Ultrafast dynamics of exciton-polariton fluids at non-zero momenta.

In this study, we have explored the ultrafast formation and decay dynamics of exciton-polariton fluids at non-zero momenta, non-resonantly excited by a small-spot femtosecond pump pulse in a ZnO microcavity. Using the femtosecond angle-resolved spectroscopic imaging technique, multidimensional dynamics in both the energy and momentum degrees of freedom have been obtained. Two distinct regions with different decay rate in the energy dimension and various decay-channels in the momentum dimension can be well-resolved. Theoretical simulations based on the generalized Gross-Pitaevskii equation can reach a qualitative agreement with the experimental observations, demonstrating the significance of the initial potential barrier induced by the pump pulse during the decay process. The finding of our study can provide additional insights into the fundamental understanding of exciton-polariton condensates, enabling further advancements for controlling the fluids and practical applications.

Erratum: Circular RNA Hsa_circRNA_101996 promotes the development of Gastric Cancer via Upregulating Matrix Metalloproteinases-2/Matrix Metalloproteinases-9 through MicroRNA-143/Ten-eleven translocation-2 Pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.62121.].

Site-Selective Polyfluoroaryl Modification and Unsymmetric Stapling of Unprotected Peptides.

Peptide stapling is recognized as an effective strategy for improving the proteolytic stability and cell permeability of peptides. In this study, we present a novel approach for the site-selective unsymmetric perfluoroaryl stapling of Ser and Cys residues in unprotected peptides. The stapling reaction proceeds smoothly under very mild conditions, exhibiting a remarkably rapid reaction rate. It can furnish stapled products in both liquid and solid phases, and the presence of nucleophilic groups other than Cys thiol within the peptide does not impede the reaction, resulting in uniformly high yields. Importantly, the chemoselective activation of Ser ß-C(sp3)-H enables the unreacted -OH to serve as a reactive handle for subsequent divergent modification of the staple moiety with various therapeutic functionalities, including a clickable azido group, a polar moiety, a lipid tag, and a fluorescent dye. In our study, we have also developed a visible-light-induced chemoselective C(sp3)-H polyfluoroarylation of the Ser ß-position. This reaction avoids interference with the competitive reaction of Ser -OH, enabling the precise late-stage polyfluoroarylative modification of Ser residues in various unprotected peptides containing other highly reactive amino acid residues. The biological assay suggested that our peptide stapling strategy would potentially enhance the proteolytic stability and cellular permeability of peptides.

Microcolin H, a novel autophagy inducer, exerts potent antitumour activity by targeting PITPα/ß.

The identification of effective drug targets and the development of bioactive molecules are areas of high need in cancer therapy. The phosphatidylinositol transfer protein alpha/beta isoform (PITPα/ß) has been reported to play an essential role in integrating phosphoinositide trafficking and lipid metabolism in diverse cellular processes but remains unexplored as a potential target for cancer treatment. Herein, data analysis of clinical cancer samples revealed that PITPα/ß expression is closely correlated with the poor prognosis. Target identification by chemical proteomic methods revealed that microcolin H, a naturally occurring marine lipopeptide, directly binds PITPα/ß and displays antiproliferative activity on different types of tumour cell lines. Furthermore, we identified that microcolin H treatment increased the conversion of LC3I to LC3II, accompanied by a reduction of the level of p62 in cancer cells, leading to autophagic cell death. Moreover, microcolin H showed preeminent antitumour efficacy in nude mouse subcutaneous tumour models with low toxicity. Our discoveries revealed that by targeting PITPα/ß, microcolin H induced autophagic cell death in tumours with efficient anti-proliferating activity, which sheds light on PITPα/ß as a promising therapeutic target for cancer treatment.

Neurokinin-1 receptor drives PKCɑ-AURKA/N-Myc signaling to facilitate the neuroendocrine progression of prostate cancer.

The widespread application of antiandrogen therapies has aroused a significant increase in the incidence of NEPC, a lethal form of the disease lacking efficient clinical treatments. Here we identified a cell surface receptor neurokinin-1 (NK1R) as a clinically relevant driver of treatment-related NEPC (tNEPC). NK1R expression increased in prostate cancer patients, particularly higher in metastatic prostate cancer and treatment-related NEPC, implying a relation with the progression from primary luminal adenocarcinoma toward NEPC. High NK1R level was clinically correlated with accelerated tumor recurrence and poor survival. Mechanical studies identified a regulatory element in the NK1R gene transcription ending region that was recognized by AR. AR inhibition enhanced the expression of NK1R, which mediated the PKCα-AURKA/N-Myc pathway in prostate cancer cells. Functional assays demonstrated that activation of NK1R promoted the NE transdifferentiation, cell proliferation, invasion, and enzalutamide resistance in prostate cancer cells. Targeting NK1R abrogated the NE transdifferentiation process and tumorigenicity in vitro and in vivo. These findings collectively characterized the role of NK1R in tNEPC progression and suggested NK1R as a potential therapeutic target.

