The metacognitive experience of time passing in Chinese college students: scale development, structure verification, and influencing factors.

The experience of time passing (ETP) is also the consciousness of the progress of life. ETP contributes to time regulation and life management, which basically conforms to the metacognitive theory. Also, the traditional Chinese cultural approach to time emphasizes ETP. It is an indispensable part of Chinese education and culture to strengthen one's appreciation of time by emphasizing the passage of time. In combination with the above two points, ETP equals metacognitive experience of time passing (METP) to a certain extent. However, we currently know little about the connotations of METP. To better understand traditional Chinese time culture, and referring to the concept of metacognition and model of time experience as proposed by Western scholars, the current study combined the results of open and semi-structured interviews, to explore the structure of METP in Chinese college students and developed a questionnaire with which to measure it. Using convenience sampling, 2,876 college students were recruited, the interview, and the reliability and validity tests were carried out. Five hundred and seventy-nine college students were tested a second time to investigate the correlation validity between METP and Ruminative Responses, time attitude, and meaning in life. The results led to the development of the METP Scale which contains 15 items and assesses two factors: ruminative and emotional experience of time passing. The two-factor model was well fitted, and invariable in measurements across gender, grade, and major. The internal consistency coefficients of the scale and its two factors ranged from 0.82 to 0.89, the half-point reliability between 0.76 and 0.88, and the retest reliability ranged from 0.77 to 0.78. METP Scale has good correlation validity, meanwhile, the results of regression analysis showed that symptom rumination, positive past, negative present, positive future, and searching for meaning in life significantly predict the intensity of METP.

T lymphocyte characteristics and immune repertoires in the epicardial adipose tissue of heart failure patients.

Background: Epicardial adipose tissue (EAT) acts as an active immune organ and plays a critical role in the pathogenesis of heart failure (HF). However, the characteristics of immune cells in EAT of HF patients have rarely been elucidated. Methods: To identify key immune cells in EAT, an integrated bioinformatics analysis was performed on public datasets. EAT samples with paired subcutaneous adipose tissue (SAT), heart, and peripheral blood samples from HF patients were collected in validation experiments. T cell receptor (TCR) repertoire was assessed by high-throughput sequencing. The phenotypic characteristics and key effector molecules of T lymphocytes in EAT were assessed by flow cytometry and histological staining. Results: Compared with SAT, EAT was enriched for immune activation-related genes and T lymphocytes. Compared with EAT from the controls, activation of T lymphocytes was more pronounced in EAT from HF patients. T lymphocytes in EAT of HF patients were enriched by highly expanded clonotypes and had greater TCR clonotype sharing with cardiac tissue relative to SAT. Experiments confirmed the abundance of IFN-γ+ effector memory T lymphocytes (TEM) in EAT of HF patients. CCL5 and GZMK were confirmed to be associated with T lymphocytes in EAT of HF patients. Conclusion: EAT of HF patients was characterized by pronounced immune activation of clonally expanded IFN-γ+ TEM and a generally higher degree of TCR clonotypes sharing with paired cardiac tissue.

Preparation and properties of boron affinity molecularly imprinted mesoporous polymers based on Mn-doped ZnS quantum dots.

Sialic acid (SA), known as N-acetyl neuraminic acid, is a natural 9-carbomonosaccharide derivative. SA has been widely applied in the early diagnosis of diseases as therapeutic target. However, the abundance of SA is very low in biological samples, which is usually interfered by the similar molecules coexisting at high abundance. Combining the advantages of high selectivity and specificity of molecularly imprinted technology, high specific surface area of mesoporous materials and excellent optical properties of quantum dots, we chose Mn-doped ZnS quantum dots as signal elements, and sialic acid as the template molecule. KH-4-MAPB with recognition ability to SA was synthesized by one-step hydrothermal method using thiolene click reaction as functional monomer. Based on the principle of boron affinity, molecularly imprinted polymers with highly ordered mesoporous structure were prepared, and the structure and fluorescence properties of fluorescent molecularly imprinted polymers were studied. FT-IR, XRD, TEM and nitrogen adsorption-desorption experiments were used to characterize the structure and morphology of the molecularly imprinted polymers. The results showed that the prepared molecularly imprinted polymers had highly ordered mesoporous structure and a large number of imprinted holes, which ensured the specific selectivity of the molecularly imprinted polymers. The fluorescence properties of MIMPs were characterized and analyzed by fluorescence spectra, equilibrium adsorption kinetics experiments were conducted and imprinting properties were recorded under different pH. The above experimental results showed that the fluorescence quenching was successfully achieved when the template molecule SA was captured by the molecularly imprinted polymer. When the concentration of SA was 1.25-100 × 10-2 g/L, the fluorescence quenching degree of MIMPs showed a fine linear relationship with SA. The correlation coefficient was 0.9946, and the detection equation was F0/F - 1 = 0.0215 [CSA] + 0.0241. MIMPs had a high recognition ability for SA, and the imprinting factor was 2.44. As a fluorescent sensor for SA, the response time of MIMPs was 20 min. When the buffer solution pH was 7, the imprinting factor was the largest. Under the best conditions, MIMPs revealed good selectivity and specificity for the fluorescence recognition of SA. MIMPS were also applied to the analysis of SA in real human serum samples with satisfactory results.

