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The development of facile, reliable, and accurate assays for pathogenic bacteria is critical to environmental pollution surveillance, traceability analysis, prevention, and control. Here, we proposed a rolling circle amplification (RCA) strategy-driven visual photothermal smartphone-based biosensor for achieving highly sensitive monitoring of

BACKGROUND Quantitative hepatitis B core-related antigen (qHBcrAg) has a better correlation with intrahepatic hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) than HBV DNA or hepatitis B e antigen (HBeAg), but data are still lacking for its clinical application. AIM The aim was to investigate serum qHBcrAg levels in patients with chronic hepatitis B and assess the correlation of serum qHBcrAg with pregenomic RNA (pgRNA), cccDNA, and HBeAg seroconversion. METHODS This study was a secondary analysis of patients who underwent percutaneous liver biopsy between July 2014 and June 2019 in two multicenter randomized controlled clinical trials of peginterferon vs nucleos(t)ide analog (NUC)-based therapy (NCT03509688 and NCT03546530). Serum qHBcrAg, pgRNA, HBV DNA, hepatitis B core antigen, HBeAg, liver cccDNA, and HBV DNA were measured. The correlations of serum qHBcrAg with other biomarkers were analyzed. RESULTS A total of 139 patients were included. The mean qHBcrAg levels were 5.32 ± 1.18 log10 U/mL at baseline and decreased during treatment (all P < 0.0001). Serum qHBcrAg levels were positively correlated with pgRNA (r = 0.597, P < 0.0001) and cccDNA (r = 0.527, P < 0.0001) levels. The correlation of serum qHBcrAg level and intrahepatic HBV DNA levels at baseline was weak but significant (r = 0.399, P < 0.0001). HBcrAg predicted HBeAg seroconversion, with areas under the receiver operating characteristics curve of 0.788 at 24 wk and 0.825 at 48 wk. Log HBcrAg at wk 24 and 48 was independently associated with HBeAg seroconversion [odds ratio (OR) = 2.402, 95% confidence interval (CI): 1.314-4.391, P = 0.004; OR = 3.587, 95%CI: 1.315-9.784, P = 0.013]. CONCLUSION Serum HBcrAg levels were correlated with HBV virological markers and could be used to predict HBeAg seroconversion.

Rapid and sensitive point-of-care testing (POCT) is an extremely critical mission in practical applications, especially for rigorous military medicine, home health care, and in the third world. Here, we report a visual POCT method for adenosine triphosphate (ATP) detection based on Taylor rising in the corner of quadratic geometries between two rod surfaces. We discuss the principle of Taylor rising, demonstrating that it is significantly influenced by contact angle, surface tension, and density of the sample, which are controlled by ATP-dependent rolling circle amplification (RCA). In the presence of ATP, RCA reaction effectively suppresses Taylor-rising behavior, due to the increased contact angle, density, and decreased surface tension. Without addition of ATP, untriggered RCA reaction is favorable for Taylor rising, resulting in a significant height. With this proposed method, visual sensitive detection of ATP without the aid of other instruments is realized with only a 5 μL droplet, which has good selectivity and a low detection limit (17 nM). Importantly, this visual method provides a promising POCT tool for user-friendly molecular diagnostics.

Background Perivascular epithelioid cell tumor (PEComa) is an uncommon tumor of mesenchymal origin. Cases of PEComa in the liver are extremely rare. Aim To analyze the clinicopathological features and treatment of hepatic PEComa and to evaluate the prognosis after different treatments. Methods Clinical and pathological data of 26 patients with hepatic PEComa were collected. All cases were analyzed by immunohistochemistry and clinical follow-up. Results This study included 17 females and 9 males, with a median age of 50 years. Lesions were located in the left hepatic lobe in 13 cases, in the right lobe in 11, and in the caudate lobe in 2. The median tumor diameter was 6.5 cm. Light microscopy revealed that the tumor cells were mainly composed of epithelioid cells. The cytoplasm contained heterogeneous eosinophilic granules. There were thick-walled blood vessels, around which tumor cells were radially arranged. Immunohistochemical analysis of pigment-derived and myogenic markers in PEComas revealed that 25 cases were HMB45 (+), 23 were Melan-A (+), and 22 SMA (+). TFE3 and Desmin were negative in all cases. All the fluorescence in situ hybridization samples were negative for TFE3 gene break-apart probe. Tumor tissues were collected by extended hepatic lobe resection or simple hepatic tumor resection as the main treatments. Median follow-up was 62.5 mo. None of the patients had metastasis or recurrence, and there were no deaths due to the disease. Conclusion Hepatic PEComa highly expresses melanin and smooth muscle markers, and generally exhibits an inert biological behavior. The prognosis after extended hepatic lobe resection and simple hepatic tumor resection is semblable.

Age-related macular degeneration (AMD) is a major vision-threatening disease. Although mesenchymal stem cells (MSCs) exhibit beneficial neural protective effects, their limited differentiation capacity in vivo attenuates their therapeutic function. Therefore, the differentiation of MSCs into retinal pigment epithelial (RPE) cells in vitro and their subsequent transplantation into the subretinal space is expected to improve the outcome of cell therapy. Here, we transdifferentiated human umbilical cord MSCs (hUCMSCs) into induced RPE (iRPE) cells using a cocktail of five transcription factors (TFs): CRX, NR2E1, C-MYC, LHX2, and SIX6. iRPE cells exhibited RPE specific properties, including phagocytic ability, epithelial polarity, and gene expression profile. In addition, high expression of PTPN13 in iRPE cells endows them with an epithelial-to-mesenchymal transition (EMT)-resistant capacity through dephosphorylating syntenin1, and subsequently promoting the internalization and degradation of transforming growth factor-β receptors. After grafting into the subretinal space of the sodium iodate-induced rat AMD model, iRPE cells demonstrated a better therapeutic function than hUCMSCs. These results suggest that hUCMSC-derived iRPE cells may be promising candidates to reverse AMD pathophysiology.

Background Multi-Agent Simulation is an essential technique for exploring complex systems. In research of contagious diseases, it is widely exploited to analyze their spread mechanisms, especially for preventing COVID-19. Nowadays, transmission dynamics and interventions of COVID-19 have been elaborately established by this method, but its computation performance is seldomly concerned. As it usually suffers from inadequate CPU utilization and poor data locality, optimizing the performance is challenging and important for real-time analyzing its spreading. Results This paper explores approaches to optimize multi-agent simulation for COVID-19 disease. The focus of this work is on the algorithm and data structure designs for improving performance, as well as its parallelization strategies. We propose two successive methods to optimize the computation. We construct a case-focused iteration algorithm to improve data locality, and propose a fast data-mapping scheme called hierarchical hash table to accelerate hash operations. As a result, The case-focused method degrades $$\sim 90 \%$$ ∼ 90 % cache references and achieves $$\times 4.3$$ × 4.3 speedup. Hierarchical hash table can further boost computation speed by 47%. And parallel implementation with 20 threads on CPU achieves $$\times 80$$ × 80 speedup consequently. Conclusions In this work, we propose optimizations for multi-agent simulation of COVID-19 transmission from aspects of algorithm and data structure. Benefit from improvement of locality and multi-thread implementation, our methods can significantly accelerate the simulation computation. It is promising in supporting real-time prevention of COVID-19 and other infectious diseases in the future.

