Search

The design of void-confined tubular nanostructures has aroused significant interest for catalytic applications because of their distinct microenvironment to modulate the reaction kinetics. Herein, we propose a facile wrapping-pyrolysis strategy to confine Fe

Here, silica microspheres were decorated with two-dimensional metal–organic frameworks (2D MOFs) nanosheets and ionic liquids, and evaluated as the mixed-mode stationary phase for chromatographic separation. The ionic liquids were used to assist the synthesis of 2D MOFs nanosheets, and also acted as adhesives among the nanosheets and silica. In contrast with the 2D MOFs-based column without ionic liquids and commercial columns, the prepared column exhibited enhanced chromatographic separation performance for partially hydrophilic compounds such as alkaloids, sulfonamides and antibiotics, etc. In addition to excellent chromatographic repeatability and stability, it has also been verified that the composites could be easily and repeatedly prepared. The relative standard deviation of the retention time of the same type of analyte between the three batches of materials was ranging from 0.21% to 1.7%. In short, these results indicated that the synthesized composites were promising separation material for liquid chromatography, which made it possible to broaden the application of 2D MOFs in the field of chromatography.

Abstract Purpose Hepatocellular carcinoma (HCC) is a highly vascularized solid carcinoma and tumor vessel–targeted molecular imaging might be effective for early diagnosis of HCC. Herein, we developed a novel trimeric affibody (ZTRI) with highly specific binding to the platelet-derived growth factor receptor beta (PDGFRβ). The aim of this study is to evaluate the feasibility of 68Ga-radiolabeled ZTRI ([68Ga]Ga-DOTA-ZTRI) as PET tracer for diagnosis of HCC. Methods The bioinformatics analysis of clinical database and immunoblotting of clinical specimens were performed to validate the potential of PDGFRβ as HCC biomarker. The trimeric affibody ZTRI was conjugated with DOTA-NHS-ester and radiolabeled with 68Ga to produce [68Ga]Ga-DOTA-ZTRI conjugate. Immunoreactivity and specific uptake of [68Ga]Ga-DOTA-ZTRI were assessed by dose-dependent cell binding, autoradiography, and biodistribution analysis. [68Ga]Ga-DOTA-ZTRI PET/CT scanning of diethylnitrosamine (DEN)-induced primary HCC rats and a rare case of idiopathical HCC rhesus monkey was performed to evaluate the imaging capability and radiation dosimetry of [68Ga]Ga-DOTA-ZTRI in vivo. Results Excessive PDGFRβ was validated as a representative biomarker of HCC neovascularization. The radiolabeling of [68Ga]Ga-DOTA-ZTRI was achieved at more than 95% radiochemical yield. In vitro assays showed specific uptake of [68Ga]Ga-DOTA-ZTRI in HCC tumor vessels by autoradiography. Animal PET/CT imaging with [68Ga]Ga-DOTA-ZTRI successfully visualized the tumor lesions in primary HCC rats and rhesus monkey, and indicated radiation absorbed dose of 2.03E-02 mSv/MBq for each scanning. Conclusions Our results demonstrated that [68Ga]Ga-DOTA-ZTRI conjugate could be applied as a promising PET tracer for early diagnosis of hepatocellular carcinoma.