Visual detection of different metal ions based on the tug of war between triangular Au nanoparticles and metal ions against mercaptans.

Herein, a new colorimetric sensor array was developed for the first time, which can rapidly recognize 9 types of metal ions (e.g., Ni2+, Zn2+, Cd2+, Cu2+, Cr3+, Fe2+, Se2+, Mn2+, and Mg2+). The colorimetric characteristics of the sensor array were closely related to the oxidation etching of the triangular gold nanoplates (AuNPLs) by hydrogen peroxide (H2O2), catalyzed by horseradish peroxidase (HRP). In the design, two types of thiols (glutathione (GSH) and cysteine (Cys)) as recognition elements were employed to construct the sensor units (AuNPLs/GSH and AuNPLs/Cys) and adjust the etching degrees of AuNPLs in the presence of various metal ions. The differential binding affinities between metal ions and thiols will lead to different degrees of oxidation etching of AuNPLs with hydrogen peroxide, exhibiting characteristic colors, which can be visually distinguished by the naked eye. Thus, the colorimetric sensor array provides a new way for the discrimination of various metal ions, thereby simplifying the water quality analysis.

New insight into adsorption and co-adsorption of arsenic and tetracycline using a Y-immobilized graphene oxide-alginate hydrogel: Adsorption behaviours and mechanisms.

Heavy metals (e.g., arsenic (As)) and tetracycline (TC) usually coexist in wastewater from livestock farm, whereas the co-adsorption behaviours and mechanisms of As(V) and TC were not well-known. This study investigated the adsorption and co-adsorption of As(V) and TC by a novel yttrium-immobilized-graphene oxide-alginate hydrogel (Y-GO-SA) to explore the adsorption behaviours and mechanisms. The adsorption of As(V) and TC was pH-dependent. The maximum adsorption capacities under the studied concentrations were 273.39 mg/g for As(V), and 477.9 mg/g for TC, respectively, which are much higher than many other reported adsorbents. Furthermore, As(V) adsorption was due to ion exchange between hydroxyl groups and H2AsO42- groups and H-bonds formed with O-containing groups on Y-GO-SA, and the adsorption of TC by Y-GO-SA was mainly ascribed to electrostatic interaction, H-bonds, π - π EDA interaction, n-π EDA interaction, and cation-bonding bridge effects. The co-adsorption of As(V) and TC in binary system indicated that the presence of TC obviously suppressed the adsorption of As(V) due to the competition for active sites, whereas the effect of presence of As(V) on adsorption of TC can be negligible due to the balance contributions from its contrary effects, i.e. enhancement (anion-π interaction) and reduction (competition for Y ions) in TC adsorption. Finally, the hydrogels performed well in the treatment of livestock farm waste water. It can be anticipated that the prepared 3D hydrogel can be used as a powerful adsorbent in the practical application of waste water treatment, owing to its easy separation, high adsorption and good reusability.

Potential resistant mutations within HBV reverse transcriptase sequences in nucleos(t)ide analogues-experienced patients with hepatitis B virus infection.

This study was performed to analyze the potential resistant mutations within HBV reverse transcriptase (RT) sequences against nucleos(t)ide analogues (NA). HBV DNA RT region spanning from amino acid 169 to 250 was amplified and sequenced from 435 HBV patients who experienced NA treatment. Among study's cohort, genotypes B and C infected patients were 55.9% and 44.1%, respectively. Mutations were recorded in 54.7% (238/435) patients at 22 positions. Genotype C displayed significant higher frequency of potential NA resistant mutations than genotype B (63.0% vs. 48.1%, P = 0.003). Moreover, eight mutation sites, including 180, 181, 191, 200, 202, 221, 229 and 224, in genotype C showed significant higher frequencies than in genotype B. In contrast, mutation at site 236 was more common in genotype B. Notably, 11 mutations at position 169, 202, 250, 173, 180, 200, 207, 214, 237, 242 and 245 coexisted with M204I or V. Substitutions at nine non-classical mutation sites (191, 207, 213, 218, 221, 224, 229, 238 and 242) were detected in patients with virological breakthrough. Particularly, tenofovir (TDF) resistance was observed in one patient undergoing TDF monotherapy and experienced several NA treatment before. These results might provide clinical useful information under antiviral therapy.