Pneumonia is a serious pediatric lung injury disease caused by Mycoplasma pneumoniae (M. pneumoniae) with increasing global prevalence every year. The WHO has reported that nearly 19% of children die due to pneumonia worldwide.The present research was conducted to discover the ameliorative properties of geraniol against M. pneumoniae-provoked pneumonia in mice through the modulation of inflammatory responses.The pneumonia was provoked in the male Swiss albino mice via infecting animals with 100 µl of M. pneumoniae for 2 days and supplemented concurrently with 20 mg/kg of geraniol for 3 days. 100 mg/kg of azithromycin was used as a standard drug. The nitric oxide (NO) level and MPO activity were measured using kits. The SOD activity, GSH, and MDA levels were studied using standard methods. The polymerase chain reaction (PCR) study was performed to examine the M. pneumoniae DNA load. The inflammatory cytokines status was assessed by assay kits. The ERK1/2, JNK1/2, and NF-κB expressions were studied by reverse-transcription (RT-PCR). The lung tissues were analyzed microscopically to investigate the histological alterations.Geraniol treatment effectively reduced lung weight, NO level, and MPO activity in the pneumonia mice. The total cells and M. pneumoniae DNA load were also decreased by the geraniol. The SOD activity and GSH level were improved and MDA was decreased by the geraniol treatment. The IL-1, IL-6, IL-8, TNF-α, and TGF status were appreciably depleted by the geraniol in the pneumonia mice. Geraniol also suppressed the ERK1/2 and NF-κB expressions in the lung tissues. Histological findings also suggest the therapeutic roles of geraniol against pneumonia in mice.In summary, our results proved the beneficial roles of geraniol against the M. pneumoniae-provoked pneumonia. Geraniol could be a hopeful therapeutic agent to treat pneumonia in the future.

BackgroundNot all lung adenocarcinoma (LUAD) patients with activating epidermal growth factor receptor (EGFR) mutations respond to tyrosine kinase inhibitors (TKIs) as intended. Thus, biomarkers are needed to identify patients who benefit most from EGFR-targeted therapy. Our previous in vitro data has shown that the co-signal molecule B7-H3 determines EGFR-TKI gefitinib susceptibility ofEGFR-mutated LUAD cell lines, based on the potential crosslinking between B7-H3-induced signaling and EGFR signaling.MethodsWe detected tumoral B7-H3 expression in the original biopsy from 56 treatment-naïve LUAD patients and analyzed the association between high/low B7-H3 expression with the clinical outcomes of first-line anti-EGFR therapy. The main criteria for the analysis of response were overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS), and the secondary criterion was overall survival (OS).ResultsIn the subgroups of B7-H3 high and low expression, the ORR were 16.0% (4/25) and 74.2% (23/31) (ppp=0.001]. The median OS was 15.9 (95% CI 10.0–21.8) months in the B7-H3 high cohort and 25.7 (95% CI 9.0–42.4) months in the B7-H3 low subjects [HR 2.08 (95% CI 1.07–4.02),p=0.03], respectively. Both the univariate and multivariate analyses identified B7-H3 as an independent factor associated with poor PFS (p=0.001,p=0.000) and OS (p=0.03,p=0.015).ConclusionB7-H3 may serve as a potential biomarker to predict clinical outcomes inEGFR-mutated LUAD patients treated with first-line EGFR-TKIs.

Adverse drug reactions (ADRs) pose health threats to humans. Therefore, the risk re-evaluation of post-marketing drugs has become an important part of the pharmacovigilance work of various countries. In China, drugs are mainly divided into three categories, from high-risk to low-risk drugs, namely, prescription drugs (Rx), over-the-counter drugs A (OTC-A), and over-the-counter drugs B (OTC-B). Until now, there has been a lack of automated evaluation methods for the three status switch of drugs. Based on China Food and Drug Administration’s (CFDA) spontaneous reporting database (CSRD), we proposed a classification model to predict risk level of drugs by using feature enhancement based on Generative Adversarial Networks (GAN) and Synthetic Minority Over-Sampling Technique (SMOTE). A total of 985,960 spontaneous reports from 2011 to 2018 were selected from CSRD in Jiangsu Province as experimental data. After data preprocessing, a class-imbalance data set was obtained, which contained 887 Rx (accounting for 84.72%), 113 OTC-A (10.79%), and 47 OTC-B (4.49%). Taking drugs as the samples, ADRs as the features, and signal detection results obtained by proportional reporting ratio (PRR) method as the feature values, we constructed the original data matrix, where the last column represents the category label of each drug. Our proposed model expands the ADR data from both the sample space and the feature space. In terms of feature space, we use feature selection (FS) to screen ADR symptoms with higher importance scores. Then, we use GAN to generate artificial data, which are added to the feature space to achieve feature enhancement. In terms of sample space, we use SMOTE technology to expand the minority samples to balance three categories of drugs and minimize the classification deviation caused by the gap in the sample size. Finally, we use random forest (RF) algorithm to classify the feature-enhanced and balanced data set. The experimental results show that the accuracy of the proposed classification model reaches 98%. Our proposed model can well evaluate drug risk levels and provide automated methods for status switch of post-marketing drugs.

Objective To investigate whether miR-203a-3p can regulate the biological behaviors of ovarian cancer cells by targeting ATM to affect the Akt/GSK-3β/Snail signaling pathway. Methods The expression levels of miR-203a-3p and ATM were detected by qRT-PCR, immunohistochemical staining and Western blotting in ovarian cancer tissues and adjacent normal tissues obtained from 152 subjects. A dual-luciferase reporter gene assay was performed to verify the relationship between miR-203a-3p and ATM. Human ovarian cancer cell lines (A2780 and SKOV3) were used to generate the Blank, miR-NC, miR-203a-3p mimic, Control siRNA, ATM siRNA, and miR-203a-3p inhibitor + ATM siRNA groups. The biological behaviors of ovarian cancer cells were evaluated by CCK-8, wound healing, and Transwell invasion assays, annexin V-FITC/PI staining and flow cytometry. The levels of Akt/GSK-3β/Snail pathway-related proteins were assessed by Western blotting. Results Ovarian cancer tissues showed lower miR-203a-3p levels and higher ATM levels than adjacent normal tissues, both of which were associated with the FIGO stage, grade and prognosis of ovarian cancer. As confirmed by a dual-luciferase reporter gene assay, miR-203a-3p could target ATM. Furthermore, the miR-203a-3p mimic had multiple effects, including the inhibition of the proliferation, invasion and migration of A2780 and SKOV3 cells, the promotion of cell apoptosis, the arrest of the cell cycle at the G1 phase, and the blockage of the Akt/GSK-3β/Snail signaling pathway. ATM siRNA had similar effects on the biological behaviors of ovarian cancer cells, and these effects could be reversed by a miR-203a-3p inhibitor. Conclusion miR-203a-3p was capable of hindering proliferation, migration, and invasion and facilitating the apoptosis of ovarian cancer cells through its modulation of the Akt/GSK-3β/Snail signaling pathway by targeting ATM, and therefore it could serve as a potential therapeutic option for ovarian cancer.

To observe the levels of leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in blood, peritoneal fluid, ectopic endometrial tissue, and ectopic endometrial stromal cells of patients with endometriosis, and to compare expression of IL-6, LIF and VEGF expression between endometriotic and non-endometriotic patients underwent laparoscopic surgery. Thirty-one patients who underwent laparoscopic surgery for endometriosis in our hospital from January 2018 to January 2020 were included in the observation group, and 32 patients who underwent laparoscopic surgery for uterine fibroids, ovarian serous cystadenoma, and ovarian teratomas, were included in the control group. The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the two groups of patients were detected. The levels of LIF, IL-6 and VEGF in ectopic endometrial tissue and self-paired eutopic endometrial tissue, ectopic endometrial stromal cells and self-paired eutopic endometrial stromal cells of patients in the observation group were detected. After treating the primary cultured ectopic endometrial stromal cells with LIF and IL-6 alone or in combination, the changes of VEGF mRNA of ectopic endometrial stromal cells and the VEGF levels in the supernatant were observed. The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the observation group were all higher than those of the control group (P

The conserved C-terminal end segment of troponin I (TnI) plays a critical role in regulating muscle relaxation. This function is retained in the isolated C-terminal 27 amino acid peptide (residues 184-210) of human cardiac TnI (HcTnI-C27): When added to skinned muscle fibers, HcTnI-C27 reduces the Ca2+-sensitivity of activated myofibrils and facilitates relaxation without decreasing the maximum force production. However, the underlying mechanism of HcTnI-C27 function is unknown. We studied the conformational preferences of HcTnI-C27 and a myopathic mutant, Arg192His, (HcTnI-C27-H). Both peptides were mainly disordered in aqueous solution with a nascent helix involving residues from Trp191 to Ile195, as shown by NMR analysis and molecular dynamics simulations. The population of nascent helix was smaller in HcTnI-C27-H than in HcTnI-C27, as shown by circular dichroism (CD) titrations. Fluorescence and isothermal titration calorimetry (ITC) showed that both peptides bound tropomyosin (alpha Tm), with a detectably higher affinity (similar to 10 mu M) of HcTnI-C27 than that of HcTnI-C27-H (similar to 15 mu M), consistent with an impaired Ca2+-desensitization effect of the mutant peptide on skinned muscle strips. Upon binding to aTm, HcTnI-C27 acquired a weakly stable helix-like conformation involving residues near Trp191, as shown by transferred nuclear Overhauser effect spectroscopy and hydrogen/deuterium exchange experiments. With the potent Ca2+-desensitization effect of HcTnI-C27 on skinned cardiac muscle from a mouse model of hypertrophic cardiomyopathy, the data support that the C-terminal end domain of TnI can function as an isolated peptide with the intrinsic capacity of binding tropomyosin, providing a promising therapeutic approach to selectively improve diastolic function of the heart.

