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Aggregation-induced emission (AIE) is exploited for several optoelectronic applications, but synthesizing molecules that respond to multiple stimuli is challenging. Here, the authors report a hydroquinone bearing an AIE-active core that responds to both redox and pH changes.

PurposeTo investigate the effects of high-intensity use of smartphones on ocular surface homeostasis and to explore whether high-intensity use of handheld digital devices can cause false increase of dry eye diagnostic rate.MethodsIn this prospective self-control study, 60 subjects (120 eyes) were recruited and asked to read on smartphones provided by the same manufacturer for two consecutive hours. This study was conducted during 8:00 – 10:00 AM to eliminate the influence of digital equipment used the previous day. Ophthalmological examinations [non-invasive tear breakup time (NIBUT), fluorescein breakup time (FBUT), Schirmer I test, corneal fluorescein staining (CFS), bulbar conjunctival redness and meibomian gland (MG) assessment] and a questionnaire survey were conducted before and after the reading test. Based on the collected data, the changes in ocular surface damage and subjective symptoms of the subjects were evaluated, and the differences in the diagnostic rate of dry eye before and after high-intensity use of smartphones were compared.ResultsThe diagnostic rate of dry eye was sharply increased (61.7% vs. 74.2%). The severity of dry eye also changed significantly, and the moderate and severe degree increased after reading (10% vs. 15%; 5% vs. 10.8%). The aggravated severity subjects had lower MG expressibility and more evident bulbar conjunctival redness compared to the non-aggravated severity subjects. After 2 h of continuous reading, NIBUT-First, NIBUT-Average and FBUT-Average were significantly decreased, while the proportion of BUT ≤ 5 s increased significantly. Non-invasive keratograph tear meniscus height(NIKTMH) decreased significantly compared to the baseline level, while the proportion of NIKTMH

Infection with human papillomavirus (HPV) is one of the main causes of malignant neoplasms, especially cervical, anogenital, and oropharyngeal cancers. Although we have developed preventive vaccines that can protect from HPV infection, there are still many new cases of HPV-related cancers worldwide. Early diagnosis and therapy are therefore important for the treatment of these diseases. As HPVs are the major contributors to these cancers, it is reasonable to develop reagents, kits, or devices to detect and eliminate HPVs for early diagnosis and therapeutics. Immunological methods are precise strategies that are promising for the accurate detection and blockade of HPVs. During the last decades, the mechanism of how HPVs induce neoplasms has been extensively elucidated, and several oncogenic HPV early proteins, including E5, E6, and E7, have been shown to be positively related to the oncogenesis and malignancy of HPV-induced cancers. These oncoproteins are promising biomarkers for diagnosis and as targets for the therapeutics of HPV-related cancers. Importantly, many specific monoclonal antibodies (mAbs), or newly designed antibody mimics, as well as new immunological kits, devices, and reagents have been developed for both the immunodiagnosis and immunotherapeutics of HPV-induced cancers. In the current review, we summarize the research progress in the immunodiagnosis and immunotherapeutics based on HPV for HPV-induced cancers. In particular, we depict the most promising serological methods for the detection of HPV infection and several therapeutical immunotherapeutics based on HPV, using immunological tools, including native mAbs, radio-labelled mAbs, affitoxins (affibody-linked toxins), intracellular single-chain antibodies (scFvs), nanobodies, therapeutical vaccines, and T-cell-based therapies. Our review aims to provide new clues for researchers to develop novel strategies and methods for the diagnosis and treatment of HPV-induced tumors.

At present, the clinical detection method of human papillomavirus (HPV) is mainly based on the PCR method. However, this method can only be used to detect HPV DNA and HPV types, and cannot be used to accurately predict cervical cancer. HPV16 E7 is an oncoprotein selectively expressed in cervical cancers. In this study, we prepared an HPV16 E7-histidine (HIS) fusion oncoprotein by using a prokaryotic expression and gained several mouse anti-HPV16 E7-HIS fusion oncoprotein monoclonal antibodies (mAbs) by using hybridoma technology. Two mAbs, 69E2 (IgG2a) and 79A11 (IgM), were identified. Immunocytochemistry, immunofluorescence, immunohistochemistry, and Western blot were used to characterize the specificity of these mAbs. The sequences of the nucleotide bases and predicted amino acids of the 69E2 and 79A11 antibodies showed that they were novel antibodies. Indirect enzyme-linked immunosorbent assay (ELISA) with overlapping peptides, indirect competitive ELISA, and 3D structural modeling showed that mAbs 69E2 and 79A11 specifically bound to the three exposed peptides of the HPV16 E7 (HPV16 E749−66, HPV16 E773−85, and HPV16 E791−97). We used these two antibodies (79A11 as a capture antibody and 69E2 as a detection antibody) to establish a double-antibody sandwich ELISA based on a horseradish peroxidase (HRP)-labeled mAb and tetramethylbenzidine (TMB) detection system for quantitative detection of the HPV16 E7-HIS fusion oncoprotein, however, it was not ideal. Then we established a chemiluminescence immunoassay based on a labeled streptavidin-biotin (LSAB)-ELISA method and luminol detection system—this was sufficient for quantitative detection of the HPV16 E7-HIS fusion oncogenic protein in ng levels and was suitable for the detection of HPV16-positive cervical carcinoma tissues. Collectively, we obtained two novel mouse anti-HPV16 E7 oncoprotein mAbs and established an LSAB-lumino-dual-antibody sandwich ELISA method for the detection of the HPV16 E7-HIS fusion oncogenic protein, which might be a promising method for the diagnosis of HPV16-type cervical cancers in the early stage.

