Autophagy, as a type II programmed cell death, plays crucial roles with autophagy-related (ATG) proteins in cancer. Up to now, the dual role of autophagy both in cancer progression and inhibition ...remains controversial, in which the numerous ATG proteins and their core complexes including ULK1/2 kinase core complex, autophagy-specific class III PI3K complex, ATG9A trafficking system, ATG12 and LC3 ubiquitin-like conjugation systems, give multiple activities of autophagy pathway and are involved in autophagy initiation, nucleation, elongation, maturation, fusion and degradation. Autophagy plays a dynamic tumor-suppressive or tumor-promoting role in different contexts and stages of cancer development. In the early tumorigenesis, autophagy, as a survival pathway and quality-control mechanism, prevents tumor initiation and suppresses cancer progression. Once the tumors progress to late stage and are established and subjected to the environmental stresses, autophagy, as a dynamic degradation and recycling system, contributes to the survival and growth of the established tumors and promotes aggressiveness of the cancers by facilitating metastasis. This indicates that regulation of autophagy can be used as effective interventional strategies for cancer therapy.
Lipid droplets (LDs) have been known as a non-negligible cellular organelle for lipid storage and metabolism. Fluorescent probes for imaging LDs would be paramount for depicting their functions in ...cells. Although commercially available Nile Red and BODIPY
493/503 have been widely used for labelling LDs, they exhibit unsatisfactory specificity and spectroscopic properties. This feature article reviews the recent advances in organic fluorescent probes for imaging LDs. We first introduce the key points for probe design, including regulating hydrophobicity and enhancing fluorescence quantum yield in LDs. Then, we summarize the structural features and biological applications of some representative LD probes classified by their frameworks. In addition, the current challenges and future research trends for the fluorescent probes of LDs are discussed as well.
Development of efficient, mild, and easily operable stereoselective glycosylations is of critical importance to access sufficient amounts of pure and structurally well‐defined carbohydrates for ...studies of their biological functions. Such studies will facilitate our understanding of the role of complex oligosaccharides and glycoconjugates in biological processes as well as the development of carbohydrate‐based effective therapeutic agents. This review highlights recent advances in the transition metal catalyzed stereoselective glycosylations for the synthesis of a variety of structurally complex and biologically significant O‐, N‐, C‐, and S‐glycosides.
Development of efficient, mild, and easily operable stereoselective glycosylations is of critical importance to access sufficient amounts of pure and structurally well‐defined carbohydrates for studies of their biological functions. Such studies will facilitate our understanding of the role of complex oligosaccharides and glycoconjugates in biological processes as well as the development of carbohydrate‐based effective therapeutic agents. This review highlights recent advances in the transition metal catalyzed stereoselective glycosylations for the synthesis of a variety of structurally complex and biologically significant O‐, N‐, C‐, and S‐glycosides.
The whole picture: Carbon nanodots labeled with two fluorescent dyes have been developed as a tunable ratiometric pH sensor to measure intracellular pH. The nanosensor shows good biocompatibility and ...cellular dispersibility. Quantitative determinations on intact HeLa cells and pH fluctuations associated with oxidative stress were performed.
Carrier frequency offset (CFO) mitigation is critical for orthogonal frequency-division multiplexing (OFDM)-based cooperative transmissions because even small CFO per transmitter may lead to severe ...performance loss, especially when the number of cooperative transmitters is large. In this paper, we show that cyclic prefix (CP) can be exploited to mitigate or even remove completely the CFO. The mitigation performance increases along with the CP length. In particular, long CP with length proportional to NI , where N is the fast Fourier transform (FFT) block length and I is the number of cooperative transmitters, can guarantee a complete CFO removal. While this comes with a reduction in bandwidth efficiency, the long CP in the proposed scheme is exploited to enhance transmission power efficiency in a way similar to spread-spectrum systems, and thus is different from conventional CP that degrades both bandwidth and power efficiency. An efficient CFO-mitigation algorithm is developed that has complexity at most O( NI 2 ), or even linear in N approximately in some cases. Implemented as a preprocessing procedure independently from cooperative encoding/decoding details, this algorithm makes the CFO problem effectively transparent to and thus has general applications in OFDM-based transmissions.
