Abstract
The receptor‐binding domain (RBD) of spike recognizing the receptor angiotensin‐converting enzyme 2 (ACE2) initiates membrane fusion between severe acute respiratory syndrome coronavirus 2 ...(SARS‐CoV‐2) and cell membrane. Although the structure of the RBD_ACE2 complex has been well studied, its functional mechanism in membrane fusion is still not fully understood. Here, using an in vitro cell–vesicle content‐mixing assay, it is found that the cleavage at the S2’ site by thrombin (Thr) protease strongly accelerates membrane fusion, compared to that of cleavage at the S1/S2 site by PreScission (3C) protease. Moreover, mutations at the RBD_ACE2 interface resulted in a positive correlation between binding affinity and fusion probability. In both the cell–vesicle and cell–cell fusion assays, by crosslinking two membranes via the neutravidin (NTV)_biotin interaction or complementary DNA strands, it is found that spike drives membrane fusion in the absence of ACE2, and a suitable distance between two membranes is critical for spike‐mediated membrane fusion. Finally, unsuitable membrane crosslinkers significantly inhibited the fusion probability in the presence of ACE2. Taken together, the results suggest that the RBD_ACE2 complex may act as a crosslinker to bridge the viral and cell membranes at a suitable distance, which is critical, but also substitutable for spike‐mediated SARS‐CoV‐2 entry.
In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune ...diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases. The mean follow-up duration was 5.3 ± 2.9 years with a total of 67,930 person-years, and the annual incidence of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases were not assessable due to few events. Body mass index ≥24 kg/m
was an independent predictor of the low incidence of SLE or RA (hazard ratio 0.40, 95% confidence interval 0.17-0.93, p = 0.034). A sustained virological response (SVR) to PR therapy was not associated with the low incidence of SLE or RA in any subgroup analysis. CHC patients achieving SVR to PR therapy did not exhibit an impact on the incidence of SLE or RA compared with non-SVR patients.
Novel P(VDF-TrFE)/organosilicate composite membrane was fabricated by electrospinning. The electrospun composite membrane containing as little as 2 wt% of organosilicate demonstrated significant ...improvements in strength, modulus, and toughness by about 103%, 45%, and 97%, respectively, when compared with those of electrospun pure P(VDF-TrFE) membrane, while maintaining high porosity and good breathability and piezoelectricity. We believe that such an organosilicate-reinforced durable, porous, and piezoelectric P(VDF-TrFE) membrane has huge advantages in various applications such as flexible sensors, wearable electronics, filter membrane, tissue engineering, battery separator, and polymer electrolyte.
The year 2022 marks the 30th anniversary of heart transplant service in Hong Kong (HK). In this study, we describe prevailing trends and outcomes of advanced heart failure (AHF), including heart ...transplantations (HTx), in HK over the past 30 years.
Trends in heart failure prevalence in HK from 1993 to 2021 were analyzed based on data from the Hospital Authority Clinical Data and Reporting System. All AHF patients referred for HTx consideration between 1992 and 2021 were reviewed. The bridge-to-transplant (BTT) utilization of short-term mechanical circulatory support (ST-MCS) devices, including venoarterial extracorporeal membrane oxygenation (VA-ECMO) and durable left ventricular assist devices (LVADs), from 2010 to 2021 was reviewed.
Overall, 237 heart transplants were performed in HK, with 10-year posttransplant and median survival of 68.1% and 18.7 years, respectively. An increase in AHF clinic referrals was correlated with increasing heart failure prevalence (R
=0.635, P<0.001). In total, 146 referrals were made for ST-MCS, and an observed increase in ST-MCS referrals was correlated with increasing VA-ECMO utilization (R
=0.849, P<0.001). Among 62 patients accepted for AHF therapy, those with durable LVAD implementation had better 1-year survival (71.5%) than those receiving an extracorporeal CentriMag (Levitronix) device as BTT (40%, P=0.008). In total, 143 LVADs were implanted, with 130 as BTT or bridge-to-candidacy (BTC) methods. The survival rate among the 130 BTT/BTC LVAD patients resembled that of HTx recipients (73.8% vs. 69.8% at 9 years, P=0.296).
The burden of AHF management has increased and gained complexity over the past 30 years in Hong Kong.
In this study, plasma enhanced atomic layer deposition was used to prepare ZnGaO thin films with different ZnO cycle ratios from 0 % to 50 %, which were employed to fabricate the MSM-type and ...TFT-type solar-blind photodetector. The properties of the films and the performance of the solar blind photodetector are greatly affected by the ZnO cycle ratio. Appropriate Zn doping content decreases the ratio of oxygen vacancies and Zn interstitials in Ga2O3, while excessive Zn doping degrades the quality of the film. Compared to MSM-type photodetector, an obviously improved performance of ZnGaO TFT-type photodetector has been observed due to its self-amplified photocurrent and the reduced dark current controlled by gate voltage. At a ZnO cycle ratio of 40 %, a superior performance of TFT-type solar-blind photodetector with an ultra-low dark current ∼4.5 × 10−13 A, an excellent light switching ratio ∼2.2 × 107, and an outstandingly high sensitivity ∼34.31 A/W has been obtained. These results demonstrate that the incorporation of Zn dopants can effectively modulate the performance of Ga2O3 TFT-type photodetector providing a great perspective for cost-effective and high-performance solar-blind PDs.
•The ZnGaO films with various ZnO cycle ratios have been obtained using plasma enhanced atomic layer deposition.•TFT-type photodetector shows improved performance due to self-amplified photocurrent and reduced dark current.•A superior performance of TFT-type solar-blind photodetector has been achieved.