Multidrug resistance (MDR), which is common in colorectal cancer (CRC), induces high mortality in patients. Due to its robust and selective apoptosis induction in some CRC cells with MDR, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is attractive as a novel tool for CRC therapy. However, TRAIL is limited by its poor tumor-homing ability and inefficient apoptosis induction in CRC cells expressing low levels of death receptor (DR). Here, the tumor-homing RGR peptide (CRGRRST) was fused to TRAIL to produce RGR-TRAIL. Compared with TRAIL, RGR-TRAIL showed greater cell binding and cytotoxicity in CRC cells. In addition, RGR-TRAIL exerted significantly enhanced tumor uptake and growth suppression in mice bearing CRC tumor xenografts. Notably, RGR-TRAIL eradicated all tumor xenografts of DR-overexpressing COLO205 cells. However, TRAIL only showed mild tumor growth suppression under the same conditions, indicating that RGR fusion significantly increased the antitumor effect of TRAIL in DR-overexpressing CRC cells by improving tumor homing. Nevertheless, RGR fusion did not significantly enhance the antitumor effect of TRAIL in HT29 cells expressing low levels of DR. We found that DR expression in HT29 cells was enhanced by epidermal growth factor receptor (EGFR)-targeted photodynamic therapy (PDT). Moreover, both the in vitro and in vivo antitumor effects of RGR-TRAIL were significantly improved by combination with PDT. HT29 tumor xenografts (∼20%) were even eradicated by combination therapy. These results indicate that it is valuable to further evaluate the combination therapy of RGR-TRAIL and tumor-targeted PDT for clinical therapy of CRC with MDR.

To investigate the refractive and biometrical developments of children with retinopathy of prematurity (ROP) who received laser photocoagulation (LP) or intravitreal ranibizumab injection as treatment.This case-control study involved cases with Zone II Stage 3 ROP. Fourteen children (28 eyes) who received single LP were included in the laser group, and 14 children (27 eyes) who received single intravitreal ranibizumab injection were included in the injection group. The mean age at operation was 37.00±1.72 and 36.36±1.66 weeks for the laser and injection groups, respectively (P=0.161), and refraction measurements and biometry were performed at the mean age of 5.00±1.63 and 5.00±0.94 years for the laser and injection groups, respectively (P=1.000). Spherical equivalent (SE) after mydriatic refraction and best corrected visual acuity (BCVA) were measured by refraction test. Central corneal thickness (CCT), anterior corneal surface curvature and curvature radius, anterior chamber depth (ACD), lens thickness (LT) and axial length (AL) were measured by biometry using the IOL Master700 biometric instrument (Carl Zeiss Meditec AG). The biometrical images were reanalysed using a self-developed program in MATLAB (R2016a, MathWorks, Inc.) to obtain additional eye parameters, including the curvatures of the posterior cornea and the anterior and posterior surfaces of the lens. SPSS (V.23.0) was used for statistical analysis. Independent sample t test was used to compare the eyeball biological and refractive state measures of the two groups, and Pearson correlation coefficient was used to evaluate the correlation between SE and the biological parameters.1. (1) Cornea-related parameters: CCT (0.54±0.04mm vs 0.55±0.02mm, P0.05), anterior corneal surface curvature radius (7.56±0.26 mm vs 7.67±0.43mm, P0.05) and posterior corneal surface curvature radius (6.82±0.27mm vs 6.79±0.42mm, P0.05). (2) ACD (3.21 ± 0.25mm vs 3.22 ± 0.19mm, P0.05). (3) Lens-related parameters: anterior lens surface curvature radius (10.04±0.89mm vs 9.82±1.08mm, P0.05), posterior lens surface curvature radius (5.49±0.55mm vs 5.92±0.73mm, P0.05) and LT (3.80±0.14mm vs 3.59±0.16mm, P0.05). (4) AL (21.82±1.07 vs 22.68±1.61, P0.05). (5) Parameters related to refractive state: SE (-2.43±3.56 vs -0.53±3.12, P0.05) and BCVA (log MAR, 0.17±0.14 vs 0.21±0.18, P0.05). 2. (1) The SE of children in the laser group was positively correlated with LT (r=0.438, P0.05), negatively correlated with ACD (r=-0.437, P0.05) and had no significant correlation with other eyeball biological indicators (P0.05). (2) The SE of children in the injection group was negatively correlated with AL (r=-0.537, P0.05), positively correlated with CCT (r=0.455, P0.05) and had no significant correlation with other eyeball biological indicators (P0.05).LP and intravitreal ranibizumab injection as ROP treatments produce myopic refraction with increased degree of myopia in children who received LP than in children who received ranibizumab injection. The increased myopia after LP is due to the increases in LT and posterior lens curvature and a shallow ACD.

