One-pot synthesis of phosphorylnaphth[2,1-d]oxazoles and products as P,N-ligands in C-N and C-C formation.

Phosphanylnaphtho[2,1-d]oxazoles were synthesized successfully through one-pot phosphonation of naphthoquinone with diaryl(alkyl)phosphine oxides and Cu-catalyzed oxidative condensation with imines, followed by methylation and reduction. Upon applying 4-phosphanylnaphtho[2,1-d]oxazole as a P,N-chelating ligand, Pd-catalyzed C-N formation of amines or nitrobenzene as well as Ni-catalyzed C-C formation and the synthesis of quinoline proceeded successfully. The reaction was facilely scaled up to give N-benzylaniline 15a in a gram scale synthesis. This research provided a facile and convenient protocol to synthesize phosphanylnaphtho[2,1-d]oxazoles, which could be applied as an efficient P,N-ligand in transition-metal-catalyzed C-N and C-C formation to produce the desired products in high yields with wide functional group tolerance under small catalyst loading, solvent-free conditions in many reactions.

CD147 is increased in HCC cells under starvation and reduces cell death through upregulating p-mTOR in vitro.

Transarterial chemoembolization (TACE) is the standard of care for treatment of intermediate hepatocellular carcinoma (HCC), however, key molecules involved in HCC cell survival and tumor metastasis post-TACE remain unclear. CD147 is a member of the immunoglobulin superfamily that is overexpressed on the surface of HCC cells and is associated with malignant potential and poor prognosis in HCC patients. In this study, using an Earle's Balanced Salt Solution medium culture model that mimics nutrient deprivation induced by TACE, we investigated the regulation of CD147 expression on HCC cells under starvation conditions and its functional effects on HCC cell death. During early stages of starvation, the expression of CD147 was considerably upregulated in SMMC7721, HepG2 and HCC9204 hepatoma cell lines at the protein levels. Downregulation of CD147 by specific small interfering RNA (siRNA) significantly promoted starvation-induced cell death. In addition, CD147 siRNA-transfected SMMC7721 cells demonstrated significantly increased levels of both apoptosis and autophagy as compared to cells transfected with control siRNA under starvation conditions, whereas no difference was observed between the two treatment groups under normal culture conditions. Furthermore, silencing of CD147 resulted in a remarkable downregulation of phosphorylated mammalian target of rapamycin (p-mTOR) in starved SMMC7721 cells. Finally, the combined treatment of starvation and anti-CD147 monoclonal antibody exhibited a synergistic HCC cell killing effect. Our study suggests that upregulation of CD147 under starvation may reduce hepatoma cell death by modulating both apoptosis and autophagy through mTOR signaling, and that CD147 may be a novel potential molecular target to improve the efficacy of TACE.

Ultrafast all-optical graphene modulator.

Graphene is an optical material of unusual characteristics because of its linearly dispersive conduction and valence bands and the strong interband transitions. It allows broadband light-matter interactions with ultrafast responses and can be readily pasted to surfaces of functional structures for photonic and optoelectronic applications. Recently, graphene-based optical modulators have been demonstrated with electrical tuning of the Fermi level of graphene. Their operation bandwidth, however, was limited to about 1 GHz by the response of the driving electrical circuit. Clearly, this can be improved by an all-optical approach. Here, we show that a graphene-clad microfiber all-optical modulator can achieve a modulation depth of 38% and a response time of ∼ 2.2 ps, limited only by the intrinsic carrier relaxation time of graphene. This modulator is compatible with current high-speed fiber-optic communication networks and may open the door to meet future demand of ultrafast optical signal processing.

CD305 participates in abnormal activation of memory CD4+ T cells in patients with RA and attenuates collagen-induced arthritis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that mainly affects the joints. Studies have shown that memory CD4+ T cells play an important role in the pathogenesis of RA. This study investigated the expression and function of CD305 on human memory CD4+ T cells and the effects of CD305 activating antibody on collagen-induced arthritis. The results showed that CD305 expression was significantly decreased on circulating memory CD4+ T cells from patients with RA and its mean fluorescence intensity (MFI) was negatively correlated with DAS28. Moreover, CD305 inhibited the activation of memory CD4+ T cells by down-regulating CD69 and CD25 and the production of IFN-γ, IL-4, and IL-17A induced by anti-CD3/CD28 antibodies. In addition, activation of CD305 inhibited the severity of disease in collagen-induced arthritis. In summary, CD305 reduction may mediate the excessive activation of memory CD4+ T cells and participate in the development of RA. It can be used as a predictive marker of disease activity and has potential medicinal value in the treatment of RA.