To describe the prognostic value of pulmonary artery (PA) trunk enlargement on the admission of in-hospital patients with severe COVID-19 infection by unenhanced CT image.In-hospital patients confirmed COVID-19 from January 18, 2020, to March 7, 2020, were retrospectively enrolled. PA trunk diameters on admission and death events were collected to calculate the optimum cutoff using a receiver operating characteristic curve. According to the cutoff, the subjects on admission were divided into two groups. Then the in-hospital various parameters were compared between the two groups to assess the predictive value of PA trunk diameter.In the 180 enrolled in-hospital patients (46.99 ± 14.95 years; 93 (51.7%) female, 14 patients (7.8%) died during their hospitalization. The optimum cutoff PA trunk diameter to predict in-hospital mortality was 29 mm with a sensitivity of 92.59% and a specificity of 91.11%. Kaplan-Meier survival curves for PA trunk diameter on admission showed that a PA trunk diameter 29 mm was a significant predictor of subsequent death (log-rank 0.001, median survival time of PA 29 mm was 28 days).PA trunk enlargement can be a useful predictive factor for distinguishing between mild and severe COVID-19 disease progression.

To assess the prevalence of calcification surrounding the odontoid process (odontoid calcification) with crowned dens syndrome (CDS) and without CDS (non-CDS) and investigate factors that may related to the onset of CDS.Retrospective review of consecutive patients visited Sir Run Run Shaw Hospital between 1 January 2018 and 5 November 2019 who were identified to have odontoid calcification on cervical computed tomography (CT) images. Those who presented with an acute or subacute episode of cervico-occipital pain were defined as CDS, others were non-CDS.We diagnosed 69 cases of odontoid calcification among 2902 cervical CTs of 2556 patients (69/2556, 2.70%), 19 (19/2556, 0.74%) cases of which were CDS, 50 (50/2556, 1.96%) cases were non-CDS. Mean age was 71 (54-86) years old in odontoid calcification patients. The male-to-female ratio of patients with odontoid calcification was 27:42 (0.64). The prevalence of odontoid calcification was 69/1497 (6.14%) in individuals over 50 years old, The prevalence was 0.59% (4/679), 5.05% (26/515), 11.49% (27/235) and 20% (12/60) in patients aged 50-59, 60-69, 70-79 and 80-89 years old, respectively. Age and female gender were predictive factors of odontoid calcification. Lower hemoglobin (Hgb), red blood cell count (RBC), higher C-reactive protein (CRP), pain scale score were found in CDS patients comparing with non-CDS group. No difference of age, gender, hypertension, diabetes mellitus, smoking, alcohol history, creatinine, white blood cell count, mean corpuscular volume, uric acid, calcium was found between the two groups.Odontoid calcification is a common radiological entity in patients older than 50 years. Lower Hgb, RBC, higher CRP, pain scale score were found in CDS patients comparing with non-CDS.

Background In some previous studies, serum hepatitis B virus RNA (HBV RNA) was proposed as an HBV viral marker during therapy. However, the dynamic change of HBV RNA, the correlation of HBV RNA with cccDNA, and the combination of HBV RNA with known HBV markers in predicting entecavir (ETV) treatment outcome in the same cohort are rarely reported. Methods A total of 111 HBeAg-positive patients were enrolled in our study. The dynamic changes of serum HBV RNA and the correlation of HBV RNA with other HBV markers were investigated in the early treatment period of 144-week ETV treatment. Intrahepatic cccDNA was detected at baseline and week 48. Receiver operating characteristic analyses were used to identify HBV RNA levels associated with HBeAg seroconversion. Results The serum HBV RNA levels decreased more rapidly in patients with HBeAg seroconversion than those without HBeAg seroconversion. The levels of HBV RNA decreased slower compared with the serum HBV DNA, irrespective of whether the patients achieved HBeAg seroconversion or not. Although the serum HBV RNA was positively correlated with cccDNA at baseline among all patients, no significant correlation was observed in the patients with HBeAg seroconversion at week 48 (r = 0.094, P = 0.588). The area under the receiver operating characteristic (AUROC) of HBV RNA and HBeAg at week 24 was 0.754 and 0.800, respectively. The AUROC of the HBV RNA and HBeAg combination had a higher value (AUROC = 0.821). Conclusions The level of HBV RNA at week 24 was a powerful predictor of HBeAg seroconversion in HBeAg-positive patients after 144-week ETV treatment, while the combination of HBV RNA and HBeAg was superior to HBV RNA alone in predicting HBeAg seroconversion.

Inspired by nature, superwettable material-based biosensors have aroused wide interests due to their potential in cancer biomarker detection. This mini review mainly summarized the superwettable materials as novel biosensing substrates for the development of evaporation-induced enrichment-based signal amplification and visual biosensing method. Biosensing applications based on the superhydrophobic surfaces, superwettable micropatterned surfaces, and slippery lubricant-infused porous surfaces for various cancer biomarker detections were described in detail. Finally, an insight of remaining challenges and perspectives of superwettable biosensor is proposed.

Protein N-glycosylation is ubiquitous in the brain and is closely related to cognition and memory. Alzheimer's disease (AD) is a multifactorial disorder that lacks a clear pathogenesis and treatment. Aberrant N-glycosylation has been suggested to be involved in AD pathology. However, the systematic variations in protein N-glycosylation and their roles in AD have not been thoroughly investigated due to technical challenges. Here, we applied multilayered N-glycoproteomics to quantify the global protein expression levels, N-glycosylation sites, N-glycans, and site-specific N-glycopeptides in AD (APP/PS1 transgenic) and wild-type mouse brains. The N-glycoproteomic landscape exhibited highly complex site-specific heterogeneity in AD mouse brains. The generally dysregulated N-glycosylation in AD, which involved proteins such as glutamate receptors as well as fucosylated and oligomannose glycans, were explored by quantitative analyses. Furthermore, functional studies revealed the crucial effects of N-glycosylation on proteins and neurons. Our work provides a systematic multilayered N-glycoproteomic strategy for AD and can be applied to diverse biological systems.

Genetically modified mice are widely used as experimental models to study human heart function and diseases. However, the fast rate of normal mouse heart at 400–600 bpm limits its capacity of assessing kinetic parameters that are important for the physiology and pathophysiology of human heart that beats at a much slower rate (75–180 bpm). To extend the value of mouse models, we established a protocol to study ex vivo mouse working hearts at a human-like heart rate. In the presence of 300 μM Lidocaine to lower pacemaker and conductive activities and prevent arrhythmia, a stable rate of 120–130 bpm at 37°C is achieved for ex vivo mouse working hearts. The negative effects of decreased heart rate on force-frequency dependence and lidocaine as a myocardial depressant on intracellular calcium can be compensated by using a higher but still physiological level of calcium (2.75 mM) in the perfusion media. Multiple parameters were studied to compare the function at the human-like heart rate with that of ex vivo mouse working hearts at the standard rate of 480 bpm. The results showed that the conditions for slower heart rate in the presence of lidocaine did not have depressing effect on left ventricular pressure development, systolic and diastolic velocities and stroke volume with maintained positive inotropic and lusitropic responses to β-adrenergic stimulation. Compared with that at 480 bpm, the human-like heart rate increased ventricular filling and end diastolic volume with enhanced Frank-Starling responses. Coronary perfusion was increased from longer relaxation time and interval between beats whereas cardiac efficiency was significantly improved. Although the intrinsic differences between mouse and human heart remain, this methodology for ex vivo mouse hearts to work at human-like heart rate extends the value of using genetically modified mouse models to study cardiac function and human heart diseases.