As the main flavor components of tea, the contents of epigallocatechin-3-gallate (EGCG), theanine and caffeine are regulated by ambient temperature. However, whether the biosynthesis of EGCG, theanine and caffeine in response to temperature is regulated by endogenous hormones and its mechanism is still unclear. In this study, tea cuttings cultivated in the phytotron which treated at different temperatures 15℃, 20℃, 25℃ and 30℃, respectively. The UPLC and ESI-HPLC-MS/MS were used to determine the contents of EGCG, theanine, caffeine and the contents of phytohormones in one leaf and a bud. The results showed that indoleacetic acid (IAA), gibberellin 1(GA1) and gibberellin 3 (GA3) were significantly correlated with the content of EGCG; Jasmonic acid (JA), jasmonate-isoleucine (JA-Ile) and methyl jasmonate (MeJA) were strongly correlated with theanine content; IAA, GA1 and gibberellin 4 (GA4) were significantly correlated with caffeine content at different temperatures. In order to explore the internal intricate relationships between the biosynthesis of these three main taste components, endogenous hormones, and structural genes in tea plants, we used multi-omics and multidimensional correlation analysis to speculate the regulatory mechanisms: IAA, GA1 and GA3 up-regulated the expressions of chalcone synthase (CsCHS) and trans-cinnamate 4-monooxygenase (CsC4H) mediated by the signal transduction factors auxin-responsive protein IAA (CsIAA) and DELLA protein (CsDELLA), respectively, which promoted the biosynthesis of EGCG; IAA, GA3 and GA1 up-regulated the expression of CsCHS and anthocyanidin synthase (CsANS) mediated by CsIAA and CsDELLA, respectively, via the transcription factor WRKY DNA-binding protein (CsWRKY), and promoted the biosynthesis of EGCG; JA, JA-Ile and MeJA jointly up-regulated the expression of carbonic anhydrase (CsCA) and down-regulated the expression of glutamate decarboxylase (CsgadB) mediated by the signal transduction factors jasmonate ZIM domain-containing protein (CsJAZ), and promoted the biosynthesis of theanine; JA, JA-Ile and MeJA also jointly inhibited the expression of CsgadB mediated by CsJAZ via the transcription factor CsWRKY and AP2 family protein (CsAP2), which promoted the biosynthesis of theanine; IAA inhibited the expression of adenylosuccinate synthase (CspurA) mediated by CsIAA via the transcription factor CsWRKY; GA1 and gibberellin 4 (GA4) inhibited the expression of CspurA mediated by CsDELLA through the transcription factor CsWRKY, which promoted the biosynthesis of caffeine. In conclusion, we revealed the underlying mechanism of the biosynthesis of the main taste components in tea plant in response to temperature was mediated by hormone signal transduction factors, which provided novel insights into improving the quality of tea.

Background Prenatal diagnosis of cleft palate is still challenging. To describe a practical and efficient method, sequential sector-scan through oral fissure (SSTOF), to evaluate palate. Methods According to the characteristics of the fetal oral anatomy and ultrasonic directivity, we designed a practical method, sequential sector-scan through oral fissure, to evaluate the fetal palate, and the approach was verified efficiently by following up results of those fetuses with orofacial cleft who were induced because of their accompanied lethal malformations. Then, the 7098 fetuses were evaluated using sequential sector-scan through oral fissure. Fetuses were followed up after birth or induction to validate and analyze prenatal diagnosis. Result According to the scanning design, sequential sector-scan through oral fissure was performed successfully from the soft palate to the upper alveolar ridge in induced labor fetuses, and the structures were displayed clearly. Among 7098 fetuses, satisfactory images were obtained for 6885 fetuses and the remaining 213 fetuses’ images were unsatisfactory because of fetuses’ positions and pregnant women with high BMI. Among 6885 fetuses, 31cases were diagnosed CLP or CP, which were confirmed after delivery or termination. There were no missing cases. Conclusions SSTOF is a practical and efficient method to diagnose cleft palate, which might be applied to evaluate the fetal palate in prenatal diagnosis.

