Many intercellular solute transport processes require an apoplasmic step, that is, efflux from one cell and subsequent uptake by an adjacent cell. Cellular uptake transporters have been identified ...for many solutes, including sucrose; however, efflux transporters have remained elusive for a long time. Cellular efflux of sugars plays essential roles in many processes, such as sugar efflux as the first step in phloem loading, sugar efflux for nectar secretion, and sugar efflux for supplying symbionts such as mycorrhiza, and maternal efflux for filial tissue development. Furthermore, sugar efflux systems can be hijacked by pathogens for access to nutrition from hosts. Mutations that block recruitment of the efflux mechanism by the pathogen thus cause pathogen resistance. Until recently, little was known regarding the underlying mechanism of sugar efflux. The identification of sugar efflux carriers, SWEETs (Sugars Will Eventually be Exported Transporters), has shed light on cellular sugar efflux. SWEETs appear to function as uniporters, facilitating diffusion of sugars across cell membranes. Indeed, SWEET sprobably mediate sucrose efflux from putative phloem parenchyma into the phloem apoplasm, a key step proceeding phloem loading. Engineering of SWEET mutants using transcriptional activator-like effector nuclease (TALEN)- based genomic editing allowed the engineering of pathogen resistance. The widespread expression of the SWEET family promises to provide insights into many other cellular efflux mechanisms.
Abstract
Protein
fold recognition is critical for studying the structures and functions of proteins. The existing protein fold recognition approaches failed to efficiently calculate the pairwise ...sequence similarity scores of the proteins in the same fold sharing low sequence similarities. Furthermore, the existing feature vectorization strategies are not able to measure the global relationships among proteins from different protein folds. In this article, we proposed a new computational predictor called DeepSVM-fold for protein fold recognition by introducing a new feature vector based on the pairwise sequence similarity scores calculated from the fold-specific features extracted by deep learning networks. The feature vectors are then fed into a support vector machine to construct the predictor. Experimental results on the benchmark dataset (LE) show that DeepSVM-fold obviously outperforms all the other competing methods.
Natural selection endows animals with the abilities to store lipid when food is abundant and to synthesize lipid when it is limited. However, the relevant adaptive strategy of lipid metabolism has ...not been clearly elucidated in fish. This study examined the systemic metabolic strategies of Nile tilapia to maintain lipid homeostasis when fed with low‐ or high‐fat diets. Three diets with different lipid contents (1%, 7%, and 13%) were formulated and fed to tilapias for 10 weeks. At the end of the feeding trial, the growth rate, hepatic somatic index, and the triglyceride (TG) contents of serum, liver, muscle, and adipose tissue were comparable among three groups, whereas the total body lipid contents and the mass of adipose tissue increased with the increased dietary lipid levels. Overall quantitative PCR, western blotting and transcriptomic assays indicated that the liver was the primary responding organ to low‐fat (LF) diet feeding, and the elevated glycolysis and accelerated biosynthesis of fatty acids (FA) in the liver is likely to be the main strategies of tilapia toward LF intake. In contrast, excess ingested lipid was preferentially stored in adipose tissue through increasing the capability of FA uptake and TG synthesis. Increasing numbers, but not enlarging size, of adipocytes may be the main strategy of Nile tilapia responding to continuous high‐fat (HF) diet feeding. This is the first study illuminating the systemic adaptation of lipid metabolism responding to LF or HF diet in fish, and our results shed new light on fish physiology.
We illustrated the adaptive strategy of lipid metabolism responding to low or high fat diets in Nile tilapia. Briefly, the elevated glycolysis and accelerated biosynthesis of fatty acids in the liver were the main strategies of tilapia towards low fat intake. Increasing numbers, but not enlarging size, of adipocytes was the main strategy of Nile tilapia responding to continuous high‐fat diet feeding.
Rheumatoid arthritis is a long-term, progressive autoimmune disease. It is characterized by synovial hyperplasia leading to swelling, stiffness, and joint deformity in more than one joint. ...Fibroblast-like synoviocytes are the major cell types that make up the synovial intima structure, which is one of the decisive factors in the development and course of rheumatoid arthritis.
The potential therapeutic effects of MSCs-derived miRNA-124a overexpression exosomes were evaluated in vitro by the method including MTT assay and cell cycle test for cell proliferation, scratch wound closure and transwell for cell migration, flow cytometry and western for the apoptosis detection.
