. We also found differential expression of Slc2a2 in delta cells and a potentially stronger cellular function and metabolism in GLUT2low delta cells than GLUT2high delta cells. Moreover, an increased proportion of ACE2low alpha cells and CD81low beta cells, with a constant proportion of GLUT2low delta cells, were observed in HFD-induced glucose intolerance. CONCLUSIONS/INTERPRETATION: We identified ACE2, CD81 and GLUT2 as surface markers to distinguish, respectively, alpha, beta and delta cell subpopulations with heterogeneous maturation and function. The changes in the proportion and functional status of islet endocrine subpopulations reflect the metabolic adaptation of islets to high-fat stress, which weakened the function of alpha cells and enhanced the function of beta and delta cells to bring about glycaemic homeostasis. Our findings provide a fundamental resource for exploring the mechanisms maintaining each islet endocrine subpopulation's fate and function in health and disease. DATA AVAILABILITY: The scRNA-seq analysis datasets from the current study are available in the Gene Expression Omnibus (GEO) repository under the accession number GSE203376.

Interaction between the GCKR rs1260326 variant and serum HDL cholesterol contributes to HOMA-ß and ISIMatusda in the middle-aged T2D individuals.

This study aims to investigate the correlations between islet function/ insulin resistance and serum lipid levels, as well as to assess whether the strength of such correlations is affected by the GCKR rs1260326 variant in healthy and T2D individuals. We performed an oral glucose tolerance test (OGTT) on 4889 middle-aged adults, including 3135 healthy and 1754 T2D individuals from the REACTION population study in the Nanjing region. We also measured their serum lipid levels and genotyped for rs1260326. We found that serum high-density lipoprotein (HDL) cholesterol and triglyceride (TG) levels were independently correlated with indexes of islet function (HOMA-ß and IGI [insulinogenic index]) and insulin resistance (HOMO-IR and ISIMatsuda) in both healthy and T2D individuals. The correlations were significantly decreased in T2D individuals, with significant heterogeneities compared to healthy controls (I2 > 75%, Phet < 0.05). Although no correlation was observed between serum total cholesterol (TC) level and islet function/ insulin resistance in healthy controls, significant correlations were found in T2D individuals, with significant heterogeneity to healthy controls in the correlation with ISIMatsuda(I2 = 85.3%, Phet = 0.009). Furthermore, we found significant interactions of the GCKR rs1260326 variant for the correlations between serum HDL cholesterol and HOMA-ß/ISIMatsuda in T2D subjects (P = 0.015 and 0.038, respectively). These findings illustrate that distinct correlations between serum lipid levels and islet function/ insulin resistance occurred in T2D subjects compared to healthy individuals. Common gene variants, such as rs1260326, might interact substantially when studied in specific populations, especially T2D disease status.

Soluble Urokinase Plasminogen Activator Receptor Levels and Outcomes in Patients with Heart Failure.

BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of immune activation and pathogenic factor for kidney disease shown to predict cardiovascular outcomes including heart failure (HF) in various populations. We characterized suPAR levels in patients with HF and compared its ability to discriminate risk to that of B-type natriuretic peptide (BNP). METHODS AND RESULTS: We measured plasma suPAR and BNP levels in 3,437 patients undergoing coronary angiogram and followed for a median of 6.2 years. We performed survival analyses for the following outcomes: all-cause death, cardiovascular death, and hospitalization for HF. We then assessed suPAR's ability to discriminate risk for the aforementioned outcomes. We identified 1116 patients with HF (age 65±12, 67.2% male, 20.0% Black, 67% with reduced ejection fraction). The median suPAR level was higher in HF compared to those without HF (3370 [IQR 2610-4371] vs. 2880 [IQR 2270-3670] pg/mL, respectively, P<0.001). In patients with HF, suPAR levels (log-base 2) were associated with outcomes including all-cause death (adjusted hazard ratio aHR 2.30, 95%CI[1.90-2.77]), cardiovascular death (aHR 2.33 95%CI[1.81-2.99]) and HF hospitalization (aHR 1.96, 95%CI[1.06-1.25]) independently of clinical characteristics and BNP levels. The association persisted across subgroups and did not differ between patients with reduced or preserved ejection fraction, or those with ischemic or non-ischemic cardiomyopathy. Addition of suPAR to a model including BNP levels significantly improved the C-statistic for death (Δ0.027), cardiovascular death (Δ0.017) and hospitalization for HF (Δ0.017). CONCLUSIONS: SuPAR levels are higher in HF compared to non-HF, are strongly predictive of outcomes, and combined with BNP, significantly improved risk prediction.