Perfluorodecanoic acid (PFDA) is a member of the perfluoroalkyl substances, which are toxic to organic functions. Recently, it has been found in follicular fluid, seriously interfering with reproduction. Follicular fluid provides the oocyte with necessary resources during the process of oocytes maturation. However, the effects of PFDA on the oocyte need investigation. Our study evaluated the impacts of PFDA on the meiosis and development potential of mouse oocytes by exposing oocytes to PFDA in vitro at 350, 400, and 450 μM concentrations. The results showed that exposure to PFDA resulted in the first meiotic prophase arrest by obstructing the function of the maturation-promoting factor. It also induced the dysfunction of the spindle assembly checkpoint, expedited the progression of the first meiotic process, and increased the risk of aneuploidy. The oocytes treated with PFDA had a broken cytoskeleton which also contributed to meiotic maturation failure. Besides, PFDA exposure caused mitochondria defections, increased the reactive oxygen species level in oocytes, and consequently induced oocyte apoptosis. Moreover, PFDA produced epigenetic modifications in oocytes and increased the frequency of mature oocytes with declined development potential. In summary, our data indicated that PFDA disturbs the meiotic process and induces oocyte quality deterioration.

Background and aimsHBV infection represents a major health problem worldwide, but the immunological mechanisms by which HBV causes chronic persistent infection remain only partly understood. Recently, cell subsets with suppressive features have been recognised among monocytes and natural killer (NK) cells. Here we examine the effects of HBV on monocytes and NK cells.MethodsMonocytes and NK cells derived from chronic HBV-infected patients and healthy controls were purified and characterised for phenotype, gene expression and cytokines secretion by flow cytometry, quantitative real-time (qRT)-PCR, ELISA and western blotting. Culture and coculture of monocytes and NK cells were used to determine NK cell activation, using intracellular cytokines staining.ResultsIn chronic HBV infection, monocytes express higher levels of PD-L1, HLA-E, interleukin (IL)-10 and TGF-β, and NK cells express higher levels of PD-1, CD94 and IL-10, compared with healthy individuals. HBV employs hepatitis B surface antigen (HBsAg) to induce suppressive monocytes with HLA-E, PD-L1, IL-10 and TGF-β expression via the MyD88/NFκB signalling pathway. HBV-treated monocytes induce NK cells to produce IL-10, via PD-L1 and HLA-E signals. Such NK cells inhibit autologous T cell activation.ConclusionsOur findings reveal an immunosuppressive cascade, in which HBV generates suppressive monocytes, which initiate regulatory NK cells differentiation resulting in T cell inhibition.

Two new platinum(II) complexes 7a and 7b with methyl hydrazinecarbodithioate derivatives of indolin-2-one have been prepared and characterized by single-crystal X-ray diffraction, NMR spectroscopy and mass spectrometry. Antiproliferative activity of the two complexes and their ligands 6a and 6b against HCT-116, MCF-7 and MDA-MB-231 cell lines was determined by the MTS assay. Complexes 7a and 7b exhibited stronger antiproliferative activity against three cell lines than compounds 6a and 6b (IC50, 1.89-5.60 versus 6.52-35.13 μM). Moreover, treatment of HCT-116 cells with the complexes resulted in an obvious sub-G1 peak by cell cycle profile analysis, and an increase of cleaved PARP1 and caspases 3, 7, and 9 by immunoblotting analysis. Live cell imaging showed that nucleus shrinkage and condensation started to appear when MCF-7 cells were treated with 7a for 8 h. Fluorescent spectrophotometric analysis revealed that the complexes physically associated with calf thymus DNA. Competitive DNA binding assays uncovered that the complexes non-covalently bind to DNA. Taken together, our results indicated that the two new platinum(II) complexes 7a and 7b non-covalently bind to DNA with high affinity and exhibit cytotoxicity against cancer cells by inducing apoptosis.

// Xiang Lin 1, * , Jin-Jing Li 1, * , Wen-Jing Qian 2, * , Qi-Jie Zhang 1 , Zhong-Feng Wang 2 , Ying-Qian Lu 1 , En-Lin Dong 1 , Jin He 1 , Ning Wang 1 , Li-Xiang Ma 3 and Wan-Jin Chen 1, 4 1 Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China 2 Institutes of Brain Science, Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China 3 Department of Anatomy, Histology & Embryology, Shanghai Medical College, Fudan University, Shanghai 200032, China 4 Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou 350005, China * These authors have contributed equally to this work Correspondence to: Wan-Jin Chen, email: wanjinchen75@fjmu.edu.cn Li-Xiang Ma, email: lxma@fudan.edu.cn Keywords: spinal muscular atrophy (SMA), induced pluripotent stem cells (iPSCs) derived enriched motor neurons (MNs), survival motor neuron (SMN) protein, neurite outgrowth, neuronal activity Received: August 20, 2016 Accepted: December 27, 2016 Published: January 31, 2017 ABSTRACT Spinal muscular atrophy (SMA) is a devastating motor neuron disease caused by mutations of the survival motor neuron 1 ( SMN1 ) gene. SMN2 , a paralogous gene to SMN1 , can partially compensate for the loss of SMN1 . On the basis of age at onset, highest motor function and SMN2 copy numbers, childhood-onset SMA can be divided into three types (SMA I-III). An inverse correlation was observed between SMN2 copies and the differential phenotypes of SMA. Interestingly, this correlation is not always absolute. Using SMA induced pluripotent stem cells (iPSCs), we found that the SMN was significantly decreased in both SMA III and SMA I iPSCs derived postmitotic motor neurons (pMNs) and γ-aminobutyric acid (GABA) neurons. Moreover, the significant differences of SMN expression level between SMA III (3 copies of SMN2 ) and SMA I (2 copies of SMN2 ) were observed only in pMNs culture, but not in GABA neurons or iPSCs. From these findings, we further discovered that the neurite outgrowth was suppressed in both SMA III and SMA I derived MNs. Meanwhile, the significant difference of neurite outgrowth between SMA III and SMA I group was also found in long-term cultures. However, significant hyperexcitability was showed only in SMA I derived mature MNs, but not in SMA III group. Above all, we propose that SMN protein is a major factor of phenotypic modifier. Our data may provide a new insight into recognition for differential phenotypes of SMA disease.

Squamous cell carcinoma (SCC) of pancreas is a rare histotype of pancreatic ductal carcinoma which is distinct from pancreatic adenocarcinoma (AC). Although there are standard treatments for pancreatic AC, no precise therapies exist for pancreatic SCC. Here, we screened 1033 cases of pancreatic cancer and identified 2 cases of pure SCC, which were pathologically diagnosed on the basis of finding definite intercellular bridges and/or focal keratin peal formation in the tumor cells. Immunohistochemistry assay confirmed the positive expression of CK5/6 and p63 in pancreatic SCC. To verify the genomic characteristics of pancreatic SCC, we employed in-solution hybrid capture targeting 137 cancer-related genes accompanied by high throughput sequencing (HTS) to compare the different genetic variants in SCC and AC of pancreas. We compared the genetic alterations of known biomarkers of pancreatic adenocarcinoma in different pancreatic cancer tissues, and identified nine mutated genes in SCC of pancreas: C7orf70, DNHD1, KPRP, MDM4, MUC6, OR51Q1, PTPRD, TCF4, TET2, and nine genes (ABCB1, CSF1R, CYP2C18, FBXW7, ITPA, KIAA0748, SOD2, SULT1A2, ZNF142) that are mutated in pancreatic AC. This study may have taken one step forward on the discovery of potential biomarkers for the targeted treatment of SCC of the pancreas.

