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In this study, a novel exopolysaccharide (EPS) was extracted from Leuconostoc mesenteroides Shen Nong's (SN)-8 which can be obtained from Dajiang. After the purification step, EPS-8-2 was obtained with molecular weights of 1.46 × 10 5 Da. The structural characterization of EPS indicated that the EPS belonged to the class polysaccharide, mainly composed of glucan and also contained certain mannose residues that were found to be connected by α-1,6 glycosidic bonds. Moreover, the results demonstrated that EPS displayed a significant capacity to scavenge free radical to some extent, and this anti-oxidant potential was found to be concentration dependent. The results further revealed that EPS displayed a significant inhibitory potential on the growth of HepG2 cells by promoting apoptosis and induced cell cycle arrest in G1 and G2 phases. Overall, these results suggested that EPS can be explored as a possible anti-cancer agent., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Yan, Liu, Luo, Li, Cao, Li, Han, Wang, Wu and Zhang.)

Objective: This study set out to investigate the relationships between the neutrophil-to-albumin ratio (NAR) in the early stages of aneurysmal subarachnoid hemorrhage (aSAH) and the occurrence of delayed cerebral ischemia (DCI)., Methods: A total of 439 patients with aSAH were included in this retrospective study. NAR assessment was conducted on admission. The relationship between NAR and DCI was analyzed., Results: Eighty-four patients (23.7%) experienced DCI. NAR levels were significantly higher in patients with DCI after aSAH than without DCI (median [interquartile range] 0.350 [0.274-0.406] vs. 0.240 [0.186-0.300]; P < 0.001). NAR levels were correlated with World Federation of Neurological Surgeons (WFNS) grade and modified Fisher (mFisher) grade (r = 0.505 and 0.394, respectively). NAR and mFisher grade were the independent predictors of DCI. Under receiver operating characteristic curve, NAR levels exhibited a significant discriminatory capability (area under the curve [95% confidence interval] 0.812 [0.740-0.823]; P < 0.001). The predictive power of NAR levels was similar to mFisher grade (P > 0.05)., Conclusions: NAR, in positive correlation with the severity of hemorrhage, appears to be a novel predictive biomarker of DCI after aSAH., (Copyright © 2020 Elsevier Inc. All rights reserved.)

J-domain proteins (JDPs) play essential roles in Hsp70 function by assisting Hsp70 in client trapping and regulating the Hsp70 ATPase cycle. Here, we report that JDPs can further enhance the targeting competence of Hsp70-bound client proteins during tail-anchored protein (TA) biogenesis. In the guided-entry-of-tail-anchored protein pathway in yeast, nascent TAs are captured by cytosolic Hsp70 and sequentially relayed to downstream chaperones, Sgt2 and Get3, for delivery to the ER. We found that two JDPs, Ydj1 and Sis1, function in parallel to support TA targeting to the ER in vivo. Biochemical analyses showed that, while Ydj1 and Sis1 differ in their ability to assist Hsp70 in TA trapping, both JDPs enhance the transfer of Hsp70-bound TAs to Sgt2. The ability of the JDPs to regulate the ATPase cycle of Hsp70 is essential for enhancing the transfer competence of Hsp70-bound TAs in vitro and for supporting TA insertion in vivo. These results demonstrate a role of JDPs in regulating the conformation of Hsp70-bound clients during membrane protein biogenesis., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Enterovirus D68 (EVD68) is an emerging pathogen that recently caused a large worldwide outbreak of severe respiratory disease in children. However, the relationship between EVD68 and host cells remains unclear. Caspases are involved in cell death, immune response, and even viral production. We found that caspase-3 was activated during EVD68 replication to induce apoptosis. Caspase-3 inhibitor (Z-DEVD-FMK) inhibited viral production, protected host cells from the cytopathic effects of EVD68 infection, and prevented EVD68 from regulating the host cell cycle at G0/G1. Meanwhile, caspase-3 activator (PAC-1) increased EVD68 production. EVD68 infection therefore activates caspase-3 for virus production. This knowledge provides a potential direction for the prevention and treatment of disease related to EVD68.