Extracellular vesicles: emerging anti-cancer drugs and advanced functionalization platforms for cancer therapy.

Increasing evidences show that unmodified extracellular vesicles (EVs) derived from various cells can effectively inhibit the malignant progression of different types of tumors by delivering the bioactive molecules. Therefore, EVs are expected to be developed as emerging anticancer drugs. Meanwhile, unmodified EVs as an advanced and promising nanocarrier that is frequently used in targeted delivery therapeutic cargos and personalized reagents for the treatment and diagnosis of cancer. To improve the efficacy of EV-based treatments, researchers are trying to engineering EVs as an emerging nanomedicine translational therapy platform through biological, physical and chemical approaches, which can be broaden and altered to enhance their therapeutic capability. EVs loaded with therapeutic components such as tumor suppressor drugs, siRNAs, proteins, peptides, and conjugates exhibit significantly enhanced anti-tumor effects. Moreover, the design and preparation of tumor-targeted modified EVs greatly enhance the specificity and effectiveness of tumor therapy, and these strategies are expected to become novel ideas for tumor precision medicine. This review will focus on reviewing the latest research progress of functionalized EVs, clarifying the superior biological functions and powerful therapeutic potential of EVs, for researchers to explore new design concepts based on EVs and build next-generation nanomedicine therapeutic platforms.

Circular RNA Hsa_circRNA_101996 promotes the development of Gastric Cancer via Upregulating Matrix Metalloproteinases-2/Matrix Metalloproteinases-9 through MicroRNA-143/Ten-eleven translocation-2 Pathway.

Background: The long-term survival rate of gastric cancer (GC) patients at advanced stages remains low worldwide. Circular RNAs (circRNAs) a newly studied type of non-coding RNA that play an important role in the pathogenesis and diagnosis of various diseases. In this research, we aimed to explore the functions of hsa_circRNA_101996 in GC cells and an animal model of GC. Methods: The expression of hsa_circRNA_101996, microRNA (miR)-143, and ten-eleven translocation (TET)-2 in GC tissues, the adjacent tissues, and cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Transwell assays were used to analyze the knockdown effects of hsa_circRNA_101996, miR-143, and overexpression of TET2 on cell proliferation, migration, and invasion abilities. Western blotting was used to analyze the expression of matrix metalloproteinases (MMP)2/MMP9. Binding interactions between, hsa_circRNA_101996 and miR-143 and between, miR-143 and TET2 were detected by Dual-luciferase reporter assays. Levels of protein expression were analyzed by Western blotting. Tumor models were established by subcutaneous injection of tumor cells in Bl6/Rag2/GammaC double knockout mice. Results: The result showed that hsa_circRNA_101996 expression was significantly upregulated in GC tissues compared to that in the adjacent tissues, and its level in cancer tissue was correlated with tumor size, lymphatic metastasis, and distant metastasis. Compared with the low hsa_circRNA_101996 expression group, the three-year survival rate of patients in the high hsa_circRNA_101996 expression group was significantly lower. The knockdown of hsa_circRNA_101996 dramatically suppressed the cell migration, invasion, and proliferation of GC cells by sponging to absorb miR-143 and elevated the expression of TET2. In vivo studies showed that the knockdown of hsa_circRNA_101996 delayed tumor growth. Furthermore, we revealed that TET2 regulates MMP2/MMP9 expression through the DNA demethylation pathway. Conclusion: Our findings indicate that hsa_circRNA_101996 promotes GC development by upregulating MMP2/MMP9 through miR-143/TET2 pathway, which may provide a novel target for GC.

Metal Cation-Responsive and Excitation-Dependent Nontraditional Multicolor Fluorescent Hydrogels for Multidimensional Information Encryption.