A pH-responsive superwettable chip is described whose surface can switch between superhydrophobic and superhydrophilic. It can be used for the visual detection of the prostate specific antigen (PSA) based on contact angle readout. Magnetic beads were modified with primary antibody against PSA. After immunobinding, gold nanoparticles loaded with secondary antibody labeled with glucose oxidase is added. On addition of glucose, gluconic acid is formed which causes a drop in the local pH value. This results in a wettability switch of the pH-responsive superwettable chip from hydrophobic to hydrophilic. Under the optimized conditions, PSA can be quantified with a 3.2 pg mL−1 limit of detection by analyzing the contact angle and the related color that changes from blue via orange to red. The method is applicable to PSA detection in serum samples and for visual classification by cancer patients and healthy persons. It is also suitable for color-blind and color-weak individuals. Conceivably, this kind of assay can be transferred to the determination of various kinds of other bioanalytes including nucleotide, proteins, and even of ions and small organic molecules, and thus is has a wide scope.

The C-terminal end segment of troponin subunit I (TnI) is a structure highly conserved among the three muscle type-specific isoforms and across vertebrate species. Partial deletion or point mutation in this segment impairs cardiac muscle relaxation. In the present study, we characterized the C-terminal 27 amino acid peptide of human cardiac TnI (HcTnI-C27) for its role in modulating muscle contractility. Biologically or chemically synthesized HcTnI-C27 peptide retains an epitope structure in physiological solutions similarly to that in intact TnI as recognized by an anti-TnI C-terminus monoclonal antibody (mAb TnI-1). Protein binding studies found that HcTnI-C27 retains the binding affinity for tropomyosin as previously shown with intact cardiac TnI. A restrictive cardiomyopathy mutation R192H in this segment abolishes the bindings to mAb TnI-1 and tropomyosin, demonstrating a pathogenic loss of function. Contractility studies using skinned muscle preparations demonstrated that addition of HcTnI-C27 peptide reduces the Ca(2+)-sensitivity of myofibrils without decreasing maximum force production. The results indicate that the C-terminal end segment of TnI is a regulatory element of troponin, which retains the native configuration in the form of free peptide to confer an effect on myofilament Ca(2+)-desensitization. Without negative inotropic impact, this short peptide may be developed into a novel reagent to selectively facilitate cardiac muscle relaxation at the activated state as a potential treatment for heart failure.

Current visual biosensing methods, including colorimetric-based, fluorescence-based and chemiluminescence-based methods, are inappropriate for the hundreds of millions of people affected by color blindness and color weakness. Compared with these available methods, a droplet motion-based strategy might be a promising protocol for extension to a wider user base. Here we report a protocol for manipulating the hydrophobicity of DNA, which offers a droplet motion-based biosensing platform for the visual detection of small molecules (ATP), nucleic acids (microRNA) and proteins (thrombin). The protocol starts with target-triggered rolling-circle amplification that can readily generate short single-stranded DNA (ssDNA) fragments or long ssDNA. By exploiting macroscopic wetting behavior and molecular interaction, one can tailor the conformation of ssDNA on the water-oil interface to control the relevant DNA hydrophobicity. The wettability of DNA can be translated into visual signals via reading the sliding speed or the critical sliding angle. The time range for the entire protocol is ∼1 d, and the detection process takes ∼1 min.

Recently, the incidence of hepatocellular carcinoma has increased worldwide. Cembranoid-type diterpenes (CBDs) from tobacco exhibit good antimicrobial, antitumor, and neuroprotective activities. Therefore, in this study, we isolated CBDs from Nicotiana tabacum L. and evaluated their antitumor activity against hepatoma cell lines. Particularly, the anti-tumor activity of &alpha, 2,7,11-cyprotermine-4,6-diol (&alpha, CBD) was investigated against HepG2, SMMC-7721, and HL-7702 cells. The MTT assay revealed that &alpha, CBD reduced the formation of cell clones and inhibited the proliferation of hepatocellular carcinoma cells. Morphological observations showed that &alpha, CBD altered cell morphology and membrane permeability before inducing apoptosis. To further explore the antitumor mechanism of &alpha, CBD, flow cytometry and transcriptome analysis were performed using HepG2 cells. The results showed that the number of HepG2 cells increased from 10.4% to 29.8%, indicating that &alpha, CBD inhibits the proliferation of hepatocellular carcinoma cells in the S phase. The gene expression analysis of HepG2 cells treated with &alpha, CBD showed 3068 genes with altered expression, among which 1289 were upregulated and 1779 were downregulated. Apoptosis induced by these differentially expressed genes might be mediated by the p53-PUMA, PI3K-Akt, and IL-1-NF-&kappa, B-IAP pathways. Comprehensively, our study shows that &alpha, CBD isolated from N. tabacum L. can be potentially used as a natural antitumor agent.

Endometrial cancer is a life‑threatening malignancy that affects women all over the world, and it has an increasing incidence. MicroRNAs (miRNAs/miRs) have been reported to be involved in cellular activities in endometrial cancer. The present study aimed to examine the effects of miR‑183‑5p on the epithelial‑mesenchymal transition (EMT), proliferation, invasion, migration and apoptosis of human endometrial cancer cells by targeting Ezrin. Primary endometrial cancer tissues and adjacent normal tissues were obtained for the investigation. The protein expression of Ezrin in tissues was detected by immunohistochemistry. The expression level of miR‑183‑5p and the mRNA and protein expression levels of Ezrin and EMT‑associated genes were determined by reverse transcription‑quantitative polymerase chain reaction and western blot analyses. Endometrial cancer cells were treated with miR‑183‑5p inhibitors, small interfering RNA targeting Ezrin or miR‑183‑5p inhibitors. Cell proliferation, cell cycle, apoptosis, migration and invasion were then evaluated using an MTT assay, flow cytometry, scratch test and Transwell assay, respectively. Compared with normal adjacent tissues, the expression of miR‑183‑5p was decreased in endometrial cancer tissues, and the expression of Ezrin was significantly increased in endometrial cancer tissues. The protein expression of Ezrin was correlated with the severity and poor prognosis of endometrial cancer. Notably, the target prediction program and the luciferase reporter gene assay confirmed that miR‑183‑5p targeted and negatively regulated the expression of Ezrin. In vivo experiments revealed that the increased expression of miR‑183‑5p and decreased expression of Ezrin inhibited EMT, cell proliferation, migration and invasion, but promoted cell apoptosis in Ishikawa cells. These results suggested that the upregulated expression of miR‑183‑5p promoted apoptosis and suppressed the EMT, proliferation, invasion and migration of human endometrial cancer cells by downregulating Ezrin.

To investigate the value of transvaginal three-dimensional (3D) power Doppler ultrasound in the diagnosis of benign and malignant endometrial diseases. A total of 144 patients with endometrial thickness ≥4 mm were enrolled. Endometrial thickness was measured by transvaginal 3D B-mode ultrasound, while blood signals were detected by 3D power Doppler ultrasound. Endometrial volume (EV), vascularization index (VI), blood flow index (FI), and vascularization flow index (VFI) were calculated. All histopathological diagnoses of endometrium were obtained. There were 86 benign and 58 malignant cases. There were statistically significant differences between two groups in endometrial thickness [1.50 (1.30, 1.80) vs 2.30 (1.80, 3.20), P .05). Transvaginal 3D power Doppler ultrasound is valuable in the differentiating benign and malignant endometrial lesions.

We describe the natural history of ‘Amish’ nemaline myopathy (ANM), an infantile-onset, lethal disease linked to a pathogenic c.505G>T nonsense mutation of TNNT1, which encodes the slow fiber isoform of troponin T (TNNT1; a.k.a. TnT). The TNNT1 c.505G>T allele has a carrier frequency of 6.5% within Old Order Amish settlements of North America. We collected natural history data for 106 ANM patients born between 1923 and 2017. Over the last two decades, mean age of molecular diagnosis was 16 ± 27 days. TNNT1 c.505G>T homozygotes were normal weight at birth but failed to thrive by age 9 months. Presenting neonatal signs were axial hypotonia, hip and shoulder stiffness, and tremors, followed by progressive muscle weakness, atrophy and contractures. Affected children developed thoracic rigidity, pectus carinatum and restrictive lung disease during infancy, and all succumbed to respiratory failure by 6 years of age (median survival 18 months, range 0.2–66 months). Muscle histology from two affected children showed marked fiber size variation owing to both Type 1 myofiber smallness (hypotrophy) and Type 2 fiber hypertrophy, with evidence of nemaline rods, myofibrillar disarray and vacuolar pathology in both fiber types. The truncated slow TNNT1 (TnT) fragment (p.Glu180Ter) was undetectable in ANM muscle, reflecting its rapid proteolysis and clearance from sarcoplasm. Similar functional and histological phenotypes were observed in other human cohorts and two transgenic murine models (Tnnt1(−/−) and Tnnt1 c.505G>T). These findings have implications for emerging molecular therapies, including the suitably of TNNT1 gene replacement for newborns with ANM or other TNNT1-associated myopathies.