Exosomes derived from human MSCs that overexpression miRNA-124a were prepared and characterized. We found that the pretreatment of this exosome was able to inhibit the proliferation and migration of fibroblast-like synoviocyte cell line and promote the apoptosis of this cell during the co-incubation.
Exosomes derived from MSCs were proved to be a suitable vector for the delivery of therapeutic miRNA-124a, and such miRNA-124a overexpression exosomes were expected to provide a new medicine and strategy for the treatment of rheumatoid arthritis.
Transition metal (TM)‐based bimetallic spinel oxides can efficiently activate peroxymonosulfate (PMS) presumably attributed to enhanced electron transfer between TMs, but the existing model cannot ...fully explain the efficient TM redox cycling. Here, we discover a critical role of TM−O covalency in governing the intrinsic catalytic activity of Co3−xMnxO4 spinel oxides. Experimental and theoretical analysis reveals that the Co sites significantly raises the Mn valence and enlarges Mn−O covalency in octahedral configuration, thereby lowering the charge transfer energy to favor MnOh–PMS interaction. With appropriate MnIV/MnIII ratio to balance PMS adsorption and MnIV reduction, the Co1.1Mn1.9O4 exhibits remarkable catalytic activities for PMS activation and pollutant degradation, outperforming all the reported TM spinel oxides. The improved understandings on the origins of spinel oxides activity for PMS activation may inspire the development of more active and robust metal oxide catalysts.
The Mn−O covalency was enlarged by the Co sites mainly in the octahedral configuration, which results in a decreased charge transfer energy to favor Mn–PMS interaction and enhance MnIV reduction to boost PMS activation activity of Co‐Mn spinel oxides.
Photothermal therapy (PTT) is one of the most promising approaches to combat multidrug‐resistant bacteria with less potential to induce resistance and systemic toxicity. However, uncontrollable ...distribution of photothermal agents leads to lethal temperatures for normal cells, and failure to offer timely and effective antibacterial stewardship. A pH switchable nanoplatform for persistent luminescence imaging‐guided precise PTT to selectively destroy only pathological cells while protecting nearby normal cells in bacterial infected microenvironment is shown. The PLNP@PANI‐GCS is fabricated by grafting polyaniline (PANI) and glycol chitosan (GCS) onto the surface of persistent luminescence nanoparticles (PLNPs). It takes advantage of the long persistent luminescence of PLNPs to realize autofluorescence‐free imaging, the pH‐dependent light–heat conversion property of PANI to get a stronger photothermal effect at pH 6.5 than pH 7.4, and the pH environment responsive surface charge transition of GCS. Consequently, PLNP@PANI‐GCS enables effective response to bacterial‐infected acid region and electrostatic bonding to bacteria in vivo, ensuring the spatial accuracy of near‐infrared light irradiation and specific heating directly to bacteria. In vivo imaging‐guided PTT to bacterial infection abscess shows effective treatment. PLNP@PANI‐GCS has great potential in treating multidrug‐resistant bacterial infection with low possibility of developing microbial drug resistance and little harm to normal cells.
A pH switchable nanoplatform is developed for in vivo persistent luminescent imaging and precise photothermal therapy of bacterial infections. This nanoplatform exhibits specific photothermal therapy to acidic bacterial‐infected regions but no damage to normal tissues.
Abstract
Protein fold recognition is one of the most critical tasks to explore the structures and functions of the proteins based on their primary sequence information. The existing protein fold ...recognition approaches rely on features reflecting the characteristics of protein folds. However, the feature extraction methods are still the bottleneck of the performance improvement of these methods. In this paper, we proposed two new feature extraction methods called MotifCNN and MotifDCNN to extract more discriminative fold-specific features based on structural motif kernels to construct the motif-based convolutional neural networks (CNNs). The pairwise sequence similarity scores calculated based on fold-specific features are then fed into support vector machines to construct the predictor for fold recognition, and a predictor called MotifCNN-fold has been proposed. Experimental results on the benchmark dataset showed that MotifCNN-fold obviously outperformed all the other competing methods. In particular, the fold-specific features extracted by MotifCNN and MotifDCNN are more discriminative than the fold-specific features extracted by other deep learning techniques, indicating that incorporating the structural motifs into the CNN is able to capture the characteristics of protein folds.