Fluorescent polymeric hydrogels especially multicolor fluorescent polymeric hydrogels (MFPHs) have important applications in information storage, encryption, and encoding. MFPHs are generally prepared by incorporating multiple traditional fluorescent materials into hydrogels. In recent years, nontraditional luminescent polymers without any traditional π-conjugated chromophores have received increasing attention. Here, we report a novel type of nontraditional MFPHs prepared by in situ polymerization of acrylamide (AAm) in the presence of poly(itaconic acid) (PITAc). The hydrogen-bonded mechanically strong PAAm/PITAc hydrogels show strong intrinsic fluorescence, and the fluorescence emission is excitation-dependent and metal cation-responsive. More impressively, the hydrogels treated with metal cations also possess excitation-dependent fluorescence. We developed a multi-ion inkjet printing (MIIP) technique to print texts or designed patterns onto the hydrogel surface using different metal cation solutions as inks, and then variable texts or patterns appear under the irradiation of UV, violet, and blue lights. Patterns can be further changed by selective printing, erasing, or reprinting on some regions. Therefore, multidimensional information encryption is achieved. This work provides a new strategy for preparing MFPHs for wide applications.

Mapping Mimotopes for House Dust Mite Allergen Der f 7 Using a Specific Monoclonal Antibody.

BACKGROUND: The dust mite Dermatophagoides farinae is a common worldwide cause of indoor allergies induced by its proteins, including the mid-tier allergen Der f 7. OBJECTIVE: To identify conformational epitopes in Der f 7 using mimotope mapping and computational modelling. METHODS: Here, we used standard hybridoma technology to generate 3 new monoclonal antibodies against Der f 7 and performed mimotope mapping by probing a random peptide phage display library. Computational tools, including Minox and the DiscoTope-2.0 Server were used to assess the structure and potential position of antigenic residues within Der f 7. RESULTS: Thirteen mimotopes sharing the common sequence --XX[LST]P[-E][LI]MLPLR[-S]- were identified. Further, computationally-predicted conformational epitopes were found at residues 1-7, 10, 27, 76-81, 92, and 130-133 of Der f 7, and the key amino acids for these epitopes were deduced to be 2P, 3I, 10E, 27E, 78E, 79E, 81I, 130S, and 132E based on the common mimotope sequence. CONCLUSION: We identified Der f 7 peptide mimotopes that may model binding sites for blocking antibodies. These may guide the development of immunotherapy for individuals with hypersensitivity to Der f 7.

Transcriptomics-Based Identification of Aquaporin Diversity in the House Dust Mite Dermatophagoides farinae (Acariformes: Pyroglyphidae).

Aquaporin water channel proteins are highly conserved across many diverse species. Some evidence indicates that aquaporins in insects may contribute to insect-related mammalian diseases and inflammation, and thus these proteins may represent viable therapeutic targets. Here, we used RNA sequencing and bioinformatics to identify putative aquaporins from the house dust mite, Dermatophagoides farinae. Six putative aquaporins were identified based on sequence similarity with aquaporins from other species. These putative aquaporins, deposited in GenBank and named DerfAQP1-4 (KY231248, KY231249, KY231250, and KY231251, respectively), DerfAQP5.01, and DerfAQP5.02 (KY231252 and KY231253), were successfully cloned into a bacterial plasmid. The identification of full-length aquaporin sequences from D. farinae provides a foundation for future molecular and biochemical studies of these proteins in D. farinae and related species.

Identification of three aquaporin subgroups from Blomia tropicalis by transcriptomics.

Aquaporins (AQPs), or water channel proteins, are highly conserved across species. These transmembrane proteins promote water and solute transport across cell membranes. No AQP­related proteins have been identified in mites to date. The present study used transcriptomics (RNA­sequencing) to identify potential AQPs in the mite species Blomia tropicalis. Molecular cloning techniques were then used to obtain the full­length gene sequences encoding these AQP family members, and bioinformatics analyses were used to categorize them based on similarity to AQPs in other species. This approach led to the identification of 5 putative AQP­coding sequences, known as BlotAQP1­5 (GenBank accession numbers: KX655540, KX655541, KX655542, KX655543 and KX655544, respectively), which were indexed into all three subgroups, i.e., AQPs, aquaglyceroporins and superAQPs. To the best of our knowledge, these represent the first known AQPs in any mite species. Further studies are required to investigate their functional roles in water transport and their potential as drug targets.

The Clinical Significance of Changes in the Expression Levels of MicroRNA-1 and Inflammatory Factors in the Peripheral Blood of Children with Acute-Stage Asthma.