Multimodal ultrasound-based carotid plaque risk biomarkers predict poor functional outcome in patients with ischemic stroke or TIA.

BACKGROUND: Carotid vulnerable plaque is an important risk factor for stroke occurrence and recurrence. However, the relationship between risk parameters related to carotid vulnerable plaque (plaque size, echogenicity, intraplaque neovascularization, and plaque stiffness) and neurological outcome after ischemic stroke or TIA is unclear. This study investigates the value of multimodal ultrasound-based carotid plaque risk biomarkers to predict poor short-term functional outcome after ischemic stroke or TIA. METHODS: This study was a single-center, prospective, continuous, cohort study to observe the occurrence of adverse functional outcomes (mRS 2-6/3-6) 90 days after ischemic stroke or TIA in patients, where the exposure factors in this study were carotid plaque ultrasound risk biomarkers and the risk factors were sex, age, disease history, and medication history. Patients with ischemic stroke or TIA (mRS ≤3) whose ipsilateral internal carotid artery stenosis was ≥50% within 30 days were included. All patients underwent multimodal ultrasound at baseline, including conventional ultrasound, superb microvascular imaging (SMI), and shear wave elastography (SWE). Continuous variables were divided into four groups at interquartile spacing for inclusion in univariate and multifactorial analyses. After completion of a baseline ultrasound, all patients were followed up at 90 days after ultrasound, and patient modified neurological function scores (mRSs) were recorded. Multivariate Cox regression and ROC curves were used to assess the risk factors and predictive power for predicting poor neurological function. RESULTS: SMI revealed that 20 (30.8%) patients showed extensive neovascularization in the carotid plaque, and 45 (69.2%) patients showed limited neovascularization in the carotid plaque. SWE imaging showed that the mean carotid plaque stiffness was 51.49 ± 18.34 kPa (23.19-111.39 kPa). After a mean follow-up of 90 ± 14 days, a total of 21 (32.3%) patients had a mRS of 2-6, and a total of 10 (15.4%) patients had a mRS of 3-6. Cox regression analysis showed that the level of intraplaque neovascularization and plaque stiffness were independent risk factors for a mRS of 2-6, and the level of intraplaque neovascularization was an independent risk factor for a mRS of 3-6. After correcting for confounders, the HR of intraplaque neovascularization level and plaque stiffness predicting a mRS 2-6 was 3.06 (95% CI 1.05-12.59, P = 0.041) and 0.51 (95% CI 0.31-0.83, P = 0.007), respectively; the HR of intraplaque neovascularization level predicting a mRS 3-6 was 6.11 (95% CI 1.19-31.45, P = 0.031). For ROC curve analysis, the mRSs for intraplaque neovascularization level, plaque stiffness, and combined application to predict 90-day neurological outcome ranged from 2 to 6, with AUCs of 0.73 (95% CI 0.59-0.87), 0.76 (95% CI 0.64-0.89) and 0.85 (95% CI 0.76-0.95), respectively. The mRSs for the intraplaque neovascularization level to predict 90-day neurological outcome ranged from 3 to 6, with AUCs of 0.79 (95% CI 0.63-0.95). CONCLUSION: Intraplaque neovascularization level and plaque stiffness may be associated with an increased risk of poor short-term functional outcome after stroke in patients with recent anterior circulation ischemic stroke due to carotid atherosclerosis. The combined application of multiple parameters has efficacy in predicting poor short-term functional outcome after stroke.

Mesoporous polydopamine delivering 8-gingerol for the target and synergistic treatment to the spinal cord injury.

In the treatment of spinal cord injury (SCI), the complex process of secondary injury is mainly responsible for preventing SCI repair or even exacerbating the injury. In this experiment, we constructed the 8-gingerol (8G)-loaded mesoporous polydopamine (M-PDA), M@8G, as the in vivo targeting nano-delivery platform, and investigated the therapeutic effects of M@8G in secondary SCI and its related mechanisms. The results indicated that M@8G could penetrate the blood-spinal cord barrier to enrich the spinal cord injury site. Mechanism research has shown that all of the M-PDA,8G and M@8G displayed the anti-lipid peroxidation effect, and then M@8G can inhibit the secondary SCI by suppressing the ferroptosis and inflammation. In vivo assays showed that M@8G significantly diminished the local injury area, reduced axonal and myelin loss, thus improving the neurological and motor recovery in rats. Based on the analysis of cerebrospinal fluid samples from patients, ferroptosis occurred locally in SCI and continued to progress in patients during the acute phase of SCI as well as the stage after their clinical surgery. This study showcases effective treatment of SCI through the aggregation and synergistic effect of M@8G in focal areas, providing a safe and promising strategy for the clinical treatment of SCI.

