Molecular characterization of Cryptosporidium in wild rodents from the Inner Mongolian Autonomous Region and Liaoning Province, China: assessing host specificity and the potential for zoonotic transmission.

Introduction: Wild rodents are key hosts for Cryptosporidium transmission, yet there is a dearth of information regarding their infection status in the Inner Mongolian Autonomous Region and Liaoning Province of China. Therefore, the present study was conducted to determine the prevalence and genetic characteristics of Cryptosporidium among wild rodents residing in these two provinces. Methods: A total of 486 rodents were captured, and fresh feces were collected from each rodent's intestine for DNA extraction. Species identification of rodents was performed through PCR amplification of the vertebrate cytochrome b (cytb) gene. To detect the presence of Cryptosporidium in all fecal samples, PCR analysis and sequencing of the partial small subunit of the ribosomal RNA (rRNA) gene were performed. Results: Four species of rodents were identified: Rattus norvegicus, Mus musculus, Apodemus agrarius, and Cricetulus barabensis. Positive results for Cryptosporidium were obtained for 9.2% (18/195), 6.6% (7/106), 5.6% (5/89), and 6.3% (6/96) of these rodents, respectively, with an average infection rate of 7.4% (36/486). The identification revealed the presence of five Cryptosporidium species, C. ubiquitum (n = 8), C. occultus (n = 5), C. muris (n = 2), C. viatorum (n = 1), and C. ratti (n = 1), along with two Cryptosporidium genotypes: Rat genotype III (n = 10) and Rat genotype IV (n = 9). Discussion: Based on the molecular evidence presented, the wild rodents investigated were concurrently infected with zoonotic (C. muris, C. occultus, C. ubiquitum and C. viatorum) as well as rodent-adapted (C. ratti and Rat genotype III and IV) species/genotypes, actively participating in the transmission of cryptosporidiosis.

Differing effects of gain and loss feedback on rule-based and information-integration category learning.

Although most category-learning studies use feedback for training, little attention has been paid to how individuals use feedback value and framing of feedback as gains or losses to support learning. We compared learning of rule-based (RB) and information-integration (II) categories with point-valued feedback in which participants gained or lost higher point values for more difficult category members (those closer to the decision bound). We implemented point-valued feedback in four different conditions: Gain (earn points for correct answers), Loss (lose points for incorrect answers), Gain+Loss (earn points for correct answers and lose points for incorrect answers), and Control (accuracy feedback only without point gain or loss). Participants were trained until they reached criterion. Overall, point-valued feedback led to better learning than control conditions. However, the patterns differed across category-learning tasks. In the II task participants reached learning criterion fastest when they received both Gains and Losses. This is consistent with the reliance of II learning on reinforcement-based mechanisms and research showing common coding of gains and losses in neural regions underlying II learning. In contrast, in the RB task, participants reached criterion most rapidly when they received either Gains or Losses, but not both Gains and Losses together. The relative impairment in the Gain+Loss condition in RB learning may be due to conflicting executive function demands for interpreting and using the separate Gain and Loss information, and is consistent with reliance of RB learning on explicit hypothesis-testing mechanisms.

The function of SOX2 in breast cancer and relevant signaling pathway.