IntroductionInnate lymphoid cells (ILCs) are key components of the immune system, yet the similarity and distinction of the properties across tissues under homeostasis, inflammation and tumor process remain elusive.MethodsHere we performed integrative inference of ILCs to reveal their transcriptional profiles and heterogeneity from single-cell genomics. We collected a large number of ILCs from human six different tissues which can represent unique immune niches (circulation, lymphoid tissue, normal and inflamed mucosa, tumor microenvironment), to systematically address the transcriptional imprinting.ResultsILCs are profoundly imprinted by their organ of residence, and tissue-specific distinctions are apparent under pathological conditions. In the hepatocellular carcinoma microenvironment, we identified intermediate c-kit+ ILC2 population, and lin-CD127- NK-like cells that expressed markers of cytotoxicity including CCL5 and IFNG. Additionally, CD127+CD94+ ILC1s were preferentially enriched in inflamed ileum from patients with Crohn’s disease.DiscussionThese analyses depicted a comprehensive characterization of ILC anatomical distribution and subset heterogeneity, and provided a base line for future temporal or spatial studies focused on tissue-specific ILC-mediated immunity.

Background：Retinopathy of prematurity (ROP) is one of the leading causes of babies’ visual impairment and blindness. There is no effective intervention with ROP so far, and thus a deeper understanding of oxygen-induced metabolism may offer novel potential therapeutic approaches to ROP. The aim of this study is to explore a correlation of oxygen-induced renal metabolism with those in eyes and blood from ROP patients or a mouse model of oxygen-induced retinopathy (OIR). Methods：At postnatal day 7 (P7), 30 healthy C57BL6/J mice were randomly selected and divided into two groups, an OIR group and a WT group. The R-OIR group (N = 8) and R-WT group (N = 8) were examined for renal untargeted metabolomics; Targeted metabolomics analysis was performed to detect vitreous in V-OIR group (N = 7) and V-WT group (N = 7). Network association analysis was performed with the above results and previous studies: retinal-targeted metabolomics of OIR and human blood-targeted metabolomics of ROP. Results：The levels of metabolites in the R-OIR group were slightly higher than those in the R-WT group, especially in lipids. However, nucleotides of the R-OIR group were lower than the R-WT group. There were 9 canonical signaling pathways enriched, in which the initiation and progression of pathologic retinal neovascularization were closely associated with purine metabolism, arginine biosynthesis, histidine metabolism, pantothenate and CoA biosynthesis, alanine, aspartate and glutamate metabolism; arginine and proline metabolism, tryptophan metabolism, beta-Alanine metabolism, and D-glutamine as well as D-glutamate metabolism. In addition, L-histidinol, Isoguanosine, guanosine, guanine, nicotyrine, quinoxaline-2-carboxylic acid, L-3-hydroxykynurenine, N-gamma-glutamyl-S-propylcysteine, alanine, adenosine diphosphate, and ribose were potential biomarkers of ROP. Conclusion：Shikimic acid and PC(14:1(9Z)/20:2(11Z,14Z)) are highly specific biomarkers of renal metabolomics of OIR. Arginine biosynthesis is the best common pathway of kidney-untargeted OIR metabolomics, vitreous-, and retina-targeted OIR metabolomics, and blood-targeted metabolomics of ROP, indicating that arginine biosynthesis is the common pathway of ROP and neonatal kidney injury.