Palladium‐catalyzed allylic alkylation of nonstabilized carbon nucleophiles is difficult and remains a major challenge. Reported here is a highly chemo‐ and regioselective direct palladium‐catalyzed ...C‐allylation of hydrazones, generated from carbonyls, as a source of umpolung unstabilized alkyl carbanions and surrogates of alkyl organometallic reagents. Contrary to classical allylation techniques, this umpolung reaction utilizes hydrazones prepared not only from aryl aldehydes but also from alkyl aldehydes and ketones as renewable feedstocks. This strategy complements the palladium‐catalyzed coupling of unstabilized nucleophiles with allylic electrophiles by providing an efficient and selective catalytic alternative to the traditional use of highly reactive alkyl organometallic reagents.
Surrogates: A highly chemo‐ and regioselective direct palladium‐catalyzed C‐allylation of hydrazones was developed using umpolung carbonyls as a source of unstabilized alkyl carbanions and surrogates of highly reactive alkyl organometallic reagents. The method requires only a catalytic amount of both metal and ligand, delivers products in high yields, is easily scaled‐up, and demonstrates wide substrate scope and good functional‐group compatibility.
Nonlinear energy sink (NES) is an appropriately designed nonlinear oscillator without positive linear stiffness. NES can suppress vibrations over a wide frequency range due to its targeted energy ...transfer characteristics. Thus, investigations on NES have attracted a lot of attention since a NES was proposed. Designs, analysis, and applications of NESs are still active since different configurations are needed in various practical circumstances. The present work provides a comprehensive review of state-of-the-art researches on NESs. The work begins with a survey of the generation of a NES and its important vibration control characteristics. The work highlights possible complex dynamics resulting in a NES coupled to a structure. The work also summarizes some significant design on the implements of optimal damping effects and the offsets of NES shortcomings. Then, the work details the applications of NESs in all engineering fields. The concluding remarks suggest further promising directions, such as NESs for multidirectional vibration reduction, NESs with nonlinearities beyond the cubic, potential deterioration caused by a NES, low-cost NESs, NESs for extremely low frequency range, and NESs integrated into active vibration controls. There are 383 references in the review, including some publications of the authors.
Osteoporosis is a serious health issue among aging postmenopausal women. The majority of postmenopausal women with osteoporosis have bone loss related to estrogen deficiency. The rapid bone loss ...results from an increase in bone turnover with an imbalance between bone resorption and bone formation. Osteoporosis can also result from excessive glucocorticoid usage, which induces bone demineralization with significant changes of spatial heterogeneities of bone at microscale, indicating potential risk of fracture. This review is a summary of current literature about the molecular mechanisms of actions, the risk factors, and treatment of estrogen deficiency related osteoporosis (EDOP) and glucocorticoid induced osteoporosis (GIOP). Estrogen binds with estrogen receptor to promote the expression of osteoprotegerin (OPG), and to suppress the action of nuclear factor-κβ ligand (RANKL), thus inhibiting osteoclast formation and bone resorptive activity. It can also activate Wnt/β-catenin signaling to increase osteogenesis, and upregulate BMP signaling to promote mesenchymal stem cell differentiation from pre-osteoblasts to osteoblasts, rather than adipocytes. The lack of estrogen will alter the expression of estrogen target genes, increasing the secretion of IL-1, IL-6, and tumor necrosis factor (TNF). On the other hand, excessive glucocorticoids interfere the canonical BMP pathway and inhibit Wnt protein production, causing mesenchymal progenitor cells to differentiate toward adipocytes rather than osteoblasts. It can also increase RANKL/OPG ratio to promote bone resorption by enhancing the maturation and activation of osteoclast. Moreover, excess glucocorticoids are associated with osteoblast and osteocyte apoptosis, resulting in declined bone formation. The main focuses of treatment for EDOP and GIOP are somewhat different. Avoiding excessive glucocorticoid use is mandatory in patients with GIOP. In contrast, appropriate estrogen supplement is deemed the primary treatment for females with EDOP of various causes. Other pharmacological treatments include bisphosphonate, teriparatide, and RANKL inhibitors. Nevertheless, more detailed actions of EDOP and GIOP along with the safety and effectiveness of medications for treating osteoporosis warrant further investigation.
PDF