Genome-Wide Identification and Expression Analysis of the Starch Synthase Gene Family in Sweet Potato and Two of Its Closely Related Species.

The starch synthase (SS) plays important roles in regulating plant growth and development and responding to adversity stresses. Although the SS family has been studied in many crops, it has not been fully identified in sweet potato and its two related species. In the present study, eight SSs were identified from Ipomoea batatas (I. batata), Ipomoea trifida (I. trifida), and Ipomoea trlioba (I. trlioba), respectively. According to the phylogenetic relationships, they were divided into five subgroups. The protein properties, chromosomal location, phylogenetic relationships, gene structure, cis-elements in the promoter, and interaction network of these proteins were also analyzed; stress expression patterns were systematically analyzed; and real-time polymerase chain reaction (qRT-PCR) analysis was performed. Ipomoea batatas starch synthase (IbSSs) were highly expressed in tuber roots, especially Ipomoea batatas starch synthase 1 (IbSS1) and Ipomoea batatas starch synthase 6 (IbSS6), which may play an important role in root development and starch biosynthesis. At the same time, the SS genes respond to potassium deficiency, hormones, cold, heat, salt, and drought stress. This study offers fresh perspectives for enhancing knowledge about the roles of SSs and potential genes to enhance productivity, starch levels, and resistance to environmental stresses in sweet potatoes.

Identification and functional characterization of the SUMO system in sweet potato under salt and drought stress.

Sumoylation is a crucial post-translation modification (PTM) that is the covalent attachment of SUMO molecules to the substrate catalyzed by enzyme cascade. Sumoylation is essential in almost every physiological process of plants, particularly in response to abiotic stress. However, little is known about sumoylation in sweet potato (Ipomoea batatas), the world's seventh most important food crop. In this study, 17 sweet potato SUMO system genes have been cloned and functionally characterized. Multiple sequence alignment and phylogenetic analysis showed sweet potato SUMO system proteins had conserved domains and activity sites. IbSUMOs, IbSAE1, and IbSCE1 were localized in the cytoplasm and nucleus. E3 SUMO ligases showed nuclear or punctate localization. In vitro sumoylation assay confirmed the catalytic activity of sweet potato SUMO system components. Heterologous expression of IbSIZ1 genes in Arabidopsis atsiz1 mutant rescued the defective germination and growth phenotype. IbSCE1a/b and IbSIZ1a/b/c were salt and drought responsive genes. Heterologous expression of IbSCE1a/b/c improved the drought tolerance of Arabidopsis thaliana, while IbSIZ1a/b/c significantly enhanced the salt and drought tolerance. Our findings define that the SUMO system in sweet potato shared with conserved function but also possessed specific characterization. The resources presented here would facilitate uncovering the significance of sumoylation in sweet potato.

Coal-Rock Dynamic Disaster Prevention Mechanism Based on the Dual Loads of Dynamic Barrier and Static Pressure Relief by Hydraulic Slotting.

According to the characteristics of coal-rock dynamic disasters and hydraulic slotting, the mechanism of dynamic load barrier and static load pressure relief in hydraulic slotting is proposed. The stress distribution in a coal mining face and the slotted area of a section coal pillar is analyzed by numerical simulation. The results show that the slot formed by hydraulic slotting can effectively alleviate the stress concentration and transfer the high-stress area to a deeper coal seam. When slotting and blocking the dynamic load propagation path in a coal seam, the wave intensity of the stress wave transmitted into the slot is greatly reduced, so the risk of a coal-rock dynamic disaster is reduced. A field application of hydraulic slotting prevention technology was carried out in the Hujiahe coal mine. An investigation of microseismic events and an evaluation of the rock noise system show that the average event energy within 100 m mining mileage decreased by 18%, the microseismic energy per unit footage decreased by 37%, the times of strong mine pressure behavior evaluated in the working face decreased by 17%, and the number of risks decreased by 89%. In conclusion, hydraulic slotting technology can effectively reduce the risk of coal-rock dynamic disasters in mining faces and provides a more effective technical means for coal-rock dynamic disaster prevention.

General approach to splicing optical microfibers via polymer nanowires.