This study assessed the changes and clinical significance of microRNA-1 (miR-1) and inflammatory factors in the peripheral blood of children with acute-stage asthma. 100 children with acute-stage asthma (study group) and 100 healthy children (control group) were enrolled. For all enrolled children, the peripheral blood levels of miR-1, interleukin-4 (IL-4), IL-5, IL-8, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) were measured. The relative expression levels of miR-1 and IFN-γ in the peripheral blood of children in the study group were significantly lower than those in the control group, whereas expression levels of IL-4, IL-5, IL-8, and TNF-α were significantly higher. Moreover, these levels changed to a greater extent in patients with severe disease (P < 0.05). Further analyses showed that the miR-1 expression level positively correlated with IFN-γ and negatively correlated with IL-4, IL-5, IL-8, and TNF-α expression levels (P < 0.05). ROC curve analysis to identify diagnostic specificity and sensitivity showed that, for diagnosing exacerbation in asthma, the area under the curve (AUC) for miR-1 was the highest (AUC = 0.900, P < 0.05) of all tested markers; this held true for diagnosing severe asthma as well (AUC = 0.977, P < 0.05). Compared to healthy children, children with acute-stage asthma had a low miR-1 expression level and a Th1/Th2 imbalance in their peripheral blood. The changes were closely related, became more exaggerated with an increase in disease severity, and could be used as auxiliary variables for diagnosing asthma exacerbation and evaluating disease severity.

Epidemiology of spider mite sensitivity: a meta-analysis and systematic review.

BACKGROUND: Spider mites, including Tetranychus urticae, Panonychus citri, and Panonychus ulmi, are common pests in gardens, greenhouses, and orchards. Exposure, particularly occupational exposure, to these organisms may lead to the development of respiratory or contact allergies. However, the prevalence of sensitivity to spider mites is unclear. METHODS: We examined the literature to generate an estimate of the global prevalence of allergies to spider mites. RESULTS: Electronic databases were searched and twenty-three studies reporting the prevalence of sensitivity to spider mites (based on skin prick tests or IgE-based detection systems) in an aggregate total of 40,908 subjects were selected for analysis. The estimated overall rate of spider mite sensitivity was 22.9% (95% CI 19-26.8%). Heterogeneity was high and meta-regression analysis considering variables such as published year, country, number of study subjects, methods for allergen detection (skin prick test, ImmunoCAP, RAST testing, or intradermal test), and mite species revealed no single significant source. Twelve of the 23 studies reported rates of monosensitization (i.e., patients responsive to spider mites but no other tested allergen), yielding a global average of 7% (95% CI 5-9%), hence spider mites represent a unique source of allergens. CONCLUSIONS: Spider mites are an important cause of allergic symptoms. However, the publication bias and heterogeneity evident in this study indicate that further trials using standardized detection methods are needed to determine the association of exposure and symptoms as well as the specific patient characteristics that influence developing spider mite sensitivity.

Consideration of methods for identifying mite allergens.

House dust mites are small arthropods that produce proteins-found in their feces, body parts, and eggs-that are major triggers of human allergies worldwide. The goal of this review is to describe the current methods used to identify these allergens. A literature search for allergen identification methods employed between 1995 and 2016 revealed multiple techniques that can be broadly grouped into discovery and confirmation phases. The discovery phase employs screening for mite proteins that can bind IgEs in sera from animals or patients allergic to dust mites. The confirmation phase employs biochemical methods to isolate either native or recombinant mite proteins, confirms the IgE binding of the purified allergens, and uses either in vitro or in vivo assays to demonstrate that the purified antigen can stimulate an immune response. The methods used in the two phases are defined and their strengths and weaknesses are discussed. The majority of HDM-allergic patients may respond to just a small subset of proteins, but new protein discovery methods are still warranted in order to develop a complete panel of HDM allergens for component resolved diagnosis and patient-tailored therapies.

HucMSC exosomes-delivered 14-3-3ζ enhanced autophagy via modulation of ATG16L in preventing cisplatin-induced acute kidney injury.

The clinical application of cisplatin is restricted by its side effects of nephrotoxicity. Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-ex) have an important effect in tissue injury repair. Our previous work discovered that pretreatment with human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-ex) alleviated cisplatin-induced acute kidney injury (AKI) by activating autophagy both in vitro and in vivo. In this study, we further explored the mechanisms of hucMSC-ex in autophagy for preventing cisplatin-induced nephrotoxicity. We discovered that 14-3-3ζ was contained in hucMSC-ex, and knockdown and overexpression 14-3-3ζ reduced and enhanced the autophagic activity respectively. Furthermore, Knockdown of 14-3-3ζ alleviated the preventive effect of hucMSC-ex. In contrast, overexpression of 14-3-3ζ enhanced the effect. Further results confirmed that hucMSC-ex increased ATG16L expression and that 14-3-3ζ interacted with ATG16L, promoting the localization of ATG16L at autophagosome precursors. In this study, we revealed that hucMSC-ex-delivered 14-3-3ζ interacted with ATG16L to activate autophagy. Our findings suggest that 14-3-3ζ is a novel mechanism for MSC-exosomes-activated autophagy and provides a new strategy for the prevention of cisplatin-induced nephrotoxicity.