The electrochemical carbon dioxide reduction reaction (CO 2 RR) to produce synthesis gas (syngas) with tunable CO/H 2 ratios has been studied by supporting Pd catalysts on transition metal nitride (TMN) substrates. Combining experimental measurements and density functional theory (DFT) calculations, Pd-modified niobium nitride (Pd/NbN) is found to generate much higher CO and H 2 partial current densities and greater CO Faradaic efficiency than Pd-modified vanadium nitride (Pd/VN) and commercial Pd/C catalysts. In-situ X-ray diffraction identifies the formation of PdH in Pd/NbN and Pd/C under CO 2 RR conditions, whereas the Pd in Pd/VN is not fully transformed into the active PdH phase. DFT calculations show that the stabilized *HOCO and weakened *CO intermediates on PdH/NbN are critical to achieving higher CO 2 RR activity. This work suggests that NbN is a promising substrate to modify Pd, resulting in an enhanced electrochemical conversion of CO 2 to syngas with a potential reduction in precious metal loading., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: To investigate the distribution of CT features and also to introduce a novel described CT feature of coronavirus disease-19 (COVID-19) pneumonia., Methods: A series of radiologic signs in 11 COVID-19 patients were summarized and made morphometric analysis., Results: A special sign termed as "the arch bridge sign" owing to its morphological mimicking an arch bridge was firstly introduced. Statistical analyze showed that the subpleural area is the priority distribution location (14/14) and the sign inclined to perform in those patients in a relatively early stage (6/8) and with moderate clinical severity (8/8). Segment VI in lower lobe involved most (6/14). In this retrospective study, other characteristic radiologic signs of COVID-19 pneumonia were analyzed synchronously. A series of radiologic signs were identified in bilateral lungs with a bias towards segment VI, I + II and X. Segment VI had the largest number of each sign. Ground-glass opacities (GGOs), subpleural distribution pattern and vessels dilatation were the top three most common signs among them., Conclusions: The recognition of the arch bridge sign may benefit patient care by earlier definitive diagnosis of COVID-19 pneumonia. The lesions of COVID-19 pneumonia distributed mainly in the back-lung segments, which characteristic may light new ideas in clinical treatment and nursing strategy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-688). The authors have no conflicts of interest to declare., (2020 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

In this work, a series of fluorescent cathodically coloring electrochromic (EC) small molecules o - , m - , and p -DBFDCz with 3,5-di(9 H -carbazol-9-yl)benzene (DCz) linked to dibenzofuran (DBF) at different substitutional positions were synthesized and fully characterized. These compounds are electroactive and undergo quasi-reversible two-step single-electron reduction generating radical anions and dianions. The absorptions of o - , m - , and p -DBFDCz in the neutral states lie in the UV region (λ onset ≈ 350 nm), showing high transparency, while the absorption of their reduced states can be largely tuned across the visible region through driving voltage and substitutional positions. Initially generated spectroelectrochemically radical anions show absorption in the short-wavelength region of ∼380-500 nm with weak broad absorptions at longer wavelengths. On further reduction, these bands disappear on the cost of growing intense bands from dianions at longer wavelengths of 500-700 nm with some tail absorptions in the shorter-wavelength region. This renders the colors of the EC devices based on these materials, which are changed from green to red, yellow to magenta, and light to deep blue for o - , m - , and p -DBFDCz , respectively, covering four legs of the L * a * b * color space. Besides excellent optical contrast (>90%) and high coloration efficiency (up to 504 cm 2 C -1 ), the fluorescence observed in solution of neutral o - , m - , and p -DBFDCz can be modulated between the fluorescence and quenched states by direct electrochemical redox reactions. Both EC and electrofluorochromic (EFC) processes are reversible on cycling. This research demonstrates the feasibility of developing multifunctional EC/EFC materials with multicolored electrochromism through exploiting electrochemical properties of traditional fluorescent small molecules.

The poor gas selectivity problem has been a long-standing issue for miniaturized chemical-resistor gas sensors. The electronic nose (e-nose) was proposed in the 1980s to tackle the selectivity issue, but it required top-down chemical functionalization processes to deposit multiple functional materials. Here, we report a novel gas-sensing scheme using a single graphene field-effect transistor (GFET) and machine learning to realize gas selectivity under particular conditions by combining the unique properties of the GFET and e-nose concept. Instead of using multiple functional materials, the gas-sensing conductivity profiles of a GFET are recorded and decoupled into four distinctive physical properties and projected onto a feature space as 4D output vectors and classified to differentiated target gases by using machine-learning analyses. Our single-GFET approach coupled with trained pattern recognition algorithms was able to classify water, methanol, and ethanol vapors with high accuracy quantitatively when they were tested individually. Furthermore, the gas-sensing patterns of methanol were qualitatively distinguished from those of water vapor in a binary mixture condition, suggesting that the proposed scheme is capable of differentiating a gas from the realistic scenario of an ambient environment with background humidity. As such, this work offers a new class of gas-sensing schemes using a single GFET without multiple functional materials toward miniaturized e-noses., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

