Cancer-secreted exosomal miRNAs are emerging mediators of cancer-stromal cross-talk in the tumor environment. Our previous miRNAs array of cervical squamous cell carcinoma (CSCC) clinical specimens ...identified upregulation of miR-221-3p. Here, we show that miR-221-3p is closely correlated with peritumoral lymphangiogenesis and lymph node (LN) metastasis in CSCC. More importantly, miR-221-3p is characteristically enriched in and transferred by CSCC-secreted exosomes into human lymphatic endothelial cells (HLECs) to promote HLECs migration and tube formation in vitro, and facilitate lymphangiogenesis and LN metastasis in vivo according to both gain-of-function and loss-of-function experiments. Furthermore, we identify vasohibin-1 (VASH1) as a novel direct target of miR-221-3p through bioinformatic target prediction and luciferase reporter assay. Re-expression and knockdown of VASH1 could respectively rescue and simulate the effects induced by exosomal miR-221-3p. Importantly, the miR-221-3p-VASH1 axis activates the ERK/AKT pathway in HLECs independent of VEGF-C. Finally, circulating exosomal miR-221-3p levels also have biological function in promoting HLECs sprouting in vitro and are closely associated with tumor miR-221-3p expression, lymphatic VASH1 expression, lymphangiogenesis, and LN metastasis in CSCC patients. In conclusion, CSCC-secreted exosomal miR-221-3p transfers into HLECs to promote lymphangiogenesis and lymphatic metastasis via downregulation of VASH1 and may represent a novel diagnostic biomarker and therapeutic target for metastatic CSCC patients in early stages.
This work describes a strategy to produce circularly polarized thermally activated delayed fluorescence (CP-TADF). A set of two structurally similar organic emitters SFST and SFOT are constructed, ...whose spiro architectures containing asymmetric donors result in chirality. Upon grafting within the spiro frameworks, the donor and acceptor are fixed proximally in a face-to-face manner. This orientation allows intramolecular through-space charge transfer (TSCT) to occur in both emitters, leading to TADF properties. The donor units in SFST and SFOT have a sulfur and oxygen atom, respectively; such a subtle difference has great impacts on their photophysical, chiroptical, and electroluminescence (EL) properties. SFOT exhibits greatly enhanced EL performance in doped organic light-emitting diodes, with external quantum efficiency (EQE) up to 23.1%, owing to the concurrent manipulation of highly photoluminescent quantum efficiency (PLQY, ∼90%) and high exciton utilization. As a comparison, the relatively larger sulfur atom in SFST introduces heavy atom effects and leads to distortion of the molecular backbone that lengthens the donor–acceptor distance. SFST thus has lower PLQY and faster nonradiative decay rate. The collective consequence is that the EQE value of SFST, i.e., 12.5%, is much lower than that of SFOT. The chirality of these two spiro emitters results in circularly polarized luminescence. Because SFST has a more distorted molecular architecture than SFOT, the luminescence dissymmetry factor (|g lum|) of circularly polarized luminescence of one enantiomer of the former, namely, either (S)-SFST or (R)-SFST, is almost twice that of (S)-SFOT/(R)-SFOT. Moreover, the CP organic light-emitting diodes (CP-OLEDs) show obvious circularly polarized electroluminescence (CPEL) signals with g EL of 1.30 × 10–3 and 1.0 × 10–3 for (S)-SFST and (S)-SFOT, respectively.
To explore the mechanisms through which hypoxic tumor microenvironment (TME) modulates the transition of tumor‐associated macrophages (TAMs). The migration ability of RAW264.7 macrophages was ...determined by transwell assay. Flow cytometric, western blot and immunofluorescence analyses of CD206 further validated the M2 polarization of macrophages. Immunofluorescence, western blot and qRT‐PCR were performed to detect the expression of neuropilin‐1 (Nrp‐1) and carbonic anhydrase IX (CAIX). An intermittent hypobaric hypoxia (IH) animal model was established to evaluate the role of hypoxia in activating M2‐like TAMs in vivo. We also used immunohistochemistry to analyze the association between CAIX, CD163+ macrophages and Nrp‐1 in a series of 72 human cervical cancer specimens. We found that the hypoxic cervical TME educated the recruited macrophages to transform into the M2 phenotype. Nrp‐1 expression was significantly increased in hypoxia‐primed cervical cancer cells. Blocking Nrp‐1 expression prevented hypoxic cells from recruiting and polarizing macrophages towards the M2 phenotype. Hypoxia exposure significantly increased the expression of Nrp‐1 as well as the infiltration of macrophages in vivo. Consistently, immunochemical staining in serial tissue sections of cervical cancer revealed upregulated levels of Nrp‐1 in CAIX‐positive hypoxic regions along with a concurrent significant elevation of M2 macrophages. Nrp‐1 and M2‐like TAMs were related to the malignant properties of cervical cancer, such as the FIGO stage and lymph node metastasis. Nrp‐1 plays critical roles in hypoxic TME‐induced activation and pro‐tumoral effects of TAMs in cervical cancer. Interfering with Nrp‐1 may be a potential therapeutic strategy in treating cervical cancer.