We demonstrate a general approach to splicing microfibers via polymer nanowires. Chloroform dissolved polystyrene nanowires are used to splice silica, tellurite glass, and semiconductor microfibers or nanowires, with splicing loss down to 0.51 dB. Using spliced microfiber structures, we also demonstrate microfiber ring resonators and Mach-Zehnder interferometers with high robustness. The splicing technique demonstrated here promises high potentials for robust optical integration of microfibers or nanowires for functional circuits or devices.

[Progress on relationship between IL-23/IL-17 axis and inflammatory bowel disease].

Chronic inflammatory damage of intestinal mucosa is an important characteristic of inflammatory bowel disease (IBD). Studies have shown that the interleukin 23 (IL-23)/IL-17 axis is involved in intestinal mucosal inflammatory injury and plays a crucial role in the development and prognosis of IBD. IL-23 is one of the upstream molecules of IL-17, which can promote Th17 cell activation, proliferation and the secretion of inflammatory cytokines. Moreover, IL-23 is involved in the inflammatory response process of various immune cells such as neutrophils, macrophages, regulatory T cells (Tregs), the group 3 innate lymphocytes (ILC3) during IBD. Previous studies demonstrated that IL-23 and IL-17 increased in IBD, which lead to an imbalance between Tregs and auto-reactive T cells to exacerbate the inflammatory pathological damage of the intestinal mucosa. Notably, although IL-23/IL-17 is potential therapeutic target for inflammation-related diseases and anti-IL-23 strategies has proven to be effective in treating IBD, the strategy of blocking IL-17 to treat IBD has failed. Therefore, a deep understanding of the relationship between IL-17/IL-23 axis and IBD is necessary for the study of IBD treatment.

Applicability and implementation of the collagen-induced arthritis mouse model, including protocols (Review).

Animal models of rheumatoid arthritis (RA) are essential for studying the pathogenesis of RA in vivo and determining the efficacy of anti-RA drugs. During the past decades, numerous rodent models of arthritis have been evaluated as potential models and the modeling methods are relatively well-developed. Among these models, the collagen-induced arthritis (CIA) mouse model is the first choice and the most widely used because it may be generated rapidly and inexpensively and is relatively similar in pathogenesis to human RA. To date, there have been numerous classic studies and reviews discussing related pathogeneses and modeling methods. Based on this knowledge, combined with the latest convenient and effective methods for CIA model construction, the present review aims to introduce the model to beginners and clarify important details regarding its use. Information on the origin and pathogenesis of the CIA model, the protocol for establishing it, the rate of successful arthritis induction and the methods used to evaluate the severity of arthritis are briefly summarized. With this information, it is expected that researchers who have recently entered the field or are not familiar with this information will be able to start quickly, avoid unnecessary errors and obtain reliable results.

Recent Advances of Sulfonylation Reactions in Water.

BACKGROUND: The sulfonyl groups are general structural moieties present in agrochemicals, pharmaceuticals, and natural products. Recently, many efforts have been focused on developing efficient procedures for preparation of organic sulfones. MATERIALS AND METHODS: Water, a proton source, is considered one of the most ideal and promising solvents in organic synthesis for its easy availability, low cost, nontoxic and nonflammable characteristics. From the green and sustainable point of view, more and more reactions are designed proceeding in water. OBJECTIVE: The review focuses on recent advances of sulfonylation reactions proceeding in water. Sulfonylation reactions using sodium sulfinates, sulfonyl hydrazides, sulfinic acids, and sulfonyl chlorides as sulfonating agents were introduced in detail. RESULTS AND DISCUSSION: In this review, sulfonylation reactions proceeding in water developed in recent four yields were presented. Sulfonylation reactions using water as solvent have attracted more and more attention because water is one of the most ideal and promising solvents in organic synthesis for its facile availability, low cost, nontoxic and nonflammable properties. CONCLUSION: Numerous sulfonating agents such as sodium sulfinates, sulfonyl hydrazides, sulfinic acid, sulfonyl chlorides and disulfides are efficient for sulfonylation reactions which proceed in water.

Direct cyanation, hydrocyanation, dicyanation and cyanofunctionalization of alkynes.