Although radiation therapy is a powerful anticancer modality, radiation- induced stress response and gene expression with adaptive resistance may severely compromise the effectiveness of radiation. The function of rotundic acid (RA) on inducing apoptosis in the human breast cancer cell line MCF-7 has been investigated in a previous study. In the present study, the combined effect of chemotherapy and radiotherapy on reducing side effects was examined. The results of an MTT assay revealed that radiation (0.5, 2 and 10 Gy) effectively inhibit MCF-7 cell viability in a dose-dependent manner, consistent with the effects of RA (2, 5 and 12.5 µM). Interestingly, a lower dose of radiation (1 Gy) combined with RA (5 µM) exhibited a greater inhibition efficiency compared with a high dose of radiation alone. Flow cytometry revealed that radiation combined with RA induced the apoptosis of MCF-7 cells. Using western blotting, it was demonstrated that radiation induced the expression of ataxia-telangiectasia mutated (ATM) and p53 protein, and that RA enhanced this effect. On examining the potential underlying mechanism, it was revealed that radiation and RA combined induce Bcl-2-associated X protein expression and cell apoptosis in MCF-7 cells. An ATM inhibitor was able to restore the effect of radiation and RA on inducing MCF-7 cell apoptosis. These results suggest that the ATM/p53 pathway directly participates in radiation and RA-induced apoptosis in MCF-7 cells. RA has the potential for development as a novel drug for the treatment of human breast cancer combined with radiation therapy, given that the combined side effects are reduced.

In mammalian cells, autophagy plays crucial roles in restricting further spread of invading bacterial pathogens. Previous studies have established that the Salmonella virulence factors SseF and SseG are required for intracellular bacterial survival and replication. However, the underlying mechanism by which these two effectors facilitate bacterial infection remains elusive. Here, we report that SseF and SseG secreted by Salmonella Typhimurium (S. Typhimurium) inhibit autophagy in host cells and thereby establish a replicative niche for the bacteria in the cytosol. Mechanistically, SseF and SseG impaired autophagy initiation by directly interacting with the small GTPase Rab1A in the host cell. This interaction abolished Rab1A activation by disrupting the interaction with its guanine nucleotide exchange factor (GEF), the TRAPPIII (transport protein particle III) complex. This disruption of Rab1A signaling blocked the recruitment and activation of Unc-51–like autophagy-activating kinase 1 (ULK1) and decreased phosphatidylinositol 3-phosphate biogenesis, which ultimately impeded autophagosome formation. Furthermore, SseF- or SseG-deficient bacterial strains exhibited reduced survival and growth in both mammalian cell lines and mouse infection models, and Rab1A depletion could rescue these defects. These results reveal that virulence factor–dependent inactivation of the small GTPase Rab1A represents a previously unrecognized strategy of S. Typhimurium to evade autophagy and the host defense system.

Background— Mutations in thin-filament proteins have been linked to hypertrophic cardiomyopathy, but it has never been demonstrated that variants identified in the TNNC1 (gene encoding troponin C) can evoke cardiac remodeling in vivo. The goal of this study was to determine whether TNNC1 can be categorized as an hypertrophic cardiomyopathy susceptibility gene, such that a mouse model can recapitulate the clinical presentation of the proband. Methods and Results— The TNNC1-A8V proband diagnosed with severe obstructive hypertrophic cardiomyopathy at 34 years of age exhibited mild-to-moderate thickening in left and right ventricular walls, decreased left ventricular dimensions, left atrial enlargement, and hyperdynamic left ventricular systolic function. Genetically engineered knock-in (KI) mice containing the A8V mutation (heterozygote=KI-TnC-A8V +/− ; homozygote=KI-TnC-A8V +/+ ) were characterized by echocardiography and pressure–volume studies. Three-month-old KI-TnC-A8V +/+ mice displayed decreased ventricular dimensions, mild diastolic dysfunction, and enhanced systolic function, whereas KI-TnC-A8V +/− mice displayed cardiac restriction at 14 months of age. KI hearts exhibited atrial enlargement, papillary muscle hypertrophy, and fibrosis. Liquid chromatography–mass spectroscopy was used to determine incorporation of mutant cardiac troponin C (≈21%) into the KI-TnC-A8V +/− cardiac myofilament. Reduced diastolic sarcomeric length, increased shortening, and prolonged Ca 2+ and contractile transients were recorded in intact KI-TnC-A8V +/− and KI-TnC-A8V +/+ cardiomyocytes. Ca 2+ sensitivity of contraction in skinned fibers increased with mutant gene dose: KI-TnC-A8V +/+ >KI-TnC-A8V +/− >wild-type, whereas KI-TnC-A8V +/+ relaxed more slowly on flash photolysis of diazo-2. Conclusions— The TNNC1-A8V mutant increases the Ca 2+ -binding affinity of the thin filament and elicits changes in Ca 2+ homeostasis and cellular remodeling, which leads to diastolic dysfunction. These in vivo alterations further implicate the role of TNNC1 mutations in the development of cardiomyopathy.

A multidimensional optical sensing platform which combines the advantages of resonance Rayleigh scattering (RRS), fluorescence, and colorimetry has been designed for detection of heparin. Phloxine B, a fluorescein derivative showing the special RRS spectrum in the long wavelength region, was selected to develop an easy-to-get system which can achieve switch-on sensing to obtain high sensitivity. The noise level of RRS in the long wavelength region is much weaker, and the reproducibility is much better; in this way, the sensitivity and selectivity can be improved. In the absence of heparin, the phloxine B and polyethyleneimine (PEI) form a complex through electrostatic interaction. Thus, the RRS signal at 554 nm is low; the phloxine B fluorescence is quenched, and the absorption signal is low. In the presence of heparin, competitive binding occurred between phloxine B and heparin toward PEI; then, phloxine B is gradually released from the phloxine B/PEI complex, causing obvious enhancement of the RRS, fluorescence, and absorption signals. Besides, the desorption of phloxine B is less effective for the heparin analogues, such as hyaluronic acid and chondroitin sulfate. In addition, the system presents a low detection limit of heparin to 5.0 × 10(-4) U mL(-1) and can also be applied to the detection of heparin in heparin sodium injection and 50% human serum samples with satisfactory results. Finally, the potential application of this method in reversible on-off molecular logic gate fabrication was discussed using the triple-channel optical signals as outputs.

Endocannabinoid receptor system is extensively expressed in the vertebrate retina. There are two types of cannabinoid receptors, CB1 and CB2. Activation of these two receptors by endocannabinoids N-arachidonoylethanolamide (anandamine, AEA) and 2-arachidonyl glycerol (2-AG) regulates multiple neuronal and glial ion channels, thus getting involved in retinal visual information processing. In this review, incorporating our results, we discuss the modulation of cannabinoid CB1 and CB2 receptors on retinal neuronal and glial ion channels and retinal synaptic transmission.

Monitoring blood glucose has attracted considerable attention because diabetes mellitus is a global public health problem. Herein, we reported a turn-on fluorescence detection strategy based on manganese dioxide (MnO2)-phenol formaldehyde resin (PFR) nanocomposite for rapid, sensitive, and selective detection of glucose levels in human blood. In this biosensing system, MnO2 nanoshell on the PFR nanoparticle surfaces serve as a quencher. PFR fluorescence can make a recovery in the presence of H2O2, reducing MnO2 to Mn2+. The sensor shows a linear range from 50nM to 90μM with a low detection limit of 20nM for H2O2 detection. Thus, the glucose can be detected on the basis of the enzymatic conversion of glucose by glucose oxidase to produce H2O2. This method exhibits a wide linear range from 5μM to 1mM with a low detection limit of 1.5μM. Because of the excellent photostability offered by PFR, the developed strategy has been successfully applied for the diagnosis of diabetes mellitus in human blood samples. Compared with commercial glucometer, our method showed satisfactory results, indicating the significant reliability. The developed turn-on fluorescent sensor might hold great promise in nanomedicine and bioanalysis.