Abnormal adenosine metabolism of neutrophils inhibits airway inflammation and remodeling in asthma model induced by Aspergillus fumigatus.

BACKGROUND: Neutrophils consume a large amount of energy when performing their functions. Compared with other white blood cells, neutrophils contain few mitochondria and mainly rely on glycolysis and gluconeogenesis to produce ATP. The inflammatory site is hypoxic and nutrient poor. Our aim is to study the role of abnormal adenosine metabolism of neutrophils in the asthmatic airway inflammation microenvironment. METHOD: In this study, an asthma model was established by intratracheal instillation of Aspergillus fumigatus extract in Ecto-5'-Nucleotidase (CD73) gene-knockout and wild-type mice. Multiple analyses from bronchoalveolar lavage fluid (BALF) were used to determine the levels of cytokines and chemokines. Immunohistochemistry was used to detect subcutaneous fibrosis and inflammatory cell infiltration. Finally, adenosine 5'-(α, ß-methylene) diphosphate (APCP), a CD73 inhibitor, was pumped subcutaneously before Aspergillus attack to observe the infiltration of inflammatory cells and subcutaneous fibrosis to clarify its therapeutic effect. RESULT: PAS staining showed that CD73 knockout inhibited pulmonary epithelial cell proliferation and bronchial fibrosis induced by Aspergillus extract. The genetic knockdownof CD73 significantly reduced the production of Th2 cytokines, interleukin (IL)-4, IL-6, IL-13, chemokine (C-C motif) ligand 5 (CCL5), eosinophil chemokine, neutrophil IL-17, and granulocyte colony-stimulating factor (G-CSF). In addition, exogenous adenosine supplementation increased airway inflammation. Finally, the CD73 inhibitor APCP was administered to reduce inflammation and subcutaneous fibrosis. CONCLUSION: Elevated adenosine metabolism plays an inflammatory role in asthma, and CD73 could be a potential therapeutic target for asthma.

Simultaneously ultrasensitive and quantitative detection of influenza A virus, SARS-CoV-2, and respiratory syncytial virus via multichannel magnetic SERS-based lateral flow immunoassay.

Respiratory viruses usually induced similar clinical symptoms at early infection. Herein, we presented a multichannel surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-based LFA) using high-performance magnetic SERS tags for the simultaneous ultrasensitive detection of respiratory viruses, namely influenza A virus (H1N1), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) in biological samples. As-prepared magnetic SERS tags can directly enrich and capture target viruses without pretreatment of samples, avoiding the interference of impurities in the samples as well as improving the sensitivity. With the capture-detection method, the detection limits of the proposed assay reached 85 copies mL-1, 8 pg mL-1, and 8 pg mL-1 for H1N1, SARS-CoV-2 and RSV, respectively. Moreover, the detection properties of the proposed method for target viruses in throat swab samples were verified, suggesting its remarkable potential for the early and rapid differential diagnosis of respiratory viruses.

Quantitative assessment of thenar to evaluate hand function after stroke by Bayes discriminant.

BACKGROUND: The incidence rate of stroke or cerebrovascular accidents ranks first in China. More than 85% of stroke patients have residual upper limb motor dysfunction, especially hand dysfunction. Normalizing the rehabilitation evaluation process and standard quantitative evaluation method is a complex and key point in rehabilitation therapy. The study aimed to establish a function model based on the Bayes discriminant by measuring the thenar stiffness with shear wave elastography (SWE) to quantitatively evaluate the hand motor function of hemiplegic patients after stroke. METHODS: This study collected 60 patients diagnosed with hemiplegia after stroke from October 2021 to October 2022. Therapists used the Brunnstrom assessment (BA)scale to divide the patients into the stage. All the patients underwent the measurement of SWE examination of abductor pollicis brevis (APB), opponens pollicis (OP), flexor pollicis long tendon (FPLT), and flexor pollicis brevis (FPB) by two sonographers. The SWE change rate of four parts of the thenar area was calculated prospectively with the non-hemiplegic side as the reference, the function equation was established by the Bayes discriminant method, and the evaluation model was fitted according to the acquired training set data. Lastly, the model was verified by self-validation, cross-validation, and external data validation methods. The classification performance was evaluated regarding the area under the ROC curve (AUC), sensitivity, and specificity. RESULTS: The median SWE values of the hemiplegic side of patients were lower than those of the non-hemiplegic side. According to the BA stage and SWER of APB, OP, FPLT, and FPB, our study established the Bayes discriminative model and validated it via self-validation and cross-validation methods. Then, the discriminant equation was used to validate 18 patients prospectively, the diagnostic coincidence rate was about 78.8%, and the misjudgment rate was approximately 21.2%. The AUC of the discriminant model for diagnosing BA stage I-VI was 0.928(95% CI: 0.839-1.0),0.858(95% CI: 0.748-0.969),1.0(95% CI: 1.0-1.0), 0.777(95% CI: 0.599-0.954),0.785(95% CI: 0.593-0.977) and 0.985(95% CI: 0.959-1.0), respectively. CONCLUSION: This Bayes discriminant model built by measuring thenar stiffness was of diagnostic value and can provide an objective basis for evaluating clinical rehabilitation.