OBJECTIVE: The purpose of this study was to explore the functional roles of SOX2 in the progression of breast cancer and relevant molecular mechanism. METHODS: A total of 108 breast cancer patients were included, and breast cancer cell line MDA-MB-231 was selected for this research. Real time-qualitative polymerase chain reaction (RT-qPCR) was conducted to measure the expression level of SOX2 mRNA. MTT and Transwell assays were used to detected the proliferation, migration and invasion of breast cancer cells, respectively. Luciferase reporter assay was conducted to reveal the relationship of SOX2 with PTEN. Western blot was performed to detect the expressions of Wnt/ß-catenin pathway-related proteins. RESULTS: The expression of SOX2 mRNA was up-regulated in breast cancer tissues and cells (P < 0.001). SOX2 expression was significantly associated with TNM stage and lymph node metastasis of breast cancer patients (P < 0.05). SOX2 knockdown significantly inhibited the proliferation, migration and invasion of breast cancer cells (P < 0.05). PTEN was a direct target of SOX2. The inhibition of PTEN could significantly suppress the progression of breast cancer cells with SOX2 overexpression. SOX2 knockdown also inhibited the expressions of ß-catenin, TCP-4, FZD7, C-myc and MMP-7 proteins. Moreover, PTEN knockdown reversed the results caused by SOX2 overexpression, that is, increased expressions of ß-catenin, TCP-4, FZD7, C-myc and MMP-7 proteins (P < 0.05). CONCLUSION: SOX2 promotes the progression of breast cancer through activating Wnt/ß-catenin signaling pathway via regulating PTEN.

A NIR-II light responsive hydrogel based on 2D engineered tungsten nitride nanosheets for multimode chemo/photothermal therapy.

A hydrogel drug cargo based on 2D tungsten nitride nanosheets was fabricated. It exhibits stable NIR-II responsive photothermal properties and drug release behaviour. Moreover, this hydrogel shows excellent tumour ablation efficiency in vivo via NIR-II triggered multiple chemo/photothermal therapy.

Multifunctional two dimensional Bi2Se3 nanodiscs for combined antibacterial and anti-inflammatory therapy for bacterial infections.

A multifunctional platform based on two-dimensional nanomaterials for combined antibacterial and anti-inflammatory therapy is developed. Bi2Se3 nanodiscs selectively eradicate Gram-positive bacteria with a low risk of drug resistance. Moreover, Bi2Se3 nanodiscs with antioxidant activity relieve intracellular oxidative stress of macrophages to suppress inflammation caused by bacterial infections.

Coordination Nanosheets of Phthalocyanine as Multifunctional Platform for Imaging-Guided Synergistic Therapy of Cancer.

"All-in-one" nanodrugs integrating various functionalities into one nanosystem are highly desired for cancer treatment. Coordination nanosheets as one type of two dimensional (2D) nanomaterials offer great opportunities, but there is lack of enough candidates. Here, a new kind of coordination nanosheets based on phthalocyanine are constructed. Manganese phthalocyanine (MnPc) tetracarboxylic acid is employed as photoactive ligand to form MnPc nanosheets; meanwhile, hyaluronic acid (HA) is coated on their surface. The obtained MnPc@HA nanosheets exhibit superior near-infrared (NIR) photothermal effect with photothermal conversion efficiency of 72.3%, much higher than those of the previously reported photothermal agents. Due to their 2D nanostructures, MnPc@HA nanosheets possess superhigh drug-loading capacity for chemotherapy drug curcumin. With HA as a targeting group, the nanosheets selectively accumulated in CD44 overexpressed tumors, followed by drug release under the control of NIR light. Moreover, MnPc@HA nanosheets with intrinsic paramagnetism can serve as T1 contrast agent for magnetic resonance imaging. The synergistic effect of phototherapy and chemotherapy endows curcumin-loaded MnPc@HA nanosheets with superior tumor-eradicating efficacy. Besides, MnPc@HA nanosheets are biocompatible and safe for biomedical applications. This work provides novel insight for developing new multifunctional platforms based on 2D coordination nanosheets to synergistically combat cancer.

Highly sensitive fluorescent detection of p53 protein based on DNA functionalized Fe3O4 nanoparticles.

