Pathfinder: Protein folding pathway prediction based on conformational sampling.

The study of protein folding mechanism is a challenge in molecular biology, which is of great significance for revealing the movement rules of biological macromolecules, understanding the pathogenic mechanism of folding diseases, and designing protein engineering materials. Based on the hypothesis that the conformational sampling trajectory contain the information of folding pathway, we propose a protein folding pathway prediction algorithm named Pathfinder. Firstly, Pathfinder performs large-scale sampling of the conformational space and clusters the decoys obtained in the sampling. The heterogeneous conformations obtained by clustering are named seed states. Then, a resampling algorithm that is not constrained by the local energy basin is designed to obtain the transition probabilities of seed states. Finally, protein folding pathways are inferred from the maximum transition probabilities of seed states. The proposed Pathfinder is tested on our developed test set (34 proteins). For 11 widely studied proteins, we correctly predicted their folding pathways and specifically analyzed 5 of them. For 13 proteins, we predicted their folding pathways to be further verified by biological experiments. For 6 proteins, we analyzed the reasons for the low prediction accuracy. For the other 4 proteins without biological experiment results, potential folding pathways were predicted to provide new insights into protein folding mechanism. The results reveal that structural analogs may have different folding pathways to express different biological functions, homologous proteins may contain common folding pathways, and α-helices may be more prone to early protein folding than ß-strands.

Self-Regulating Solar Steam Generators Enable Volatile Organic Compound Removal through In Situ H2O2 Generation.

Interfacial solar steam generation for clean water production suffers from volatile organic compound (VOC) contamination during solar-to-steam conversion. Here, we present a solar steam generator based on the integration of melamine foam (MF), polydopamine (PDA), and Ag/AgCl particles. Together with the high photothermal conversion efficiency (ca. 87.8%, 1 kW/m2) achieved by the PDA thin film, the Ag/AgCl particles can efficiently activate the localized generation of H2O2 and •OH in situ, thus degrading the VOCs during the rapid vapor generation. The generation of H2O2 and •OH in situ also facilitates the creation of a buffer zone containing H2O2 and •OH for the rapid removal of organic pollutants in the surrounding water attracted to the solar vapor generator, demonstrating a self-cleaning steam generator toward various volatile compounds such as phenol, aniline, 2,4-dichlorophenol, and N,N-dimethylformamide in a wide range of concentrations.

Photocatalytic and Adsorption Performances of Faceted Cuprous Oxide (Cu2O) Particles for the Removal of Methyl Orange (MO) from Aqueous Media.

Particles of sub-micron size possess significant capacity to adsorb organic molecules from aqueous media. Semiconductor photocatalysts in particle form could potentially be utilized for dye removal through either physical adsorption or photo-induced chemical process. The photocatalytic and adsorption capabilities of Cu2O particles with various exposed crystal facets have been studied through separate adsorption capacity test and photocatalytic degradation test. These crystals display unique cubic, octahedral, rhombic dodecahedral, and truncated polyhedral shapes due to specifically exposed crystal facet(s). For comparison, Cu2O particles with no clear exposed facets were also prepared. The current work confirms that the surface charge critically affects the adsorption performance of the synthesized Cu2O particles. The octahedral shaped Cu2O particles, with exposed {111} facets, possess the best adsorption capability of methyl orange (MO) dye due to the strongest positive surface charge among the different types of particles. In addition, we also found that the adsorption of MO follows the Langmuir monolayer mechanism. The octahedral particles also performed the best in photocatalytic dye degradation of MO under visible light irradiation because of the assistance from dye absorption. On top of the photocatalytic study, the stability of these Cu2O particles during the photocatalytic processes was also investigated. Cu(OH)2 and CuO are the likely corrosion products found on the particle surface after the photocorrosion in MO solution. By adding hole scavengers in the solution, the photocorrosion of Cu2O was greatly reduced. This observation confirms that the photocatalytically generated holes were responsible for the photocorrosion of Cu2O.

FECC-Net: A Novel Feature Enhancement and Context Capture Network Based on Brain MRI Images for Lesion Segmentation.