HucMSC exosome-transported 14-3-3ζ prevents the injury of cisplatin to HK-2 cells by inducing autophagy in vitro.

BACKGROUND AIMS: On the basis of previous studies, exosomes secreted by human umbilical cord mesenchymal stromal cell (hucMSC-ex) could prevent and repair acute kidney injury induced by cisplatin in rats. However, its potential mechanism is still unclear. In the present study, the model with hucMSC-ex pretreated human renal tubular epithelial cell lines HK-2 that could prevent the injury of cisplatin was successfully established. METHODS: First, we pretreated the HK-2 cells with hucMSC-ex for 24 h. Cisplatin was then used to injure HK-2 cells. Gain and loss of function study were used to explore the role of 14-3-3ζ. The expression level of proliferating cell nuclear antigen (PCNA) was analyzed by immunofluorescence assay and Western blot. The number of apoptotic cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and flow cytometry analysis. The formation of autophagosomes was observed under super-resolution optical microscope. Western blot was used to analyze the expression levels of LC3B, P62, 14-3-3ζ and Bax. RESULTS: Pretreating cells with hucMSC-ex could prevent the injury of cisplatin by reducing the number of apoptotic cells and increasing the expression level of PCNA. Simultaneously, the autophagic level was up-regulated. The application of autophagic inhibitor 3-methyladenine (3-MA) could reverse the protective effect of hucMSC-ex. The overexpression of 14-3-3ζ enhanced the autophagic level and protected the injury of cisplatin. The knock-down of 14-3-3ζ could reduce the autophagic level and enhance the disadvantage of cisplatin. The enhanced injury of cisplatin was reversed when the knock-down of 14-3-3ζ was replenished with hucMSC-ex. CONCLUSIONS: 14-3-3ζ transported by hucMSC-ex may up-regulate autophagic level in HK-2 cells, which can prevent the injury of cisplatin. This discovery provides the new theoretical basis for the prevention of cisplatin-induced nephrotoxicity by hucMSC-ex.

Autophagy: A new treatment strategy for MSC-based therapy in acute kidney injury (Review).

Acute kidney injury (AKI) is a common and serious medical condition associated with poor health outcomes. Autophagy is a conserved multistep pathway that serves a major role in many biological processes and diseases. Recent studies have demonstrated that autophagy is induced in proximal tubular cells during AKI. Autophagy serves a pro­survival or pro­death role under certain conditions. Furthermore, mesenchymal stem cells (MSCs) have therapeutic potential in the repair of renal injury. This review summarizes the recent progress on the role of autophagy in AKI and MSCs­based therapy for AKI. Further research is expected to prevent and treat acute kidney injury.

14-3-3 proteins: an important regulator of autophagy in diseases.

Autophagy is a cell digestion process that determines cell fate by promoting cell survival or inducing cell death in a cell context-dependent manner. Several classical signaling pathways, such as phosphoinositide-3-kinase and mammalian target of rapamycin, tightly regulate autophagy. 14-3-3 proteins regulate various signaling pathways by phosphorylation-dependent binding with partner proteins. 14-3-3 proteins also regulate autophagy by binding with autophagy-related proteins such as Beclin-1 and hVPS34. This review summarizes the role of 14-3-3 proteins in the control of autophagy in cancer, neurodegenerative diseases and other pathological conditions.

Cancer stemness and metastatic potential of the novel tumor cell line K3: an inner mutated cell of bone marrow-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) transplantation has been used for therapeutic applications in various diseases. Here we report MSCs can malignantly transform in vivo. The novel neoplasm was found on the tail of female rat after injection with male rat bone marrow-derived MSCs (rBM-MSCs) and the new tumor cell line, K3, was isolated from the neoplasm. The K3 cells expressed surface antigens and pluripotent genes similar to those of rBM-MSCs and presented tumor cell features. Moreover, the K3 cells contained side population cells (SP) like cancer stem cells (CSCs), which might contribute to K3 heterogeneity and tumorigenic capacity. To investigate the metastatic potential of K3 cells, we established the nude mouse models of liver and lung metastases and isolated the corresponding metastatic cell lines K3-F4 and K3-B6. Both K3-F4 and K3-B6 cell lines with higher metastatic potential acquired more mesenchymal and stemness-related features. Epithelial-mesenchymal transition is a potential mechanism of K3-F4 and K3-B6 formation.