Examination of a series of naturally-occurring trypsin inhibitor proteins, led to identification of a set of three residues (which we call the "interface triplet") to be determinant of trypsin ...binding affinity, hence excellent templates for small molecule mimicry. Consequently, we attempted to use the Exploring Key Orientation (EKO) strategy developed in our lab to evaluate small molecules that mimic the interface triplet regions of natural trypsin inhibitors, and hence potentially might bind and inhibit the catalytic activity of trypsin. A bis-triazole scaffold ("TT-mer") was the most promising of the molecules evaluated
. Twelve such compounds were synthesized and assayed against trypsin, among which the best showed a
of 2.1 μM. X-ray crystallography revealed a high degree of matching between an illustrative TT-mer's actual binding mode and that of the mimics that overlaid the interface triplet in the crystal structure. Deviation of the third side chain from the PPI structure seems to be due to alleviation of an unfavorable dipole-dipole interaction in the small molecule's actual bound conformation.
Pectin Modifications: A Review Chen, Jun; Liu, Wei; Liu, Cheng-Mei ...
Critical reviews in food science and nutrition,
01/2015, Letnik:
55, Številka:
12
Journal Article
Recenzirano
In recent years, the interest in studying modification of pectin has increased. A number of hydroxyl and carboxyl groups distributed along the backbone as well as a certain amount of neutral sugars ...presented as side chains make pectin capable of preparing a broad spectrum of derivatives. By forming pectin derivatives, their properties may be modified and some other new functional properties may be created. This article attempts to review the information about various methods used for pectin modification, including substitution (alkylation, amidation, quaternization, thiolation, sulfation, oxidation, etc.), chain elongation (cross-linking and grafting) and depolymerization (chemical, physical, and enzymatic degradation). Characteristics and applications of some pectin derivatives are also presented. In addition, the safety and regulatory status of pectin and its derivatives were reviewed.
Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with ...coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.
Display omitted
•Spatial proteome maps of COVID-19 myocardia and microvessels are established•SARS-CoV-2-driven inflammation leads to region-resolved dysfunction of the heart•Mechanisms of dysregulated contraction, conduction, and circulation are elaborated•Myocardia and microvessels of the left atrium are affected by inflammation the most
Leng et al. establish a region-resolved proteome map of the inflammatory myocardia and microvessels of COVID-19 hearts. The myocardia and microvessels of the left atrium are the most affected by inflammation storm. These results could provide guidance in improvement of clinical treatments for cardiovascular diseases associated with COVID-19.
Previous researches have found that chronic neck pain was closely related to depression. However, the relation between chronic neck pain, sleep quality, exercise and depression remains unclear. This ...study aims to evaluate the association between these factors, based on the assumption that sleep quality and exercise are potential mediators in the relationship between chronic neck pain and depression. This cross-sectional study enrolled 231 patients with chronic neck pain who were referred to outpatient clinics in department of neurology between July and December 2016. Data analysis was performed using a structural equation model to evaluate the mediating effects of sleep quality and exercise frequency on the relation between chronic neck pain intensity and depression. A positive correlation between neck pain intensity and depression was unveiled. In addition, sleep quality was identified as a significant positive mediator between neck pain intensity and depression, and exercise can help relieve depression. Poor sleep quality leads to an increase of the symptoms of depression for people with high neck pain intensity which can be effectively relieved via additional exercise.
Background
The significance of surgery in the treatment of hepatocellular carcinoma (HCC) extending into the inferior vena cava (IVC)/right atrium (RA) is currently unclear. We sought to clarify ...whether surgical treatment can improve survival in such patients.
Methods
A retrospective review was undertaken of patients with HCC and IVC/RA tumor thrombus who were potential candidates for surgery but who were finally treated surgically and nonsurgically between September 2000 and October 2010. The patients were subdivided according to therapeutic modalities, and the results for each group were compared.
Results
A total of 56 patients were included in this study. They were divided into three groups. Twenty-five patients underwent hepatectomy plus thrombectomy (surgical group), with minor morbidity and no mortality; the patients in this group had 1-, 3-, and 5-year survival rates of 68.0, 22.5, and 13.5 %, respectively, with a median survival of 19 months. Twenty patients were treated with transcatheter arterial chemoembolization, with 1- and 3-year survival rates of 15.0 and 5.0 %, respectively (median survival 4.5 months). Eleven patients received symptomatic treatment only, and no one in this group survived longer than 1 year (median survival 5 months). The patients in surgical group survived significantly longer than the patients in the other two groups (
p
< 0.001).
Conclusions
Although technically challenging, surgery for HCC with IVC/RA tumor thrombus can be safely performed and should be considered in patients with resectable primary tumor and sufficient hepatic reservoir because compared with transcatheter arterial chemoembolization or symptomatic treatment, it significantly improved patient survival.
Abstract
Background
As a machine learning method with high performance and excellent generalization ability, extreme learning machine (ELM) is gaining popularity in various studies. Various ELM-based ...methods for different fields have been proposed. However, the robustness to noise and outliers is always the main problem affecting the performance of ELM.
Results
In this paper, an integrated method named correntropy induced loss based sparse robust graph regularized extreme learning machine (CSRGELM) is proposed. The introduction of correntropy induced loss improves the robustness of ELM and weakens the negative effects of noise and outliers. By using the
L
2,1
-norm to constrain the output weight matrix, we tend to obtain a sparse output weight matrix to construct a simpler single hidden layer feedforward neural network model. By introducing the graph regularization to preserve the local structural information of the data, the classification performance of the new method is further improved. Besides, we design an iterative optimization method based on the idea of half quadratic optimization to solve the non-convex problem of CSRGELM.