Universal Adversarial Perturbations(UAPs), which are image-agnostic adversarial perturbations, have been demonstrated to successfully deceive computer vision models. Proposed UAPs in the case of data-dependent, use the internal layers’ activation or the output layer’s decision values as supervision. In this paper, we use both of them to drive the supervised learning of UAP, termed as fully supervised UAP(FS-UAP), and design a progressive optimization strategy to solve the FS-UAP. Specifically, we define an internal layers supervised objective relying on multiple major internal layers’ activation to estimate the deviations of adversarial examples from legitimate examples. We also define an output layer supervised objective relying on the logits of output layer to evaluate attacking degrees. In addition, we use the UAP found by previous stage as the initial solution of the next stage so as to progressively optimize the UAP stage-wise. We use seven networks and ImageNet dataset to evaluate the proposed FS-UAP, and provide an in-depth analysis for the latent factors affecting the performance of universal attacks. The experimental results show that our FS-UAP (i) has powerful capability of cheating CNNs (ii) has superior transfer-ability across models and weak data-dependent (iii) is appropriate for both untarget and target attacks.

Extended left ventricular septal myectomy remains the gold standard for the treatment of hypertrophic obstructive cardiomyopathy (HOCM) with refractory symptoms. On the basis of traditional modified transaortic Morrow myectomy, we innovatively performed a minimally invasive, video-assisted single-port thoracotomy through the right infra-axillary region. Our procedure can provide good visualization of the left ventricular outflow tract and hypertrophic ventricular septum for accurate resection. It also ensures optimal exposure of the mitral valve in the presence of complex mitral subvalvular structures.

The computing power of various Internet of Things (IoT) devices is quite different. To enable IoT devices with lower computing power to perform machine learning, all nodes can only train smaller models, which results in the waste of computing power for high-performance devices. In this paper, a heterogeneous model fusion federated learning mechanism is proposed. Each node trains learning models of different scales according to its own computing capabilities. After receiving the gradient trained by each node, the parameter server (PS) corrects the received gradient with the repeat matrix, and then update the corresponding region of the global model according to the mapping matrix. After all update operations are over, the PS assigns the compressed model to the corresponding node. The paper uses a variety of experimental schemes to evaluate the proposed method, including three datasets, two model structures, and three computational complexity levels. The proposed method have been proved it not only maximizes the use of the unbalanced computing power of edge nodes, but also enables different structural models to compensate for the shortcomings of others, improving the overall performance.

Background Postoperative adhesion is a common cause of long-term morbidity after abdominal or pelvic surgery. The development of postoperative adhesion involves oxidative stress, inflammatory response, and collagen deposition mechanisms. Here, we demonstrate that mitoquinone could be useful for the treatment of postoperative adhesion. Methods A murine adhesion model was established by induction of peritoneal ischemic buttons. Mice received different doses of mitoquinone via the tail vein. All the ischemic buttons were dissected at 1 day and 7 days after surgery to investigate the effect of mitoquinone in the early and late stage of the adhesion process, respectively. Human peritoneal mesothelial cells were treated with H2O2 to examine the potential mechanisms of mitoquinone in oxidative insult. Results Postoperative adhesion scores were markedly decreased in mitoquinone-treated mice compared with the control mice. The degree of oxidative stress, inflammatory injury, and collagen deposition were also significantly reduced in the mitoquinone-treated mice. The expression of plasminogen-activating inhibitor, interleukin-1, interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, malondialdehyde, and nitric oxide was decreased, while the expression of tissue-type plasminogen activator, glutathione, superoxide dismutase, and Nrf2 was increased in the peritoneal ischemic buttons after mitoquinone treatment. Cellular reactive oxygen species and the canonical inflammatory pathway were inhibited in mitoquinone-treated human peritoneal mesothelial cells after H2O2 challenge. Mechanistically, mitoquinone was found to enhance the activity of Nrf2 and heme oxygenase-1 and to induce nuclear translocation of Nrf2 in human peritoneal mesothelial cells. Conclusion The mitochondria-targeting antioxidant molecule mitoquinone attenuates postoperative adhesion formation by inhibiting oxidative stress, inflammation, and collagen accumulation, and therefore provides a therapeutic agent for the management of surgical adhesion.