Monoamine oxidase (MAO) has two isoforms, MAO‐A and MAO‐B, which show different functions, and thus selective fluorescence imaging is important for biological studies. Currently, however, specific ...detection of MAO‐A remains a great challenge. Herein, we report a new strategy for specific imaging of MAO‐A through the design of fluorogenic probes combining the characteristic structure of an inhibitor of the target enzyme along with propylamine as a recognition moiety. The high specificity of our representative probe is demonstrated by imaging MAO‐A in different live cells such as SH‐SY5Y (high levels of MAO‐A) and HepG2 (high levels of MAO‐B), and further validated by western blot analyses. The superior specificity of the probe may enable the accurate detection of MAO‐A in complex biosystems. Importantly, the use of the characteristic structure of an inhibitor, as demonstrated in this work, may serve as a general strategy to design specific recognition moieties for fluorogenic probes for enzymes.
Light up, light up: A strategy for designing specific fluorogenic probes by using part of the structure of an inhibitor of the target enzyme as a targeting moiety is demonstrated with the development of a probe (3) for monoamine oxidase A (MAO‐A). The performance of the resulting probe was demonstrated by imaging SH‐SY5Y and HepG2 cells, which express different levels of MAO‐A.
This paper proposes a dual-bridge (DB) LLC resonant converter for wide input applications. The topology is an integration of a half-bridge (HB) LLC circuit and a full-bridge (FB) LLC circuit. The ...fixed-frequency pulsewidth-modulated (PWM) control is employed and a range of twice the minimum input voltage can be covered. Compared with the traditional pulse frequency modulation (PFM) controlled HB/FB LLC resonant converter, the voltage gain range is independent of the quality factor, and the magnetizing inductor has little influence on the voltage gain, which can simplify the parameter selection process and benefit the design of magnetic components as well. Over the full load range, zero-voltage switching (ZVS) and zero-current switching (ZCS) can be achieved for primary switches and secondary rectifier diodes, respectively. Detailed analysis on the modulation schedule and operating principle of the proposed converter is presented along with the converter performance. Finally, all theoretical analysis and characteristics are verified by experimental results from a 120-V to 240-V input 24 V/20 A output converter prototype.
To explore whether endoplasmic reticulum (ER) stress regulates inflammation in adipose tissue of obese rats via TLR4 signaling.
Sprague Dawley rats were randomly divided into four groups, and body ...weight, food intake, and free fatty acids (FFA) were measured. Real-time PCR and Western blot were used to determine mRNA or protein expression of TLR4, TRAF6, IKKβ, TNF-α, IL-6, and GRP78. Immunohistochemistry was used to detect GRP78 protein expression.
The FFA levels in HFD, HFD+PBA, and HFD+VIPER groups were higher than that in the control group (
<0.05). Compared with the control group, HFD induced GRP78 expression significantly (
<0.05), which could be decreased by ER stress inhibitor but not by TLR4 blocker. The mRNA expression of TLR4, TRAF6, TNF-α, and IL-6, and protein levels of TLR4, TNF-α, and IKKβ in the HFD group increased significantly compared with the control group (
<0.05), while these changes could be suppressed by PBA or VIPER (
<0.05). The immunohistochemistry staining indicated GRP78 expression in the HFD group was higher than that of the control group, which could be inhibited by PBA or VIPER.
HFD could induce inflammation in adipose tissue via ER stress and its downstream TLR4 signaling.
A simple and stable fluorescent off-on probe for discrimination of cysteine (Cys) from glutathione (GSH) has been developed by combining resorufin with 7-nitrobenzofurazan. The probe, displaying ...distinct emission patterns for Cys and GSH at just one excitation wavelength, can be used for simultaneous determination of Cys and GSH in human plasma.
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