Molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) and molecular mechanics generalized Born surface area (MM/GBSA) are arguably very popular methods for binding free energy prediction since ...they are more accurate than most scoring functions of molecular docking and less computationally demanding than alchemical free energy methods. MM/PBSA and MM/GBSA have been widely used in biomolecular studies such as protein folding, protein–ligand binding, protein–protein interaction, etc. In this review, methods to adjust the polar solvation energy and to improve the performance of MM/PBSA and MM/GBSA calculations are reviewed and discussed. The latest applications of MM/GBSA and MM/PBSA in drug design are also presented. This review intends to provide readers with guidance for practically applying MM/PBSA and MM/GBSA in drug design and related research fields.
Summary
Background
Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time.
Objectives
This study aimed to clarify the ...current epidemiological characteristics and pathogen spectrum of tinea capitis in China.
Methods
A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory.
Results
Among all enrolled patients, 74·1% of the cases were in patients aged 2–8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P < 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province.
Conclusions
Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.
What is already known about this topic?
Tinea capitis is an infection of the scalp and hair caused by dermatophytes and is still common in developing countries. Prepubertal children are mainly affected.
The pathogen spectrum of tinea capitis varies across different geographical areas and changes over time.
Nationwide prospective epidemiological surveys of tinea capitis in China are rare and out of date.
What does this study add?
This study provides data concerning the epidemiological characteristics and pathogen spectrum of tinea capitis in contemporary China.
Boys aged approximately 5 years were most commonly affected and were more likely than adults to have zoophilic dermatophyte infection.
The main pathogens of tinea capitis in China are zoophilic dermatophytes, mainly Microsporum canis. In contrast to the other regions, the predominant pathogens in central China are anthropophilic dermatophytes.
Plain language summary available online
lncRNAs play important roles in the epigenetic regulation of carcinogenesis and progression. Previous studies suggest that HOTAIR contributes to gastric cancer (GC) development, and the ...overexpression of HOTAIR predicts a poor prognosis. In this study, we found that HOTAIR was more highly expressed in diffuse-type GC than in intestinal type (P=0.048). In the diffuse type, there is significant relationship between HOTAIR expression and DFS (P<0.001). CDH1 was downregulated in diffuse-type GC tissues (P=0.0007) and showed a negative relationship with HOTAIR (r(2)=0.154, P=0.0354). In addition, HOTAIR knockdown significantly repressed migration, invasion and metastasis both in vitro and vivo and reversed the epithelial-to-mesenchymal transition in GC cells. We also showed that HOTAIR recruiting and binding to PRC2 epigenetically represses miR34a, which controls the targets C-Met (HGF/C-Met/Snail pathway) and Snail, thus contributing to GC cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with microRNAs during epigenetic regulation. Our results suggest that HOTAIR acts as an EMT regulator and may be a candidate prognostic biomarker and a target for new therapies in GC patients.
Braille system is widely used worldwide for communication by visually impaired people. However, there are still some visually impaired people who are unable to learn Braille system due to various ...factors, such as the age (too young or too old), brain damage, etc. A wearable and low-cost Braille recognition system may substantially help these people recognize Braille or assist them in Braille learning. In this work, we fabricated polydimethylsiloxane (PDMS)-based flexible pressure sensors to construct an electronic skin (E-skin) for the application of Braille recognition. The E-skin mimics human touch sensing function for collecting Braille information. Braille recognition is realized with a neural network based on memristors. We utilize a binary neural network algorithm with only two bias layers and three fully connected layers. Such neural network design remarkably reduces the calculation burden and, thus, the system cost. Experiments show that the system can achieve a recognition accuracy of up to 91.25%. This work demonstrates the possibility of realizing a wearable and low-cost Braille recognition system and a Braille learning-assistance system.
Surrogate models are used to dramatically improve the design efficiency of numerical aerodynamic shape optimization, where high-fidelity, expensive computational fluid dynamics (CFD) is often ...employed. Traditionally, in adaptation, only one single sample point is chosen to update the surrogate model during each updating cycle, after the initial surrogate model is built. To enable the selection of multiple new samples at each updating cycle, a few parallel infilling strategies have been developed in recent years, in order to reduce the optimization wall clock time. In this article, an alternative parallel infilling strategy for surrogate-based constrained optimization is presented and demonstrated by the aerodynamic shape optimization of transonic wings. Different from existing methods in which multiple sample points are chosen by a single infill criterion, this article uses a combination of multiple infill criteria, with each criterion choosing a different sample point. Constrained drag minimizations of the ONERA-M6 and DLR-F4 wings are exercised to demonstrate the proposed method, including low-dimensional (6 design variables) and higher-dimensional problems (up to 48 design variables). The results show that, for surrogate-based optimization of transonic wings, the proposed method is more effective than the existing parallel infilling strategies, when the number of initial sample points are in the range from
N
v
to
8N
v
(
N
v
here denotes the number of design variables). Each case is repeated 50 times to eliminate the effect of randomness in our results.
Abstract
We report an unusual pressure-induced superconducting state that coexists with an antiferromagnetic ordering of Eu
2+
moments and shows a large upper critical field comparable to the Pauli ...paramagnetic limit in EuTe
2
. In concomitant with the emergence of superconductivity with
T
c
≈ 3–5 K above
P
c
≈ 6 GPa, the antiferromagnetic transition temperature
T
N
(
P
) experiences a quicker rise with the slope increased dramatically from d
T
N
/d
P
= 0.85(14) K/GPa for
P
≤
P
c
to 3.7(2) K/GPa for
P
≥
P
c
. Moreover, the superconducting state can survive in the spin-flop state with a net ferromagnetic component of the Eu
2+
sublattice under moderate magnetic fields
μ
0
H
≥ 2 T. Our findings establish the pressurized EuTe
2
as a rare magnetic superconductor possessing an intimated interplay between magnetism and superconductivity.
We previously demonstrated that fermitin family member 1 (FERMT1) was significantly overexpressed in colon cancer (CC) and associated with poor metastasis-free survival. This study aimed to ...investigate the precise role of FERMT1 in CC metastasis and the mechanism by which FERMT1 is involved in the epithelial-mesenchymal transition (EMT). Correlations between FERMT1 and EMT markers (E-cadherin, Slug, N-cadherin and β-catenin) were examined via immunohistochemistry in a cohort of CC tissues and adjacent normal colon mucosae. A series of in vitro and in vivo assays were performed to elucidate the function of FERMT1 in CC metastasis and underlying mechanisms. The upregulated expression of FERMT1 in CC tissues correlated positively with that of Slug, N-cadherin and β-catenin, but correlated inversely with E-cadherin expression. Altered FERMT1 expression led to marked changes in the proliferation, migration, invasion and EMT markers of CC cells both in vitro and in vivo. Investigations of underlying mechanisms found that FERMT1 interacted directly with β-catenin and activated the Wnt/β-catenin signaling pathway by decreasing the phosphorylation level of β-catenin, enhancing β-catenin nuclear translocation and increasing the transcriptional activity of β-catenin/TCF/LEF. Activation of the Wnt/β-catenin pathway by CHIR99021 reversed the effect of FERMT1 knockdown, whereas inhibition of the Wnt/β-catenin pathway by XAV939 impaired the effect of FERMT1 overexpression on EMT and cell motility. In conclusion, findings of this study suggest that FERMT1 activates the β-catenin transcriptional activity to promote EMT in CC metastasis.
PDF