Cysteine (Cys) is one of the most common cellular biothiols and is closely implicated in numerous diseases such as edema, psoriasis, Parkinson's disease, and liver damage. Therefore, detecting Cys activity in complex living organisms is highly necessary for diagnosing related diseases. This study synthesized a near-infrared (NIR) Cys-special probe (MCyA) by introducing an acrylate group to the MCyOH fluorophore. Consequently, Cys could precisely and quickly "light up" strong NIR fluorescence (711 nm) by transforming MCyA into MCyOH. Additionally, MCyA was applied to systematically detect dynamic fluctuations of Cys activity in living cells under different stimulation. The observations indicated that the endogenous Cys activity was depressed when HepG2 cells were under oxidative stress status; however, a dramatic expansion of Cys levels in HepG2 cells with omeprazole stimulation. In particular, MCyA has been successfully used to image the upregulation of Cys level in HepG2 cells in the presence of methionine (Met). Overall, MCyA would be a novel and practical tool to study Cys-related physiological and pathological processes.

The circadian clock is a master regulator in coordinating daily oscillations of physiology and behaviors. Nevertheless, how the circadian rhythm affects endochondral ossification is poorly understood. Here we showed that endochondral bone formation exhibits circadian rhythms, manifested as fast DNA replication in the daytime, active cell mitosis, and matrix synthesis at night. Circadian rhythm disruption led to endochondral ossification deformities. The mechanistic dissection revealed that melatonin receptor 1 (MTR1) periodically activates the AMPKβ1 phosphorylation, which then orchestrates the rhythms of cell proliferation and matrix synthesis via destabilizing the clock component CRY1 and triggering BMAL1 expression. Accordingly, the AMPKβ1 agonist is capable of alleviating the abnormity of endochondral ossification caused by circadian dysrhythmias. Taken together, these findings indicated that the central circadian clock could control endochondral bone formation via the MTR1/AMPKβ1/BMAL1 signaling axis in chondrocytes. Also, our results suggested that the AMPKβ1 signaling activators are promising medications toward endochondral ossification deformities.

As a tightly controlled biological process, cardiogenesis requires the specification and migration of a suite of cell types to form a particular three-dimensional configuration of the heart. Many genetic factors are involved in the formation and maturation of the heart, and any genetic mutations may result in severe cardiac failures. The neuron navigator (NAV) family consists of three vertebrate homologs (NAV1, NAV2, and NAV3) of the neural guidance molecule Uncoordinated-53 (UNC-53) in Caenorhabditis elegans. Although they are recognized as neural regulators, their expressions are also detected in many organs, including the heart, kidney, and liver. However, the functions of NAVs, regardless of neural guidance, remain largely unexplored. In our study, we found that nav3 gene was expressed in the cardiac region of zebrafish embryos from 24 to 48 hours post-fertilization (hpf) by means of in situ hybridization (ISH) assay. A CRISPR/Cas9-based genome editing method was utilized to delete the nav3 gene in zebrafish and loss-of-function of Nav3 resulted in a severe deficiency in its cardiac morphology and structure. The similar phenotypic defects of the knockout mutants could recur by nav3 morpholino injection and be rescued by nav3 mRNA injection. Dual-color fluorescence imaging of ventricle and atrium markers further confirmed the disruption of the heart development in nav3-deleted mutants. Although the heart rate was not affected by the deletion of nav3, the heartbeat intensity was decreased in the mutants. All these findings indicate that Nav3 was required for cardiogenesis in developing zebrafish embryos.

A Ni–Ir alloy network electrocatalyst, which is prepared via a galvanic replacement engineering route, presents remarkable electrocatalytic properties for both the HER and the OER due to its porous architecture and synergistic effect between Ni and Ir.

1D bifunctional RuO2/Ru-CNFs-350 catalyst is fabricated to show high activity and remarkable durability toward both OER and HER due to the formation of a RuO2/Ru heterostructure and the carbon substrate.

The occurrence of numerous neurodegenerative diseases is associated with abnormal levels of butyrylcholinesterase (BChE).