Direct methanol fuel cells (DMFC) are studied extensively owing to their simple cell configuration, high volume energy density, short start-up time and operation reliability. However, the major ...drawbacks include high production cost, catalyst and methanol crossover poisoning. This study presents a simple method for Pt–M/C catalyst preparation using a magnetron sputtering (MS) and metal-plasma ion implantation (MPII) technique. The Pt catalysts were sputtered onto a gas diffusion layer (GDL), followed by implanting Cr, Fe, Ni, and Mo catalysts using MPII (accelerating voltage is 20
kV and implantation fluence is 1
×
10
16
ions/cm
2). The crystallinity and microstructure of the catalyst films were analyzed using X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electronic microscopy (SEM) and transmission electronic microscopy (TEM). The cell performance was tested using potential stat/galvano station. The results indicate that the membrane electrode assembly for Pt–Ni/C, Pt–Fe/C and Pt–Cr/C catalysts can enhance DMFC cell performance, compared with traditional Pt/C and Pt–Ru/C. The maximum Pt–Ni/C power density is 2.4
mW/cm
2 with an open circuit voltage (OCV) 0.334
V when tested at a methanol concentration of 1
M.
Prevalence of an abnormal Papanicolaou smear was significantly increased in lupus patients in cross-sectional studies, associated with a higher prevalence of high-risk human papillomavirus (HPV) ...infection. The nucleic acid-specific Toll-like receptors (TLRs) locate at the endolysosomal compartments and trigger the induction of cytokines for the innate immune response. This study evaluated whether abnormal host innate immune response in lupus patients may enhance HPV persistence.
Protein levels of TLRs 3, 7, 8 and 9 in cervical epithelial cells of lupus patients and controls with or without HPV infection were assessed using flow cytometry. Characteristics associated with the differential expression of TLRs in systemic lupus erythematosus (SLE) were elucidated. The effect and interferon-stimulated genes (ISGs) (ISG15 and Mx-1) gene expressions were then measured in oncogenic HeLa (HPV18), CaSki (HPV) and C33A (HPV negative) cell lines using flow cytometry and quantitative real-time PCR. Ex vivo productions of cytokines and interferon-gamma (IFN-γ) upon TLR ligands stimulations were subsequently measured using cytometric bead array and ELISA.
For subjects with HPV infection, levels of TLR3 and TLR7 were significantly lower in lupus patients compared with controls. Significantly decreased TLRs 7, 8 and 9 levels were observed in HPV-negative SLE compared to healthy controls. For SLE with and without HPV infection, TLR7 and 9 levels were significantly lower in infected SLE than those in HPV-negative patients. Independent explanatory variables associated with down-regulation of TLR7 level included HPV infection and a higher cumulative dose of prednisolone; while a higher cumulative dose of hydroxychloroquine and HPV infection were associated with down-regulation of TLR9 level. In cervical cell lines, TLRs 3, 7, 8, 9 protein levels and antiviral ISG15 and Mx-1 gene expressions were inhibited in two oncogenic HPV types. Functional data showed that the induction of pro-inflammatory cytokines by TLR ligands (R837, ssRNA and ODN2395) was greatly impaired in CaSki and HeLa than C33A cells.
In conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate protein levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response against HPV infection. Upon infection, HPV further down-regulate TLR7 and 9 levels for viral persistence. Furthermore, reduction of nucleic acid-sensing TLRs 7, 8 and 9 in carcinogenic HPVs ensures that the expression of inducible pro-inflammatory cytokines is minimized to prevent the expression of antiviral ISGs (ISG15 and Mx-1) on a biologically relevant antiviral response.
Activation of IκB kinase β (IKK-β) and nuclear factor (NF)-κB signaling contributes to cancer pathogenesis and inflammatory disease; therefore, the IKK-β-NF-κB signaling pathway is a potential ...therapeutic target. Current drug design strategies focus on blocking NF-κB signaling by binding to specific cysteine residues on IKK-β. However, mutations in IKK-β have been found in patients who may eventually develop drug resistance. For these patients, a new generation of IKK-β inhibitors are required to provide novel treatment options. We demonstrate in vitro that cysteine-46 (Cys-46) is an essential residue for IKK-β kinase activity. We then validate the role of Cys-46 in the pathogenesis of inflammation using delayed-type hypersensitivity (DTH) and an IKK-β C46A transgenic mouse model. We show that a novel IKK-β inhibitor, dihydromyricetin (DMY), has anti-inflammatory effects on WT DTH mice but not IKK-β C46A transgenic mice. These findings reveal the role of Cys-46 in the promotion of inflammatory responses, and suggest that Cys-46 is a novel drug-binding site for the inhibition of IKK-β.
Conditional colorings of graphs Lai, Hong-Jian; Lin, Jianliang; Montgomery, Bruce ...
Discrete mathematics,
08/2006, Letnik:
306, Številka:
16
Journal Article
Recenzirano
Odprti dostop
For an integer
r
>
0
, a
conditional
(
k
,
r
)
-
coloring of a graph
G is a proper
k-coloring of the vertices of
G such that every vertex of degree at least
r in
G will be adjacent to vertices with ...at least
r different colors. The smallest integer
k for which a graph
G has a conditional
(
k
,
r
)
-coloring is the
rth order conditional chromatic number
χ
r
(
G
)
. In this paper, the behavior and bounds of conditional chromatic number of a graph
G are investigated.
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