Purpose: The purpose of this study is to evaluate the effectiveness of chronic suppurative lacrimal canaliculitis treatment using chalazion forceps. Patients and Methods: A prospective study was performed on consecutive patients who accepted the aid of chalazion forceps to treat chronic suppurative lacrimal canaliculitis. Two different treatment methods using chalazion forceps were performed according to the degree of lacrimal canaliculitis. Postoperatively, the patients received 0.5% levofloxacin eye drops four times per day and 0.5 g oral levofloxacin tablets once per day for 4 days. The follow-up period was more than 3 months. Lacrimal irrigation, the condition of the lacrimal punctum, and patients′ symptoms were carefully evaluated. Results: In total, 32 patients met the criteria for chronic suppurative lacrimal canaliculitis. Included were 6 males and 26 females. Their average age was 51.7 ± 14.9 years (range; 19-80 years), and all had unilateral canaliculitis. The mean duration of the symptoms was 18.9 ± 9.8 months (range; 3-48 months). The mean follow-up time was 14.7 ± 7.8 months. The signs and symptoms resolved completely in all patients within 15 days, and no recurrence was observed. No patients reported epiphora after the treatment. Conclusions: The use of chalazion forceps is effective in treating chronic suppurative lacrimal canaliculitis. The forceps may offer an alternative treatment technology in the management of suppurative lacrimal canaliculitis.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established therapeutic option for a range of inherited and acquired hematological disorders. However, graft-versus-host disease (GVHD) remains the leading cause of non-relapse mortality in allogeneic HSCT recipients. Ocular involvement occurs in up to 80% of chronic GVHD patients. In our cases, the diagnosis of vitamin A deficiency was suspected for GVHD patients. Serum vitamin A measurements were conducted to confirm clinical suspicions. Our study revealed significant decrease in serum levels of vitamin A in chronic liver GVHD patients. Although there have been many studies evaluating ocular manifestations in patients with GVHD, the present study is, to our knowledge, the first to study the relationship between vitamin A and ocular manifestations of GVHD in humans. Our data suggest that vitamin A deficiency affects the severity of ocular GVHD in adults.

Neutrophils release neutrophil extracellular traps (NETs) in a pathogen-killing process called NETosis. Excessive NETs formation, however, is implicated in disease pathogenesis. Therefore, to understand how NETosis is regulated, we examined the effect of dexamethasone (DXM), an anti-inflammatory drug, on this process and the role of toll-like receptors (TLRs). We stimulated human neutrophils with phorbol 12-myristate 13-acetate (PMA) or Staphylococcus aureus (S. aureus) and quantified NETs formation. We also examined the effect of DXM on the bactericidal effect of NETs and the role of reactive oxygen species (ROS) and nuclear factor (NF)-κB in DXM-regulated NETosis. DXM significantly inhibited S. aureus-induced NETosis and extracellular bacterial killing. ROS production and NF-κB activation were not involved in DXM-regulated NETosis. TLR2 and TLR4, but not TLR5 or TLR6, modified S. aureus-induced NETs formation. Neither DXM nor TLRs were involved in PMA-induced NETosis. Furthermore, TLR2 and TLR4 agonists rescued DXM-inhibited NETosis, and neither TLR2 nor TLR4 antagonists could further inhibit NETosis reduction induced by DXM, indicating that DXM may inhibit NETosis by regulating TLR2 and TLR4. In conclusion, the mechanisms of S. aureusand PMA-induced NETosis are different. DXM decreases NETs formation independently of oxidant production and NF-κB phosphorylation and possibly via a TLR-dependent mechanism. [ABSTRACT FROM AUTHOR]