The accurate quantification of p53 protein expression level is of great importance for cancer diagnosis. Here, a highly sensitive fluorescent sensor based on DNA functionalized magnetic nanoparticles was developed for the detection of p53 protein expression. Instead of a monoclonal antibody, a consensus DNA was employed to capture p53 protein. Meanwhile the fluorescent dye tethered DNA was used as the signal output instead of enzyme tagged nanoparticle or antibody. Consequently, our developed method is cost-effective for both the p53 capture and detection by compared with the conventional immunoassay. The biosensor developed by the above strategy was used to quantitatively detect p53, which yields a detection limit of 8 p.M. with the linear range of 50 p.M. to 2 nM. The sensitive for specific p53 detection was achieved due to the facile magnetic separation from the complex condition, and the reduced non-specific absorption effect by dextran. Moreover, the method is able to measure p53 from real cell lysate without extensive sample pretreatment/separation. The developed p53 biosensor has high sensitivity, good selectivity and reliable accuracy. It demonstrates great potential in clinical cancer diagnosis and early detection of cancer.

Biomimetic nanothylakoids for efficient imaging-guided photodynamic therapy for cancer.

Biomimetic nanothylakoids, which are constructed from the thylakoid membrane of vegetable leaves, show high efficiency in tumor microenvironment modulation and photodynamic antitumor therapy under near infrared fluorescence guidance. Furthermore, their outstanding biosafety, facile preparation and low cost make nanothylakoids suitable for further clinical applications.

Marriage of artificial catalase and black phosphorus nanosheets for reinforced photodynamic antitumor therapy.

Two dimensional (2D) semiconducting nanomaterials have shown great potential for antitumor therapy. However, their clinical applications are seriously hampered by the tumour microenvironments. Bearing this in mind, we propose to improve the performance of 2D semiconducting nanomaterials using artificial catalase. In this work, we decorate black phosphorus (BP) nanosheets with Pt nanoparticles (NPs) through an in situ growth strategy. Pt NPs as artificial catalases can efficiently decompose the accumulated H2O2 in tumours to relieve tumour hypoxia, and thereafter improve the photodynamic antitumor activity of BP nanosheets. This work paves a new avenue for the functionalization of 2D semiconducting nanomaterials, which will promote the development of 2D semiconductor based nanodrugs.

A black phosphorus based synergistic antibacterial platform against drug resistant bacteria.

In the fight against pathogenic bacteria, traditional antibiotic therapy is challenged by low efficiency and drug resistance. These drawbacks motivate the development of synergistic antibacterial therapy, but there is a lack of efficient synergistic platforms. Herein, with methicillin-resistant Staphylococcus aureus (MRSA) as a pathogenic bacterial model, we explored the potential of black phosphorus (BP) as a synergistic therapeutic platform for drug resistant bacterial infection. Acting as a substrate, reductant and stabilizer, BP nanosheets were decorated with Ag nanoparticles (NP) through an in situ growth strategy. The photothermal effect of the BP nanosheets allows Ag@BP nanohybrids to rapidly disrupt a bacterial membrane under near infrared (NIR) light irradiation. Moreover, the slowly released Ag+ elevates oxidative stress and sustainably suppresses bacterial proliferation for a long time. The combination of these two aspects endows the Ag@BP nanohybrids with synergistically enhanced antibacterial performance. Different from traditional antibiotics, the antibacterial effects of the Ag@BP nanohybrids are independent of the bacterial structure, which bypasses the issue of drug resistance. The in vivo studies show that the Ag@BP nanohybrids efficiently decrease the MRSA bacterial burden in mice and minimize infection associated tissue lesions. Besides, the excellent biocompatibility of the Ag@BP nanohybrids guarantees their biosafety for future clinical applications. Accordingly, this work demonstrates the potential of the BP nanosheets in the synergistic antibacterial therapy against drug resistant bacteria, and paves the way for developing 2D semiconductor based synergistic antibacterial nanodrugs.

Up-Regulated Expression of SPRY4-IT1 Predicts Poor Prognosis in Colorectal Cancer.