This paper considers the nonfragile <inline-formula> <tex-math notation="LaTeX">H_\infty </tex-math></inline-formula> estimation problem for a class of complex networks with switching topologies and ...quantization effects. The network architecture is assumed to be dynamic and evolves with time according to a random process subject to a sojourn probability. The coupled signal is to be quantized before transmission due to power and bandwidth constraints, and the quantization errors are transformed into sector-bounded uncertainties. The concept of nonfragility is introduced by inserting randomly occurred uncertainties into the estimator parameters to cope with the unavoidable small gain variations emerging from the implementations of estimators. Both the quantizers and the estimators have several operation modes depending on the switching signal of the underlying network structure. A sufficient condition is provided via a linear matrix inequality approach to ensure the estimation error dynamic to be stochastically stable in the absence of external disturbances, and the <inline-formula> <tex-math notation="LaTeX">H_\infty </tex-math></inline-formula> performance with a prescribed index is also satisfied. Finally, a numerical example is presented to clarify the validity of the proposed method.
In this paper, we study the interacting multiple model (IMM) estimator for networked control systems with packet loss but without packet acknowledgment (ACK). The ACK is a signal sent by the actuator ...to inform the estimator of whether control packets are lost or not. A system with ACK is usually called a transmission control protocol (TCP) like system; otherwise, it is called a user datagram protocol (UDP) like system. We show that the stability of the IMM estimator for UDP-like systems is determined by the observation packet arrival rate (p.a.r.) and is independent of the control p.a.r. and control inputs. The IMM estimator is stable if the observation p.a.r. is greater than a critical value. We show that this critical value is the same as the critical value for the stability of the optimal estimator for its corresponding TCP-like system. If control inputs eventually tend to zero, the error covariance of the IMM estimator converges to that of the optimal estimator for TCP-like systems. We characterize the impact of the control/observation p.a.r. and the control input on estimation performance. Finally, we prove that the average estimation performance of the IMM estimator approximates that of the optimal estimator within a finite bound, and is superior to that of the linear minimum mean square error estimator.
This paper investigates the fuzzy adaptive practical tracking problem for a class of nonlinear pure-feedback systems with quantized input signal. In the control scheme design process, the considered ...system is transformed into a plant with a strict-feedback form by borrowing the mean value theorem of differential, then fuzzy logic systems are used to compensate for some uncertain nonlinearities in the considered plant and the classical adaptive technique is employed to handle some unknown parameters. In the backstepping design, some nonnegative switching functions are introduced to develop the desired fuzzy controller, and Barbalat's lemma is used to analyze the stability and the control performance of the closed-loop system. It can be shown that under the novel adaptive fuzzy controller, all the closed-loop signals are semiglobally uniformly ultimately bounded, and especially the tracking error satisfies the accuracy assigned a priori. A simulation example is presented to verify the effectiveness of the proposed control method.
Taiwan experienced two waves of imported infections with Coronavirus Disease 2019 (COVID-19). This study aimed at investigating the genomic variation of severe acute respiratory syndrome coronavirus ...2 (SARS-CoV-2) in Taiwan and compared their evolutionary trajectories with the global strains. We performed culture and full-genome sequencing of SARS-CoV-2 strains followed by phylogenetic analysis. A 382-nucleotides deletion in open reading frame 8 (ORF8) was found in a Taiwanese strain isolated from a patient on February 4, 2020 who had a travel history to Wuhan. Patients in the first wave also included several sporadic, local transmission cases. Genomes of 5 strains sequenced from clustered infections were classified into a new clade with ORF1ab-V378I mutation, in addition to 3 dominant clades ORF8-L84S, ORF3a-G251V and S-D614G. This highlighted clade also included some strains isolated from patients who had a travel history to Turkey and Iran. The second wave mostly resulted from patients who had a travel history to Europe and Americas. All Taiwanese viruses were classified into various clades. Genomic surveillance of SARS-CoV-2 in Taiwan revealed a new ORF8-deletion mutant and a virus clade that may be associated with infections in the Middle East, which contributed to a better understanding of the global SARS-CoV-2 transmission dynamics.