In this review, direct cyanation, hydrocyanation, dicyanation, cyanofunctionalization and other cyanation reactions of alkynes were highlighted. Firstly, the use of nitriles and development of cyanation was simply introduced. After presenting the natural properties of alkynes, cyanation reactions of alkynes were classified and introduced in detail. Transition metal catalysed direct cyanation and hydrocyanation of alkynes gave alkynyl cyanides and alkenyl nitriles in good yields. Dicyanation of alkynes produced 1,2-dicyano adducts. Cyanofunctionalization of alkynes afforded functional cyanated compounds. Thiocyanation and selenocyanation yielded the expected functional vinylthiocyanates and vinylselenocyanates. A plausible reaction mechanism is presented if available.

A Potential Mechanism of Temozolomide Resistance in Glioma-Ferroptosis.

Temozolomide (TMZ) is the first-line chemotherapy drug that has been used to treat glioma for over a decade, but the benefits are limited by half of the treated patients who acquired resistance. Studies have shown that glioma TMZ resistance is a complex process with multiple factors, which has not been fully elucidated. Ferroptosis, which is a new type of cell death discovered in recent years, has been reported to play an important role in tumor drug resistance. The present study reviews the relationship between ferroptosis and glioma TMZ resistance, and highlights the role of ferroptosis in glioma TMZ resistance. Finally, the investigators discussed the future orientation for ferroptosis in glioma TMZ resistance, in order to promote the clinical use of ferroptosis induction in glioma treatment.

The Emerging Role of Myeloid-Derived Suppressor Cells in the Glioma Immune Suppressive Microenvironment.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid progenitor and precursor cells at different stages of differentiation, which play an important role in tumor immunosuppression. Glioma is the most common and deadliest primary malignant tumor of the brain, and ample evidence supports key contributions of MDSCs to the immunosuppressive tumor microenvironment, which is a key factor stimulating glioma progression. In this review, we summarize the source and characterization of MDSCs, discuss their immunosuppressive functions, and current approaches that target MDSCs for tumor control. Overall, the review provides insights into the roles of MDSC immunosuppression in the glioma microenvironment and suggests that MDSC control is a powerful cellular therapeutic target for currently incurable glioma tumors.

The mechanism of propofol in cancer development: An updated review.

Cancer is a key cause of death worldwide. Despite the development of radiotherapy, chemotherapy and even immunotherapy, surgery remains the standard treatment for cancer patients. Recently, many studies have shown that propofol, a commonly used anesthetic drug, can affect the prognosis of cancer. In this review, we provide an overview of the molecular mechanisms of propofol in the development of cancer. Propofol not only affects epigenetic pathways, such as those involving miRNA, lncRNA and histone acetylation, but also modulates genetic signaling pathways, including the hypoxia, NF-κB, MAPK, SLUG and Nrf2 pathways. In addition, propofol influences the immune function of patients and impacts the degree of immunosuppression. Furthermore, we briefly summarize the clinical trials on the effect of propofol in cancer development. Ultimately, further studies distinguishing the types of tumors in clinical trials are needed to clarify the correlation between propofol and cancer.

Role and mechanism of LAIR-1 in the development of autoimmune diseases, tumors, and malaria: A review.

The levels of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), a type I transmembrane glycoprotein broadly expressed on the majority of hematopoietic cells, such as T/B cells and natural killer cells, vary significantly during cell differentiation and activation. Previous studies focused mainly on the role of LAIR-1 in physiology and some pathological conditions, including autoimmune diseases. It has been shown that LAIR-1 mediates immune suppression, further resulting in uncontrolled inflammation. Furthermore, recent studies showed that LAIR-1 participates in the development of hematopoietic and non-hematopoietic tumors as well as malaria. This review summarizes the current findings on LAIR-1 in various diseases, its potential roles in pathogenesis, and provides new insight into the treatment of patients through suppression of the function of LAIR-1.

Endface reflectivities of optical nanowires.

Endface reflectivities (ERs) of optical nanowires are investigated using three-dimensional finite-difference time-domain simulations. Typical ERs of both free-standing and substrate-supported silica, tellurite, PMMA and semiconductor nanowires or nanofibers are obtained. Unlike in conventional waveguides such as optical fibers, ERs of nanowires are usually considerably lower when operated in single mode. Dependences of ER on the diameter and the refractive index of the nanowire, and the wavelength of the guided light are also investigated. These results are helpful for estimating and understanding ERs in optical nanowires with diameters close to or smaller than the wavelengths of the light, and may offer valuable references for practical applications such as nanowire or nanofiber-based resonators and lasers.