The electrochemical CO 2 reduction reaction (CO 2 RR) to yield synthesis gas (syngas, CO and H 2 ) has been considered as a promising method to realize the net reduction in CO 2 emission. However, it is challenging to balance the CO 2 RR activity and the CO/H 2 ratio. To address this issue, nitrogen-doped carbon supported single-atom catalysts are designed as electrocatalysts to produce syngas from CO 2 RR. While Co and Ni single-atom catalysts are selective in producing H 2 and CO, respectively, electrocatalysts containing both Co and Ni show a high syngas evolution (total current >74 mA cm -2 ) with CO/H 2 ratios (0.23-2.26) that are suitable for typical downstream thermochemical reactions. Density functional theory calculations provide insights into the key intermediates on Co and Ni single-atom configurations for the H 2 and CO evolution. The results present a useful case on how non-precious transition metal species can maintain high CO 2 RR activity with tunable CO/H 2 ratios., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hand, foot, and mouth disease (HFMD) is a febrile exanthematous disease with typical or atypical symptoms. Typical HFMD is usually caused by enterovirus 71 (EV71) or coxsackievirus A16, while atypical HFMD is usually caused by coxsackievirus A6 (CA6). In recent years, worldwide outbreaks of CA6-associated HFMD have dramatically increased, although the pathogenic mechanism of CA6 is still unclear. EV71 has been established to induce caspase-dependent apoptosis, but in this study, we demonstrate that CA6 infection promotes a distinct pathway of cell death that involves loss of cell membrane integrity. Necrostatin-1, an inhibitor of necroptosis, blocks the cell death induced by CA6 infection, but Z-DEVD-FMK, an inhibitor of caspase-3, has no effect on CA6-induced cell death. Furthermore, CA6 infection up-regulates the expression of the necroptosis signaling molecule RIPK3. Importantly, necrostatin-1 inhibits CA6 viral production, as assessed by its ability to inhibit levels of VP1 protein and genomic RNA and infectious particles. CA6-induced necroptosis is not dependent on the generation of reactive oxygen species; however, viral 3D protein can directly bind RIPK3, which is suggestive of a direct mechanism of necroptosis induction. Therefore, these results indicate that CA6 induces a mechanism of RIPK3-dependent necroptosis for viral production that is distinct from the mechanism of apoptosis induced by typical HFMD viruses., (Copyright © 2020 Zhang, Yu, Meng, Huo, Su, Liu, Liu, Zhang, Wang and Yu.)

Accurate identification of intrinsically disordered proteins/regions (IDPs/IDRs) is critical for predicting protein structure and function. Previous studies have shown that IDRs of different lengths have different characteristics, and several classification-based predictors have been proposed for predicting different types of IDRs. Compared with these classification-based predictors, the previously proposed predictor IDP-CRF exhibits state-of-the-art performance for predicting IDPs/IDRs, which is a sequence labeling model based on conditional random fields (CRFs). Motivated by these methods, we propose a predictor called IDP-FSP, which is an ensemble of three CRF-based predictors called IDP-FSP-L, IDP-FSP-S, and IDP-FSP-G. These three predictors are specially designed to predict long, short, and generic disordered regions, respectively, and they are constructed based on different features. To the best of our knowledge, IDP-FSP is the first predictor that combines a sequence labeling algorithm with IDRs of different lengths. Experimental results using two independent test datasets show that IDP-FSP achieves better or at least comparable predictive performance with 26 existing state-of-the-art methods in this field, proving the effectiveness of IDP-FSP., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Esophageal squamous cell neoplasia (ESCN) has a significant risk for progression to cancer. Current treatment options, endoscopic mucosal resection (EMR) or submucosal dissection (ESD), have their limitations. The cryoballoon focal ablation system (CbFAS) is a novel endoscopic ablation therapy device. We aimed to assess the safety, tolerability, and efficacy of CbFAS for eradication of ESCN., Methods: In this single-center prospective trial in China, patients with 1 flat unstained lesion (USL) on Lugol chromoendoscopy that contained moderate- or high-grade intraepithelial neoplasia (MGIN or HGIN, respectively) were enrolled. CbFAS was performed using side-by-side applications of 10 seconds, treatment was repeated at 3-month intervals until a complete response (CR) was established. The response at 12 months was the primary trial endpoint. Safety phone calls were performed at 2, 7, and 30 days after the initial CbFAS., Results: We enrolled 80 patients (59 MGIN, 21 HGIN) with a median USL length of 3 cm (interquartile range [IQR], 3-4). Seventy-nine received treatment, with a median of 5 side-by-side applications (IQR, 4-7) per patient over a median of 8 minutes (IQR, 5-10). After a single treatment, 70 of 78 patients (90%) exhibited CR, and 1 was lost to follow-up. The other 8 with persisting USLs were retreated, and all achieved CR after this second treatment. At 12 months after the initial CbFAS, 76 of 78 patients (97%) exhibited CR and 2 (3%) had recurrent MGIN. No strictures or serious adverse events occurred. Four patients developed self-limiting mucosal lacerations on balloon inflation. The postprocedure median pain score was 1 of 10 (IQR, 0-2) at day 2 and 0 (0-0) at days 7 and 30., Conclusions: The results suggest that the CbFAS is safe, well tolerated, and effective in inducing endoscopic and histologic remission in patients with ESCN of limited size. (Clinical trial registration number: NCT02605759.)., (Copyright © 2019. Published by Elsevier Inc.)