In recent years, the increasing incidence of morbidity of brain stroke has made fast and accurate segmentation of lesion areas from brain MRI images important. With the development of deep learning, segmentation methods based on the computer have become a solution to assist clinicians in early diagnosis and treatment planning. Nevertheless, the variety of lesion sizes in brain MRI images and the roughness of the boundary of the lesion pose challenges to the accuracy of the segmentation algorithm. Current mainstream medical segmentation models are not able to solve these challenges due to their insufficient use of image features and context information. This paper proposes a novel feature enhancement and context capture network (FECC-Net), which is mainly composed of an atrous spatial pyramid pooling (ASPP) module and an enhanced encoder. In particular, the ASPP model uses parallel convolution operations with different sampling rates to enrich multi-scale features and fully capture image context information in order to process lesions of different sizes. The enhanced encoder obtains deep semantic features and shallow boundary features in the feature extraction process to achieve image feature enhancement, which is helpful for restoration of the lesion boundaries. We divide the pathological image into three levels according to the number of pixels in the real mask area and evaluate FECC-Net on an open dataset called Anatomical Tracings of Lesions After Stroke (ATLAS). The experimental results show that our FECC-Net outperforms mainstream methods, such as DoubleU-Net and TransUNet. Especially in small target tasks, FECC-Net is 4.09% ahead of DoubleU-Net on the main indicator DSC. Therefore, FECC-Net is encouraging and can be relied upon for brain MRI image applications.

The protective effects of rutaecarpine on acute pancreatitis.

Acute pancreatitis (AP) is the acute inflammation of the pancreas. The morbidity of AP has increased in recent years. Certain patients eventually develop severe AP (SAP), which rapidly progresses to multiple organ dysfunction; the incidence of this occurring in patients with AP is 20-30%. To date, no specific drugs or methods exist to treat this disease. Rutaecarpine relaxes vascular smooth muscle by stimulating calcitonin gene-related peptide (CGRP) release via activation of vanilloid receptor subtype 1 (VR1). It has been demonstrated that rutaecarpine induces a therapeutic effect on SAP. The present study was conducted to characterize the molecular mechanisms underlying the protective effects of rutaecarpine against AP using a rat model of AP. Gross pathological changes of the pancreas, as well as the pancreatic tissue histopathological score, were assessed following treatment with rutaecarpine, capsazepine or a combination of the two. Serum amylase activity was detected using an automatic biochemistry analyzer. Changes in the serum concentrations of interleukin (IL)-6, tumor necrosis factor (TNF-α), IL-10 and CGRP were assessed by ELISA and radioimmunoassay. The results demonstrated that pre-treatment with rutaecarpine markedly decreased pancreatic inflammation and necrosis, reduced the volume of ascites, and significantly increased the plasma concentration of CGRP and the serum concentration of IL-10, an anti-inflammatory cytokine. However, serum concentrations of the inflammatory cytokines IL-6 and TNF-α were decreased. The effect of rutaecarpine treatment markedly improved with increases in the drug dose. Capsazepine, as a competitive vanilloid receptor antagonist, abolished these protective effects of rutaecarpine against AP. Therefore, the results of the present study indicate that rutaecarpine protects against AP in rats by upregulating endogenous CGRP release via activation VR1 of, to improving the microcirculation of the pancreatic tissue and regulate the expression of inflammatory factors.

Cell motility and spreading promoted by CEACAM6 through cyclin D1/CDK4 in human pancreatic carcinoma.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) belongs to the human carcino-embryonic antigen (CEA) family. Numerous lines of studies have indicated that altered expression of CEACAM6 may have a role in carcinogenesis and development. However, few studies have defined functional roles and mechanisms of action. In the present study, the relationship between clinical and pathological parameters was also analyzed. The relative CEACAM6 protein expression of pancreatic carcinoma was significantly higher than that in non-cancerous tissue. Different clinical stages and lymph node metastasis between groups were significantly different (P<0.05). We used siRNA and forced-expression in multiple cell lines to define the role of CEACAM6 in the regulation of proliferation of pancreatic carcinoma in vitro and in vivo. Knockdown of endogenous CEACAM6 decreased proliferation of BxPC-3 and SW1990 cells. These changes significantly reduced cyclin D1 and CDK4 protein levels. Conversely, overexpression of CEACAM6 in MIA PaCa-2 cells stimulated proliferation and increased cyclin D1 and CDK4 protein levels. Our results confirm that CEACAM6 promoted cell proliferation, and these changes were mediated by cyclin D1/CDK4. These observations contribute to our understanding of the important roles of CEACAM6 in pancreatic carcinoma development and progression and could be a promising molecular target for the development of new diagnostic and therapeutic strategies of pancreatic carcinoma.