Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly ...conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Diagnosis of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC), particularly HCC independent of cirrhosis etiology, presents a great challenge because of a lack of biomarkers. Here we ...test the hypothesis that expression profiles of microRNAs (miRNAs) in serum can serve as biomarkers for diagnosis of HBV infection and HBV-positive HCC. We recruited 513 subjects (210 controls and 135 HBV-, 48 hepatitis C virus (HCV)-, and 120 HCC-affected individuals) and employed a strategy of initial screening by Solexa sequencing followed by validation with TaqMan probe-based quantitative reverse transcription-PCR assay. First, because of a close link between chronic hepatitis B and HCC, we compared miRNA expression profiles in HBV serum with that in control serum and successfully obtained 13 miRNAs that were differentially expressed in HBV serum. This 13-miRNA-based biomarker accurately discriminated not only HBV cases from controls and HCV cases, but also HBV-positive HCC cases from control and HBV cases. Second, we directly compared miRNA expressions in HCC serum with those in controls and identified 6 miRNAs that were significantly upregulated in HCC samples. Interestingly, 2 of these miRNAs, miR-375 and miR-92a, were also identified by our first approach as HBV specific. When we employed 3 of these miRNAs (miR-25, miR-375, and let-7f) as biomarkers, we could clearly separate HCC cases from controls, and miR-375 alone had an ROC of 0.96 (specificity: 96%; sensitivity: 100%) in HCC prediction. In conclusion, our study demonstrates for the first time that serum miRNA profiles can serve as novel and noninvasive biomarkers for HBV infection and HBV-positive HCC diagnosis.
Long-Term Efficacy of a Hepatitis E Vaccine Zhang, Jun; Zhang, Xue-Feng; Huang, Shou-Jie ...
The New England journal of medicine,
03/2015, Volume:
372, Issue:
10
Journal Article
Peer reviewed
Open access
Hepatitis E virus is a common cause of illness worldwide and is associated with severe complications, especially in pregnant women. In this report, the long-term efficacy, immunogenicity, and safety ...of a hepatitis E vaccine are described.
Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide.
1
,
2
HEV infection occurs in two distinct epidemiologic patterns.
3
The most common pattern is waterborne infection, which is caused by HEV genotype 1 or 2 and occurs mainly in resource-limited countries, often in large, protracted outbreaks or in sporadic cases associated with high mortality among pregnant women.
4
–
6
The other pattern is transmission from animals and humans, which is caused by HEV genotype 3 or 4 and occurs widely in both resource-limited and developed countries.
1
,
7
–
9
Rein et al.
10
estimated the incidence of hepatitis E in areas . . .
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in ...antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear.
We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases.
The number of total T cells, CD4
and CD8
T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8
T cells or CD4
T cells lower than 800, 300, or 400/μL, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-α concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-α concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages.
T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/μL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.
The outbreak of 2019 novel coronavirus (2019-nCoV) pneumonia was reported in Wuhan, Hubei Province, China in December 2019 and has spread internationally. This article discusses how radiology ...departments can most effectively respond to this public health emergency.
•A novel convexity-oriented time-dependent reliability-based topology optimization (CTRBTO) scheme is proposed.•The full-dimensional convex set collocation approach is presented to reveal the convex ...process of displacement responses.•The convex time-dependent reliability (CTR) index is defined and its design sensitivity about design variables is deduced.
In this work, a novel convexity-oriented time-dependent reliability-based topology optimization (CTRBTO) framework is investigated with overall consideration of universal uncertainties and time-varying natures in configuration design. For uncertain factors, the initial static ones are quantified by the convex set model and nodal dynamic responses are then expressed by the convex process model, where both the boundary rules and time-dependency properties are revealed by the full-dimensional convex-set collocation theorem. Unlike the original deterministic constraints in topology optimization schemes, a new convex time-dependent reliability (CTR) index is defined to give a reasonable failure judgment of local dynamic stiffness and impel the overall CTRBTO strategy. In addition, the gradient-based iterative algorithm is utilized to guarantee the computational robustness and the CTR-driven design sensitivities are explicitly analyzed by the Lagrange multiplier method. Several numerical examples are used to illustrate the effectiveness of the proposed method, and numerical results reflect the significance of this study to a certain extent.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
New nanostructure means new nanotechnology and nanoscience. The need of complex nanostructure‐based advanced functional nanomaterials has promoted the appearance of several kinds of multifluid ...electrospinning processes, such as tri‐axial electrospinning, quad‐fluid coaxial electrospinning, tri‐fluid side‐by‐side electrospinning, and coaxial electrospinning with a side‐by‐side core. These multifluid processes can greatly expand the capability of electrospinning in generating new types of nanostructures with different organization manner of the inner parts, and from both spinnable and unspinnable working fluids. The key elements for conducting a multifluid electrospinning lie in a well‐designed spinneret, compatibility of the working fluids, and special operational parameters. The complex nanostructures can be created through direct electrospinning of multiple fluids, through after‐treatment of the electrospun products, and through ingenious design of the components, compositions and their spatial distributions as well. This article provides a simple review on the most recent publications about the multifluid electrospinning processes and the corresponding complex nanostructures.
This article is characterized under:
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Implantable Materials and Surgical Technologies > Nanomaterials and Implants
Multifluid electrospinning for the generation of complex nanostructures.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Amorphous materials are metastable solids with only short-range order at the atomic scale, which results from local intermolecular chemical bonding. The lack of long-range order typical of crystals ...endows amorphous nanomaterials with unconventional and intriguing structural features, such as isotropic atomic environments, abundant surface dangling bonds, highly unsaturated coordination, etc. Because of these features and the ensuing modulation in electronic properties, amorphous nanomaterials display potential for practical applications in different areas. Motivated by these elements, here we provide an overview of the unique structural features, the general synthetic methods, and the potential for applications covered by contemporary research in amorphous nanomaterials. Furthermore, we discussed the possible theoretical mechanism for amorphous nanomaterials, examining how the unique structural properties and electronic configurations contribute to their exceptional performance. In particular, the structural benefits of amorphous nanomaterials as well as their enhanced electrocatalytic, optical, and mechanical properties, thereby clarifying the structure–function relationships, are highlighted. Finally, a perspective on the preparation and utilization of amorphous nanomaterials to establish mature systems with a superior hierarchy for various applications is introduced, and an outlook for future challenges and opportunities at the frontiers of this rapidly advancing field is proposed.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
SARS-CoV-2 caused a major outbreak of severe pneumonia (COVID-19) in humans. Viral RNA was detected in multiple organs in COVID-19 patients. However, infectious SARS-CoV-2 was only isolated from ...respiratory specimens. Here, infectious SARS-CoV-2 was successfully isolated from urine of a COVID-19 patient. The virus isolated could infect new susceptible cells and was recognized by its' own patient sera. Appropriate precautions should be taken to avoid transmission from urine.
We construct the supersymmetric
β
and (
q
,
t
)-deformed Hurwitz–Kontsevich partition functions through
W
-representations and present the corresponding character expansions with respect to the Jack ...and Macdonald superpolynomials, respectively. Based on the constructed
β
and (
q
,
t
)-deformed superoperators, we further give the supersymmetric
β
and (
q
,
t
)-deformed partition function hierarchies through
W
-representations. We also present the generalized super Virasoro constraints, where the constraint operators obey the generalized super Virasoro algebra and null super 3-algebra. Moreover, the superintegrability for these (non-deformed) supersymmetric hierarchies is shown by their character expansions, i.e.,
<
c
h
a
r
a
c
t
e
r
>
∼
c
h
a
r
a
c
t
e
r
.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