Intrinsically disordered proteins and regions are widely distributed in proteins, which are associated with many biological processes and diseases. Accurate prediction of intrinsically disordered proteins and regions is critical for both basic research (such as protein structure and function prediction) and practical applications (such as drug development). During the past decades, many computational approaches have been proposed, which have greatly facilitated the development of this important field. Therefore, a comprehensive and updated review is highly required. In this regard, we give a review on the computational methods for intrinsically disordered protein and region prediction, especially focusing on the recent development in this field. These computational approaches are divided into four categories based on their methodologies, including physicochemical-based method, machine-learning-based method, template-based method and meta method. Furthermore, their advantages and disadvantages are also discussed. The performance of 40 state-of-the-art predictors is directly compared on the target proteins in the task of disordered region prediction in the 10th Critical Assessment of protein Structure Prediction. A more comprehensive performance comparison of 45 different predictors is conducted based on seven widely used benchmark data sets. Finally, some open problems and perspectives are discussed.

In this study, the nano-heterostructures of Zn 1-x Cd x S (0 < x < 1) nanoparticles and small g-C 3 N 4 nanosheets (Zn 1-x Cd x S/CN) were prepared via in situ growth. Bulk g-C 3 N 4 was first delaminated into thin layers by an acid and alkali assisted ultrasound method. Zn 1-x Cd x S nanoparticles were deposited on the surface of small g-C 3 N 4 nanosheets in situ to fabricate Zn 1-x Cd x S/CN photocatalysts. The absorption band edges of the as-prepared Zn 1-x Cd x S/CN composites shifted to a longer wavelength region compared to g-C 3 N 4 . The Zn 1-x Cd x S/CN heterojunctions revealed super-enhanced visible-light photocatalytic activities compared to pure g-C 3 N 4 and Zn 1-x Cd x S nanoparticles. To investigate the composition dependence, the mass ratios of Zn 1-x Cd x S and g-C 3 N 4 were adjusted. Zn 0.8 Cd 0.2 S nanoparticles (5 wt%) grown in situ on g-C 3 N 4 nanosheets as sample 5-Zn 0.8 Cd 0.2 S/CN revealed a very high photocatalytic activity compared to other Zn 0.8 Cd 0.2 S/CN and CdS/CN samples where the degradation of RhB was up to 99% within 15 min under visible light irradiation. This was ascribed to the well-matched band gap structure, large specific surface area and intimately contacted interfaces. The controllable band gap of the Zn 1-x Cd x S/CN composites was a key factor for their enhanced photocatalytic performance. In addition, O 2 - was the leading reactive oxidative species in this photocatalytic process in the 5-Zn 0.8 Cd 0.2 S/CN composite system.

Herein, we develop FePt@Fe2O3 core-shell magnetic nanoparticles as a T2 magnetic resonance (MR) imaging contrast agent as well as a drug carrier for potential cancer theranostic applications. The FePt@Fe2O3 core-shell nanoparticles are synthesized and then functionalized with polyethylene glycol (PEG). Folic acid (FA) is conjugated on the surface of FePt@Fe2O3-PEG nanoparticles for effective targeting of folate receptor (FR)-positive tumor cells. A chemotherapy drug, doxorubicin (DOX), is then loaded onto those nanoparticles via hydrophobic physical adsorption, for targeted intracellular drug delivery and selective cancer cell killing. We then use those FePt@Fe2O3-PEG nanoparticles for in vivo MR imaging, observing obvious tumor MR contrasts, which resulted from both passive tumor accumulation and active tumor targeting of nanoparticles. Moreover, both in vitro and in vivo studies uncover no obvious toxicity for FePt@Fe2O3-PEG nanoparticles. Therefore, our PEGylated FePt@Fe2O3 core-shell nanoparticles could serve as a promising multifunctional theranostic nano-platform in imaging guided cancer therapy., From the Clinical Editor: In this study of PEGylated FePt@Fe2O3 core-shell magnetic nanoparticles, both therapeutic and diagnostic applications are demonstrated. Folic acid surface-conjugation resulted in uptake by folate receptor positive cancer cells, the iron oxide particles enabled MRI imaging using T2* weighted sequences, and the absorbed doxorubicin provided treatment effects in this model. Similar multi-modality approaches will hopefully find their way to clinical applications in the near future., (Copyright © 2013 Elsevier Inc. All rights reserved.)