Aptamer-assisted superparamagnetic iron oxide nanoparticles as multifunctional drug delivery platform for chemo-photodynamic combination therapy.

Superparamagnetic iron oxide nanoparticles (SPION) were widely employed as targeted drug delivery platform due to their unique magnetic property and effortless surface modification. However, the lack of targeting accuracy has been a big obstacle for SPION used in precise medicine. Herein, the tumor-targeting of SPION was enhanced by the conjugation of an aptamer-hybridized nucleic acid structure. The aptamer modified on the surface of SPION was composed of a double-stranded DNA (dsDNA) and a G-quadruplex DNA (AS1411) structure, which carried a chemical anticancer drug, daunomycin (DNM) and a photosensitizer molecule, namely 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP), respectively. The aptamer-dsDNA conjugated SPION nanocarriers (named Apt-S8@SPION) exhibited good stability in serum and nuclease DNase I. The drug-loaded nanocarriers (TMPyP&DNM&Apt-S8@SPION) have high cellular cytotoxicity to A549 and C26 cells which are represently nucleolin-overexpressing cancer cells. The nucleolin-blocking experiments unambiguously evidenced that the formed nanomedicine could target to the cell surface via the specific AS1411-nucleolin interaction, which increased the efficiency of cell uptake. Meanwhile, the TMPyP&DNM&Apt-S8@SPION nanospheres could produce cytotoxic reactive oxygen species efficiently by irradiation of visible light for establishing a new type of PDT to cancer cells. Therefore, the designed TMPyP&DNM&Apt-S8@SPION nanoparticles have magnetic-aptamer dual targeting and combined chemo-photodynamic therapy, and thus were supposed to be ideal drug delivery vehicles with great potential in the era of precision medicine.

Parameter sensitivity analysis for a stochastic model of mitochondrial apoptosis pathway.

Understanding how gene alterations induce oncogenesis plays an important role in cancer research and may be instructive for cancer prevention and treatment. We conducted a parameter sensitivity analysis to the mitochondrial apoptosis model. Both a nonlinear bifurcation analysis of the deterministic dynamics and energy barrier analysis of the corresponding stochastic models were performed. We found that the parameter sensitivity ranking according to the change of the bifurcation-point locations in deterministic models and the change of the barrier heights from a living to death state of the cell in stochastic models are highly correlated. For the model we considered, in combination with previous knowledge that the parameters significantly affecting the system's bifurcation point are strongly associated with frequently mutated oncogenic genes, we conclude that the energy barrier height can be used as indicator of oncogenesis as well as bifurcation point. We provide a possible mechanism that may help elucidate the logic of cancer initiation from the view of stochastic dynamics and energy landscape. And we show the equivalence of energy barrier height and bifurcation-point location in determining the parameter sensitivity spectrum for the first time.

Calcium carbonate end-capped, folate-mediated Fe3O4@mSiO2 core-shell nanocarriers as targeted controlled-release drug delivery system.

Magnetic mesoporous silica nanospheres (MMSN) were prepared and the surface was modified with cancer cell-specific ligand folic acid. Calcium carbonate was then employed as acid-activated gatekeepers to cap the mesopores of the MMSN, namely, MMSN-FA-CaCO3. The formation of the MMSN-FA-CaCO3 was proved by several characterization techniques, viz. transmission electron microscopy, zeta potential measurement, Fourier transform infrared spectroscopy, BET surface area measurement, and UV-Vis spectroscopy. Daunomycin was successfully loaded in the MMSN-FA-CaCO3 and the system exhibited sensitive pH stimuli-responsive release characteristics under blood or tumor microenvironment. Cellular uptake by folate receptor (FR)-overexpressing HeLa cells of the MMSN-FA-CaCO3 was higher than that by non-folated-conjugated ones. Intracellular-uptake studies revealed preferential uptake of these nanoparticles into FR-positive [FR(+)] HeLa than FR-negative [FR(-)]A549 cell lines. DAPI stain experiment showed high apoptotic rate of MMSN-FA-DNM-CaCO3 to HeLa cells. The present data suggest that the CaCO3 coating and folic acid modification of MMSN are able to create a targeted, pH-sensitive template for drug delivery system with application in cancer therapy.