This study investigated the content, distribution, and contamination levels of toxic metals (Cd, Cr, Cu, Pb, and Zn) in street dust in Lanzhou, an industrial city in Northwest China. Meanwhile, the risk these metals posed to the urban ecosystem and human health was also evaluated using the potential ecological risk index and human exposure model. Results showed that concentrations of these metals in the dust are higher than the background value of local soil, with Cu having the highest levels. The districts of Anning and Xigu had the most extreme levels of contamination, while Chengguan and Qilihe districts were lightly contaminated, which can be partly attributed to human activities and traffic densities. In comparison with the concentrations of selected metals in other cities, the concentrations of heavy metals in Lanzhou were generally at moderate or low levels. Heavy metal concentration increased with decreasing dust particle size. The pollution indices of Cr, Cd, Cu, Pb, and Zn were in the range of 0.289–2.09, 0.332–2.15, 1.38–6.21, 0.358–2.59, and 0.560–1.83 with a mean of 1.37, 1.49, 3.18, 1.48, and 0.897, respectively. The geo-accumulation index (I geo) suggested that Zn in street dust was of geologic origin, while Cd, Cr, Pb, and Cu were significantly impacted by anthropogenic sources. The comprehensive pollution index showed that urban dust poses a high potential ecological risk in Lanzhou. Non-carcinogenic and carcinogenic effects due to exposure to urban street dust were assessed for both children and adults. For non-carcinogenic effects, ingestion appeared to be the main route of exposure to dust particles and thus posed a higher health risk to both children and adults for all metals, followed by dermal contact. Hazard index values for all studied metals were lower than the safe level of 1, and Cr exhibited the highest risk value (0.249) for children, suggesting that the overall risk from exposure to multiple metals in dust is low. The carcinogenic risk for Cd and Cr was all below the acceptable level (

Purpose: To study the expression of insulin-like growth factor binding proteins (IGFBPs) in paclitaxel-treated gastric cancer SGC-7901 cells, and to further investigate underlying mechanisms. Materials and Methods: Real time PCR and Western blot assays were applied to detect the mRNA and protein expression of IGFBP-2, -3 and -5 after paclitaxel (10 nM) treatment of SGC-7901 cells. In addition IGFBP-3 expression was silenced by RNA interference to determine effects. Cell viability was determined by MTT assay. Cell cycling and apoptosis were assessed by flow cytometry. Results: Compared to the control group, only IGFBP-3 expression was elevated significantly after paclitaxel (10 nM) treatment ( p

The Arg194Trp polymorphism in the X-ray cross-complementing group 1 (XRCC1) had been implicated in cancer susceptibility. The previous published data on the association between XRCC1 Arg194Trp polymorphism and cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and XRCC1 Arg194Trp (59,227 cases and 81,587 controls from 201 studies) polymorphism in different inheritance models. We used odds ratios with 95 % confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was found (recessive model: (odds ration [OR] = 1.18, 95 % confidence interval [CI] = 1.09–1.27; homozygous model: OR = 1.21, 95 % CI = 1.10–1.33; additive model: OR = 1.05, 95 % CI = 1.01–1.09) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, significantly increased glioma risk was found among Asians, significantly decreased lung cancer risk was found among Caucasians, and significant increased breast cancer risk was found among hospital-based studies. In summary, this meta-analysis suggests that Arg194Trp polymorphism may be associated with increased breast cancer risk, Arg194Trp polymorphism is associated with increased glioma risk among Asians, and Arg194Trp polymorphism is associated with decreased lung cancer risk among Caucasians. In addition, our work also points out the importance of new studies for Arg194Trp association in some cancer types, such as gastric, pancreatic, prostate, and nasopharyngeal cancers, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC1 Arg194Trp polymorphism in cancer development (I 2 > 75 %).

An interesting, simple, and label-free strategy for the detection of hydrogen peroxide and glucose has been developed with polyethyleneimine (PEI)-capped copper nanoclusters as a fluorescence probe in aqueous solution. The PEI-templated Cu nanoclusters which we have synthesized have an average diameter of 1.8 nm and show a blue emission at 480 nm. In the presence of hydrogen peroxide, the fluorescence of the Cu nanoclusters is quenched. Similarly, glucose oxidase catalyzes the oxidation of glucose to gluconic acid and H 2 O 2 , so we can also use this probe to detect glucose. Because of the high zymolyte specificity of glucose oxidase, the detection of glucose has good selectivity. Under the optimized experimental conditions, the linear ranges for H 2 O 2 and glucose are 0.5–10 μM and 10–100 μM, respectively. And the detection limits for H 2 O 2 and glucose are 0.4 and 8 μM, respectively. Furthermore, we discussed the mechanism of fluorescence quenching which is caused by the interaction between H 2 O 2 and Cu nanoclusters. This sensing system has been applied successfully to the detection of glucose in human serum samples.

// Mei-juan Liu 1,* , Zhong-feng Liu 2,* , Yuan-yuan Hou 3 , Yan-Ming Men 1 , Yu-Xi Zhang 1 , Ling-Yun Gao 1 and Hao Liu 4 1 Department of Ultrasound, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China 2 Department of Ultrasound, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China 3 Department of Obstetrics and Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China 4 Department of Ultrasound, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong, China * These authors have contributed equally to this work Correspondence to: Hao Liu, email: // Keywords : medullary thyroid carcinoma; papillary thyroid carcinoma; ultrasound; diagnosis Received : December 28, 2016 Accepted : February 20, 2017 Published : March 04, 2017 Abstract This study was designed to explore differences in the ultrasonographic characteristics of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC). This study included 35 cases of MTC and 96 cases of PTC that were surgically and pathologically confirmed. Preoperative ultrasound images were retrospectively reviewed by two physicians (with 5 years’ experience in thyroid ultrasound) under the premise of unknown pathological results. Various ultrasonic features of nodules were assessed objectively. The clinical features of components were determined by other physicians. Age, sex, unilateral or bilateral involvement of thyroid gland, lesion size, margin, shape, echogenicity, calcification, intranodular blood flow, cervical lymph node, and tumor node metastasis (TNM) stage were compared between MTC and PTC groups. Age, sex, involvement of the thyroid gland, margin, and calcification were similar for the MTC and PTC groups. Compared with the PTC group, the lesion size in the MTC group was significantly larger ( P 1) was significantly less likely in the MTC group than the PTC group ( P < 0.001). A mixed echogenicity was significantly more common in the MTC group than the PTC group ( P = 0.003). The MTC group had significantly enhanced intranodular blood flow ( P < 0.001). The TNM stage of the MTC group was significantly higher than that of PTC group ( P = 0.001). Medullary thyroid carcinomas differ significantly from PTCs in lesion size, shape, echogenicity, and intranodular blood flow.

The efficiency of photon-to-electron conversion is extremely restricted by the electron–hole recombinant. Here, a new photoelectrochemical (PEC) sensing platform has been established based on the signal amplification of click chemistry (CC) via hybridization chain reaction (HCR) for highly sensitive microRNA (miRNA) assay. In this proposal, a preferred electron donor dopamine (DA) was first assembled with designed ligation probe (probe-N3) via amidation reaction to achieve DA-coordinated signal probe (PDA-N3). The PDA-N3 served as a flexible trigger to signal amplification through efficiently suppressing the electron–hole recombinant. Specifically, the PDA-N3 can be successfully ligated into the trapped hairpins (H1 and H2) via the superior ligation method of metal-catalyst-free CC, in which the electron donor DA was introduced into the assay system. Moreover, the enzyme-free HCR, employed as a versatile amplification way, ensures that lots of PDA-N3 can be attached to the substrate. This PEC sensing for ...