Introduction of multilayered quantum dot nanobeads into competitive lateral flow assays for ultrasensitive and quantitative monitoring of pesticides in complex samples.

A competitive fluorescent lateral flow assay (CFLFA) is proposed for direct, ultrasensitive, quantitative detection of common pesticides imidacloprid (IMI) and carbendazim (CBZ) in complex food samples by using silica-core multilayered quantum dot nanobeads (SiO2-MQB) as liquid fluorescent tags. The SiO2-MQB nanostructure comprises a 200-nm SiO2 core and a shell of hundreds of carboxylated QDs (excitation/emission maxima ~365/631 nm), and can generate better stability, superior dispersibility, and higher luminescence than traditional fluorescent beads, greatly improving the sensitivity of current LFA methods for pesticides. Moreover, using liquid SiO2-MQB directly instead of via the conjugate pad both simplifies the structure of LFA system and improves the efficiency of immunobinding reactions between nanotags and the targets. Applying these methods, the established CFLFA realized the stable and accurate detection of IMI and CBZ in 12 min, with detection limits down to 1.94 and 14.79 pg/mL, respectively. The SiO2-MQB-CFLFA is practicable for application to real food samples (corn, apple, cucumber, and cabbage), and undoubtedly a promising and low-cost tool for on-site monitoring of trace pesticide residues.

Deflection Estimation of Truss Structures Using Inverse Finite Element Method.

It is well recognized that strain and deflection data are important indexes to judge the safety of truss structures. Specifically, the shape sensing technology can estimate the deformation of a structure by exploiting the discrete strain data without considering the material property conditions. To fill the gap in which most of the methods in SHM (structural health monitoring) cannot be directly used to predict the displacement field, this paper proposed a novel inverse finite element method (iFEM) algorithm based on the equivalent stiffness theory. A deflection sensor is fabricated to focus on predicting the distributed deflection variation of the truss structure. The performance of the deflection sensor was evaluated by a calibration test and a stability test. Finally, it was applied to distributed deflection monitoring in the testing of truss structures. Results of all tests verify that the deflection sensor based on the i-FEM algorithm can predict the distributed deflection variation of the truss structure accurately, in real time, and dynamically.

Study on the correlation between cardiac function indices measured by velocity vector imaging and disease severity in patients with Parkinson disease.

AIM: This study aimed to evaluate cardiac function, particularly left ventricular systolic function, in patients with Parkinson disease (PD) using velocity vector imaging (VVI), and to determine whether a correlation exists between left ventricular global systolic function and PD severity. METHODS: A case-control study design was used to select 56 PD patients and 30 healthy controls from January 2019 to December 2019. The characteristics of age, sex, BMI and course of disease were collected. The Hoehn-Yahr (H-Y) score was collected to record the grading of PD. The left ventricular systolic function of all patients was evaluated by variable vapor injection (VVI). The left ventricular systolic function was compared between the case group and the control group, and the correlation between cardiac dysfunction and the severity of PD symptoms was assessed using the modified H-Y scale. RESULTS: Compared with control group, left ventricular global systolic function18.22 (17.08, 19.12) vs 18.88 (18.12, 20.01) was lower in PD patients as indicated by left ventricular global longitudinal strain (GLS), and the difference was statistically significant (P = 0.039). Additionally, H-Y scores (r = -0.404) and PD duration(r = -0.323) were significantly correlated with reduced left ventricular ejection fraction (P < 0.01), GLS (P < 0.001), left ventricular global radial strain (GRS; P < 0.001), and left ventricular global circumferential strain (GCS; P < 0.001), along with their associated peak strain rates (GLSr, GRSr, and GCSr; P < 0.001). CONCLUSION: Subclinical left ventricular global systolic dysfunction in patients with PD can be detected using VVI, and reduced left ventricular systolic function correlates with the modified H-Y score and duration of the disease.