Relationship between cancer mutations and parameter sensitivity in Rb pathway.

It has long been known that formation of all sorts of tumors is largely owing to the genomic variations. Oncogenic mutations are often found focused on one or more important pathways which indicate that it is meaningful to investigate oncogenic mutations and oncogenic mechanisms from the point of view of biological network. Recently, we found that in apoptosis pathway of mammalian cell, mutations that cause large variations on the bifurcation point are more probably oncogenic mutations. Here, we used the Rb-E2F pathway in mammalian cell in response to growth factor as another example to verify this correlation. To conduct this study, nonlinear dynamics equations that describe the behavior of the Rb-E2F pathway was first constructed. Then we identified sensitive parameters which have a great influence on the system's bifurcation point. And we found that the sensitive parameters are highly related to high-frequency oncogenic mutations after comparing the results of parameter sensitivity analysis with profile of known cancer mutations. Moreover, the position of bifurcation point rather than concentration of a certain protein is a better measurement to determine biological network's function. Our results further confirm that nonlinear dynamics analysis of biological networks is an important way to understand oncogenesis. And the analysis method can become a powerful tool to understand and analyze the function of biological network.

Portal vein tumor thrombus in advanced hepatocellular carcinoma: A case report.

Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) is a common entity. However, the prognosis of patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is extremely poor. The current study reports a case of HCC with PVTT, including a description of the gross surgical pathology and discussion of the relevance of assessing the growth of the tumor thrombus to the outcome of this disease. This case suggests that destruction of the primary tumor and PVTT must be considered according to the growth characteristics and modality of PVTT. It also indicates that transcatheter arterial embolization may be a suitable strategy for palliative treatment of patients with advanced HCC with PVTT.

Long-term outcomes after nucleos(t)ide analogues discontinuation in chronic hepatitis B patients with HBeAg-negative.

BACKGROUND: Hepatitis B e Antigen (HBeAg)-negative chronic hepatitis B (CHB) patients have an active liver disease with a high risk of progression to decompensated cirrhosis and hepatocellular carcinoma. The management strategy for HBeAg-negative CHB patients treated with nucleos(t)ide analogues (NUCs) is a topic of concern. To observe the outcomes for this population after NUCs withdrawal, HBeAg-negative CHB patients with loss of hepatitis B surface antigen (HBsAg) or sustained undetectable HBV DNA levels who had discontinued NUCs therapy were included in the study. METHODS: A total of 66 patients (2 patients with HBsAg loss and 64 patients with sustained undetectable HBV DNA levels) were examined. HBV DNA levels and alanine aminotransferase (ALT) levels were monitored regularly after discontinuation of NUCs therapy. Relapse was defined as HBV DNA levels >2,000 IU/mL while off therapy in at least two determinations more than 4 weeks apart. RESULTS: The time to achieve undetectable HBV DNA levels was 14 weeks (interquartile range (IQR): 12-24 weeks). The time until consolidation therapy was 144 weeks (IQR: 96-168 weeks). No relapses occurred in either of the HBsAg loss patients. Among the 64 patients with undetectable HBV DNA levels, 19 (29.7%) patients demonstrated evidence of relapse. All the relapses occurred within 96 weeks after discontinuation. The median duration of relapse was 36 weeks (IQR: 12-48 weeks). Elevation of HBV DNA and ALT levels over baseline was only observed in 10% of the relapse patients. There were no significant differences among the baseline characteristics (sex, HBV genotype, age, or ALT level) or the time until consolidation therapy between relapse and sustained-response patients. CONCLUSIONS: NUC discontinuation is feasible after achieving undetectable HBV DNA levels in HBeAg-negative CHB patients. Prolonging the time until consolidation therapy may be a good strategy to decrease the rate of relapse. More than 96 weeks of sustained response is a predictive marker of long-term sustained response.

Expression of PPARgamma and Cbfalpha1 mRNA in bone marrow cells in Type 2 diabetic rats and its correlation with impaired fracture healing.