The object of this study was to investigate the possible role of local voltage potentials (LVPs) in mapping the ventricular arrhythmias originating from right ventricular outflow (RVOT).Forty-seven patients with RVOT VAs (ventricular arrhythmias), referred for radiofrequency catheter ablation to our hospital, were analysed retrospectively for the prevalence, characteristics and electrophysiological evaluation of the LVPs recorded in successful and unsuccessful ablation sites.Radiofrequency ablation was successful immediately in all the 47 cases. Catheter ablation was performed at a mean of 8 +/- 6 sites per patient. There were 58 effective ablation sites, 5 cases with changing morphology of ventricular arrhythmias (VAs), and 318 invalid ablation sites. Activation times at effective ablation sites were slightly earlierthan those at invalid ablation sites (-28 +/- 8 ms vs-24 +/- 7 ms, P0.05). The LVPs appeared during VAs in 47 sites of the 58 effective ablation sites (81.0%), far more than the 22 sites of the 318 invalid ablation sites (6.9%) (P0.01). In two cases VAs recurred during follow-up. They received a second catheter ablation.Local ventricular potentials can be recorded in most patients with idiopathic VAs originating from the right outflow tract.The local potentials may facilitate successful radiofrequency ablation.

Chromatographic separation of a marine algal-derived endophytic fungus Penicillium chrysogenum AD-1540, which was isolated from the inner tissue of the marine red alga Grateloupia turuturu, yielded two new benzophenone derivatives, chryxanthones A and B (compounds 1 and 2, respectively). Their structures were undoubtedly determined by comprehensive analysis of spectroscopic data (1D/2D NMR and HRESIMS). The relative and absolute configurations were assigned by analysis of the coupling constants and time-dependent density functional theory (TDDFT) calculations of their electronic circular dichroism (ECD) spectra, respectively. Both compounds possessed an unusual dihydropyran ring (ring D) fused to an aromatic ring, rather than the commonly occurring prenyl moiety, and a plausible biosynthetic pathway was postulated. The cytotoxicities of compounds 1 and 2 were evaluated against six human cell lines, and both of the compounds demonstrated weak to moderate cytotoxicities with IC50 values ranging from 20.4 to 46.4 μM. These new compounds further demonstrate the potential of marine-derived fungi as an untapped source of pharmaceutical components with unique properties that could be developed as drug candidates.

A novel series of 4-substituted-piperazine-1-carbodithioate derivatives of 2,4-diaminoquinazoline were synthesized and tested for their antiproliferative activities against five human cancer cell lines including A549 (lung cancer), MCF-7 (breast adenocarcinoma), HeLa (cervical carcinoma), HT29 and HCT-116 (colorectal cancer). Most of the synthesized compounds showed broad spectrum antiproliferative activity (IC50 1.47–11.83 μM), of which 8f, 8m and 8q were the most active members with IC50 values in the range of 1.58–2.27, 1.84–3.27 and 1.47–4.68 μM against five cancer cell lines examined, respectively. Further investigations revealed that compounds 8f, 8m and 8q exhibited weak inhibition against dihydrofolate reductase and no activity against thymidylate synthase, while induced DNA damage and activated the G2/M checkpoint in HCT-116 cells.

Totally 96 elderly patients with spleen-kidney Yang deficiency type hypertension were selected in this study. Patients were randomly divided into study and control group. It was treated with the Jingui Shenqi pill combined nifedipine sustained-release tablets in the study group and only nifedipine sustained-release tablets for the control group. Meanwhile, the clinical features including reducing blood pressure, blood lipid and traditional Chinese medicine (TCM) syndromes of the two groups were observed pre and post treatment. Finally, the results showed that it could significantly reduce the hypertensive, hyperlipidemia and TCM syndromes in the study group compared with the control group (P0.05), which indicated that the combination of the Jingui Shenqi pill with nifedipine sustained-release tablets was effective for the patients with hypertension with spleen-kidney Yang deficiency type, especially for decreasing TCM syndromes and the blood lipid.

The purpose of this study was to evaluate the effect and safety of Jinlong capsule combined with chemotherapy or radio-therapy for non-small cell lung cancer (NSCLS) using Meta-analysis. PubMed, Embase, CNKI and Wanfang databases were all searched without language restriction, and searching time was from January 1990 to July 2015. All eligible published studies were included in this study for quality assessment and data extraction. All the data were analyzed using Revman 5.3. A total of ten studies including 736 subjects (370 in Jinlong capsule plus chemoradiotherapy and 366 in chemoradiotherapy only) were finally included in this Meta-analysis. The result of Meta analysis showed that compared with pure chemoradiotherapy group, Jinlong capsule combined with chemoradiotherapy for NSCLC could improve the patients' curative effect (OR = 1.77, 95% CI: 1.29-2.43, P0.05), clinical benefit rate (OR = 1.89, 95% CI: 1.22-2.91, P0.05), life quality improvement rate (OR = 2. 56, 95% CI: 1.61-4.05, P0.05), and decrease leucopenia incidence rate (OR = 0.35, 95% CI: 0. 22-0.56, P0.05) and gastrointestinal reaction rate (OR = 0.67, 95% CI: 0.40-1.11, P0.05). The pooled results showed that Jinlong capsule combined with chemoradiotherapy for NSCLC could improve the curative effect and life quality, and decrease the adverse reaction of patients.

OBJECTIVE: To compare the clinical features of children with different clinical forms of congenital hepatic fibrosis (CHF), and provides a description of the characteristics of childhood CHF. METHODS: Sixty children with CHF between January 2002 and June 2015 were enrolled, including 26 children with portal hypertensive CHF (PH CHF), 3 children with cholangitic CHF, 30 children with combined portal hypertensive and cholangitic CHF (mixed CHF), and 1 child with latent forms of CHF. The medical data of 26 children with PH CHF and 30 children with mixed CHF, including gender, age, clinical manifestations, physical signs, laboratory tests and imaging characteristics, were retrospectively studied. RESULTS: Fever, jaundice and hepatomegaly were more frequently noted in children with mixed CHF than in those with PH CHF (P < 0.05). Splenomegaly and liver cirrhosis occurred more often in children with CHF, but there was no significant difference in the incidences of splenomegaly and liver cirrhosis between the children with PH CHF and mixed CHF. The plasma prothrombin activity, white blood cell counts, platelet counts, mean platelet volume, serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyl transferase, leucine aminopeptidase, and total bile acids in children with mixed CHF were higher than in those with PH CHF (P < 0.05). The decreased international normalized ratio and lower serum albumin levels were more frequently observed in children with mixed CHF than in those with PH CHF (P < 0.05). CONCLUSIONS: PH and mixed CHF are common forms in childhood CHF. The children with the two forms of PH usually manifest portal hypertension such as cirrhosis and hepatosplenomegaly. The liver damage may be common in children with mixed CHF.

To explore the clinical therapeutic effect and safety of application of Ilizarov technique combined with flap instant expansion technique in correcting tibia angular deformity combined with skin contracture by one stage.From January 2010 to January 2013, 30 cases of tibial deformity with skin contracture were corrected by Ilizarov technique combined with flap instant expansion technique at one stage, including 21 males and 9 females with an average age of(40.2±5.5) years ranging from 25 to 60 years. All patients underwent regular reexamination of X-ray. After removal of the Ilizarov external fixation, knee joint function were assessed by American Hospital for Special Surgery (HSS) scoring criteria, and the pain was evaluated by visual simulation score(VAS).All patients were followed up for 6 to 35 months with an average of 22 months. Among them, the incision of 29 patients were primary healing, 1 patient had wound infection complicated by osteomyelitis, 2 patients complicated with fixed screw loosening, there were no expanded skin flap necrosis and neurovascular injury symptoms. The external fixators were removed at 4 to 7 months after operation with an average of(5.2±1.1) months. Correction angle was 10° to 35° degrees with an average of (25.5±3.5)°. HSS total score was 92.5±6.6 and the result was excellent in 25 cases, good in 4 cases, fair in 1 case; the VAS score was 1.2±1.5.The application of Ilizarov technique combined with flap instant expansion technique is a good method for correction of tibial angular deformity with skin contracture by one stage, with a shorter time of external fixation frame, without skin necrosis and neurological symptoms, early load exercise and improve the limb function.