BACKGROUND Long non-coding RNA SPRY4 intronic transcript 1 (lncRNA SPRY4-IT1) has been reported to be associated with the progression of several cancers, but its expression level in colorectal cancer (CRC) has rarely been reported. The purpose of this study was to estimate the clinical significance of SPRY4-IT1 in CRC. MATERIAL AND METHODS The relative expression levels of SPRY4-IT1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in diseased tissues and the adjacent normal tissues of 106 CRC patients. Chi-square method was used to evaluate the association between SPRY4-IT1 expression and the clinical features. Additionally, we assessed the overall survival at different expression levels of SPRY4-IT1 using Kaplan-Meier method. The prognostic significance of SPRY4-IT1 was estimated by Cox regression analysis. RESULTS Up-regulated level of SPRY4-IT1 was detected in pathologic tissues of CRC patients compared with adjacent normal tissues (P=0.000). The relative expression of SPRY4-IT1 was associated with the tumor size, the depth of invasion, lymph node invasion, distant invasion, and tumor stage (P<0.05). Patients with high expression of SPRY4-IT1 had poor overall survival compared with those with high level (39.3 vs. 49.3 months, log-rank test, P=0.016). Cox regression analysis showed that SPRY4-IT1 could act as an independent prognostic factor in CRC (HR=2.341, 95% CI=1.136-4.826, P=0.021). CONCLUSIONS SPRY4-IT1 might be associated with tumorigenesis and progression of CRC, and it may be a promising biomarker for prognosis in patients with CRC.

Insights into HER2 signaling from step-by-step optimization of anti-HER2 antibodies.

HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer; however, resistance to trastuzumab is common. The development of monoclonal antibodies that have complementary mechanisms of action results in a more comprehensive blockade of ErbB2 signaling, especially HER2/HER3 signaling. Use of such antibodies may have clinical benefits if these antibodies can become widely accepted. Here, we describe a novel anti-HER2 antibody, hHERmAb-F0178C1, which was isolated from a screen of a phage display library. A step-by-step optimization method was employed to maximize the inhibitory effect of this anti-HER2 antibody. Crystallographic analysis was used to determine the three-dimensional structure to 3.5 Å resolution, confirming that the epitope of this antibody is in domain III of HER2. Moreover, this novel anti-HER2 antibody exhibits superior efficacy in blocking HER2/HER3 heterodimerization and signaling, and its use in combination with pertuzumab has a synergistic effect. Characterization of this antibody revealed the important role of a ligand binding site within domain III of HER2. The results of this study clearly indicate the unique potential of hHERmAb-F0178C1, and its complementary inhibition effect on HER2/HER3 signaling warrants its consideration as a promising clinical treatment.

Risk of severe diarrhea with dual anti-HER2 therapies: a meta-analysis.

Although promising progress has been made with dual HER2 blockade in patients with HER2-positive breast cancer, whether the strategy of combined HER2 blockade increases the risk of severe diarrhea remains inclusive. In the present study, we investigated the overall incidence and risk of severe diarrhea when patients were treated with a combination of anti-HER2 therapies compared to anti-HER2 monotherapy. Studies that evaluated the administration of an anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) versus anti-HER2 combination therapy (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) in breast cancer were identified from the PubMed database (1966-2013), the Cochrane library, abstracts presented at the American Society of Clinical Oncology annual conference (2004-2013), and the Web of Science database (1998-2013). Eligible studies were those in which the only systematic difference between the study arms was the type of anti-HER2 therapy used. Incidence, relative risk (RR), and 95% confidence intervals (CIs) were calculated using random effects or fixed-effects models based on the heterogeneity of the included studies. Seven trials were considered eligible. The overall incidence results for severe diarrhea in the combined anti-HER2 therapy and the anti-HER2 monotherapy were 3.48% (95% CI: 11.60-15.37%) and 8.68% (9 % CI: 7.33-10.03%), respectively. The odds ratio (OR) of severe diarrhea between anti-HER2 combination therapy and monotherapy was 1.67 (95% CI: 1.38 -5.57, p = 0.00001). This meta-analysis provides evidence that the incidence rates of severe diarrhea are comparable between anti-HER2 combination therapy and anti-HER2 monotherapy.