OBJECTIVE: To investigate the relationship between impaired fracture healing and the expression of peroxisome proliferator activated-receptor gamma (PPARgamma) and core binding factor alpha 1 (Cbfalpha1) mRNA in the bone marrow of Type 2 diabetic rats. METHODS: Thirty male Sprague-Dawley rats were divided into a control group (n=15, normal diet) and an experiment group (n=20, high fat and sucrosum diet). After 8 weeks, one eyeball was culled for blood collection. The experiment group was intraperitoneally injected with streptozotocin and the control group received citrate buffer. After another 2 weeks, the other eyeball was culled again to collect blood. The model of distraction osteogenesis in the left tibias of the rats was established. After 14 days, we sacrificed all the rats and collected the blood and left tibias. Both femurs were harvested with germ free. We observed the callus formation in the distraction gap by X-ray and the formation of primary matrix front and microcolumn by histological examination. We observed adipocytes in adjacent bone marrow of left tibia and computed the percentage of adipocytes accounting for the area of bone cavity. We measured the expression of PPARgamma and Cbfalpha1 mRNA in femurs marrow by RT-PCR. RESULTS: In the experimental rats, the level of triglyceride was obviously elevated (P<0.01), so was the total cholesterol (P<0.05), while the level of fasting blood glucose and serum insulin did not obviously differ (P>0.05) after 8 weeks. The level of fasting blood glucose and triglyceride was obviously elevated (P<0.01), and so was the total cholesterol (P<0.05), while the level of serum insulin was not obviously different in the experiment group after 10 and 12 weeks. Callus formation in the distraction gap was obviously diminished by X-ray in the experimental rats. The array of microcolumn formation was disordered and the area of primary matrix front was catachromasis in the controls by histology examination. The number of adipocytes in both the bone marrow and the percentage of adipocyte accounting for the area of bone cavity increased (P<0.01) in the experiment group. In the experiment group, the expression of PPARgamma mRNA was up-regulated (P<0.05) while Cbfalpha1 mRNA was down-regulated (P<0.05) in double femur marrow. CONCLUSION: Increased expression of PPARgamma mRNA and decreased expression of Cbfalpha1 mRNA in the bone marrow may cause impaired fracture healing in rats with Type 2 diabetes.

[Autologous bone marrow stem cell transplantation for treatment terminal liver diseases].

OBJECTIVE: To evaluate the effect of autologous bone marrow-derived stem cell (BMSCs) transplantation in the treatment of liver failure and decompensated hepatic cirrhosis. METHODS: Bone marrow was harvested (65-95 ml) from 24 patients in the transplantation group. The BMSCs were isolated and infused into liver or spleen of patients via hepatic or splenic artery. At different time points after the transplantation, the patients' liver function and prothrombin time (PT) were evaluated, and the survival rate and symptoms of the patients were recorded. RESULTS: All the serum biochemical indexes remained stable 2 weeks after the transplantation, and at 4 weeks after transplantation, albumin level increased significantly in comparison with the preoperative level (P<0.05). At 12 weeks, the albumin level further increased (P<0.01) along with Pre-ALB (P<0.01), while total bilirubin, tolal bile acid, PT and fibrinogen were all significantly lowered (P<0.05), and globulin, ALT, and AST remained unchanged (P>0.05). One week after the transplantation, improved appetite was observed in 22 cases (91.67%), and 21 cases (87.5%) showed better physical strength; at 2 weeks, hepatic face improved in 15 cases (62.5%), and spider telangiectasia was significantly reduced in one case; at 12 weeks, the survival rate of the patients was 62.5%, and 9 died or gave up treatment due to chronic liver failure complicated by spontaneous bacterial peritonitis, hepatorenal syndrome, or DIC. No complications associated with the transplantation occurred in these patients. CONCLUSION: BMSC transplantation can significantly improve the liver function of patients with terminal liver disease with good safety and effectiveness.

Preparation, in vitro and in vivo evaluation of liposomal/niosomal gel delivery systems for clotrimazole.

Clotrimazole, which is an imidazole derivative antifungal agent, was widely used for the treatment of mycotic infections of the genitourinary tract. To develop alternative formulation for the vaginal administration of clotrimazole to provide sustained and controlled release of appropriate drug for local vaginal therapy, liposomes/niosomes were evaluated as delivery vehicles. To optimize the preparation of liposomes/niosomes with regard to size and entrapment efficiency, multilamellar liposomes/niosomes containing drug were prepared by lipid hydration method. The prepared liposomes/niosomes were incorporated into 2% carbopol gel, and the systems were evaluated for drug stability in phosphate-buffered saline (pH 7.4) and simulated vaginal fluid at 37 +/- 1 degrees C. Further, the vesicle gel system was evaluated by antifungal activity and tolerability on tissue level in rat.