Sampled-data state feedback control with stochastic sampling periods for Boolean control networks (BCNs) is investigated in this article. First, based on the algebraic form of BCNs, stochastic ...sampled-data state feedback control is applied to stabilize the considered system to a fixed point or a given set. Two kinds of distributions of stochastic sampling periods are considered. First, the distribution of sampling periods is assumed to be independent identically distributed (i.i.d.) in the range of any positive integers and the second distribution of sampling periods is assumed to follow an infinite Markov process. A BCN with infinite stochastic sampling periods proves to be equivalent to a finite stochastic switched system, based on which, necessary and sufficient conditions are given to guarantee the stabilization and set stabilization of the BCN with stochastic sampling periods. For the first one, two algorithms are given to guarantee the stabilization and set stabilization of the considered system. For the second one, necessary and sufficient conditions are all presented in the linear programming form. Examples are listed to show the effectiveness of our results.
The basement of the Argun massif in the northern Great Hinggan Range consists of the metamorphic supracrustal rocks of the Xinghuadukou Group and associated granitic complexes. The metamorphic ...supracrustal rocks were previously interpreted as Paleoproterozoic, while the granitic complexes were considered Mesoproterozoic in age. This paper presents new zircon LA-MC-ICP-MS U–Pb ages of biotite-plagioclase leptynite and biotite schist from the Xinghuadukou Group in the Lulin Forest area, Heilongjiang Province; zircon SHRIMP U–Pb ages of biotite-plagioclase gneiss from the Xinghuadukou Group in Lulin Forest; and quartz diorite and monzogranite from the granitic complexes in Mohe County, Heilongjiang Province. New geochronological data from the three metasedimentary rock samples of the Xinghuadukou Group can be preliminarily divided into five groups: (1) 2017–2765Ma, (2) 1736–1942Ma, (3) 1359–1610Ma, (4) 749–1239Ma, and (5) 448–716Ma. Except for the zircons of the 448–716Ma group belonging to a metamorphic origin, the other age groups had the youngest age of 749±17Ma, indicating that the Xinghuadukou Group formed during the Neoproterozoic era (at least <749Ma). These detrital zircon ages cluster at ca. 2.0–1.8Ga and ca. 1.0–0.80Ga, suggesting that the Argun massif had connections with both Columbia and Rodinia and implying that the provenance of the Xinghuadukou Group metamorphosed sediments must be characteristic of felsic–intermediate igneous rocks with ages of ca. 2.0–1.8Ga and ca. 1.0–0.80Ga. The quartz diorite and monzogranite from the granitic complexes of the basement within the Argun massif yielded weighted mean ages of 516±10Ma and 504±9Ma, respectively, indicating that these rocks emplaced in the Early Paleozoic. Considering the geochemical and chronological data together, we propose that the Xinghuadukou Group was most likely deposited in a back-arc basin environment, whereas the granitic complexes emplaced in a post-collisional setting. A wide age spectrum of detrital zircons ranging from 749±9 to 2765±11Ma with ages clustering approximately 2.0–1.8Ga and 1.0–0.80Ga suggests that the basement rocks of the Argun massif are chiefly composed of the Neoproterozoic metasedimentary sequence and Early Paleozoic granitic complexes, with a few Meso- to Paleoproterozoic and even Neoarchean metamorphic rocks.
In the postharvest processing of tea leaves, withering is the first indispensable manufacturing process which produces the mellow, umami and sweet taste of white tea. In this study, we aimed to ...determine the dynamic changes of the main metabolites and clarify the key differentially expressed genes (DEGs) involved in forming the characteristic taste of white tea during withering. Phytochemical analyses revealed that the contents of total catechins and starch decreased continuously, whereas the contents of theaflavin, γ-aminobutyric acid (GABA), maltose, and soluble sugars increased significantly during withering (from 0–48 h). Meanwhile, the elevation of α-amylase (AMY), β-amylase (BAM), total amylase, and glutamate decarboxylase (GAD) activities may be correlated with the accumulation of GABA and maltose. By transcriptome sequencing, we detected 9 707, 15 921, 17 353, and 17 538 DEGs at 12, 24, 36, and 48 h of the withering process, respectively, compared with 0 h sample (fresh leaves). The transcript levels of most of the DEGs involved in catechin biosynthesis were significantly inhibited, whereas those involved in catechin oxidation were significantly up-regulated, which could be correlated to a decrease in catechin content and an increase in theaflavin content. The DEGs involved in GABA biosynthesis were considerably up-regulated, and the down-regulation of SPMS could reduce the competition for converting spermidine to GABA. The up-regulation of the AMY and BAM genes could trigger starch degradation, resulting in the increase of soluble sugar content. These results provide new insights into the importance of the withering process to the characteristic taste of white tea.
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