Conclusions
The classification results on the benchmark dataset show that CSRGELM can obtain better classification results compared with other methods. More importantly, we also apply the new method to the classification problems of cancer samples and get a good classification effect.
To control the ongoing COVID‐19 pandemic, a variety of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines have been developed. However, the rapid mutations of SARS‐CoV‐2 spike (S) ...protein may reduce the protective efficacy of the existing vaccines which is mainly determined by the level of neutralizing antibodies targeting S. In this study, we screened prevalent S mutations and constructed 124 pseudotyped lentiviral particles carrying these mutants. We challenged these pseudoviruses with sera vaccinated by Sinovac CoronaVac and ZF2001 vaccines, two popular vaccines designed for the initial strain of SARS‐CoV‐2, and then systematically assessed the susceptivity of these SARS‐CoV‐2 variants to the immune sera of vaccines. As a result, 14 S mutants (H146Y, V320I + S477N, V382L, K444R, L455F + S477N, L452M + F486L, F486L, Y508H, P521R, A626S, S477N + S698L, A701V, S477N + T778I, E1144Q) were found to be significantly resistant to neutralization, indicating reduced protective efficacy of the vaccines against these SARS‐CoV‐2 variants. In addition, F486L and Y508H significantly enhanced the utilization of human angiotensin‐converting enzyme 2, suggesting a potentially elevated infectivity of these two mutants. In conclusion, our results show that some prevalent S mutations of SARS‐CoV‐2 reduced the protective efficacy of current vaccines and enhance the infectivity of the virus, indicating the necessity of vaccine renewal and providing direction for the development of new vaccines.
The scope of hydrogel applications can be greatly expanded by the improvement of mechanical properties. However, enhancement of nanocomposite hydrogels (NC gels) has been severely limited because the ...size of crosslinking nanoparticles is too large, at least in one dimension. Here we report a new strategy to synthesize non-aggregated spherulite nanoparticles, with diameters <5 nm, in aqueous solution, and their enhancement to hydrogel. The stress and stretch ratio at rupture of our NC gel are 430 and 121 KPa with only 40-p.p.m. nanoparticle content. The NC gel containing 200-p.p.m. nanoparticles can revert to 90% of its original size after enduring 100-MPa compressive stress. Our results demonstrate that the suppression of nanoparticle size without aggregation helps to establish a super stretchable and high-toughness hydrogel network at very low inorganic content.
The effects of photo-degradation on the utilization of pesticides in agricultural production has been investigated. Various influencing factors were compared, with results showing that the initial ...pesticide concentration, light source, water quality and pH possessed different effects on neonicotinoids photo-degradation. The initial concentration and pH were found to be most critical effects. The photo-degradation rate decreased by a factor of 2-4 when the initial concentration increased from 5 mg L-1 to 20 mg L-1, particularly for acetamiprid and imidacloprid. The photo-degradation pathways and products of the five neonicotinoids were also investigated, with similar pathways found for each pesticide, except for acetamiprid. Degradation pathways mainly involved photo-oxidation processes, with products identified using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) found to be consistent with literature reported results. Bamboo vinegar exerted a photo-quenching effect on the neonicotinoids, with an improved efficiency at higher vinegar concentrations. The photo-quenching rates of thiamethoxam and dinotefuran were 381.58% and 310.62%, respectively, when a 30-fold dilution of vinegar was employed. The photo-degradation products in bamboo vinegar were identical to those observed in methanol, with acetic acid being the main factor influencing the observed quenching effects.
Mitochondria play a pivotal role in the orchestration of cell death pathways. Here, we show that the control of ubiquitin dynamics at mitochondria contributes to the regulation of apoptotic cell ...death. The unique mitochondrial deubiquitylase, USP30, opposes Parkin‐dependent ubiquitylation of TOM20, and its depletion enhances depolarization‐induced cell death in Parkin‐overexpressing cells. Importantly, USP30 also regulates BAX/BAK‐dependent apoptosis, and its depletion sensitizes cancer cells to BH3‐mimetics. These results provide the first evidence for a fundamental role of USP30 in determining the threshold for mitochondrial cell death and suggest USP30 as a potential target for combinatorial anti‐cancer therapy.
Synopsis
USP30, recently described to counteract Parkin E3 ligase activity on mitochondria, is shown to regulate the mitochondrial pathway of apoptotic cell death in response to Parkin overexpression and the broadly used BH3‐mimetic therapeutic compounds.
hTERT‐RPE1‐cells stably overexpressing YFP‐Parkin undergo depolarisation‐induced, PINK1‐ and caspase‐dependent cell death, which is sensitive to proteasome but not lysosomal inhibitors.
USP30 depletion promotes Parkin‐dependent ubiquitylation of TOM20 and its subsequent degradation.
USP30 depletion enhances depolarization‐induced and Parkin‐dependent cell death.
Depletion of USP30 sensitizes RPE1, U2‐OS and MCF7 cells to BH3‐mimetics and promotes BAX/BAK‐dependent apoptotic cell death.
USP30, recently described to counteract Parkin E3 ligase activity on mitochondria, is shown to regulate the mitochondrial pathway of apoptotic cell death in response to Parkin overexpression and the broadly used BH3‐mimetic therapeutic compounds.
PDF