Neuroblastoma is the one of the most common extracranial childhood malignancies, accounting for ~15% of tumor-associated deaths in children. It is generally considered that neuroblastoma originates from neural crest cells in the paravertebral sympathetic ganglia and the adrenal medulla. However, the mechanism by which neuroblastoma arises during sympathetic neurogenesis and the cellular mechanism that drives neuroblastoma development remains unclear. The present study investigated the cell components during neuroblastoma development in the tyrosine hydroxylase-v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (TH-MYCN) mouse model, a transgenic mouse model of human neuroblastoma. The present study demonstrates that paired-like homeobox 2b (Phox2B)+ neuronal progenitors are the major cellular population in hyperplastic lesions and primary tumors. In addition, Phox2B+ neuronal progenitors in hyperplastic lesions or primary tumors were observed to be in an actively proliferative and undifferentiated state. The current study also demonstrated that high expression levels of Phox2B promotes neuroblastoma cell proliferation and xenograft tumor growth. These findings indicate that the proliferation of undifferentiated Phox2B+ neuronal progenitors is a cellular mechanism that promotes neuroblastoma development and indicates that Phox2B is a critical regulator in neuroblastoma pathogenesis. [ABSTRACT FROM AUTHOR]

Neuroblastoma is a common solid malignant tumor of the sympathetic nervous system, which contributes to 15% of cancer-related mortality in children. The differentiation status of neuroblastoma is correlated with clinical outcome, and the induction of differentiation thus constitutes a therapeutic approach in this disease. However, the molecular mechanisms that control the differentiation of neuroblastoma remain poorly understood. The present study aimed to define whether GATA3 is involved in the differentiation of neuroblastoma cells. The results demonstrated that GATA3 is a prognostic marker for survival in patients with neuroblastoma, and that high-level GATA3 expression is associated with increased self-renewal and proliferation of neuroblastoma cells. Retinoic acid treatment led to GATA3 downregulation together with neuronal differentiation, suppression of cell proliferation and inhibition of tumorigenecity in neuroblastoma cells. These findings suggest that GATA3 is a key regulator of neuroblastoma differentiation, and provide a novel potential therapeutic strategy for the induction of neuroblastoma differentiation. [ABSTRACT FROM AUTHOR]

Triptolide is a diterpene triepoxide, extracted from the Chinese herb Tripterygium wilfordii Hook F, which has been shown to have antitumor activity in a number of cancers. Neuroblastoma is an aggressive extracranial pediatric solid tumor, with significant chemotherapeutic resistance. In this study, triptolide was hypothesized to be a potential therapeutic agent for neuroblastoma. The effects of triptolide on neuroblastoma cell growth and tumor development were investigated. Cell growth and proliferation were evaluated using a cell counting kit-8 assay and a 5-bromo-2-deoxyuridine staining assay. Cell cycle and apoptosis were detected by flow cytometry. Reverse transcription-quantitative polymerase chain reaction was conducted to detect the expression levels of the apoptosis-associated proteins, caspase-3 and caspase-9. The tumorigenicity of neuroblastoma cells was assessed by a soft agar clonogenic assay and an in vivo tumorigenic assay. The results demonstrated that exposure of BE(2)-C human neuroblastoma cells to triptolide resulted in a reduction in cell growth and proliferation, and the induction of cell death and apoptosis, together with cell cycle arrest in the S phase. A soft agar assay indicated that triptolide inhibited the colony-forming ability of BE(2)-C neuroblastoma cells. The xenograft experiment showed that triptolide significantly reduced tumor growth and development in vivo. The data suggested that this Chinese herb may be a potential novel chemotherapeutic agent for neuroblastoma. [ABSTRACT FROM AUTHOR]

The type 111 secretion system (T3SS) is a key factor in the pathogenesis Moreof Pseudomonas syringae pv. actinidiae biovar 3( Ps£13 ). the causal agent of a global kiwifruit bacterial canker pandemic. To monitor the T3SS expression levels in Ps£,3, we constructed a luciferase reporter plasmid-expressing HrpApm, 3-NLuc fusion protein. The expression of HrPA-NLuc was induced in h, p-inducing conditions whereas the level of luciferase naactivity correlated with the expression of h,-p/h·c· genes in Ps£13 confirmed the reliability of the reporter construct. Based on the readout of the NLuc reporter construct, three small molecule compounds 4-methoxy-cinnamic acid, sulforaphane, and ferulic acid were determined as T3SS inhibitors in Psal whereas sodium acetate was determined to be a T3SS inducer. Moreof over, the aqueous extract of fruit inhibited the accumulation of HrpA - NLuc iii Psa3 in medium and in planta. Additionally, the T3SS inhibitors suppress Psa3 vii·ulence, whereas the T3SS inducer promotes Ps£13 virulence on kiwifruit. Thus, our findings may provide clues to why the fi-uit is not infected by P.,·a3. and the Psa3 TJSS inhibitors have potential as alter naactivity tives to current nonspecific antimicrobials for disease management. [ABSTRACT FROM AUTHOR]