Shikonin inhibits proliferation and induces apoptosis in glioma cells via downregulation of CD147.

Shikonin, a traditional Chinese medicine, has been identified as being capable of inducing apoptosis in various tumors, including glioma, and is thus considered to be a promising therapeutic agent for tumor therapy. However, little is known about the molecular mechanism of shikonin in glioma. The present study investigated the influence of shikonin on the proliferation and apoptosis of glioma cells U251 and U87MG and explored the potential molecular mechanisms. It was identified that shikonin was able to induce apoptosis in human glioma cells in a time­ and dose­dependent manner, and a decreased expression level of cluster of differentiation (CD)147 was observed in shikonin­treated U251 and U87MG cells. Knockdown of CD147 inhibited U251 and U87MG cell growth, whereas CD147 overexpression enhanced cell growth and decreased shikonin­induced apoptosis. Additionally, an increased expression level of CD147 suppressed the elevated production of reactive oxygen species and mitochondrial membrane potential levels induced by shikonin. The data indicated that shikonin­induced apoptosis in glioma cells was associated with the downregulation of CD147 and the upregulation of oxidative stress. CD147 may be an optional target of shikonin­induced cell apoptosis in glioma cells.

Long non­coding RNA UCA1 promotes papillary thyroid cancer cell proliferation via miR­204­mediated BRD4 activation.

Long non­coding RNA (lncRNA) urothelial carcinoma­associated 1 (UCA1) has been used in tumor development and progression in many types of cancer. However, the function and mechanism underlying the action of UCA1 in papillary thyroid cancer (PTC) remains unclear. Therefore, these topics were investigated in the present study by in vitro and in vivo experiments. It was demonstrated that the expression level of UCA1 was more significantly upregulated in PTC cell lines and tissues when compared with the immortal human thyroid follicular cell line and adjacent normal tissues, respectively. UCA1 knockdown significantly inhibited PTC cell viability, colony formation and the bromodomain containing 4 (BRD4) expression level in vitro, and retarded PTC tumor growth in vivo. In the previous study, microRNA (miR)­204 inhibited thyroid cancer progression and was regulated by UCA1 in other types of cancer. In addition, by conducting dual luciferase reporter assays, it was confirmed that miR­204 directly binds to UCA1 and the 3'­untranslated region of BRD4. Furthermore, UCA1 competed with BRD4 for miR­204 binding. miR­204 knockdown enhanced BRD4 expression, which can be partially restored by short hairpin­UCA1. The results of the present study illustrated that UCA1 promotes PTC progression by acting as a competing endogenous RNA by sponging miR­204. In conclusion, UCA1 may be regarded as an oncogenic lncRNA, promoting PTC cell proliferation, and be a potential target for human PTC treatment.

Disrupted in schizophrenia 1 (DISC1) inhibits glioblastoma development by regulating mitochondria dynamics.

Glioblastoma(GBM) is one of the most common and aggressive malignant primary tumors of the central nervous system and mitochondria have been proposed to participate in GBM tumorigenesis. Previous studies have identified a potential role of Disrupted in Schizophrenia 1 (DISC1), a multi-compartmentalized protein, in mitochondria. But whether DISC1 could regulate GBM tumorigenesis via mitochondria is still unknown. We determined the expression level of DISC1 by both bioinformatics analysis and tissue analysis, and found that DISC1 was highly expressed in GBM. Knocking down of DISC1 by shRNA in GBM cells significantly inhibited cell proliferation both in vitro and in vivo. In addition, down-regulation of DISC1 decreased cell migration and invasion of GBM and self renewal capacity of glioblastoma stem-like cells. Furthermore, multiple independent rings or spheres could be observed in mitochondria in GBM depleted of DISC1, while normal filamentous morphology was observed in control cells, demonstrating that DISC1 affected the mitochondrial dynamic. Dynamin-related protein 1 (Drp1) was reported to contribute to mitochondrial dynamic regulation and influence glioma cells proliferation and invasion by RHOA/ ROCK1 pathway. Our data showed a significant decrease of Drp1 both in mRNA and protein level in GBM lack of DISC1, indicating that DISC1 maybe affect the mitochondrial dynamic by regulating Drp1. Taken together, our findings reveal that DISC1 affects glioblastoma cell development via mitochondria dynamics partly by down regulation of Drp1.